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Sample records for factor homolog zvegf3

  1. Colored sl(N) link homology via matrix factorizations

    CERN Document Server

    Wu, Hao

    2011-01-01

    The Reshetikhin-Turaev sl(N) polynomial of links colored by wedge powers of the defining representation has been categorified via several different approaches. Here, we give a concise introduction to the categorification using matrix factorizations, which is a direct generalization of the Khovanov-Rozansky homology. Full details of the construction are given in [arXiv:0907.0695]. We also briefly review deformations and applications of this categorification given in [arXiv:1002.2662, arXiv:1011.2254, arXiv:1102.0586].

  2. A quality metric for homology modeling: the H-factor

    Science.gov (United States)

    2011-01-01

    Background The analysis of protein structures provides fundamental insight into most biochemical functions and consequently into the cause and possible treatment of diseases. As the structures of most known proteins cannot be solved experimentally for technical or sometimes simply for time constraints, in silico protein structure prediction is expected to step in and generate a more complete picture of the protein structure universe. Molecular modeling of protein structures is a fast growing field and tremendous works have been done since the publication of the very first model. The growth of modeling techniques and more specifically of those that rely on the existing experimental knowledge of protein structures is intimately linked to the developments of high resolution, experimental techniques such as NMR, X-ray crystallography and electron microscopy. This strong connection between experimental and in silico methods is however not devoid of criticisms and concerns among modelers as well as among experimentalists. Results In this paper, we focus on homology-modeling and more specifically, we review how it is perceived by the structural biology community and what can be done to impress on the experimentalists that it can be a valuable resource to them. We review the common practices and provide a set of guidelines for building better models. For that purpose, we introduce the H-factor, a new indicator for assessing the quality of homology models, mimicking the R-factor in X-ray crystallography. The methods for computing the H-factor is fully described and validated on a series of test cases. Conclusions We have developed a web service for computing the H-factor for models of a protein structure. This service is freely accessible at http://koehllab.genomecenter.ucdavis.edu/toolkit/h-factor. PMID:21291572

  3. Homologous radioimmunoassay for human epidermal growth factor (urogastrone)

    Energy Technology Data Exchange (ETDEWEB)

    Dailey, G.E.; Kraus, J.W.; Orth, D.N.

    1978-06-01

    Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +- 3.0 and 52.0 +- 3.5 (mean +- SE) ..mu..g/total vol, or 29.7 +- 1.1 and 39.8 +- 1.7 ..mu..g/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +- 2.7 ..mu..g/g creatinine; P < 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and ..beta..-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +- 2.6 ..mu..g/g creatinine) than normal men, but this was not significant (P > 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion.

  4. Fibroblast growth factor homologous factors in the heart: a potential locus for cardiac arrhythmias.

    Science.gov (United States)

    Wei, Eric Q; Barnett, Adam S; Pitt, Geoffrey S; Hennessey, Jessica A

    2011-10-01

    The four fibroblast growth factor homologous factors (FHFs; FGF11-FGF14) are intracellular proteins that bind and modulate voltage-gated sodium channels (VGSCs). Although FHFs have been well studied in neurons and implicated in neurologic disease, their role in cardiomyocytes was unclear until recently. This review discusses the expression profile and function of FHFs in mouse and rat ventricular cardiomyocytes. Recent data show that FGF13 is the predominant FHF in the murine heart, directly binds the cardiac VGSC α subunit, and is essential for normal cardiac conduction. FHF loss-of-function mutations may be unrecognized causes of cardiac arrhythmias, such as long QT and Brugada syndromes.

  5. SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia

    Science.gov (United States)

    Musa, Hassan; Kline, Crystal F.; Sturm, Amy C.; Murphy, Nathaniel; Adelman, Sara; Wang, Chaojian; Yan, Haidun; Johnson, Benjamin L.; Csepe, Thomas A.; Kilic, Ahmet; Higgins, Robert S. D.; Janssen, Paul M. L.; Fedorov, Vadim V.; Weiss, Raul; Salazar, Christina; Hund, Thomas J.; Pitt, Geoffrey S.; Mohler, Peter J.

    2015-01-01

    Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia, and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants that directly affect Nav channel permeability or gating. However, a new class of human Nav channelopathies has emerged based on channel variants that alter regulation by intracellular signaling or cytoskeletal proteins. Fibroblast growth factor homologous factors (FHFs) are a family of intracellular signaling proteins linked with Nav channel regulation in neurons and myocytes. However, to date, there is surprisingly little evidence linking Nav channel gene variants with FHFs and human disease. Here, we provide, to our knowledge, the first evidence that mutations in SCN5A (encodes primary cardiac Nav channel Nav1.5) that alter FHF binding result in human cardiovascular disease. We describe a five*generation kindred with a history of atrial and ventricular arrhythmias, cardiac arrest, and sudden cardiac death. Affected family members harbor a novel SCN5A variant resulting in p.H1849R. p.H1849R is localized in the central binding core on Nav1.5 for FHFs. Consistent with these data, Nav1.5 p.H1849R affected interaction with FHFs. Further, electrophysiological analysis identified Nav1.5 p.H1849R as a gain-of-function for INa by altering steady-state inactivation and slowing the rate of Nav1.5 inactivation. In line with these data and consistent with human cardiac phenotypes, myocytes expressing Nav1.5 p.H1849R displayed prolonged action potential duration and arrhythmogenic afterdepolarizations. Together, these findings identify a previously unexplored mechanism for human Nav channelopathy based on altered Nav1.5 association with FHF proteins. PMID:26392562

  6. An integumentary mucin (FIM-B.1) from Xenopus laevis homologous with von Willebrand factor.

    Science.gov (United States)

    Probst, J C; Gertzen, E M; Hoffmann, W

    1990-07-03

    We present a new protein from X. laevis skin termed "frog integumentary mucin B.1" (FIM-B.1) with a general structure similar to FIM-A.1 (formerly "spasmolysin"). The central region consisting of tandem repeats of 11 amino acid residues is probably a target for extensive O-glycosylation, whereas the C-terminal cysteine-rich domain shows pronounced homology with the C1-C2 domains and the C-terminal end of von Willebrand factor. Furthermore, we describe homology with antistasin, an anticoagulant peptide from a leech. We also discuss some implications concerning the evolutionary origin of von Willebrand factor. In situ hybridization studies revealed the expression of FIM-B.1 exclusively in mucous glands of the skin. This is comparable with FIM-A.1 but is in contrast to all other physiologically active peptides, which are synthesized in granular glands.

  7. Hepatoma-derived growth factor-related protein 2 promotes DNA repair by homologous recombination

    Science.gov (United States)

    Baude, Annika; Aaes, Tania Løve; Zhai, Beibei; Al-Nakouzi, Nader; Oo, Htoo Zarni; Daugaard, Mads; Rohde, Mikkel; Jäättelä, Marja

    2016-01-01

    We have recently identified lens epithelium-derived growth factor (LEDGF/p75, also known as PSIP1) as a component of the homologous recombination DNA repair machinery. Through its Pro-Trp-Trp-Pro (PWWP) domain, LEDGF/p75 binds to histone marks associated with active transcription and promotes DNA end resection by recruiting DNA endonuclease retinoblastoma-binding protein 8 (RBBP8/CtIP) to broken DNA ends. Here we show that the structurally related PWWP domain-containing protein, hepatoma-derived growth factor-related protein 2 (HDGFRP2), serves a similar function in homologous recombination repair. Its depletion compromises the survival of human U2OS osteosarcoma and HeLa cervix carcinoma cells and impairs the DNA damage-induced phosphorylation of replication protein A2 (RPA2) and the recruitment of DNA endonuclease RBBP8/CtIP to DNA double strand breaks. In contrast to LEDGF/p75, HDGFRP2 binds preferentially to histone marks characteristic for transcriptionally silent chromatin. Accordingly, HDGFRP2 is found in complex with the heterochromatin-binding chromobox homologue 1 (CBX1) and Pogo transposable element with ZNF domain (POGZ). Supporting the functionality of this complex, POGZ-depleted cells show a similar defect in DNA damage-induced RPA2 phosphorylation as HDGFRP2-depleted cells. These data suggest that HDGFRP2, possibly in complex with POGZ, recruits homologous recombination repair machinery to damaged silent genes or to active genes silenced upon DNA damage. PMID:26721387

  8. Conserved steroid hormone homology converges on nuclear factor κB to modulate inflammation in asthma.

    Science.gov (United States)

    Payne, Asha S; Freishtat, Robert J

    2012-01-01

    Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity, yet it has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing (Pediatr Pulmonol Suppl. 1997;15:9-12). Despite the complex pathogenesis of asthma, steroid hormones (eg, glucocorticoids) are ubiquitous in the short-term and long-term management of all types of asthma. Overall, steroid hormones are a class of widely relevant, biologically active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they use rapid, nongenomic actions to affect cellular products. Steroid hormones comprise several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggests that each of these is part of a dynamic system of hormone interaction, likely involving an overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these 3 groups of steroid hormones (ie, glucocorticoids, sex steroid hormones, and secosteroids), identifying nuclear factor κB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (eg, glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be a better understanding of the interplay of classic, nonclassic, and nongenomic steroid hormone functions. However, clues from the conserved homology steroid hormone structure and function and signaling pathways offer

  9. Regulation of Steroidogenesis, Development, and Cell Differentiation by Steroidogenic Factor-1 and Liver Receptor Homolog-1.

    Science.gov (United States)

    Yazawa, Takashi; Imamichi, Yoshitaka; Miyamoto, Kaoru; Khan, Md Rafiqul Islam; Uwada, Junsuke; Umezawa, Akihiro; Taniguchi, Takanobu

    2015-08-01

    Steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1) belong to the nuclear receptor superfamily and are categorized as orphan receptors. In addition to other nuclear receptors, these play roles in various physiological phenomena by regulating the transcription of target genes. Both factors share very similar structures and exhibit common functions. Of these, the roles of SF-1 and LRH-1 in steroidogenesis are the most important, especially that of SF-1, which was originally discovered and named to reflect such roles. SF-1 and LRH-1 are essential for steroid hormone production in gonads and adrenal glands through the regulation of various steroidogenesis-related genes. As SF-1 is also necessary for the development of gonads and adrenal glands, it is also considered a master regulator of steroidogenesis. Recent studies have clearly demonstrated that LRH-1 also represents another master regulator of steroidogenesis, which similarly to SF-1, can induce differentiation of non-steroidogenic stem cells into steroidogenic cells. Here, we review the functions of both factors in these steroidogenesis-related phenomena.

  10. Employing libraries of zinc finger artificial transcription factors to screen for homologous recombination mutants in Arabidopsis.

    Science.gov (United States)

    Lindhout, Beatrice I; Pinas, Johan E; Hooykaas, Paul J J; van der Zaal, Bert J

    2006-11-01

    A library of genes for zinc finger artificial transcription factors (ZF-ATF) was generated by fusion of DNA sequences encoding three-finger Cys(2)His(2) ZF domains to the VP16 activation domain under the control of the promoter of the ribosomal protein gene RPS5A from Arabidopsis thaliana. After introduction of this library into an Arabidopsis homologous recombination (HR) indicator line, we selected primary transformants exhibiting multiple somatic recombination events. After PCR-mediated rescue of ZF sequences, reconstituted ZF-ATFs were re-introduced in the target line. In this manner, a ZF-ATF was identified that led to a 200-1000-fold increase in somatic HR (replicated in an independent second target line). A mutant plant line expressing the HR-inducing ZF-ATF exhibited increased resistance to the DNA-damaging agent bleomycin and was more sensitive to methyl methanesulfonate (MMS), a combination of traits not described previously. Our results demonstrate that the use of ZF-ATF pools is highly rewarding when screening for novel dominant phenotypes in Arabidopsis.

  11. DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Yuxin Feng

    Full Text Available Estrogen receptor alpha (ERα, a ligand-dependent transcription factor, mediates the expression of its target genes by interacting with corepressors and coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor cofactors have been identified, which orchestrate target gene transcription. Aberrant activity of ER or its accessory proteins results in a number of diseases including breast cancer. Here we identified SFR1, a protein involved in DNA homologous recombination, as a novel binding partner of ERα. Initially isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERα was confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co-localized with ERα in the nucleus, potentiated ER's ligand-dependent and ligand-independent transcriptional activity, and occupied the ER binding sites of its target gene promoters. Knockdown of SFR1 diminished ER's transcriptional activity. Manipulating SFR1 expression by knockdown and overexpression revealed a role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1 differs from SRC1 by the lack of an intrinsic activation function. Taken together, we propose that SFR1 is a novel transcriptional modulator for ERα and a potential target in breast cancer therapy.

  12. Isolation of novel human cDNA (hGMF-gamma) homologous to Glia Maturation Factor-beta gene.

    Science.gov (United States)

    Asai, K; Fujita, K; Yamamoto, M; Hotta, T; Morikawa, M; Kokubo, M; Moriyama, A; Kato, T

    1998-03-13

    A novel full-length human cDNA homologous to Glia Maturation Factor-beta (GMF-beta) gene was isolated. Sequence analysis of the entire cDNA revealed an open reading frame of 426 nucleotides with a deduced protein sequence of 142 amino acid residues. The deduced amino acid sequences of its putative product is highly homologous to human GMF-beta (82% identity) and named for GMF-gamma. Northern blot analysis indicated that a message of 0.9 kb long, but not 4.1 kb of GMF-beta, is predominantly expressed in human lung, heart, and placenta.

  13. Homolog of allograft inflammatory factor-1 induces macrophage migration during innate immune response in leech.

    Science.gov (United States)

    Schorn, Tilo; Drago, Francesco; Tettamanti, Gianluca; Valvassori, Roberto; de Eguileor, Magda; Vizioli, Jacopo; Grimaldi, Annalisa

    2015-03-01

    Allograft inflammatory factor-1 (AIF-1) is a 17-kDa cytokine-inducible calcium-binding protein that, in vertebrates, plays an important role in the allograft immune response. Its expression is mostly limited to the monocyte/macrophage lineage. Until recently, AIF-1 was assumed to be a novel molecule involved in inflammatory responses. To clarify this aspect, we have investigated the expression of AIF-1 after bacterial challenge and its potential role in regulating the innate immune response in an invertebrate model, the medicinal leech (Hirudo medicinalis). Analysis of an expressed sequence tag library from the central nervous system of Hirudo revealed the presence of the gene Hmaif-1/alias Hmiba1, showing high homology with vertebrate aif-1. Immunohistochemistry with an anti-HmAIF-1 polyclonal antibody revealed the constitutive presence of this protein in spread CD68(+) macrophage-like cells. A few hours after pathogen (bacterial) injection into the body wall, the amount of these immunopositive cells co-expressing HmAIF-1 and the common leucocyte marker CD45 increased at the injected site. Moreover, the recombinant protein HmAIF-1 induced massive angiogenesis and was a potent chemoattractant for macrophages. Following rHmAIF-1 stimulation, macrophage-like cells co-expressed the macrophage marker CD68 and the surface glycoprotein CD45, which, in vertebrates, seems to have a role in the integrin-mediated adhesion of macrophages and in the regulation of the functional responsiveness of cells to chemoattractants. CD45 is therefore probably involved in leech macrophage-like cell activation and migration towards an inflammation site. We have also examined its potential effect on HmAIF-1-induced signalling.

  14. The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation

    OpenAIRE

    Vivanco, Igor; Rohle, Daniel; Versele, Matthias; Iwanami, Akio; Kuga, Daisuke; Oldrini, Barbara; Tanaka, Kazuhiro; Dang, Julie; Kubek, Sara; Palaskas, Nicolaos; Hsueh, Teli; Evans, Michael; Mulholland, David; Wolle, Daniel; Rajasekaran, Sigrid

    2010-01-01

    The phosphatase and tensin homolog (PTEN) is a tumor suppressor that is inactivated in many human cancers. PTEN loss has been associated with resistance to inhibitors of the epidermal growth factor receptor (EGFR), but the molecular basis of this resistance is unclear. It is believed that unopposed phosphatidylinositol-3-kinase (PI3K) activation through multiple receptor tyrosine kinases (RTKs) can relieve PTEN-deficient cancers from their “dependence” on EGFR or any other single RTK for surv...

  15. Homologous and cross-reactive immune responses to enterotoxigenic Escherichia coli colonization factors in Bangladeshi children.

    Science.gov (United States)

    Qadri, Firdausi; Ahmed, Firoz; Ahmed, Tanvir; Svennerholm, Ann-Mari

    2006-08-01

    We have studied homologous (HoM) and cross-reacting (CR) immunoglobulin A (IgA) antibody responses to colonization factors (CFs) in Bangladeshi children with diarrhea due to enterotoxigenic E. coli (ETEC) strains of the CF antigen I (CFA/I) group (CFA/I, n = 25; coli surface antigen 4 [CS4], n = 8; CS14, n = 11) and the CS5 group (CS5, n = 15; CS7, n = 8), respectively. The responses to the HoM, CR, and heterologous (HeT) CF antigens in each group of patient were studied and compared to that seen in healthy children (n = 20). In the CFA/I group (CFA/I and CS14), patients responded with antibody-secreting cell (ASC) responses to HoM CFs (geometric mean, 156 to 329 ASCs/10(6) peripheral blood mononuclear cells [PBMCs]) and to CR CFs ( approximately 15 to 38 ASCs/10(6) PBMCs) but least of all to the HeT CS5 antigen (2 to 4 ASCs/10(6) PBMCs). For the CS5 group of patients with ETEC (CS5 and CS7), likewise, responses to HoM CFs (230 to 372 ASCs/10(6) PBMCs) and CR CFs (27 to 676 ASCs/10(6) PBMCs) were seen, along with lower responses to the HeT CFA/I antigen (9 to 38 ASCs/10(6) PBMCs). Both groups of patients responded with CF-specific IgA antibodies to HoM and CR antigens in plasma but responded less to the HeT CFs. The responses in patients were seen very soon after the onset of diarrhea and peaked around 1 week after onset. Vaccinees who had received two doses of the oral, killed whole-cell ETEC vaccine (CF-BS-ETEC) responded with plasma IgA antibodies to CFA/I, a component of the vaccine, but also to the CR CS14 antigen, which was not included in the vaccine, showing that antibody responses can be stimulated by a CFA/I-containing ETEC vaccine to a CR-reacting antigen in individuals in countries where ETEC is endemic.

  16. Pf-Rel, a Rel/Nuclear Factor-κB Homolog Identified from the Pearl Oyster, Pinctada fucata

    Institute of Scientific and Technical Information of China (English)

    Xi WU; Xunhao XIONG; Liping XIE; Rongqing ZHANG

    2007-01-01

    Transcription factor Rel/nuclear factor-kappa B (NF-κB) has been the focus of many studies since its discovery in 1986. Different homologs of Rel/NF-κB have been found in both vertebrate and invertebrate.A cDNA clone encoding a putative Rel/NF-κB homolog (designated Pf-Rel) was isolated from the pearl oyster, Pinctadafucata. The sequence of Pf-Rel consists of the Rel homology domain, IPT NF-κB domain and C-terminal transactivation domain. Sequence analysis of Pf-Rel shows that it shares high similarity with other Rel/NF-κB family proteins, especially within the conserved domains. Reverse transcription-polymerase chain reaction analysis revealed that Pf-Rel mRNA was expressed ubiquitously. Further in situ hybridization analysis showed that Pf-Rel mRNA was expressed mainly at the outer epithelial cells of the middle fold and the inner epithelial cells of the outer fold. The identification and characterization of pearl oyster Pf-Rel help to further investigate the involvement of Rel/NF-κB in oyster immunity and other biological processes.

  17. Heterogeneous dynamics in DNA site discrimination by the structurally homologous DNA-binding domains of ETS-family transcription factors.

    Science.gov (United States)

    He, Gaofei; Tolic, Ana; Bashkin, James K; Poon, Gregory M K

    2015-04-30

    The ETS family of transcription factors exemplifies current uncertainty in how eukaryotic genetic regulators with overlapping DNA sequence preferences achieve target site specificity. PU.1 and Ets-1 represent archetypes for studying site discrimination by ETS proteins because their DNA-binding domains are the most divergent in sequence, yet they share remarkably superimposable DNA-bound structures. To gain insight into the contrasting thermodynamics and kinetics of DNA recognition by these two proteins, we investigated the structure and dynamics of site discrimination by their DNA-binding domains. Electrophoretic mobilities of complexes formed by the two homologs with circularly permuted binding sites showed significant dynamic differences only for DNA complexes of PU.1. Free solution measurements by dynamic light scattering showed PU.1 to be more dynamic than Ets-1; moreover, dynamic changes are strongly coupled to site discrimination by PU.1, but not Ets-1. Interrogation of the protein/DNA interface by DNA footprinting showed similar accessibility to dimethyl sulfate for PU.1/DNA and Ets-1/DNA complexes, indicating that the dynamics of PU.1/DNA complexes reside primarily outside that interface. An information-based analysis of the two homologs' binding motifs suggests a role for dynamic coupling in PU.1's ability to enforce a more stringent sequence preference than Ets-1 and its proximal sequence homologs. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. The Tiam1 Guanine Nucleotide Exchange Factor is Auto-inhibited by its Pleckstrin Homology Coiled-Coil Extension Domain.

    Science.gov (United States)

    Xu, Zhen; Gakhar, Lokesh; Bain, Fletcher E; Spies, Maria; Fuentes, Ernesto J

    2017-09-07

    T-cell lymphoma invasion and metastasis 1 (Tiam1) is a Dbl-family guanine nucleotide exchange factor (GEF) that specifically activates the Rho-family GTPase Rac1 in response to upstream signals, thereby regulating cellular processes including cell adhesion and migration. Tiam1 contains multiple domains, including an N-terminal Pleckstrin homology coiled-coiled extension (PHn-CC-Ex) and catalytic Dbl-homology and C-terminal Pleckstrin homology (DH-PHc) domain. Previous studies indicate that larger fragments of Tiam1, such the region encompassing the N-terminal to C-terminal Pleckstrin homology domains (PHn-PHc) are auto-inhibited. However, the domains in this region responsible for inhibition remain unknown. Here, we show that the PHn-CC-Ex domain inhibits Tiam1 GEF activity by directly interacting with the catalytic DH-PHc domain, preventing Rac1 binding and activation. Enzyme kinetics experiments suggested that Tiam1 is auto-inhibited through occlusion of the catalytic site, rather than by allostery. Small angle X-ray scattering and ensemble modeling yielded models of the PHn-PHc fragment that indicate it is in equilibrium between open and closed conformational states. Finally, single-molecule experiments support a model in which conformational sampling between the open and closed states of Tiam1 contributes to Rac1 dissociation. Our results highlight the role of the PHn-CC-Ex domain in Tiam1 GEF regulation, and suggest a combinatorial model for GEF inhibition and activation of the Rac1 signaling pathway. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  19. Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

    Science.gov (United States)

    Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

    2017-02-01

    Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as

  20. Genomic identification of WRKY transcription factors in carrot (Daucus carota) and analysis of evolution and homologous groups for plants.

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    Li, Meng-Yao; Xu, Zhi-Sheng; Tian, Chang; Huang, Ying; Wang, Feng; Xiong, Ai-Sheng

    2016-03-15

    WRKY transcription factors belong to one of the largest transcription factor families. These factors possess functions in plant growth and development, signal transduction, and stress response. Here, we identified 95 DcWRKY genes in carrot based on the carrot genomic and transcriptomic data, and divided them into three groups. Phylogenetic analysis of WRKY proteins from carrot and Arabidopsis divided these proteins into seven subgroups. To elucidate the evolution and distribution of WRKY transcription factors in different species, we constructed a schematic of the phylogenetic tree and compared the WRKY family factors among 22 species, which including plants, slime mold and protozoan. An in-depth study was performed to clarify the homologous factor groups of nine divergent taxa in lower and higher plants. Based on the orthologous factors between carrot and Arabidopsis, 38 DcWRKY proteins were calculated to interact with other proteins in the carrot genome. Yeast two-hybrid assay showed that DcWRKY20 can interact with DcMAPK1 and DcMAPK4. The expression patterns of the selected DcWRKY genes based on transcriptome data and qRT-PCR suggested that those selected DcWRKY genes are involved in root development, biotic and abiotic stress response. This comprehensive analysis provides a basis for investigating the evolution and function of WRKY genes.

  1. The role of Candida albicans homologous recombination factors Rad54 and Rdh54 in DNA damage sensitivity

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    White Theodore C

    2011-09-01

    Full Text Available Abstract Background The fungal pathogen Candida albicans is frequently seen in immune suppressed patients, and resistance to one of the most widely used antifungals, fluconazole (FLC, can evolve rapidly. In recent years it has become clear that plasticity of the Candida albicans genome contributes to drug resistance through loss of heterozygosity (LOH at resistance genes and gross chromosomal rearrangements that amplify gene copy number of resistance associated genes. This study addresses the role of the homologous recombination factors Rad54 and Rdh54 in cell growth, DNA damage and FLC resistance in Candida albicans. Results The data presented here support a role for homologous recombination in cell growth and DNA damage sensitivity, as Candida albicans rad54Δ/rad54Δ mutants were hypersensitive to MMS and menadione, and had an aberrant cell and nuclear morphology. The Candida albicans rad54Δ/rad54Δ mutant was defective in invasion of Spider agar, presumably due to the altered cellular morphology. In contrast, mutation of the related gene RDH54 did not contribute significantly to DNA damage resistance and cell growth, and deletion of either Candida albicans RAD54 or Candida albicans RDH54 did not alter FLC susceptibility. Conclusions Together, these results support a role for homologous recombination in genome stability under nondamaging conditions. The nuclear morphology defects in the rad54Δ/rad54Δ mutants show that Rad54 performs an essential role during mitotic growth and that in its absence, cells arrest in G2. The viability of the single mutant rad54Δ/rad54Δ and the inability to construct the double mutant rad54Δ/rad54Δ rdh54Δ/rdh54Δ suggests that Rdh54 can partially compensate for Rad54 during mitotic growth.

  2. The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

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    Brock J. Sishc

    2017-07-01

    Full Text Available DNA double-strand breaks (DSBs are deleterious DNA lesions that if left unrepaired or are misrepaired, potentially result in chromosomal aberrations, known drivers of carcinogenesis. Pathways that direct the repair of DSBs are traditionally believed to be guardians of the genome as they protect cells from genomic instability. The prominent DSB repair pathway in human cells is the non-homologous end joining (NHEJ pathway, which mediates template-independent re-ligation of the broken DNA molecule and is active in all phases of the cell cycle. Its role as a guardian of the genome is supported by the fact that defects in NHEJ lead to increased sensitivity to agents that induce DSBs and an increased frequency of chromosomal aberrations. Conversely, evidence from tumors and tumor cell lines has emerged that NHEJ also promotes chromosomal aberrations and genomic instability, particularly in cells that have a defect in one of the other DSB repair pathways. Collectively, the data present a conundrum: how can a single pathway both suppress and promote carcinogenesis? In this review, we will examine NHEJ’s role as both a guardian and a disruptor of the genome and explain how underlying genetic context not only dictates whether NHEJ promotes or suppresses carcinogenesis, but also how it alters the response of tumors to conventional therapeutics.

  3. A point mutation in the extracellular domain activates LET-23, the Caenorhabditis elegans epidermal growth factor receptor homolog.

    Science.gov (United States)

    Katz, W S; Lesa, G M; Yannoukakos, D; Clandinin, T R; Schlessinger, J; Sternberg, P W

    1996-01-01

    The let-23 gene encodes a Caenorhabditis elegans homolog of the epidermal growth factor receptor (EGFR) necessary for vulval development. We have characterized a mutation of let-23 that activates the receptor and downstream signal transduction, leading to excess vulval differentiation. This mutation alters a conserved cysteine residue in the extracellular domain and is the first such point mutation in the EGFR subfamily of tyrosine kinases. Mutation of a different cysteine in the same subdomain causes a strong loss-of-function phenotype, suggesting that cysteines in this region are important for function and nonequivalent. Vulval precursor cells can generate either of two subsets of vulval cells (distinct fates) in response to sa62 activity. The fates produced depended on the copy number of the mutation, suggesting that quantitative differences in receptor activity influence the decision between these two fates. PMID:8552080

  4. Structural motifs and potential sigma homologies in the large subunit of human general transcription factor TFIIE.

    Science.gov (United States)

    Ohkuma, Y; Sumimoto, H; Hoffmann, A; Shimasaki, S; Horikoshi, M; Roeder, R G

    1991-12-05

    The general transcription factor TFIIE has an essential role in eukaryotic transcription initiation together with RNA polymerase II and other general factors. Human TFIIE consists of two subunits of relative molecular mass 57,000 (TFIIE-alpha) and 34,000 (TFIIE-beta) and joins the preinitiation complex after RNA polymerase II and TFIIF. Here we report the cloning and structure of a complementary DNA encoding a functional human TFIIE-alpha. TFIIE-alpha is necessary for transcription initiation together with TFIIE-beta, and recombinant TFIIE-alpha can fully replace the natural subunit in an in vitro transcription assay. The sequence contains several interesting structural motifs (leucine repeat, zinc finger and helix-turn-helix) and sequence similarities to bacterial sigma factors that suggest direct involvement in the regulation of transcription initiation.

  5. Enhanced somatic embryogenesis in Theobroma cacao using the homologous BABY BOOM transcription factor.

    Science.gov (United States)

    Florez, Sergio L; Erwin, Rachel L; Maximova, Siela N; Guiltinan, Mark J; Curtis, Wayne R

    2015-05-16

    Theobroma cacao, the chocolate tree, is an important economic crop in East Africa, South East Asia, and South and Central America. Propagation of elite varieties has been achieved through somatic embryogenesis (SE) but low efficiencies and genotype dependence still presents a significant limitation for its propagation at commercial scales. Manipulation of transcription factors has been used to enhance the formation of SEs in several other plant species. This work describes the use of the transcription factor Baby Boom (BBM) to promote the transition of somatic cacao cells from the vegetative to embryonic state. An ortholog of the Arabidopsis thaliana BBM gene (AtBBM) was characterized in T. cacao (TcBBM). TcBBM expression was observed throughout embryo development and was expressed at higher levels during SE as compared to zygotic embryogenesis (ZE). TcBBM overexpression in A. thaliana and T. cacao led to phenotypes associated with SE that did not require exogenous hormones. While transient ectopic expression of TcBBM provided only moderate enhancements in embryogenic potential, constitutive overexpression dramatically increased SE proliferation but also appeared to inhibit subsequent development. Our work provides validation that TcBBM is an ortholog to AtBBM and has a specific role in both somatic and zygotic embryogenesis. Furthermore, our studies revealed that TcBBM transcript levels could serve as a biomarker for embryogenesis in cacao tissue. Results from transient expression of TcBBM provide confirmation that transcription factors can be used to enhance SE without compromising plant development and avoiding GMO plant production. This strategy could compliment a hormone-based method of reprogramming somatic cells and lead to more precise manipulation of SE at the regulatory level of transcription factors. The technology would benefit the propagation of elite varieties with low regeneration potential as well as the production of transgenic plants, which

  6. Directed homology

    DEFF Research Database (Denmark)

    Fahrenberg, Uli

    2004-01-01

    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....

  7. Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.

    Science.gov (United States)

    Twu, Olivia; Dessí, Daniele; Vu, Anh; Mercer, Frances; Stevens, Grant C; de Miguel, Natalia; Rappelli, Paola; Cocco, Anna Rita; Clubb, Robert T; Fiori, Pier Luigi; Johnson, Patricia J

    2014-06-03

    The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.

  8. Characterization of an Nmr homolog that modulates GATA factor-mediated nitrogen metabolite repression in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    I Russel Lee

    Full Text Available Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis.

  9. Crystal Structure of a Fibroblast Growth Factor Homologous Factor (FHF) Defines a Conserved Surface on FHFs for Binding and Modulation of Voltage-gated Sodium Channels

    Energy Technology Data Exchange (ETDEWEB)

    Goetz, R.; Dover, K; Laezza, F; Shtraizent, N; Huang, X; Tchetchik, D; Eliseenkova, A; Goldfarb, M; Mohammadi, M; et. al.

    2009-01-01

    Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel binding in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.

  10. The maize OST1 kinase homolog phosphorylates and regulates the maize SNAC1-type transcription factor.

    Directory of Open Access Journals (Sweden)

    Belmiro Vilela

    Full Text Available The Arabidopsis kinase OPEN STOMATA 1 (OST1 plays a key role in regulating drought stress signalling, particularly stomatal closure. We have identified and investigated the functions of the OST1 ortholog in Z. mays (ZmOST1. Ectopic expression of ZmOST1 in the Arabidopsis ost1 mutant restores the stomatal closure phenotype in response to drought. Furthermore, we have identified the transcription factor, ZmSNAC1, which is directly phosphorylated by ZmOST1 with implications on its localization and protein stability. Interestingly, ZmSNAC1 binds to the ABA-box of ZmOST1, which is conserved in SnRK2s activated by ABA and is part of the contact site for the negative-regulating clade A PP2C phosphatases. Taken together, our results indicate that ZmSNAC1 is a substrate of ZmOST1 and delineate a novel osmotic stress transcriptional pathway in maize.

  11. Tumor necrosis factor alpha of teleosts: in silico characterization and homology modeling

    Directory of Open Access Journals (Sweden)

    Tran Ngoc Tuan

    2016-10-01

    Full Text Available Tumor necrosis factor alpha (TNF- is known to be crucial in many biological activities of organisms. In this study, physicochemical properties and modeling of TNF- protein of fish was analyzed using in silico approach. TNF- proteins selected from fish species, including grass carp (Ctenopharyngodon idella, zebra fish (Danio rerio, Nile tilapia (Oreochromis niloticus, goldfish (Carassius auratus, and rainbow trout (Oncorhynchus mykiss were used in this study. Physicochemical characteristics with molecular weight, theoretical isoelectric point, extinction coefficient, aliphatic index, instability index, total number of negatively charged residues and positively charged residues, and grand average of hydropathicity were computed. All proteins were classified as transmembrane proteins. The “transmembrane region” and “TNF” domain were identified from protein sequences. The function prediction of proteins was also performed. Alpha helices and random coils were dominating in the secondary structure of the proteins. Three-dimensional structures were predicted and verified as good structures for the investigation of TNF- of fish by online server validation.

  12. Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors

    Science.gov (United States)

    Oyallon, Justine; Apitz, Holger; Miguel-Aliaga, Irene; Timofeev, Katarina; Ferreira, Lauren; Salecker, Iris

    2012-01-01

    During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail. PMID:22796650

  13. Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors.

    Science.gov (United States)

    Oyallon, Justine; Apitz, Holger; Miguel-Aliaga, Irene; Timofeev, Katarina; Ferreira, Lauren; Salecker, Iris

    2012-09-15

    During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail.

  14. Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation.

    Directory of Open Access Journals (Sweden)

    Eugénie Ansseau

    Full Text Available Hundreds of double homeobox (DUX genes map within 3.3-kb repeated elements dispersed in the human genome and encode DNA-binding proteins. Among these, we identified DUX4, a potent transcription factor that causes facioscapulohumeral muscular dystrophy (FSHD. In the present study, we performed yeast two-hybrid screens and protein co-purifications with HaloTag-DUX fusions or GST-DUX4 pull-down to identify protein partners of DUX4, DUX4c (which is identical to DUX4 except for the end of the carboxyl terminal domain and DUX1 (which is limited to the double homeodomain. Unexpectedly, we identified and validated (by co-immunoprecipitation, GST pull-down, co-immunofluorescence and in situ Proximal Ligation Assay the interaction of DUX4, DUX4c and DUX1 with type III intermediate filament protein desmin in the cytoplasm and at the nuclear periphery. Desmin filaments link adjacent sarcomere at the Z-discs, connect them to sarcolemma proteins and interact with mitochondria. These intermediate filament also contact the nuclear lamina and contribute to positioning of the nuclei. Another Z-disc protein, LMCD1 that contains a LIM domain was also validated as a DUX4 partner. The functionality of DUX4 or DUX4c interactions with cytoplasmic proteins is underscored by the cytoplasmic detection of DUX4/DUX4c upon myoblast fusion. In addition, we identified and validated (by co-immunoprecipitation, co-immunofluorescence and in situ Proximal Ligation Assay as DUX4/4c partners several RNA-binding proteins such as C1QBP, SRSF9, RBM3, FUS/TLS and SFPQ that are involved in mRNA splicing and translation. FUS and SFPQ are nuclear proteins, however their cytoplasmic translocation was reported in neuronal cells where they associated with ribonucleoparticles (RNPs. Several other validated or identified DUX4/DUX4c partners are also contained in mRNP granules, and the co-localizations with cytoplasmic DAPI-positive spots is in keeping with such an association. Large muscle RNPs

  15. Homological descent for motivic homology theories

    OpenAIRE

    Geisser, Thomas

    2014-01-01

    The purpose of this paper is to give homological descent theorems for motivic homology theories (for example, Suslin homology) and motivic Borel-Moore homology theories (for example, higher Chow groups) for certain hypercoverings.

  16. Entamoeba histolytica-Encoded Homolog of Macrophage Migration Inhibitory Factor Contributes to Mucosal Inflammation during Amebic Colitis.

    Science.gov (United States)

    Ngobeni, Renay; Abhyankar, Mayuresh M; Jiang, Nona M; Farr, Laura A; Samie, Amidou; Haque, Rashidul; Moonah, Shannon N

    2017-04-15

    Understanding the mechanisms by which Entamoeba histolytica drives gut inflammation is critical for the development of improved preventive and therapeutic strategies. E. histolytica encodes a homolog of the human cytokine macrophage migration inhibitory factor (MIF). Here, we investigated the role of E. histolytica MIF (EhMIF) during infection. We found that the concentration of fecal EhMIF correlated with the level of intestinal inflammation in persons with intestinal amebiasis. Mice treated with antibodies that specifically block EhMIF had reduced chemokine expression and neutrophil infiltration in the mucosa. In addition to antibody-mediated neutralization, we used a genetic approach to test the effect of EhMIF on mucosal inflammation. Mice infected with parasites overexpressing EhMIF had increased chemokine expression, neutrophil influx, and mucosal damage. Together, these results uncover a specific parasite protein that increases mucosal inflammation, expands our knowledge of host-parasite interaction during amebic colitis, and highlights a potential immunomodulatory target. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  17. A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF) and Liver Receptor Homolog-1 (LRH-1).

    Science.gov (United States)

    Weikum, Emily R; Tuntland, Micheal L; Murphy, Michael N; Ortlund, Eric A

    2016-10-27

    Oct4 is a transcription factor required for maintaining pluripotency and self-renewal in stem cells. Prior to differentiation, Oct4 must be silenced to allow for the development of the three germ layers in the developing embryo. This fine-tuning is controlled by the nuclear receptors, liver receptor homolog-1 and germ cell nuclear factor. Liver receptor homolog-1 is responsible for driving the expression of Oct4 where germ cell nuclear factor represses its expression upon differentiation. Both receptors bind to a DR0 motif located within the Oct4 promoter. Here, we present the first structure of mouse germ cell nuclear factor DNA binding domain in complex with the Oct4 DR0. The overall structure revealed two molecules bound in a head-to-tail fashion on opposite sides of the DNA. Additionally, we solved the structure of the human liver receptor homolog-1 DNA binding domain bound to the same element. We explore the structural elements that govern Oct4 recognition by these two nuclear receptors.

  18. Mitochondrial pAL2-1 plasmid homologs are senescence factors in Podospora anserina independent of intrinsic senescence

    NARCIS (Netherlands)

    Diepeningen, van A.D.; Debets, A.J.M.; Slakhorst-Wandel, S.M.; Hoekstra, R.F.

    2008-01-01

    Since the first description of a linear mitochondrial plasmid in Podospora anserina, pAL2-1, and homologous plasmids have gone from being considered beneficial longevity plasmids, via neutral genetic elements, toward mutator plasmids causing senescence. The plasmid has an invertron structure, with t

  19. Mitochondrial pAL2-1 plasmid homologs are senescence factors in Podospora anserina independent of intrinsic senescence

    NARCIS (Netherlands)

    Diepeningen, van A.D.; Debets, A.J.M.; Slakhorst-Wandel, S.M.; Hoekstra, R.F.

    2008-01-01

    Since the first description of a linear mitochondrial plasmid in Podospora anserina, pAL2-1, and homologous plasmids have gone from being considered beneficial longevity plasmids, via neutral genetic elements, toward mutator plasmids causing senescence. The plasmid has an invertron structure, with

  20. Mitochondrial pAL2-1 plasmid homologs are senescence factors in Podospora anserina independent of intrinsic senescence

    NARCIS (Netherlands)

    van Diepeningen, Anne D; Debets, Alfons J M; Slakhorst, S Marijke; Hoekstra, Rolf F

    Since the first description of a linear mitochondrial plasmid in Podospora anserina, pAL2-1, and homologous plasmids have gone from being considered beneficial longevity plasmids, via neutral genetic elements, toward mutator plasmids causing senescence. The plasmid has an invertron structure, with

  1. Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition.

    OpenAIRE

    Schreiber, M; Sedger, L; McFadden, G

    1997-01-01

    The myxoma virus tumor necrosis factor (TNF) receptor homolog, M-T2, is expressed both as a secreted glycoprotein that inhibits the cytolytic activity of rabbit TNF-alpha and as an endoglycosidase H-sensitive intracellular species that prevents myxoma virus-infected CD4+ T lymphocytes from undergoing apoptosis. To compare the domains of M-T2 mediating extracellular TNF inhibition and intracellular apoptosis inhibition, recombinant myxoma viruses expressing nested C-terminal truncations of M-T...

  2. Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

    Directory of Open Access Journals (Sweden)

    Philippe Thullier

    Full Text Available The lethal toxin (LT of Bacillus anthracis, composed of the protective antigen (PA and the lethal factor (LF, plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF to form the edema toxin (ET, which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF. Here, we report that scFv 2LF cross-reacts with EF and cross-neutralizes ET, and we present an in silico method taking advantage of this cross-reactivity to map the epitope of scFv 2LF on both LF and EF. This method identified five epitope candidates on LF, constituted of a total of 32 residues, which were tested experimentally by mutating the residues to alanine. This combined approach precisely identified the epitope of scFv 2LF on LF as five residues (H229, R230, Q234, L235 and Y236, of which three were missed by the consensus epitope candidate identified by pre-existing in silico methods. The homolog of this epitope on EF (H253, R254, E258, L259 and Y260 was experimentally confirmed to constitute the epitope of scFv 2LF on EF. Other inhibitors, including synthetic molecules, could be used to target these epitopes for therapeutic purposes. The in silico method presented here may be of more general interest.

  3. CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor.

    Science.gov (United States)

    Inohara, N; Koseki, T; Chen, S; Wu, X; Núñez, G

    1998-05-01

    DFF45 is a subunit of the DNA fragmentation factor (DFF) that is cleaved by caspase-3 during apoptosis. However, the mechanism by which DFF45 regulates apoptotic cell death remains poorly understood. Here we report the identification and characterization of two mammalian genes, CIDE-A and CIDE-B, encoding highly related proteins with homology to the N-terminal region of DFF45. CIDE-A and CIDE-B were found to activate apoptosis in mammalian cells, which was inhibited by DFF45 but not by caspase inhibitors. Expression of CIDE-A induced DNA fragmentation in 293T cells, which was inhibited by DFF45, further suggesting that DFF45 inhibits the apoptotic activities of CIDEs. In addition to mammalian CIDE-A and CIDE-B, we identified DREP-1, a Drosophila melanogaster homolog of DFF45 that could inhibit CIDE-A-mediated apoptosis. Mutant analysis revealed that the C-terminal region of CIDE-A was necessary and sufficient for killing whereas the region with homology to DFF45 located in the N-terminus was required for DFF45 to inhibit CIDE-A-induced apoptosis. CD95/Fas-mediated apoptosis was enhanced by CIDEs but inhibited by DFF45. These studies suggest that DFF45 is evolutionarily conserved and implicate CIDEs as DFF45-inhibitable effectors that promote cell death and DNA fragmentation.

  4. Constitutive expression of human coagulating factor IX in HeLa cells by homologous recombination of the promoter

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Constitutive expression of hFIX protein in nonhepatocytes wasstudied. The gene targeting vector was constructed and transferred into HeLa cells. With the detection system of PCR, we demonstrated that the endogenous hFIX promoter was replaced with an hCMV promoter when targeted insertion of the constructor was directed by the sequence homology. The expression of hFIX in the modified HeLa cells, 11.2 ng/106 cell/24 h, strongly suggested that hFIX gene could be activated by a powerful promoter in nonhepatocytes. The results would make it possible to examine the feasibility of re-regulate gene expression by promoter replacement.

  5. A polymerase chain reaction-based approach to cloning sigma factors from eubacteria and its application to the isolation of a sigma-70 homolog from Chlamydia trachomatis.

    Science.gov (United States)

    Engel, J N; Ganem, D

    1990-05-01

    Taking advantage of the known sequence conservation of portions of bacterial sigma factor proteins, we have designed degenerate oligonucleotides corresponding to these domains and used these synthetic DNA sequences as primers in a polymerase chain reaction (PCR) to amplify DNA sequences from the chlamydial genome. The PCR products were used as a probe to recover the genomic fragments from a library of cloned murine Chlamydia trachomatis DNA. Sequence analysis of one of these clones revealed striking homology to the sigma-70 protein of Escherichia coli and the sigma-43 protein of Bacillus subtilis, strongly implying that this locus (sigA) encodes the major vegetative sigma factor of murine C. trachomatis. This PCR-based approach will be broadly applicable to the cloning of major sigma factors from other eubacteria.

  6. Homology and causes.

    Science.gov (United States)

    Van Valen, L M

    1982-09-01

    Homology is resemblance caused by a continuity of information. In biology it is a unified developmental phenomenon. Homologies among and within individuals intergrade in several ways, so historical homology cannot be separated sharply from repetitive homology. Nevertheless, the consequences of historical and repetitive homologies can be mutually contradictory. A detailed discussion of the rise and fall of the "premolar-analogy" theory of homologies of mammalian molar-tooth cusps exemplifies such a contradiction. All other hypotheses of historical homology which are based on repetitive homology, such as the foliar theory of the flower considered phyletically, are suspect.

  7. Substrate specificity and recognition is conferred by the pleckstrin homology domain of the Dbl family guanine nucleotide exchange factor P-Rex2.

    Science.gov (United States)

    Joseph, Raji E; Norris, F A

    2005-07-29

    Dbl family guanine nucleotide exchange factors (GEFs) are characterized by the presence of a catalytic Dbl homology domain followed invariably by a lipid-binding pleckstrin homology (PH) domain. To date, substrate recognition and specificity of this family of GEFs has been reported to be mediated exclusively via the Dbl homology domain. Here we report the novel and unexpected finding that, in the Dbl family Rac-specific GEF P-Rex2, it is the PH domain that confers substrate specificity and recognition. Moreover, the beta3beta4 loop of the PH domain of P-Rex2 is the determinant for Rac1 recognition, as substitution of the beta3beta4 loop of the PH domain of Dbs (a RhoA- and Cdc42-specific GEF) with that of P-Rex2 confers Rac1-specific binding capability to the PH domain of Dbs. The contact interface between the PH domain of P-Rex2 and Rac1 involves the switch loop and helix 3 of Rac1. Moreover, substitution of helix 3 of Cdc42 with that of Rac1 now enables the PH domain of P-Rex2 to bind this Cdc42 chimera. Despite having the ability to recognize this chimeric Cdc42, P-Rex2 is unable to catalyze nucleotide exchange on Cdc42, suggesting that recognition of substrate and catalysis are two distinct events. Thus substrate recognition can now be added to the growing list of functions that are being attributed to the PH domain of Dbl family GEFs.

  8. Mouse Dac, a novel nuclear factor with homology to Drosophila dachshund shows a dynamic expression in the neural crest, the eye, the neocortex, and the limb bud.

    Science.gov (United States)

    Caubit, X; Thangarajah, R; Theil, T; Wirth, J; Nothwang, H G; Rüther, U; Krauss, S

    1999-01-01

    Dac is a novel nuclear factor in mouse and humans that shares homology with Drosophila dachshund (dac). Alignment with available sequences defines a conserved box of 117 amino acids that shares weak homology with the proto-oncogene Ski and Sno. Dac expression is found in various neuroectodermal and mesenchymal tissues. At early developmental stages Dac is expressed in lateral mesoderm and in neural crest cells. In the neural plate/tube Dac expression is initially seen in the prosencephalon and gets gradually restricted to the presumptive neocortex and the distal portion of the outgrowing optic vesicle. Furthermore, Dac transcripts are detected in the mesenchyme underlying the Apical Ectodermal Ridge (AER) of the extending limb bud, the dorsal root ganglia and chain ganglia, and the mesenchyme of the growing genitalia. Dac expression in the Gli 3 mutant extra toes (Xt/Xt) shows little difference compared to the expression in wild-type limb buds. In contrast, a significant expansion of Dac expression are observed in the anterior mesenchyme of the limb buds of hemimelic extra toes (Hx/+) mice. FISH analysis reveals that human DAC maps to chromosome 13q22.3-23 and further fine-mapping defined a position of the DAC gene at 54cM or 13q21.1, a locus that associates with mental retardation and skeletal abnormalities.

  9. Deletion of the znuA virulence factor attenuates Actinobacillus pleuropneumoniae and confers protection against homologous or heterologous strain challenge.

    Science.gov (United States)

    Yuan, Fangyan; Liao, Yonghong; You, Wujin; Liu, Zewen; Tan, Yongqiang; Zheng, Chengkun; BinWang; Zhou, Danna; Tian, Yongxiang; Bei, Weicheng

    2014-12-05

    The znuA gene is known to be important for growth and survival in Escherichia coli, Haemophilus spp., Neisseria gonorrhoeae, and Pasteurella multocida under low Zn(2+) conditions. This gene is also present in Actinobacillus pleuropneumoniae serotype 1; therefore, the aim of this study was to investigate the existence of a similar role for the znuA gene in the growth and virulence of this organism. A precisely defined ΔznuA deletion mutant of A. pleuropneumoniae was constructed based on the sequence of the wild-type SLW01 using transconjugation and counterselection. This mutation was found to be lethal in low-Zn(2+) medium. Furthermore, the ΔznuA mutant strain exhibited attenuated virulence (≥22-fold) as well as reduced mortality and morbidity in a murine (Balb/C) model of infection. The majority of the bacteria were cleared from the lungs within 2 weeks. The ΔznuA mutant strain caused no adverse effects in pigs at doses of up to 1.0×10(9) CFU/mL. The ΔznuA mutant strain induced a significant immune response and conferred 80% and 100% protection on immunised pigs against challenge with A. pleuropneumoniae strains belonging to homologous or heterologous serovars, respectively, compared to the blank controls. The data obtained in this study indicate the potential of the mutant ΔznuA strain for development as a live vaccine capable of inducing reliable cross-serovar protection following intratracheal immunisation. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Homology, Analogy, and Ethology.

    Science.gov (United States)

    Beer, Colin G.

    1984-01-01

    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…

  11. Hydroxylation of aspartic acid in domains homologous to the epidermal growth factor precursor is catalyzed by a 2-oxoglutarate-dependent dioxygenase.

    Science.gov (United States)

    Stenflo, J; Holme, E; Lindstedt, S; Chandramouli, N; Huang, L H; Tam, J P; Merrifield, R B

    1989-01-01

    3-Hydroxyaspartic acid and 3-hydroxyasparagine are two rare amino acids that are present in domains homologous to the epidermal growth factor precursor in vitamin K-dependent plasma proteins as well as in proteins that do not require vitamin K for normal biosynthesis. They are formed by posttranslational hydroxylation of aspartic acid and asparagine, respectively. The first epidermal growth factor-like domain in factor IX (residues 45-87) was synthesized with aspartic acid in position 64, replacing 3-hydroxyaspartic acid. It was used as substrate in a hydroxylase assay with rat liver microsomes as the source of enzyme and reaction conditions that satisfy the requirements of 2-oxoglutarate-dependent dioxygenases. The synthetic peptide stimulated the 2-oxoglutarate decarboxylation in contrast to synthetic, modified epidermal growth factor (Met-21 and His-22 deleted and Glu-24 replaced by Asp) and synthetic peptides corresponding to residues 60-71 in human factor IX. This indicates that the hydroxylase is a 2-oxoglutarate-dependent dioxygenase with a selective substrate requirement. Images PMID:2492106

  12. Zinc finger artificial transcription factor-based nearest inactive analogue/nearest active analogue strategy used for the identification of plant genes controlling homologous recombination.

    Science.gov (United States)

    Jia, Qi; van Verk, Marcel C; Pinas, Johan E; Lindhout, Beatrice I; Hooykaas, Paul J J; van der Zaal, Bert J

    2013-12-01

    In previous work, we selected a particular transcription factor, designated VP16-HRU, from a pool of zinc finger artificial transcription factors (ZF-ATFs) used for genome interrogation. When expressed in Arabidopsis thaliana under control of the ribosomal protein S5A promoter, the RPS5A::VP16-HRU construct led to a 200- to 300-fold increase in the frequency of somatic intrachromosomal homologous recombination (iHR). Because the expression of each ZF-ATF leads to a large number of transcriptional changes, we designed a strategy employing a collection of structurally similar ZF-ATFs to filter out the transcriptional changes relevant to the phenotype by deep sequencing. In that manner, 30 transcripts were found to be consistently induced in plants with enhanced homologous recombination (HR). For 25 of the cognate genes, their effect on the HR process was assessed using cDNA/gDNA expression constructs. For three genes, ectopic expression indeed led to enhanced iHR frequencies, albeit much lower than the frequency observed when a HR-inducing ZF-ATF was present. Altogether, our data demonstrate that despite the large number of transcriptional changes brought about by individual ZF-ATFs, causal changes can be identified. In our case, the picture emerged that a natural regulatory switch for iHR does not exist but that ZF-ATFs-like VP16-HRU act as an ectopic master switch, orchestrating the timely expression of a set of plant genes that each by themselves only have modest effects, but when acting together support an extremely high iHR frequency.

  13. Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Apostolos Zavos; Alexandros Daponte; Antonios Garas; Christina Verykouki; Evangelos Papanikolaou; Georgios Anifandis; Nikolaos P Polyzos

    2013-01-01

    Male factor infertility affects 30%-50% of infertile couples worldwide,and there is an increasing interest in the optimal management of these patients.In studies comparing double and single intrauterine insemination (IUI),a trend towards higher pregnancy rates in couples with male factor infertility was observed.Therefore,we set out to perform a meta-analysis to examine the superiority of double versus single IUI with the male partner's sperm in couples with male factor infertility.An odds ratio (OR) of 95% confidence intervals (Cls) was calculated for the pregnancy rate.Outcomes were analysed by using the ManteI-Haesel or DerSimonian-Laird model according to the heterogeneity of the results.Overall,five trials involving 1125 I UI cycles were included in the meta-analysis.There was a two-fold increase in pregnancies after a cycle with a double I UI compared with a cycle with a single IUI (OR:2.0; 95% CI:1.07-3.75;P<0.03).Nevertheless,this result was mainly attributed to the presence of a large trial that weighted as almost 50% in the overall analysis.Sensitivity analysis,excluding this large trial,revealed only a trend towards higher pregnancy rates among double IUI cycles (OR:1.58; 95% CI:0.59-4.21),but without statistical significance (P=-0.20).Our systematic review highlights that the available evidence regarding the use of double I UI in couples with male factor infertility is fragmentary and weak.Although there may be a trend towards higher pregnancy rates when the number of IUIs per cycle is increased,further large and well-designed randomized trials are needed to provide solid evidence to guide current clinical practice.

  14. CUS1, a suppressor of cold-sensitive U2 snRNA mutations, is a novel yeast splicing factor homologous to human SAP 145.

    Science.gov (United States)

    Wells, S E; Neville, M; Haynes, M; Wang, J; Igel, H; Ares, M

    1996-01-15

    The function of U2 snRNA in splicing is mediated by the proteins of the U2 small nuclear ribonucleoprotein. To identify proteins that influence the function of U2 snRNA we carried out a screen for mutations in Saccharomyces cerevisiae that suppress the cold-sensitive growth defect of a mutation in U2 stem loop IIa, a structure important for the stable association of the U2 snRNP with pre-mRNA. The screen identified three dominant suppressor genes, one of which, CUS1-54, encodes an essential splicing protein required for U2 snRNP addition to the spliceosome. The suppressor protein rescues the spliceosome assembly defect of the mutant U2 in vitro, indicating that suppression is direct. Allele specificity tests show that the suppressor does not simply bypass the requirement for U2 stem loop IIa. Extra copies of wild-type CUS1, but not CUS1-54, suppress the temperature-sensitive prp11 and prp5 mutations, linking CUS1 protein to a subset of other factors required at the same step of spliceosome assembly. CUS1 is homologous to SAP 145, a component of the mammalian U2 snRNP that interacts with pre-mRNA. The yeast genome also encodes a homolog of human SAP 49, a protein that interacts strongly with both SAP 145 and pre-mRNA, underscoring the conservation of U2 snRNP proteins that function in spliceosome assembly.

  15. Combinatorial Floer Homology

    CERN Document Server

    de Silva, Vin; Salamon, Dietmar

    2012-01-01

    We define combinatorial Floer homology of a transverse pair of noncontractibe nonisotopic embedded loops in an oriented 2-manifold without boundary, prove that it is invariant under isotopy, and prove that it is isomorphic to the original Lagrangian Floer homology.

  16. Gene structure, cDNA characterization and RNAi-based functional analysis of a myeloid differentiation factor 88 homolog in Tenebrio molitor larvae exposed to Staphylococcus aureus infection.

    Science.gov (United States)

    Patnaik, Bharat Bhusan; Patnaik, Hongray Howrelia; Seo, Gi Won; Jo, Yong Hun; Lee, Yong Seok; Lee, Bok Luel; Han, Yeon Soo

    2014-10-01

    Myeloid differentiation factor 88 (MyD88), an intracellular adaptor protein involved in Toll/Toll-like receptor (TLR) signal processing, triggers activation of nuclear factor-kappaB (NF-κB) transcription factors. In the present study, we analyzed the gene structure and biological function of MyD88 in a coleopteran insect, Tenebrio molitor (TmMyD88). The TmMyD88 gene was 1380 bp in length and consisted of five exons and four introns. The 5'-flanking sequence revealed several putative transcription factor binding sites, such as STAT-4, AP-1, cJun, cfos, NF-1 and many heat shock factor binding elements. The cDNA contained a typical death domain, a conservative Toll-like interleukin-1 receptor (TIR) domain, and a C-terminal extension (CTE). The TmMyD88 TIR domain showed three significantly conserved motifs for interacting with the TIR domain of TLRs. TmMyD88 was grouped within the invertebrate cluster of the phylogenetic tree and shared 75% sequence identity with the TIR domain of Tribolium castaneum MyD88. Homology modeling of the TmMyD88 TIR domain revealed five parallel β-strands surrounded by five α-helices that adopted loop conformations to function as an adaptor. TmMyD88 expression was upregulated 7.3- and 4.79-fold after 12 and 6h, respectively, of challenge with Staphylococcus aureus and fungal β-1,3 glucan. Silencing of the TmMyD88 transcript by RNA interference led to reduced resistance of the host to infection by S. aureus. These results indicate that TmMyD88 is required for survival against Staphylococcus infection.

  17. The mammalian hypusine-containing protein, eukaryotic initiation factor 4D. Structural homology of this protein from several species.

    Science.gov (United States)

    Park, M H; Chung, S I; Cooper, H L; Folk, J E

    1984-04-10

    A single cellular protein of Mr approximately 18,000 and pI near 5.1, recently identified as eukaryotic translation initiation factor eIF-4D, contains the unusual amino acid hypusine [N epsilon-(4-amino--2-hydroxybutyl)lysine] formed post-translationally from lysine with a structural contribution from the polyamine spermidine. When the 3H-labeled hypusine-containing protein isolated from Chinese hamster ovary (CHO) cells that were grown with radioactive polyamine is digested with trypsin and the digest is subjected to two-dimensional separation, a single radioactive peptide is seen. A labeled peptide that occupies this same position is found in a digest of the [3H]hypusine protein from human lymphocytes and the single hypusine-containing tryptic peptide from purified rabbit reticulocyte eIF-4D also moves to this identical position. Stepwise Edman degradation of the tryptic digest of CHO cell hypusine-protein releases the radioactivity as a single peak in accordance with our earlier evidence for a single hypusine residue per molecule of eIF-4D. The similar patterns of radioactive peptides obtained from tryptic digests of radioiodinated eIF-4D from CHO cells, human lymphocytes, and rabbit reticulocytes suggest a highly conserved primary structure for this protein.

  18. Genetic analysis of brahma: the Drosophila homolog of the yeast chromatin remodeling factor SWI2/SNF2.

    Science.gov (United States)

    Elfring, L K; Daniel, C; Papoulas, O; Deuring, R; Sarte, M; Moseley, S; Beek, S J; Waldrip, W R; Daubresse, G; DePace, A; Kennison, J A; Tamkun, J W

    1998-01-01

    The Drosophila brahma (brm) gene encodes an activator of homeotic genes related to the yeast chromatin remodeling factor SWI2/SNF2. Here, we report the phenotype of null and dominant-negative brm mutations. Using mosaic analysis, we found that the complete loss of brm function decreases cell viability and causes defects in the peripheral nervous system of the adult. A dominant-negative brm mutation was generated by replacing a conserved lysine in the ATP-binding site of the BRM protein with an arginine. This mutation eliminates brm function in vivo but does not affect assembly of the 2-MD BRM complex. Expression of the dominant-negative BRM protein caused peripheral nervous system defects, homeotic transformations, and decreased viability. Consistent with these findings, the BRM protein is expressed at relatively high levels in nuclei throughout the developing organism. Site-directed mutagenesis was used to investigate the functions of conserved regions of the BRM protein. Domain II is essential for brm function and is required for the assembly or stability of the BRM complex. In spite of its conservation in numerous eukaryotic regulatory proteins, the deletion of the bromodomain of the BRM protein has no discernible phenotype.

  19. HRP-2, the Caenorhabditis elegans homolog of mammalian heterogeneous nuclear ribonucleoproteins Q and R, is an alternative splicing factor that binds to UCUAUC splicing regulatory elements.

    Science.gov (United States)

    Kabat, Jennifer L; Barberan-Soler, Sergio; Zahler, Alan M

    2009-10-16

    Alternative splicing is regulated by cis sequences in the pre-mRNA that serve as binding sites for trans-acting alternative splicing factors. In a previous study, we used bioinformatics and molecular biology to identify and confirm that the intronic hexamer sequence UCUAUC is a nematode alternative splicing regulatory element. In this study, we used RNA affinity chromatography to identify trans factors that bind to this sequence. HRP-2, the Caenorhabditis elegans homolog of human heterogeneous nuclear ribonucleoproteins Q and R, binds to UCUAUC in the context of unc-52 intronic regulatory sequences as well as to RNAs containing tandem repeats of this sequence. The three Us in the hexamer are the most important determinants of this binding specificity. We demonstrate, using RNA interference, that HRP-2 regulates the alternative splicing of two genes, unc-52 and lin-10, both of which have cassette exons flanked by an intronic UCUAUC motif. We propose that HRP-2 is a protein responsible for regulating alternative splicing through binding interactions with the UCUAUC sequence.

  20. Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-binding Domains of the ETS Family Transcription Factors Ets-1 and PU.1*

    Science.gov (United States)

    Wang, Shuo; Linde, Miles H.; Munde, Manoj; Carvalho, Victor D.; Wilson, W. David; Poon, Gregory M. K.

    2014-01-01

    ETS family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a “dry” mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, whereas PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high affinity PU.1·DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydration-dependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages. PMID:24952944

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

    Science.gov (United States)

    Wang, W.; Poovaiah, B. W.

    1999-01-01

    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.

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

    Science.gov (United States)

    Wang, W.; Poovaiah, B. W.

    1999-01-01

    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.

  3. Real Topological Cyclic Homology

    DEFF Research Database (Denmark)

    Høgenhaven, Amalie

    The main topics of this thesis are real topological Hochschild homology and real topological cyclic homology. If a ring or a ring spectrum is equipped with an anti-involution, then it induces additional structure on the topological Hochschild homology spectrum. The group O(2) acts on the spectrum......, where O(2) is the semi-direct product of T, the multiplicative group of complex number of modulus 1, by the group G=Gal(C/R). We refer to this O(2)-spectrum as the real topological Hochschild homology. This generalization leads to a G-equivariant version of topological cyclic homology, which we call...... real topological cyclic homology. The first part of the thesis computes the G-equivariant homotopy type of the real topological cyclic homology of spherical group rings at a prime p with anti-involution induced by taking inverses in the group. The second part of the thesis investigates the derived G...

  4. Identification and characterization of a novel bacterial virulence factor that shares homology with mammalian Toll/interleukin-1 receptor family proteins.

    Science.gov (United States)

    Newman, Ruchi M; Salunkhe, Prabhakar; Godzik, Adam; Reed, John C

    2006-01-01

    Many important bacterial virulence factors act as mimics of mammalian proteins to subvert normal host cell processes. To identify bacterial protein mimics of components of the innate immune signaling pathway, we searched the bacterial genome database for proteins with homology to the Toll/interleukin-1 receptor (TIR) domain of the mammalian Toll-like receptors (TLRs) and their adaptor proteins. A previously uncharacterized gene, which we have named tlpA (for TIR-like protein A), was identified in the Salmonella enterica serovar Enteritidis genome that is predicted to encode a protein resembling mammalian TIR domains, We show that overexpression of TlpA in mammalian cells suppresses the ability of mammalian TIR-containing proteins TLR4, IL-1 receptor, and MyD88 to induce the transactivation and DNA-binding activities of NF-kappaB, a downstream target of the TIR signaling pathway. In addition, TlpA mimics the previously characterized Salmonella virulence factor SipB in its ability to induce activation of caspase-1 in a mammalian cell transfection model. Disruption of the chromosomal tlpA gene rendered a virulent serovar Enteritidis strain defective in intracellular survival and IL-1beta secretion in a cell culture infection model using human THP1 macrophages. Bacteria with disrupted tlpA also displayed reduced lethality in mice, further confirming an important role for this factor in pathogenesis. Taken together, our findings demonstrate that the bacterial TIR-like protein TlpA is a novel prokaryotic modulator of NF-kappaB activity and IL-1beta secretion that contributes to serovar Enteritidis virulence.

  5. The Allograft Inflammatory Factor-1 (AIF-1 homologous in Hirudo medicinalis (medicinal leech is involved in immune response during wound healing and graft rejection processes

    Directory of Open Access Journals (Sweden)

    T Schorn

    2015-05-01

    Full Text Available Allograft inflammatory factor-1 (AIF-1 is a 17 kDa cytokine-inducible calcium-binding protein that in Vertebrates plays an important role in allografts immune response. Since its expression is mainly limited to the monocyte/macrophage lineage, it was recently suggested that it could play a key role during inflammatory responses, allograft rejection, as well as in the activation of macrophages. To clarify this point we have focused our research on the possible role of AIF-1 during the inflammatory response after injury in the leech Hirudo medicinalis (Annelida, Hirudinea. This invertebrate is an excellent animal model since the responses evoked during inflammation and tissue repair are clear and easily detectable and have a striking similarity with vertebrate responses. Moreover the analysis of an EST library from H. medicinalis CNS, revealed the presence of a gene, named Hmaif-1/alias Hmiba1, showing a high homology with vertebrate aif-1. Our data show that the related protein, named HmAIF-1, is constitutively expressed in unlesioned leeches and that dramatically increases 48 h after wounds and tissue transplants. Immunohistochemistry experiments, using a specific anti HmAIF-1 polyclonal antibody, shows that this factor is present in spread, CD68+ /CD45+ macrophage-like cells. A few days after experimental wounding of the body wall, the amount of these immunopositive cells increases at the lesion site. In conclusion here we propose that in leech HmAIF-1 factor is involved in inflammation events like its vertebrate counterparts.

  6. GmPHR1, a Novel Homolog of the AtPHR1 Transcription Factor, Plays a Role in Plant Tolerance to Phosphate Starvation

    Institute of Scientific and Technical Information of China (English)

    LI Xi-huan; WANG Yun-jie; WU Bing; KONG You-bin; LI Wen-long; CHANG Wen-suo; ZHANG Cai-ying

    2014-01-01

    GmPHR1 from soybean (Glycine max) was isolated and characterized. This novel homolog of the AtPHR1 transcription factor confers tolerance to inorganic phosphate (Pi)-starvation. The gene is 2 751 bp long, with an 819-bp open reading frame and ifve introns. Analysis of transcription activity in yeast revealed that the full-length GmPHR1 and its C-terminal activate the reporter genes for His, Ade and Ura, suggesting that the C-terminal peptide functions as a transcriptional activator. Quantitative real-time PCR indicated that patterns of GmPHR1 expression differed. For example, under low-Pi stress, this gene was quickly induced in the tolerant JD11 after 0.5 h, with expression then decreasing slowly before peaking at 12-24 h. By contrast, induction in the sensitive Niumaohuang (NMH) was slow, peaking at 6 h before decreasing quickly at 9 h. GmPHR1 showed sub-cellular localization in the nuclei of onion epidermal cells and Arabidopsis roots. Growth parameters in wild-type (WT) Arabidopsis plants as well as in overexpression (OE) transgenic lines were examined. Under low-Pi conditions, values for shoot, root and whole-plant dry weights, root to shoot ratios, and lengths of primary roots were signiifcantly greater in OE lines than in the WT. These data demonstrate that GmPHR1 has an important role in conferring tolerance to phosphate starvation.

  7. Full Length cDNA Cloning of Human Coagulation Factor C Homology%人凝血因子C同源物基因全长cDNA克隆

    Institute of Scientific and Technical Information of China (English)

    孙勍; 韩东一; 程静; 王国建; 刘新; 于飞; 韩冰; 陈静; 戴朴; 袁慧军

    2009-01-01

    目的 通过克隆凝血因子C同源物基因(Coagulation factor C homology,COCH)全长cDNA,为COCH编码蛋白cochlin的功能研究打下基础.方法 从听力正常人新鲜外周静脉血中提取总RNA,应用一步法RT-PCR试剂盒进行COCH反转录,转录产物进行浓缩、酶切、连接.结果 反转录COCH cDNA全长与标准基因序列比较,结果完全相符,得到完整的COCH cDNA全长序列.结论 本研究成功克隆了COCH cDNA全长序列,为COCH编码蛋白cochlin的功能研究打下了良好的基础.

  8. Arabidopsis Small Rubber Particle Protein Homolog SRPs Play Dual Roles as Positive Factors for Tissue Growth and Development and in Drought Stress Responses.

    Science.gov (United States)

    Kim, Eun Yu; Park, Ki Youl; Seo, Young Sam; Kim, Woo Taek

    2016-04-01

    Lipid droplets (LDs) act as repositories for fatty acids and sterols, which are used for various cellular processes such as energy production and membrane and hormone synthesis. LD-associated proteins play important roles in seed development and germination, but their functions in postgermination growth are not well understood. Arabidopsis (Arabidopsis thaliana) contains three SRP homologs (SRP1, SRP2, and SRP3) that share sequence identities with small rubber particle proteins of the rubber tree (Hevea brasiliensis). In this report, the possible cellular roles of SRPs in postgermination growth and the drought tolerance response were investigated. Arabidopsis SRPs appeared to be LD-associated proteins and displayed polymerization properties in vivo and in vitro. SRP-overexpressing transgenic Arabidopsis plants (35S:SRP1, 35S:SRP2, and 35S:SRP3) exhibited higher vegetative and reproductive growth and markedly better tolerance to drought stress than wild-type Arabidopsis. In addition, constitutive over-expression of SRPs resulted in increased numbers of large LDs in postgermination seedlings. In contrast, single (srp1, 35S:SRP2-RNAi, and srp3) and triple (35S:SRP2-RNAi/srp1srp3) loss-of-function mutant lines exhibited the opposite phenotypes. Our results suggest that Arabidopsis SRPs play dual roles as positive factors in postgermination growth and the drought stress tolerance response. The possible relationships between LD-associated proteins and the drought stress response are discussed. © 2016 American Society of Plant Biologists. All Rights Reserved.

  9. Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor.

    Directory of Open Access Journals (Sweden)

    Sushant K Kachhap

    Full Text Available BACKGROUND: Histone deacetylase inhibitors (HDACis re-express silenced tumor suppressor genes and are currently undergoing clinical trials. Although HDACis have been known to induce gene expression, an equal number of genes are downregulated upon HDAC inhibition. The mechanism behind this downregulation remains unclear. Here we provide evidence that several DNA repair genes are downregulated by HDAC inhibition and provide a mechanism involving the E2F1 transcription factor in the process. METHODOLOGY/PRINCIPAL FINDINGS: Applying Analysis of Functional Annotation (AFA on microarray data of prostate cancer cells treated with HDACis, we found a number of genes of the DNA damage response and repair pathways are downregulated by HDACis. AFA revealed enrichment of homologous recombination (HR DNA repair genes of the BRCA1 pathway, as well as genes regulated by the E2F1 transcription factor. Prostate cancer cells demonstrated a decreased DNA repair capacity and an increased sensitization to chemical- and radio-DNA damaging agents upon HDAC inhibition. Recruitment of key HR repair proteins to the site of DNA damage, as well as HR repair capacity was compromised upon HDACi treatment. Based on our AFA data, we hypothesized that the E2F transcription factors may play a role in the downregulation of key repair genes upon HDAC inhibition in prostate cancer cells. ChIP analysis and luciferase assays reveal that the downregulation of key repair genes is mediated through decreased recruitment of the E2F1 transcription factor and not through active repression by repressive E2Fs. CONCLUSIONS/SIGNIFICANCE: Our study indicates that several genes in the DNA repair pathway are affected upon HDAC inhibition. Downregulation of the repair genes is on account of a decrease in amount and promoter recruitment of the E2F1 transcription factor. Since HDAC inhibition affects several pathways that could potentially have an impact on DNA repair, compromised DNA repair upon HDAC

  10. Mechanistic heterogeneity in site recognition by the structurally homologous DNA-binding domains of the ETS family transcription factors Ets-1 and PU.1.

    Science.gov (United States)

    Wang, Shuo; Linde, Miles H; Munde, Manoj; Carvalho, Victor D; Wilson, W David; Poon, Gregory M K

    2014-08-01

    ETS family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a "dry" mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, whereas PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high affinity PU.1 · DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydration-dependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Lectures on functor homology

    CERN Document Server

    Touzé, Antoine

    2015-01-01

    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...

  12. Lectures on knot homology

    CERN Document Server

    Nawata, Satoshi

    2015-01-01

    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.

  13. Regulated Localization Is Sufficient for Hormonal Control of Regulator of G Protein Signaling Homology Rho Guanine Nucleotide Exchange Factors (RH-RhoGEFs)*

    Science.gov (United States)

    Carter, Angela M.; Gutowski, Stephen; Sternweis, Paul C.

    2014-01-01

    The regulator of G protein signaling homology (RH) Rho guanine nucleotide exchange factors (RhoGEFs) (p115RhoGEF, leukemia-associated RhoGEF, and PDZ-RhoGEF) contain an RH domain and are specific GEFs for the monomeric GTPase RhoA. The RH domains interact specifically with the α subunits of G12 heterotrimeric GTPases. Activated Gα13 modestly stimulates the exchange activity of both p115RhoGEF and leukemia-associated RhoGEF but not PDZ-RhoGEF. Because all three RH-RhoGEFs can localize to the plasma membrane upon expression of activated Gα13, cellular localization of these RhoGEFs has been proposed as a mechanism for controlling their activity. We use a small molecule-regulated heterodimerization system to rapidly control the localization of RH-RhoGEFs. Acute localization of the proteins to the plasma membrane activates RhoA within minutes and to levels that are comparable with activation of RhoA by hormonal stimulation of G protein-coupled receptors. The catalytic activity of membrane-localized RhoGEFs is not dependent on activated Gα13. We further show that the conserved RH domains can rewire two different RacGEFs to activate Rac1 in response to a traditional activator of RhoA. Thus, RH domains act as independent detectors for activated Gα13 and are sufficient to modulate the activity of RhoGEFs by hormones via mediating their localization to substrate, membrane-associated RhoA. PMID:24855647

  14. [Phosphatase and tensin homolog deleted on chromosome ten/phosphatidyl Inositol 3-kinase/vascular endothelial growth factor signaling pathway changes in the rabbit Kawasaki disease model].

    Science.gov (United States)

    Niu, L; Fu, M Y; Tian, J; He, X H; Zhang, H N; Wang, Q W; Wang, Y; Li, C L; Wang, Z Z; An, X J

    2016-03-01

    To observe the changes of phosphatase and tensin homolog deleted on chromosome ten(PTEN)/ phosphatidyl Inositol 3-kinase(PI3K)/ vascular endothelial growth factor(VEGF)signaling pathway in a rabbit Kawasaki disease model. Model of Kawasaki disease was established in weanling Japanese big-eared rabbits with 10% bovine serum venous injection (2.5 ml/kg, 2 times, and 2 week's interval) through the ear. Twenty four rabbits were divided into 4 groups: control group (without injection of 10% bovine serum albumin, six rabbits); 1 day group (sacrificed a the second day after the establishment of Kawasaki disease models, six rabbits); 7 day group (sacrificed at the seventh day after establishment of Kawasaki disease model, six rabbits); 30 day group (sacrificed at the thirtieth day after establishment of Kawasaki disease model, six rabbits). Pathological analysis was performed on coronary artery tissue samples. The express of PTEN and PI3K were detected by immunohistochemistry. The levels of VEGF and CK were also examined with ELISA and white blood cells were counted. (1) Coronary artery of model groups was thinner, distorted and had enlarged lumen. (2) PTEN expression in 1 d group, 7 d group and 30 d group were 58.5 ± 12.9, 73.2±9.9 and 109.6 ± 24.4, respectively, significantly higher than in the control group (25.5 ± 6.9, P0.05) and significantly lower than 1 d and 7 d group (both P0.05). (6)White blood cell count were significantly higher in 1 d group, 7 d group and 30 d group than in control group (all PKawasaki disease model and the signaling pathway might be involved in this model.

  15. The Arabidopsis homologs of CCR4-associated factor 1 show mRNA deadenylation activity and play a role in plant defence responses

    Institute of Scientific and Technical Information of China (English)

    Wenxing Liang; Changbao Li; Fang Liu; Hongling Jiang; Shuyu Li; Jiaqiang Sun; Xiaoyan Wu; Chuanyou Li

    2009-01-01

    Messenger RNA (mRNA) turnover in eukaryotic cells begins with shortening of the poly (A) tail at the 3' end, a process called deadenylation. In yeast, the deadenylation reaction is predominantly mediated by CCR4 and CCR4-associated factor 1 (CAF1), two components of the well-characterised protein complex named CCR4-NOT. We re-port here that AtCAFla and AtCAFlb, putative Arabidopsis homologs of the yeast CAFI gene, partially complement the growth defect of the yeast cafl mutant in the presence of caffeine or at high temperatures. The expression of At-CAFla and AtCAFlb is induced by multiple stress-related hormones and stimuli. Both AtCAFIa and AtCAFIb show deadenylation activity in vitro and point mutations in the predicted active sites disrupt this activity. T-DNA inser-tion mutants disrupting the expression of AtCAFla and/or AtCAFlb are defective in deadenylation of stress-related mRNAs, indicating that the two AtCAFI proteins are involved in regulated mRNA deadenylation in vivo. Interest-ingly, the single and double mutants of AtCAFla and AtCAFlb show reduced expression of pathogenesis-related (PR) genes PR1 and PR2 and are more susceptible to Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection, whereas transgenic plants over-expressing AtCAFla show elevated expression of PR1 and PR2 and increased resis-tance to the same pathogen. Our results suggest roles of the AtCAF1 proteins in regulated mRNA deadenylation and defence responses to pathogen infections.

  16. Seifert fibered homology spheres with trivial Heegaard Floer homology

    OpenAIRE

    Eftekhary, Eaman

    2009-01-01

    We show that among Seifert fibered integer homology spheres, Poincare sphere (with either orientation) is the only non-trivial example which has trivial Heegaard Floer homology. Together with an earlier result, this shows that if an integer homology sphere has trivial Heegaard Floer homology, then it is a connected sum of a number of Poincare spheres and hyperbolic homology spheres.

  17. An interpretation of E_n-homology as functor homology

    OpenAIRE

    Livernet, Muriel; Richter, Birgit

    2009-01-01

    We prove that E_n-homology of non-unital commutative algebras can be described as functor homology when one considers functors from a certain category of planar trees with n levels. For different n these homology theories are connected by natural maps, ranging from Hochschild homology and its higher order versions to Gamma homology.

  18. Mediators of homologous DNA pairing.

    Science.gov (United States)

    Zelensky, Alex; Kanaar, Roland; Wyman, Claire

    2014-10-09

    Homologous DNA pairing and strand exchange are at the core of homologous recombination. These reactions are promoted by a DNA-strand-exchange protein assembled into a nucleoprotein filament comprising the DNA-pairing protein, ATP, and single-stranded DNA. The catalytic activity of this molecular machine depends on control of its dynamic instability by accessory factors. Here we discuss proteins known as recombination mediators that facilitate formation and functional activation of the DNA-strand-exchange protein filament. Although the basics of homologous pairing and DNA-strand exchange are highly conserved in evolution, differences in mediator function are required to cope with differences in how single-stranded DNA is packaged by the single-stranded DNA-binding protein in different species, and the biochemical details of how the different DNA-strand-exchange proteins nucleate and extend into a nucleoprotein filament. The set of (potential) mediator proteins has apparently expanded greatly in evolution, raising interesting questions about the need for additional control and coordination of homologous recombination in more complex organisms. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  19. On Galaxies and Homology

    OpenAIRE

    Novak, Gregory S.; Jonsson, Patrik; Primack, Joel R.; Cox, Thomas J.; Dekel, Avishai

    2012-01-01

    The definition of homology for single-component galaxies is clear, but for multi-component (luminous and dark matter) galaxies there is some ambiguity. We attempt to clarify the situation by carefully separating the different concepts of homology that have been used to date. We argue that the most useful definition is that a set of galaxies is homologous if they are the same in all respects up to a set of three dimensional scaling constants which may differ from one galaxy to the next. Noting...

  20. Role of Flightless-I (Drosophila) homolog in the transcription activation of type I collagen gene mediated by transforming growth factor beta

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Mi-Sun; Jeong, Kwang Won, E-mail: kwjeong@gachon.ac.kr

    2014-11-21

    Highlights: • FLII activates TGFβ-mediated expression of COL1A2 gene. • TGFβ induces the association of FLII with SMAD3 and BRG1 in A549 cells. • FLII is required for the recruitment of SWI/SNF complex and chromatin accessibility to COL1A2 promoter. - Abstract: Flightless-I (Drosophila) homolog (FLII) is a nuclear receptor coactivator that is known to interact with other transcriptional regulators such as the SWI/SNF complex, an ATP-dependent chromatin-remodeling complex, at the promoter or enhancer region of estrogen receptor (ER)-α target genes. However, little is known about the role of FLII during transcription initiation in the transforming growth factor beta (TGFβ)/SMAD-dependent signaling pathway. Here, we demonstrate that FLII functions as a coactivator in the expression of type I collagen gene induced by TGFβ in A549 cells. FLII activates the reporter gene driven by COL1A2 promoter in a dose-dependent manner. Co-expression of GRIP1, CARM1, or p300 did not show any synergistic activation of transcription. Furthermore, the level of COL1A2 expression correlated with the endogenous level of FLII mRNA level. Depletion of FLII resulted in a reduction of TGFβ-induced expression of COL1A2 gene. In contrast, over-expression of FLII caused an increase in the endogenous expression of COL1A2. We also showed that FLII is associated with Brahma-related gene 1 (BRG1) as well as SMAD in A549 cells. Notably, the recruitment of BRG1 to the COL1A2 promoter region was decreased in FLII-depleted A549 cells, suggesting that FLII is required for TGFβ-induced chromatin remodeling, which is carried out by the SWI/SNF complex. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments revealed that depletion of FLII caused a reduction in chromatin accessibility at the COL1A2 promoter. These results suggest that FLII plays a critical role in TGFβ/SMAD-mediated transcription of the COL1A2 gene

  1. HOMOLOGY RIGIDITY OF GRASSMANNIANS

    Institute of Scientific and Technical Information of China (English)

    Li Fang; Duan Haibao

    2009-01-01

    Applying the theory of GrSbner basis to the Schubert presentation for the cohomology of Grassmannians [2], we extend the homology rigidity results known for the classical Grassmaniaas to the exceptional cases.

  2. Homology, convergence and parallelism.

    Science.gov (United States)

    Ghiselin, Michael T

    2016-01-05

    Homology is a relation of correspondence between parts of parts of larger wholes. It is used when tracking objects of interest through space and time and in the context of explanatory historical narratives. Homologues can be traced through a genealogical nexus back to a common ancestral precursor. Homology being a transitive relation, homologues remain homologous however much they may come to differ. Analogy is a relationship of correspondence between parts of members of classes having no relationship of common ancestry. Although homology is often treated as an alternative to convergence, the latter is not a kind of correspondence: rather, it is one of a class of processes that also includes divergence and parallelism. These often give rise to misleading appearances (homoplasies). Parallelism can be particularly hard to detect, especially when not accompanied by divergences in some parts of the body. © 2015 The Author(s).

  3. Sutures and contact homology I

    CERN Document Server

    Colin, Vincent; Honda, Ko; Hutchings, Michael

    2010-01-01

    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.

  4. Singular (Lipschitz) homology and homology of integral currents

    OpenAIRE

    Riedweg, Christian; Schäppi, Daniel

    2009-01-01

    We compare the homology groups $H_n ^{IC}(X)$ of the chain complex of integral currents with compact support of a metric space $X$ with the singular Lipschitz homology $H^L_n (X)$ and with ordinary singular homology. If $X$ satisfies certain cone inequalities all these homology theories coincide. On the other hand, for the Hawaiian Earring the homology of integral currents differs from the singular Lipschitz homology and it differs also from the classical singular homology $H_n(X)$.

  5. Braid Floer homology

    Science.gov (United States)

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

    2015-09-01

    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.

  6. Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a critical virulence factor for the development of myxomatosis in European rabbits.

    Science.gov (United States)

    Mossman, K; Nation, P; Macen, J; Garbutt, M; Lucas, A; McFadden, G

    1996-01-01

    Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively

  7. G-C heterozygosis in mutS homolog2 as a risk factor to hereditary nonpolyposis colon cancer in the absence of a family medical history

    OpenAIRE

    Jorge Alfonso Arvayo-Zatarain; José Manuel Grijalva-Chon; Reina Castro-Longoria; Alejandro Varela-Romero

    2011-01-01

    To detect the presence of point mutations in a small section of the mutS homolog2 (MSH2) gene in both healthy and affected persons treated at the General Hospital of the State of Sonora, a 353 base pair section of the MSH2 gene was amplified and sequenced from six persons affected by hereditary nonpolyposis colorectal cancer and from 19 healthy persons. The affected persons did not show the mutations reported in the scientific literature; however, six healthy persons were heterozygote and mut...

  8. Gorenstein homological dimensions

    DEFF Research Database (Denmark)

    Holm, Henrik Granau

    2004-01-01

    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...

  9. Gorenstein homological dimensions

    DEFF Research Database (Denmark)

    Holm, Henrik Granau

    2004-01-01

    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...

  10. Control of intramolecular interactions between the pleckstrin homology and Dbl homology domains of Vav and Sos1 regulates Rac binding.

    Science.gov (United States)

    Das, B; Shu, X; Day, G J; Han, J; Krishna, U M; Falck, J R; Broek, D

    2000-05-19

    Vav and Sos1 are Dbl family guanine nucleotide exchange factors, which activate Rho family GTPases in response to phosphatidylinositol 3-kinase products. A pleckstrin homology domain adjacent to the catalytic Dbl homology domain via an unknown mechanism mediates the effects of phosphoinositides on guanine nucleotide exchange activity. Here we tested the possibility that phosphatidylinositol 3-kinase substrates and products control an interaction between the pleckstrin homology domain and the Dbl homology domain, thereby explaining the inhibitory effects of phosphatidylinositol 3-kinase substrates and stimulatory effects of the products. Binding studies using isolated fragments of Vav and Sos indicate phosphatidylinositol 3-kinase substrate promotes the binding of the pleckstrin homology domain to the Dbl homology domain and blocks Rac binding to the DH domain, whereas phosphatidylinositol 3-kinase products disrupt the Dbl homology/pleckstrin homology interactions and permit Rac binding. Additionally, Lck phosphorylation of Vav, a known activating event, reduces the affinities between the Vav Dbl homology and pleckstrin homology domains and permits Rac binding. We also show Vav activation in cells, as monitored by phosphorylation of Vav, Vav association with phosphatidylinositol 3,4,5-trisphosphate, and Vav guanine nucleotide exchange activity, is blocked by the phosphatidylinositol 3-kinase inhibitor wortmannin. These results suggest the molecular mechanisms for activation of Vav and Sos1 require disruption of inhibitory intramolecular interactions involving the pleckstrin homology and Dbl homology domains.

  11. G-C heterozygosis in mutS homolog2 as a risk factor to hereditary nonpolyposis colon cancer in the absence of a family medical history

    Directory of Open Access Journals (Sweden)

    Jorge Alfonso Arvayo-Zatarain

    2011-01-01

    Full Text Available To detect the presence of point mutations in a small section of the mutS homolog2 (MSH2 gene in both healthy and affected persons treated at the General Hospital of the State of Sonora, a 353 base pair section of the MSH2 gene was amplified and sequenced from six persons affected by hereditary nonpolyposis colorectal cancer and from 19 healthy persons. The affected persons did not show the mutations reported in the scientific literature; however, six healthy persons were heterozygote and mutant-allele carriers. The heterozygote condition implies that carriers are candidates for the development of colorectal cancer. However, it is important to know the family medical history when investigating hereditary mutations.

  12. G-C heterozygosis in mutS homolog2 as a risk factor to hereditary nonpolyposis colon cancer in the absence of a family medical history.

    Science.gov (United States)

    Arvayo-Zatarain, Jorge Alfonso; Grijalva-Chon, José Manuel; Castro-Longoria, Reina; Varela-Romero, Alejandro

    2011-05-01

    To detect the presence of point mutations in a small section of the mutS homolog2 (MSH2) gene in both healthy and affected persons treated at the General Hospital of the State of Sonora, a 353 base pair section of the MSH2 gene was amplified and sequenced from six persons affected by hereditary nonpolyposis colorectal cancer and from 19 healthy persons. The affected persons did not show the mutations reported in the scientific literature; however, six healthy persons were heterozygote and mutant-allele carriers. The heterozygote condition implies that carriers are candidates for the development of colorectal cancer. However, it is important to know the family medical history when investigating hereditary mutations.

  13. G-C heterozygosis in mutS homolog2 as a risk factor to hereditary nonpolyposis colon cancer in the absence of a family medical history

    Science.gov (United States)

    Arvayo-Zatarain, Jorge Alfonso; Grijalva-Chon, José Manuel; Castro-Longoria, Reina; Varela-Romero, Alejandro

    2011-01-01

    To detect the presence of point mutations in a small section of the mutS homolog2 (MSH2) gene in both healthy and affected persons treated at the General Hospital of the State of Sonora, a 353 base pair section of the MSH2 gene was amplified and sequenced from six persons affected by hereditary nonpolyposis colorectal cancer and from 19 healthy persons. The affected persons did not show the mutations reported in the scientific literature; however, six healthy persons were heterozygote and mutant-allele carriers. The heterozygote condition implies that carriers are candidates for the development of colorectal cancer. However, it is important to know the family medical history when investigating hereditary mutations. PMID:22090720

  14. Monopole Floer homology for rational homology 3-spheres

    OpenAIRE

    Froyshov, Kim A.

    2010-01-01

    We give a new construction of monopole Floer homology for $\\text{spin}^c$ rational homology $3$ -spheres. As applications, we define two invariants of certain $4$ -manifolds with $b_1=1$ and $b^+=0$ .

  15. Algebra V homological algebra

    CERN Document Server

    Shafarevich, I

    1994-01-01

    This book, the first printing of which was published as volume 38 of the Encyclopaedia of Mathematical Sciences, presents a modern approach to homological algebra, based on the systematic use of the terminology and ideas of derived categories and derived functors. The book contains applications of homological algebra to the theory of sheaves on topological spaces, to Hodge theory, and to the theory of modules over rings of algebraic differential operators (algebraic D-modules). The authors Gelfand and Manin explain all the main ideas of the theory of derived categories. Both authors are well-known researchers and the second, Manin, is famous for his work in algebraic geometry and mathematical physics. The book is an excellent reference for graduate students and researchers in mathematics and also for physicists who use methods from algebraic geometry and algebraic topology.

  16. Rabinowitz Floer homology: A survey

    CERN Document Server

    Albers, Peter

    2010-01-01

    Rabinowitz Floer homology is the semi-infinite dimensional Morse homology associated to the Rabinowitz action functional used in the pioneering work of Rabinowitz. Gradient flow lines are solutions of a vortex-like equation. In this survey article we describe the construction of Rabinowitz Floer homology and its applications to symplectic and contact topology, global Hamiltonian perturbations and the study of magnetic fields.

  17. Regulation of Homologous Recombination by SUMOylation

    DEFF Research Database (Denmark)

    Pinela da Silva, Sonia Cristina

    factors such as the homologous recombination (HR) machinery. HR constitutes the main DSB repair pathway in Saccharomyces cerevisiae and despite being largely considered an error-free process and essential for genome stability, uncontrolled recombination can lead to loss of heterozygosity, translocations...

  18. Zinc finger artificial transcription factor-based nearest inactive analogue/nearest active analogue strategy used for the identification of plant genes controlling homologous recombination

    NARCIS (Netherlands)

    Jia, Qi; van Verk, Marcel C.; Pinas, Johan E.; Lindhout, Beatrice I.; Hooykaas, Paul J.J.; Van der Zaal, Bert J.

    2013-01-01

    In previous work, we selected a particular transcription factor, designated VP16-HRU, from a pool of zinc finger artificial transcription factors (ZF-ATFs) used for genome interrogation. When expressed in Arabidopsis thaliana under control of the ribosomal protein S5A promoter, the RPS5A::VP16-HRU c

  19. Homologous recombination and its regulation

    Science.gov (United States)

    Krejci, Lumir; Altmannova, Veronika; Spirek, Mario; Zhao, Xiaolan

    2012-01-01

    Homologous recombination (HR) is critical both for repairing DNA lesions in mitosis and for chromosomal pairing and exchange during meiosis. However, some forms of HR can also lead to undesirable DNA rearrangements. Multiple regulatory mechanisms have evolved to ensure that HR takes place at the right time, place and manner. Several of these impinge on the control of Rad51 nucleofilaments that play a central role in HR. Some factors promote the formation of these structures while others lead to their disassembly or the use of alternative repair pathways. In this article, we review these mechanisms in both mitotic and meiotic environments and in different eukaryotic taxa, with an emphasis on yeast and mammal systems. Since mutations in several proteins that regulate Rad51 nucleofilaments are associated with cancer and cancer-prone syndromes, we discuss how understanding their functions can lead to the development of better tools for cancer diagnosis and therapy. PMID:22467216

  20. [DNA homologous recombination repair in mammalian cells].

    Science.gov (United States)

    Popławski, Tomasz; Błasiak, Janusz

    2006-01-01

    DNA double-strand breaks (DSBs) are the most serious DNA damage. Due to a great variety of factors causing DSBs, the efficacy of their repair is crucial for the cell's functioning and prevents DNA fragmentation, chromosomal translocation and deletion. In mammalian cells DSBs can be repaired by non-homologous end joining (NHEJ), homologous recombination (HRR) and single strand annealing (SSA). HRR can be divided into the first and second phase. The first phase is initiated by sensor proteins belonging to the MRN complex, that activate the ATM protein which target HRR proteins to obtain the second response phase--repair. HRR is precise because it utilizes a non-damaged homologous DNA fragment as a template. The key players of HRR in mammalian cells are MRN, RPA, Rad51 and its paralogs, Rad52 and Rad54.

  1. Homologous recombination in plants: an antireview.

    Science.gov (United States)

    Lieberman-Lazarovich, Michal; Levy, Avraham A

    2011-01-01

    Homologous recombination (HR) is a central cellular process involved in many aspects of genome maintenance such as DNA repair, replication, telomere maintenance, and meiotic chromosomal segregation. HR is highly conserved among eukaryotes, contributing to genome stability as well as to the generation of genetic diversity. It has been intensively studied, for almost a century, in plants and in other organisms. In this antireview, rather than reviewing existing knowledge, we wish to underline the many open questions in plant HR. We will discuss the following issues: how do we define homology and how the degree of homology affects HR? Are there any plant-specific HR qualities, how extensive is functional conservation and did HR proteins acquire new functions? How efficient is HR in plants and what are the cis and the trans factors that regulate it? Finally, we will give the prospects for enhancing the rates of gene targeting and meiotic HR for plant breeding purposes.

  2. The Chromosomal Courtship Dance-homolog pairing in early meiosis.

    Science.gov (United States)

    Klutstein, Michael; Cooper, Julia Promisel

    2014-02-01

    The intermingling of genomes that characterizes sexual reproduction requires haploid gametes in which parental homologs have recombined. For this, homologs must pair during meiosis. In a crowded nucleus where sequence homology is obscured by the enormous scale and packaging of the genome, partner alignment is no small task. Here we review the early stages of this process. Chromosomes first establish an initial docking site, usually at telomeres or centromeres. The acquisition of chromosome-specific patterns of binding factors facilitates homolog recognition. Chromosomes are then tethered to the nuclear envelope (NE) and subjected to nuclear movements that 'shake off' inappropriate contacts while consolidating homolog associations. Thereafter, homolog connections are stabilized by building the synaptonemal complex or its equivalent and creating genetic crossovers. Recent perspectives on the roles of these stages will be discussed.

  3. Field homology: a meaningful definition.

    Science.gov (United States)

    Cookson, K

    2001-02-01

    Field homology refers to populations of cells that derive from evolutionarily conserved regions of embryos but are distributed across sets of adult morphological structures that cannot be placed in one-to-one correspondance. The concept of field homology has proven especially attractive to comparative neurologists because it allows them to deal with the fact that sets of nuclei or nuclear subdivisions often cannot be compared on a one-to-one basis across phyletic groups. However, the concept of field homology has recently come under criticism. It has been argued that field homology is theoretically impossible because it requires sequences of developmental stages to be both evolutionarily conserved and evolutionarily modified. It has also been argued that field homology allows overly vague comparisons of adult morphological structures, fails to account for homologous structures that derive from non-homologous embryonic sources, and establishes overly rigid links between embryonic and adult morphology. All of these criticisms may be adequately addressed by explaining field homology in terms of differentiation. The present paper explains field homology in terms of differentiation using the amniote dorsal thalamus to illustrate major points. It is concluded that field homology is a meaningful concept when defined in terms of differentiation, applied to appropriate cases, and properly limited in its comparisons of adult structures.

  4. Rhythmical bimanual force production: homologous and non-homologous muscles.

    Science.gov (United States)

    Kennedy, Deanna M; Boyle, Jason B; Rhee, Joohyun; Shea, Charles H

    2015-01-01

    The experiment was designed to determine participants' ability to coordinate a bimanual multifrequency pattern of isometric forces using homologous or non-homologous muscles. Lissajous feedback was provided to reduce perceptual and attentional constraints. The primary purpose was to determine whether the activation of homologous and non-homologous muscles resulted in different patterns of distortions in the left limb forces that are related to the forces produced by the right limb. The task was to rhythmically produce a 1:2 pattern of isometric forces by exerting isometric forces on the left side force transducer with the left arm that was coordinated with the pattern of isometric forces produced on the right side force transducer with the right arm. The results indicated that participants were able to 'tune-in' a 1:2 coordination patterns using homologous (triceps muscles of the left and right limbs) and using non-homologous muscles (biceps left limb and triceps right limb) when provided Lissajous feedback. However, distinct but consistent and identifiable distortions in the left limb force traces were observed for both the homologous and non-homologous tasks. For the homologous task, the interference occurred in the left limb when the right limb was initiating and releasing force. For the non-homologous task, the interference in the left limb force occurred only when the right limb was releasing force. In both conditions, the interference appeared to continue from the point of force initiation and/or release to peak force velocity. The overall results are consistent with the notion that neural crosstalk manifests differently during the coordination of the limbs depending upon whether homologous or non-homologous muscles are activated.

  5. Homology, homoplasy, novelty, and behavior.

    Science.gov (United States)

    Hall, Brian K

    2013-01-01

    Richard Owen coined the modern definition of homology in 1843. Owen's conception of homology was pre-evolutionary, nontransformative (homology maintained basic plans or archetypes), and applied to the fully formed structures of animals. I sketch out the transition to an evolutionary approach to homology in which all classes of similarity are interpreted against the single branching tree of life, and outline the evidence for the application of homology across all levels and features of the biological hierarchy, including behavior. Owen contrasted homology with analogy. While this is not incorrect it is a pre-evolutionary contrast. Lankester [Lankester [1870] Journal of Natural History, 6 (31), 34-43] proposed homoplasy as the class of homology applicable to features formed by independent evolution. Today we identify homology, convergence, parallelism, and novelties as patterns of evolutionary change. A central issue in homology [Owen [1843] Lectures on comparative anatomy and physiology of the invertebrate animals, delivered at the Royal College of Surgeons in 1843. London: Longman, Brown, Green & Longmans] has been whether homology of features-the "same" portion of the brain in different species, for example-depends upon those features sharing common developmental pathways. Owen did not require this criterion, although he observed that homologues often do share developmental pathways (and we now know, often share gene pathways). A similar situation has been explored in the study of behavior, especially whether behaviors must share a common structural, developmental, neural, or genetic basis to be classified as homologous. However, and importantly, development and genes evolve. As shown with both theory and examples, morphological and behavioral features of the phenotype can be homologized as structural or behavioral homologues, respectively, even when their developmental or genetic bases differ (are not homologous). Copyright © 2012 Wiley Periodicals, Inc.

  6. Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib

    DEFF Research Database (Denmark)

    Rossing, Henrik H; Grauslund, Morten; Urbanska, Edyta M;

    2013-01-01

    , the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations......Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase...... inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However...

  7. Computational Homology for Software Validation

    Science.gov (United States)

    2015-03-01

    COMPUTATIONAL HOMOLOGY FOR SOFTWARE VALIDATION SYRACUSE UNIVERSITY MARCH 2015 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE; DISTRIBUTION...COVERED (From - To) SEP 2011 – SEP 2014 4. TITLE AND SUBTITLE COMPUTATIONAL HOMOLOGY FOR SOFTWARE VALIDATION 5a. CONTRACT NUMBER FA8750-11-2-0275 5b...verdict as to whether the application of persistent homology to the problem of obtaining objective signatures that would indicate the present or absence

  8. p44 and p34 subunits of the BTF2/TFIIH transcription factor have homologies with SSL1, a yeast protein involved in DNA repair.

    NARCIS (Netherlands)

    S. Humbert; H. van Vuuren; Y. Lutz; J.H.J. Hoeijmakers (Jan); J-M. Egly (Jean-Marc); V. Moncollin

    1994-01-01

    textabstractThe human BTF2 (TFIIH) transcription factor is a multisubunit protein involved in transcription initiation by RNA polymerase II (B) as well as in DNA repair. In addition to the previously characterized p62 and p89/ERCC3 subunits, we have cloned two other subunits of BTF2, p44 and p34. Th

  9. Grid diagrams and Khovanov homology

    DEFF Research Database (Denmark)

    Droz, Jean-Marie; Wagner, Emmanuel

    2009-01-01

    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......–Smith symplectic link invariant coincides with the difference between the homological grading on Khovanov homology and the Jones grading on Khovanov homology. We give some evidence for the truth of the Seidel–Smith conjecture....

  10. Transcription factor avian erythroblastosis virus E26 oncogen homolog-1 is a novel mediator of renal injury in salt-sensitive hypertension.

    Science.gov (United States)

    Feng, Wenguang; Chumley, Phillip; Prieto, Minolfa C; Miyada, Kayoko; Seth, Dale M; Fatima, Huma; Hua, Ping; Rezonzew, Gabriel; Sanders, Paul W; Jaimes, Edgar A

    2015-04-01

    Transcription factor E26 transformation-specific sequence-1 (ETS-1) is a transcription factor that regulates the expression of a variety of genes, including growth factors, chemokines, and adhesion molecules. We recently demonstrated that angiotensin II increases the glomerular expression of ETS-1 and that blockade of ETS-1 ameliorates the profibrotic and proinflammatory effects of angiotensin II. The Dahl salt-sensitive rat is a paradigm of salt-sensitive hypertension associated with local activation of the renin-angiotensin system. In these studies, we determined whether: (1) salt-sensitive hypertension is associated with renal expression of ETS-1 and (2) ETS-1 participates in the development of end-organ injury in salt-sensitive hypertension. Dahl salt-sensitive rats were fed a normal-salt diet (0.5% NaCl diet) or a high-salt diet (4% NaCl) for 4 weeks. Separate groups on high-salt diet received an ETS-1 dominant-negative peptide (10 mg/kg/d), an inactive ETS-1 mutant peptide (10 mg/kg/d), the angiotensin II type 1 receptor blocker candesartan (10 mg/kg/d), or the combination high-salt diet/dominant-negative peptide/angiotensin II type 1 receptor blocker for 4 weeks. High-salt diet rats had a significant increase in the glomerular expression of the phosphorylated ETS-1 that was prevented by angiotensin II type 1 receptor blocker. ETS-1 blockade reduced proteinuria, glomerular injury score, fibronectin expression, urinary transforming growth factor-β excretion, and macrophage infiltration. Angiotensin II type 1 receptor blocker reduced proteinuria, glomerular injury score, and macrophage infiltration, whereas concomitant ETS-1 blockade and angiotensin II type 1 receptor blocker had additive effects and reduced interstitial fibrosis. Our studies demonstrated that salt-sensitive hypertension results in increased glomerular expression of phosphorylated ETS-1 and suggested that ETS-1 plays an important role in the pathogenesis of end-organ injury in salt

  11. Buoyancy instability of homologous implosions

    CERN Document Server

    Johnson, Bryan M

    2015-01-01

    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...

  12. Relative Homological Algebra Volume 1

    CERN Document Server

    2011-01-01

    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.

  13. Evolving the Concept of Homology

    Science.gov (United States)

    Naples, Virginia L.; Miller, Jon S.

    2009-01-01

    Understanding homology is fundamental to learning about evolution. The present study shows an exercise that can be varied in complexity, for which students compile research illustrating the fate of homologous fish skull elements, and assemble a mural to serve as a learning aid. The skull of the most primitive living Actinopterygian (bony fish),…

  14. Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism.

    Science.gov (United States)

    Bowl, Michael R; Mirczuk, Samantha M; Grigorieva, Irina V; Piret, Sian E; Cranston, Treena; Southam, Lorraine; Allgrove, Jeremy; Bahl, Shailini; Brain, Caroline; Loughlin, John; Mughal, Zulf; Ryan, Fiona; Shaw, Nick; Thakker, Yogini V; Tiosano, Dov; Nesbit, M Andrew; Thakker, Rajesh V

    2010-05-15

    GCMB is a member of the small transcription factor family GCM (glial cells missing), which are important regulators of development, present in vertebrates and some invertebrates. In man, GCMB encodes a 506 amino acid parathyroid gland-specific protein, mutations of which have been reported to cause both autosomal dominant and autosomal recessive hypoparathyroidism. We ascertained 18 affected individuals from 12 families with autosomal recessive hypoparathyroidism and have investigated them for GCMB abnormalities. Four different homozygous germline mutations were identified in eight families that originate from the Indian Subcontinent. These consisted of a novel nonsense mutation R39X; a missense mutation, R47L in two families; a novel missense mutation, R110W; and a novel frameshifting deletion, I298fsX307 in four families. Haplotype analysis, using polymorphic microsatellites from chromosome 6p23-24, revealed that R47L and I298fsX307 mutations arose either as ancient founders, or recurrent de novo mutations. Functional studies including: subcellular localization studies, EMSAs and luciferase-reporter assays, were undertaken and these demonstrated that: the R39X mutant failed to localize to the nucleus; the R47L and R110W mutants both lost DNA-binding ability; and the I298fsX307 mutant had reduced transactivational ability. In order to gain further insights, we undertook 3D-modeling of the GCMB DNA-binding domain, which revealed that the R110 residue is likely important for the structural integrity of helix 2, which forms part of the GCMB/DNA binding interface. Thus, our results, which expand the spectrum of hypoparathyroidism-associated GCMB mutations, help elucidate the molecular mechanisms underlying DNA-binding and transactivation that are required for this parathyroid-specific transcription factor.

  15. Quercetin enhances apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in ovarian cancer cells through reactive oxygen species (ROS) mediated CCAAT enhancer-binding protein homologous protein (CHOP)-death receptor 5 pathway

    Science.gov (United States)

    Yi, Liu; Zongyuan, Yang; Cheng, Gong; Lingyun, Zhang; GuiLian, Yu; Wei, Gong

    2014-01-01

    Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. We investigated whether quercetin, a flavonoid, can sensitize human ovarian cancer cells to TRAIL. Results indicate that quercetin sensitized cancer cells to TRAIL. The quercetin induced expression of death receptor DR5 but did not affect expression of DR4 in cancer cells. The induction of DR5 was mediated through activation of JNK and through upregulation of a transcription factor CCAAT enhancer-binding protein homologous protein (CHOP); as silencing of these signaling molecules abrogated the effect of quercetin. Upregulation of DR5 was mediated through the generation of reactive oxygen species (ROS), as ROS scavengers reduced the effect of quercetin on JNK activation, CHOP upregulation, DR induction, TRAIL sensitization, downregulated the expression of cell survival proteins and upregulated the proapoptotic proteins. Furthermore, quercetin enhances TRAIL mediated inhibition of tumor growth of human SKOV-3 xenograft was associated with induction of apoptosis, activation of caspase-3, CHOP and DR5. Overall, our data suggest that quercetin enhances apoptotic death of ovarian cancer cells to TRAIL through upregulation of CHOP-induced DR5 expression following ROS mediated endoplasmic reticulum-stress. PMID:24612139

  16. DNA strand exchange and RecA homologs in meiosis.

    Science.gov (United States)

    Brown, M Scott; Bishop, Douglas K

    2014-12-04

    Homology search and DNA strand-exchange reactions are central to homologous recombination in meiosis. During meiosis, these processes are regulated such that the probability of choosing a homolog chromatid as recombination partner is enhanced relative to that of choosing a sister chromatid. This regulatory process occurs as homologous chromosomes pair in preparation for assembly of the synaptonemal complex. Two strand-exchange proteins, Rad51 and Dmc1, cooperate in regulated homology search and strand exchange in most organisms. Here, we summarize studies on the properties of these two proteins and their accessory factors. In addition, we review current models for the assembly of meiotic strand-exchange complexes and the possible mechanisms through which the interhomolog bias of recombination partner choice is achieved.

  17. Perturbation of MicroRNA-370/Lin-28 homolog A/nuclear factor kappa B regulatory circuit contributes to the development of hepatocellular carcinoma.

    Science.gov (United States)

    Xu, Wen-Ping; Yi, Min; Li, Qian-Qian; Zhou, Wei-Ping; Cong, Wen-Ming; Yang, Yuan; Ning, Bei-Fang; Yin, Chuan; Huang, Zhao-Wei; Wang, Jian; Qian, Hui; Jiang, Cai-Feng; Chen, Yue-Xiang; Xia, Chun-Yan; Wang, Hong-Yang; Zhang, Xin; Xie, Wei-Fen

    2013-12-01

    MicroRNA 370 (miR-370) is located within the DLK1/DIO3 imprinting region on human chromosome 14, which has been identified as a cancer-associated genomic region. However, the role of miR-370 in malignances remains controversial. Here, we report that miR-370 was repressed in human hepatocellular carcinoma (HCC) tissues and hepatoma cell lines. Using gain-of-function and loss-of-function experiments, we demonstrated that miR-370 inhibited the malignant phenotype of HCC cells in vitro. Overexpression of miR-370 inhibited growth and metastasis of HCC cells in vivo. Moreover, the RNA-binding protein, LIN28A, was identified as a direct functional target of miR-370, which, in turn, blocked the biogenesis of miR-370 by binding to its precursor. LIN28A also mediated the suppressive effects of miR-370 on migration and invasion of HCC cells by post-transcriptionally regulating RelA/p65, which is an important effector of the canonical nuclear factor kappa B (NF-κB) pathway. Interleukin-6 (IL-6), a well-known NF-κB downstream inflammatory molecule, reduced miR-370 but increased LIN28A levels in HCC. Furthermore, miR-370 levels were inversely correlated with LIN28A and IL-6 messenger RNA (mRNA) levels, whereas LIN28A mRNA expression was positively correlated with IL-6 expression in human HCC samples. Interestingly, reduction of miR-370 expression was associated with the development of HCC in rats, as well as with aggressive tumor behavior and short survival in HCC patients. These data demonstrate the involvement of a novel regulatory circuit consisting of miR-370, LIN28A, RelA/p65 and IL-6 in HCC progression. Manipulating this feedback loop may have beneficial effect in HCC treatment. © 2013 by the American Association for the Study of Liver Diseases.

  18. Homology theory on algebraic varieties

    CERN Document Server

    Wallace, Andrew H

    1958-01-01

    Homology Theory on Algebraic Varieties, Volume 6 deals with the principles of homology theory in algebraic geometry and includes the main theorems first formulated by Lefschetz, one of which is interpreted in terms of relative homology and another concerns the Poincaré formula. The actual details of the proofs of these theorems are introduced by geometrical descriptions, sometimes aided with diagrams. This book is comprised of eight chapters and begins with a discussion on linear sections of an algebraic variety, with emphasis on the fibring of a variety defined over the complex numbers. The n

  19. Compositional Homology and Creative Thinking

    Directory of Open Access Journals (Sweden)

    Salvatore Tedesco

    2015-05-01

    Full Text Available The concept of homology is the most solid theoretical basis elaborated by the morphological thinking during its history. The enucleation of some general criteria for the interpretation of homology is today a fundamental tool for life sciences, and for restoring their own opening to the question of qualitative innovation that arose so powerfully in the original Darwinian project. The aim of this paper is to verify the possible uses of the concept of compositional homology in order to provide of an adequate understanding of the dynamics of creative thinking.

  20. Fivebranes and 3-manifold homology

    CERN Document Server

    Gukov, Sergei; Vafa, Cumrun

    2016-01-01

    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.

  1. Fivebranes and 3-manifold homology

    Science.gov (United States)

    Gukov, Sergei; Putrov, Pavel; Vafa, Cumrun

    2017-07-01

    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.

  2. V-ets erythroblastosis virus E26 oncogene homolog (avian)/Trefoil factor 3/high-molecular-weight cytokeratin triple immunostain: a novel tissue-based biomarker in prostate cancer with potential clinical application.

    Science.gov (United States)

    Park, Kyung; Chiu, Ya-Lin; Rubin, Mark A; Demichelis, Francesca; Mosquera, Juan Miguel

    2013-10-01

    Trefoil factor 3 (TFF3) is associated with various cancers and overexpressed in a subset of prostate cancers. Functional studies suggest that v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) down-regulates TFF3 expression in hormone-naïve prostate cancer. To characterize this inverse relationship, we developed a triple immunostain encompassing ERG, TFF3, and high-molecular-weight cytokeratin. Triple stain was performed on 96 tumors and 52 benign cases represented in tissue microarrays. Distinct ERG and TFF3 protein was expressed in 45% (43/96) and 36% (35/96) of prostate cancers, respectively. Coexpression was observed in 5% (5/96) of tumor cases, and 24% (23/96) did not express ERG or TFF3. The inverse expression of ERG and TFF3 was significant (P tumors demonstrating TFF3 expression. Sensitivity and specificity of combined ERG and TFF3 expression in detecting prostate cancer were 76% and 96%, respectively. The feasibility of triple immunostain protocol was validated in a set of 76 needle biopsies. The application of this multiplex in situ biomarker for molecular characterization of prostate cancer and as a supplemental diagnostic and prognostic tool in prostate needle biopsies should be further explored.

  3. Two highly similar DEAD box proteins, OsRH2 and OsRH34, homologous to eukaryotic initiation factor 4AIII, play roles of the exon junction complex in regulating growth and development in rice.

    Science.gov (United States)

    Huang, Chun-Kai; Sie, Yi-Syuan; Chen, Yu-Fu; Huang, Tian-Sheng; Lu, Chung-An

    2016-04-12

    The exon junction complex (EJC), which contains four core components, eukaryotic initiation factor 4AIII (eIF4AIII), MAGO/NASHI (MAGO), Y14/Tsunagi/RNA-binding protein 8A, and Barentsz/Metastatic lymph node 51, is formed in both nucleus and cytoplasm, and plays important roles in gene expression. Genes encoding core EJC components have been found in plants, including rice. Currently, the functional characterizations of MAGO and Y14 homologs have been demonstrated in rice. However, it is still unknown whether eIF4AIII is essential for the functional EJC in rice. This study investigated two DEAD box RNA helicases, OsRH2 and OsRH34, which are homologous to eIF4AIII, in rice. Amino acid sequence analysis indicated that OsRH2 and OsRH34 had 99 % identity and 100 % similarity, and their gene expression patterns were similar in various rice tissues, but the level of OsRH2 mRNA was about 58-fold higher than that of OsRH34 mRNA in seedlings. From bimolecular fluorescence complementation results, OsRH2 and OsRH34 interacted physically with OsMAGO1 and OsY14b, respectively, which indicated that both of OsRH2 and OsRH34 were core components of the EJC in rice. To study the biological roles of OsRH2 and OsRH34 in rice, transgenic rice plants were generated by RNA interference. The phenotypes of three independent OsRH2 and OsRH34 double-knockdown transgenic lines included dwarfism, a short internode distance, reproductive delay, defective embryonic development, and a low seed setting rate. These phenotypes resembled those of mutants with gibberellin-related developmental defects. In addition, the OsRH2 and OsRH34 double-knockdown transgenic lines exhibited the accumulation of unspliced rice UNDEVELOPED TAPETUM 1 mRNA. Rice contains two eIF4AIII paralogous genes, OsRH2 and OsRH34. The abundance of OsRH2 mRNA was about 58-fold higher than that of OsRH34 mRNA in seedlings, suggesting that the OsRH2 is major eIF4AIII in rice. Both OsRH2 and OsRH34 are core components of the EJC

  4. Homological Pisot Substitutions and Exact Regularity

    CERN Document Server

    Barge, Marcy; Jones, Leslie; Sadun, Lorenzo

    2010-01-01

    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.

  5. The Box H/ACA snoRNP Assembly Factor Shq1p is a Chaperone Protein Homologous to Hsp90 Cochaperones that Binds to the Cbf5p Enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Godin, Katherine S.; Walbott, Helene; Leulliot, Nicolas; van Tilbeurgh, Herman; Varani, Gabriele

    2009-05-06

    Box H/ACA small nucleolar (sno) ribonucleoproteins (RNPs) are responsible for the formation of pseudouridine in a variety of RNAs and are essential for ribosome biogenesis, modification of spliceosomal RNAs, and telomerase stability. A mature snoRNP has been reconstituted in vitro and is composed of a single RNA and four proteins. However, snoRNP biogenesis in vivo requires multiple factors to coordinate a complex and poorly understood assembly and maturation process. Among the factors required for snoRNP biogenesis in yeast is Shq1p, an essential protein necessary for stable expression of box H/ACA snoRNAs. We have found that Shq1p consists of two independent domains that contain casein kinase 1 phosphorylation sites. We also demonstrate that Shq1p binds the pseudourydilating enzyme Cbf5p through the C-terminal domain, in synergy with the N-terminal domain. The NMR solution structure of the N-terminal domain has striking homology to the ‘Chord and Sgt1’ domain of known Hsp90 cochaperones, yet Shq1p does not interact with the yeast Hsp90 homologue in vitro. Surprisingly, Shq1p has stand-alone chaperone activity in vitro. This activity is harbored by the C-terminal domain, but it is increased by the presence of the N-terminal domain. These results provide the first evidence of a specific biochemical activity for Shq1p and a direct link to the H/ACA snoRNP.

  6. Object-oriented persistent homology

    Science.gov (United States)

    Wang, Bao; Wei, Guo-Wei

    2016-01-01

    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

  7. Object-oriented Persistent Homology.

    Science.gov (United States)

    Wang, Bao; Wei, Guo-Wei

    2016-01-15

    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

  8. The semaphorontic view of homology.

    Science.gov (United States)

    Havstad, Joyce C; Assis, Leandro C S; Rieppel, Olivier

    2015-11-01

    The relation of homology is generally characterized as an identity relation, or alternatively as a correspondence relation, both of which are transitive. We use the example of the ontogenetic development and evolutionary origin of the gnathostome jaw to discuss identity and transitivity of the homology relation under the transformationist and emergentist paradigms respectively. Token identity and consequent transitivity of homology relations are shown to be requirements that are too strong to allow the origin of genuine evolutionary novelties. We consequently introduce the concept of compositional identity that is grounded in relations prevailing between parts (organs and organ systems) of a whole (organism). We recognize an ontogenetic identity of parts within a whole throughout the sequence of successive developmental stages of those parts: this is an intra-organismal character identity maintained throughout developmental trajectory. Correspondingly, we recognize a phylogenetic identity of homologous parts within two or more organisms of different species: this is an inter-species character identity maintained throughout evolutionary trajectory. These different dimensions of character identity--ontogenetic (through development) and phylogenetic (via shared evolutionary history)--break the transitivity of homology relations. Under the transformationist paradigm, the relation of homology reigns over the entire character (-state) transformation series, and thus encompasses the plesiomorphic as well as the apomorphic condition of form. In contrast, genuine evolutionary novelties originate not through transformation of ancestral characters (-states), but instead through deviating developmental trajectories that result in alternate characters. Under the emergentist paradigm, homology is thus synonymous with synapomorphy. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution Published by Wiley Periodicals, Inc.

  9. A monopole homology for integral homology 3-spheres

    OpenAIRE

    Li, Weiping

    2014-01-01

    To an integral homology 3-sphere Y, we assign a well-defined {\\mathbb Z}-graded (monopole) homology MH*(Y, Ih(Q; h0)) whose construction in principle follows from the instanton Floer theory with the dependence of the spectral flow Ih(Q; h0), where Q is the unique U(1)-reducible monopole of the Seiberg-Witten equation on Y and h0 is a reference perturbation datum. The definition uses the moduli space of monopoles on Y \\times {\\mathbb R} introduced by Seiberg-Witten in studying smooth ...

  10. Homology of locally semialgebraic spaces

    CERN Document Server

    Delfs, Hans

    1991-01-01

    Locally semialgebraic spaces serve as an appropriate framework for studying the topological properties of varieties and semialgebraic sets over a real closed field. This book contributes to the fundamental theory of semialgebraic topology and falls into two main parts. The first dealswith sheaves and their cohomology on spaces which locally look like a constructible subset of a real spectrum. Topics like families of support, homotopy, acyclic sheaves, base-change theorems and cohomological dimension are considered. In the second part a homology theory for locally complete locally semialgebraic spaces over a real closed field is developed, the semialgebraic analogue of classical Bore-Moore-homology. Topics include fundamental classes of manifolds and varieties, Poincare duality, extensions of the base field and a comparison with the classical theory. Applying semialgebraic Borel-Moore-homology, a semialgebraic ("topological") approach to intersection theory on varieties over an algebraically closed field of ch...

  11. Homology group on manifolds and their foldings

    Directory of Open Access Journals (Sweden)

    M. Abu-Saleem

    2010-03-01

    Full Text Available In this paper, we introduce the definition of the induced unfolding on the homology group. Some types of conditional foldings restricted on the elements of the homology groups are deduced. The effect of retraction on the homology group of a manifold is dicussed. The unfolding of variation curvature of manifolds on their homology group are represented. The relations between homology group of the manifold and its folding are deduced.

  12. Homological Type of Geometric Transitions

    CERN Document Server

    Rossi, Michele

    2010-01-01

    The present paper gives an account and quantifies the change in topology induced by small and type II geometric transitions, by introducing the notion of the \\emph{homological type} of a geometric transition. The obtained results agree with, and go further than, most results and estimates, given to date by several authors, both in mathematical and physical literature.

  13. Homological stability of diffeomorphism groups

    DEFF Research Database (Denmark)

    Berglund, Alexander; Madsen, Ib Henning

    2013-01-01

    In this paper we prove a stability theorem for block diffeomorphisms of 2d -dimensional manifolds that are connected sums of S d ×S d . Combining this with a recent theorem of S. Galatius and O. Randal-Williams and Morlet’s lemma of disjunction, we determine the homology of the classifying space ...

  14. A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts

    NARCIS (Netherlands)

    M.J. Noordam; S.K.M. van Daalen; S.E. Hovingh; C.M. Korver; F. van der Veen; S. Repping

    2011-01-01

    BACKGROUND: The male-specific region of the human Y chromosome (MSY) contains multiple testis-specific genes. Most deletions in the MSY lead to inadequate or absent sperm production. Nearly all deletions occur via homologous recombination between amplicons. Previously, we identified two P5/distal-P1

  15. 15-deoxy-Delta12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription.

    Science.gov (United States)

    Su, Rong-Ying; Chi, Kwan-Hwa; Huang, Duen-Yi; Tai, Ming-Hui; Lin, Wan-Wan

    2008-10-01

    Although 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) was reported to up-regulate death receptor 5 (DR5) protein expression and sensitize TRAIL-induced cytotoxicity, its action mechanism remains unclear. Using HCT116 colon cancer cells, we found that sensitization of TRAIL-induced cytotoxicity by 15dPGJ(2) resulted from up-regulation of DR5 via gene transcription but was not associated with PPAR-gamma activation. Moreover, 15dPGJ(2) induced GRP78, XBP1, and C/EBP homologous transcription factor (CHOP) expression in HCT116 cells, confirming that 15dPGJ(2) is an endoplasmic reticulum stress inducer. Knockdown of the CHOP gene by siRNA attenuated DR5 up-regulation and the sensitized cytotoxicity in colon cancer HCT116 and SW480. With deletion plasmids of DR5 promoters, we found that the CHOP-binding site was involved in activating the DR5 gene by 15dPGJ(2). A mechanistic study showed the contributions of reactive oxygen species (ROS) and intracellular calcium in CHOP and DR5 gene up-regulation. 15dPGJ(2) was also found to induce DR5 in two prostate cancer cell lines, LNCaP and PC3. Although in LNCaP DR5 up-regulation was accompanied by CHOP expression by 15dPGJ(2), no significant increase in CHOP expression or DR5 promoter activity was observed in PC3 cells. Intriguingly, 15dPGJ(2) induced ROS and calcium production in PC3 cells. This inability to induce CHOP was not due to the p53-null in PC3 cells, as similar extents of increase in CHOP protein were found due to 15dPGJ(2) in both wild-type and p53-null HCT116 cells. In summary, the effect of up-regulation of DR5 by 15dPGJ(2) in colon cancer cells is independent of PPAR-gamma and p53 but relies on CHOP induction through gene transcription involving ROS and calcium.

  16. The minimum amount of homology required for homologous recombination in mammalian cells.

    OpenAIRE

    Rubnitz, J; Subramani, S

    1984-01-01

    Although DNA sequence homology is believed to be a prerequisite for homologous recombination events in procaryotes and eucaryotes, no systematic study has been done on the minimum amount of homology required for homologous recombination in mammalian cells. We have used simian virus 40-pBR322 hybrid plasmids constructed in vitro as substrates to quantitate intramolecular homologous recombination in cultured monkey cells. Excision of wild-type simian virus 40 DNA by homologous recombination was...

  17. Minimax Rates for Homology Inference

    CERN Document Server

    Balakrishnan, Sivaraman; Sheehy, Don; Singh, Aarti; Wasserman, Larry

    2011-01-01

    Often, high dimensional data lie close to a low-dimensional submanifold and it is of interest to understand the geometry of these submanifolds. The homology groups of a manifold are important topological invariants that provide an algebraic summary of the manifold. These groups contain rich topological information, for instance, about the connected components, holes, tunnels and sometimes the dimension of the manifold. In this paper, we consider the statistical problem of estimating the homology of a manifold from noisy samples under several different noise models. We derive upper and lower bounds on the minimax risk for this problem. Our upper bounds are based on estimators which are constructed from a union of balls of appropriate radius around carefully selected points. In each case we establish complementary lower bounds using Le Cam's lemma.

  18. Sutured Floer homology and hypergraphs

    CERN Document Server

    Juhász, András; Rasmussen, Jacob

    2011-01-01

    By applying Seifert's algorithm to a special alternating diagram of a link L, one obtains a Seifert surface F of L. We show that the support of the sutured Floer homology of the sutured manifold complementary to F is affine isomorphic to the set of lattice points given as hypertrees in a certain hypergraph that is naturally associated to the diagram. This implies that the Floer groups in question are supported in a set of Spin^c structures that are the integer lattice points of a convex polytope. This property has an immediate extension to Seifert surfaces arising from homogeneous link diagrams (including all alternating and positive diagrams). In another direction, together with work in progress of the second author and others, our correspondence suggests a method for computing the "top" coefficients of the HOMFLY polynomial of a special alternating link from the sutured Floer homology of a Seifert surface complement for a certain dual link.

  19. Homologous recombination in Leishmania enriettii.

    OpenAIRE

    1991-01-01

    We have used derivatives of the recently developed stable transfection vector pALT-Neo to formally demonstrate that Leishmania enriettii contains the enzymatic machinery necessary for homologous recombination. This observation has implications for gene regulation, gene amplification, genetic diversity, and the maintenance of tandemly repeated gene families in the Leishmania genome as well as in closely related organisms, including Trypanosoma brucei. Two plasmids containing nonoverlapping del...

  20. Homologous recombination in Leishmania enriettii.

    Science.gov (United States)

    Tobin, J F; Laban, A; Wirth, D F

    1991-02-01

    We have used derivatives of the recently developed stable transfection vector pALT-Neo to formally demonstrate that Leishmania enriettii contains the enzymatic machinery necessary for homologous recombination. This observation has implications for gene regulation, gene amplification, genetic diversity, and the maintenance of tandemly repeated gene families in the Leishmania genome as well as in closely related organisms, including Trypanosoma brucei. Two plasmids containing nonoverlapping deletions of the chloramphenicol acetyltransferase (CAT) gene, as well as the neomycin-resistance gene, were cotransfected into L. enriettii. Analysis of the DNA from these cells by Southern blotting and plasmid rescue revealed that a full-length or doubly deleted CAT gene could be reconstructed by homologous crossing-over and/or gene conversion between the two deletion plasmids. Additionally, parasites cotransfected with pALT-Neo and pALT-CAT-S, a plasmid containing two copies of the chimeric alpha-tubulin-CAT gene, resulted in G418-resistant parasites expressing high levels of CAT activity. The structure of the DNA within these cells, as shown by Southern blot analysis and the polymerase chain reaction, is that which would be expected from a homologous exchange event occurring between the two plasmids.

  1. Deep homology: a view from systematics.

    Science.gov (United States)

    Scotland, Robert W

    2010-05-01

    Over the past decade, it has been discovered that disparate aspects of morphology - often of distantly related groups of organisms - are regulated by the same genetic regulatory mechanisms. Those discoveries provide a new perspective on morphological evolutionary change. A conceptual framework for exploring these research findings is termed 'deep homology'. A comparative framework for morphological relations of homology is provided that distinguishes analogy, homoplasy, plesiomorphy and synapomorphy. Four examples - three from plants and one from animals - demonstrate that homologous developmental mechanisms can regulate a range of morphological relations including analogy, homoplasy and examples of uncertain homology. Deep homology is part of a much wider range of phenomena in which biological (genes, regulatory mechanisms, morphological traits) and phylogenetic levels of homology can both be disassociated. Therefore, to understand homology, precise, comparative, independent statements of both biological and phylogenetic levels of homology are necessary.

  2. Homology requirements for recombination in Escherichia coli.

    OpenAIRE

    Watt, V M; Ingles, C J; Urdea, M S; Rutter, W J

    1985-01-01

    The DNA sequence homology required for recombination in Escherichia coli has been determined by measuring the recombination frequency between insulin DNA in a miniplasmid pi VX and a homologous sequence in a bacteriophage lambda vector. A minimum of approximately equal to 20 base pairs in a completely homologous segment is required for significant recombination. There is an exponential increase in the frequency of recombination when the length of homologous DNA is increased from 20 base pairs...

  3. Lagrangian Quantum Homology for Lagrangian cobordism

    OpenAIRE

    Singer, Berit

    2015-01-01

    We extend the definition of Lagrangian quantum homology to monotone Lagrangian cobordism and establish its general algebraic properties. In particular we develop a relative version of Lagrangian quantum homology associated to a cobordism relative to a part of its boundary and study relations of this invariant to the ambient quantum homology.

  4. Discrete homology theory for metric spaces

    NARCIS (Netherlands)

    H. Barcelo (Hélène); V. Capraro (Valerio); J. A. White; H. Barcelo (Hélène)

    2014-01-01

    htmlabstractWe define and study a notion of discrete homology theory for metric spaces. Instead of working with simplicial homology, our chain complexes are given by Lipschitz maps from an n n -dimensional cube to a fixed metric space. We prove that the resulting homology theory satisfies a

  5. Definition and identification of homology domains.

    Science.gov (United States)

    Lawrence, C B; Goldman, D A

    1988-03-01

    A method is described for identifying and evaluating regions of significant similarity between two sequences. The notion of a 'homology domain' is employed which defines the boundaries of a region of sequence homology containing no insertions or deletions. The relative significance of different potential homology domains is evaluated using a non-linear similarity score related to the probability of finding the observed level of similarity in the region by chance. The sensitivity of the method is demonstrated by simulating the evolution of homology domains and applying the method to their detection. Several examples of the use of homology domain identification are given.

  6. Topological Hochschild homology and the Bass trace conjecture

    DEFF Research Database (Denmark)

    Berrick, A. J.; Hesselholt, Lars

    2015-01-01

    We use the methods of topological Hochschild homology to shed new light on groups satisfying the Bass trace conjecture. Factorization of the Hattori–Stallings rank map through the Bökstedt–Hsiang–Madsen cyclotomic trace map leads to Linnell's restriction on such groups. As a new consequence...

  7. Virtual Khovanov homology using cobordisms

    DEFF Research Database (Denmark)

    Tubbenhauer, Daniel

    2014-01-01

    We give a geometric interpretation of the Khovanov complex for virtual links. Geometric interpretation means that we use a cobordism structure like D. Bar-Natan, but we allow non orientable cobordisms. Like D. Bar-Natans geometric complex our construction should work for virtual tangles too....... This geometric complex allows, in contrast to the geometric version of V. Turaev and P. Turner, a direct extension of the classical Khovanov complex (h=t=0) and of the variant of Lee (h=0,t=1). Furthermore we give a classification of all unoriented TQFTs which can be used to define virtual link homologies...

  8. Virtual Khovanov homology using cobordisms

    DEFF Research Database (Denmark)

    Tubbenhauer, Daniel

    2014-01-01

    We give a geometric interpretation of the Khovanov complex for virtual links. Geometric interpretation means that we use a cobordism structure like D. Bar-Natan, but we allow non orientable cobordisms. Like D. Bar-Natans geometric complex our construction should work for virtual tangles too....... This geometric complex allows, in contrast to the geometric version of V. Turaev and P. Turner, a direct extension of the classical Khovanov complex (h=t=0) and of the variant of Lee (h=0,t=1). Furthermore we give a classification of all unoriented TQFTs which can be used to define virtual link homologies...

  9. The Homological Nature of Entropy

    Directory of Open Access Journals (Sweden)

    Pierre Baudot

    2015-05-01

    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.

  10. Homologous gene replacement in Physarum

    Energy Technology Data Exchange (ETDEWEB)

    Burland, T.G. [Univ. of Wisconsin, Madison, WI (United States); Pallotta, D. [Laval Univ., Quebec (Canada)

    1995-01-01

    The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1 in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.

  11. Weak homology of elliptical galaxies

    CERN Document Server

    Bertin, G; Principe, M D

    2002-01-01

    We start by studying a small set of objects characterized by photometric profiles that have been pointed out to deviate significantly from the standard R^{1/4} law. For these objects we confirm that a generic R^{1/n} law, with n a free parameter, can provide superior fits (the best-fit value of n can be lower than 2.5 or higher than 10), better than those that can be obtained by a pure R^{1/4} law, by an R^{1/4}+exponential model, and by other dynamically justified self--consistent models. Therefore, strictly speaking, elliptical galaxies should not be considered homologous dynamical systems. Still, a case for "weak homology", useful for the interpretation of the Fundamental Plane of elliptical galaxies, could be made if the best-fit parameter n, as often reported, correlates with galaxy luminosity L, provided the underlying dynamical structure also follows a systematic trend with luminosity. We demonstrate that this statement may be true even in the presence of significant scatter in the correlation n(L). Pr...

  12. A Phenomenological and Dynamic View of Homology: Homologs as Persistently Reproducible Modules.

    Science.gov (United States)

    Suzuki, Daichi G; Tanaka, Senji

    2017-01-01

    Homology is a fundamental concept in biology. However, the metaphysical status of homology, especially whether a homolog is a part of an individual or a member of a natural kind, is still a matter of intense debate. The proponents of the individuality view of homology criticize the natural kind view of homology by pointing out that homologs are subject to evolutionary transformation, and natural kinds do not change in the evolutionary process. Conversely, some proponents of the natural kind view of homology argue that a homolog can be construed both as a part of an individual and a member of a natural kind. They adopt the Homeostatic Property Cluster (HPC) theory of natural kinds, and the theory seems to strongly support their construal. Note that this construal implies the acceptance of essentialism. However, looking back on the history of the concept of homology, we should not overlook the fact that the individuality view was proposed to reject the essentialist interpretation of homology. Moreover, the essentialist notions of natural kinds can, in our view, mislead biologists about the phenomena of homology. Consequently, we need a non-essentialist view of homology, which we name the "persistently reproducible module" (PRM) view. This view highlights both the individual-like and kind-like aspects of homologs while stripping down both essentialist and anti-essentialist interpretations of homology. In this article, we articulate the PRM view of homology and explain why it is recommended over the other two views.

  13. Regulation of Homologous Recombination by SUMOylation

    DEFF Research Database (Denmark)

    Pinela da Silva, Sonia Cristina

    Double-strand breaks (DSBs) are one of the most deleterious types of DNA lesions challenging genome integrity. The DNA damage response (DDR) promotes fast and effective detection and repair of the damaged DNA, leading to cell cycle arrest through checkpoint activation and the recruitment of repair...... factors such as the homologous recombination (HR) machinery. HR constitutes the main DSB repair pathway in Saccharomyces cerevisiae and despite being largely considered an error-free process and essential for genome stability, uncontrolled recombination can lead to loss of heterozygosity, translocations....... In this study I present new insights for the role of SUMOylation in regulating HR by dissecting the role of SUMO in the interaction between the central HR-mediator protein Rad52 and its paralogue Rad59 and the outcome of recombination. This data provides evidence for the importance of SUMO in promoting protein...

  14. In vivo importance of homologous recombination DNA repair for mouse neural stem and progenitor cells

    NARCIS (Netherlands)

    L. Rousseau (Laure); O. Etienne (Olivier); T. Roque (Telma); C. Desmaze (Chantal); C. Haton (Céline); M.-A. Mouthon (Marc-André.); J. Bernardino-Sgherri (Jacqueline); J. Essers (Jeroen); R. Kanaar (Roland); F.D. Boussin (François)

    2012-01-01

    textabstractWe characterized the in vivo importance of the homologous recombination factor RAD54 for the developing mouse brain cortex in normal conditions or after ionizing radiation exposure. Contrary to numerous homologous recombination genes, Rad54 disruption did not impact the cortical developm

  15. On 0-homology of categorical at zero semigroups

    OpenAIRE

    Novikov, B. V.; Polyakova, L. Yu.

    2008-01-01

    The isomorphism of 0-homology groups of a categorical at zero semigroup and homology groups of its 0-reflector is proved. Some applications of 0-homology to Eilenberg-MacLane homology of semigroups are given.

  16. Khovanov homology of links and graphs

    Science.gov (United States)

    Stosic, Marko

    2006-05-01

    In this thesis we work with Khovanov homology of links and its generalizations, as well as with the homology of graphs. Khovanov homology of links consists of graded chain complexes which are link invariants, up to chain homotopy, with graded Euler characteristic equal to the Jones polynomial of the link. Hence, it can be regarded as the "categorification" of the Jones polynomial. We prove that the first homology group of positive braid knots is trivial. Futhermore, we prove that non-alternating torus knots are homologically thick. In addition, we show that we can decrease the number of full twists of torus knots without changing low-degree homology and consequently that there exists stable homology for torus knots. We also prove most of the above properties for Khovanov-Rozansky homology. Concerning graph homology, we categorify the dichromatic (and consequently Tutte) polynomial for graphs, by categorifying an infinite set of its one-variable specializations. We categorify explicitly the one-variable specialization that is an analog of the Jones polynomial of an alternating link corresponding to the initial graph. Also, we categorify explicitly the whole two-variable dichromatic polynomial of graphs by using Koszul complexes. textbf{Key-words:} Khovanov homology, Jones polynomial, link, torus knot, graph, dichromatic polynomial

  17. Equivariant ordinary homology and cohomology

    CERN Document Server

    Costenoble, Steven R

    2016-01-01

    Filling a gap in the literature, this book takes the reader to the frontiers of equivariant topology, the study of objects with specified symmetries. The discussion is motivated by reference to a list of instructive “toy” examples and calculations in what is a relatively unexplored field. The authors also provide a reading path for the first-time reader less interested in working through sophisticated machinery but still desiring a rigorous understanding of the main concepts. The subject’s classical counterparts, ordinary homology and cohomology, dating back to the work of Henri Poincaré in topology, are calculational and theoretical tools which are important in many parts of mathematics and theoretical physics, particularly in the study of manifolds. Similarly powerful tools have been lacking, however, in the context of equivariant topology. Aimed at advanced graduate students and researchers in algebraic topology and related fields, the book assumes knowledge of basic algebraic topology and group act...

  18. Persistent homology and string vacua

    Energy Technology Data Exchange (ETDEWEB)

    Cirafici, Michele [Center for Mathematical Analysis, Geometry and Dynamical Systems,Instituto Superior Técnico, Universidade de Lisboa,Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Institut des Hautes Études Scientifiques,Le Bois-Marie, 35 route de Chartres, F-91440 Bures-sur-Yvette (France)

    2016-03-08

    We use methods from topological data analysis to study the topological features of certain distributions of string vacua. Topological data analysis is a multi-scale approach used to analyze the topological features of a dataset by identifying which homological characteristics persist over a long range of scales. We apply these techniques in several contexts. We analyze N=2 vacua by focusing on certain distributions of Calabi-Yau varieties and Landau-Ginzburg models. We then turn to flux compactifications and discuss how we can use topological data analysis to extract physical information. Finally we apply these techniques to certain phenomenologically realistic heterotic models. We discuss the possibility of characterizing string vacua using the topological properties of their distributions.

  19. Homology and the hierarchy of biological systems.

    Science.gov (United States)

    Sommer, Ralf J

    2008-07-01

    Homology is the similarity between organisms due to common ancestry. Introduced by Richard Owen in 1843 in a paper entitled "Lectures on comparative anatomy and physiology of the invertebrate animals", the concept of homology predates Darwin's "Origin of Species" and has been very influential throughout the history of evolutionary biology. Although homology is the central concept of all comparative biology and provides a logical basis for it, the definition of the term and the criteria of its application remain controversial. Here, I will discuss homology in the context of the hierarchy of biological organization. I will provide insights gained from an exemplary case study in evolutionary developmental biology that indicates the uncoupling of homology at different levels of biological organization. I argue that continuity and hierarchy are separate but equally important issues of homology. (c) 2008 Wiley Periodicals, Inc.

  20. Homology in Electromagnetic Boundary Value Problems

    Directory of Open Access Journals (Sweden)

    Matti Pellikka

    2010-01-01

    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.

  1. Homology-independent metrics for comparative genomics.

    Science.gov (United States)

    Coutinho, Tarcisio José Domingos; Franco, Glória Regina; Lobo, Francisco Pereira

    2015-01-01

    A mainstream procedure to analyze the wealth of genomic data available nowadays is the detection of homologous regions shared across genomes, followed by the extraction of biological information from the patterns of conservation and variation observed in such regions. Although of pivotal importance, comparative genomic procedures that rely on homology inference are obviously not applicable if no homologous regions are detectable. This fact excludes a considerable portion of "genomic dark matter" with no significant similarity - and, consequently, no inferred homology to any other known sequence - from several downstream comparative genomic methods. In this review we compile several sequence metrics that do not rely on homology inference and can be used to compare nucleotide sequences and extract biologically meaningful information from them. These metrics comprise several compositional parameters calculated from sequence data alone, such as GC content, dinucleotide odds ratio, and several codon bias metrics. They also share other interesting properties, such as pervasiveness (patterns persist on smaller scales) and phylogenetic signal. We also cite examples where these homology-independent metrics have been successfully applied to support several bioinformatics challenges, such as taxonomic classification of biological sequences without homology inference. They where also used to detect higher-order patterns of interactions in biological systems, ranging from detecting coevolutionary trends between the genomes of viruses and their hosts to characterization of gene pools of entire microbial communities. We argue that, if correctly understood and applied, homology-independent metrics can add important layers of biological information in comparative genomic studies without prior homology inference.

  2. Modeling Non-homologous End Joining

    Science.gov (United States)

    Li, Yongfeng

    2013-01-01

    Non-homologous end joining (NHEJ) is the dominant DNA double strand break (DSB) repair pathway and involves several NHEJ proteins such as Ku, DNA-PKcs, XRCC4, Ligase IV and so on. Once DSBs are generated, Ku is first recruited to the DNA end, followed by other NHEJ proteins for DNA end processing and ligation. Because of the direct ligation of break ends without the need for a homologous template, NHEJ turns out to be an error-prone but efficient repair pathway. Some mechanisms have been proposed of how the efficiency of NHEJ repair is affected. The type of DNA damage is an important factor of NHEJ repair. For instance, the length of DNA fragment may determine the recruitment efficiency of NHEJ protein such as Ku [1], or the complexity of the DNA breaks [2] is accounted for the choice of NHEJ proteins and subpathway of NHEJ repair. On the other hand, the chromatin structure also plays a role of the accessibility of NHEJ protein to the DNA damage site. In this talk, some mathematical models of NHEJ, that consist of series of biochemical reactions complying with the laws of chemical reaction (e.g. mass action, etc.), will be introduced. By mathematical and numerical analysis and parameter estimation, the models are able to capture the qualitative biological features and show good agreement with experimental data. As conclusions, from the viewpoint of modeling, how the NHEJ proteins are recruited will be first discussed for connection between the classical sequential model [4] and recently proposed two-phase model [5]. Then how the NHEJ repair pathway is affected, by the length of DNA fragment [6], the complexity of DNA damage [7] and the chromatin structure [8], will be addressed

  3. The molecular evolution of PL10 homologs

    Directory of Open Access Journals (Sweden)

    Chang Ti-Cheng

    2010-05-01

    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

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

    Directory of Open Access Journals (Sweden)

    M. Z. Kazemi-Baneh

    2016-01-01

    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.

  5. A cytohesin homolog in Dictyostelium amoebae.

    Directory of Open Access Journals (Sweden)

    Maria Christina Shina

    Full Text Available BACKGROUND: Dictyostelium, an amoeboid motile cell, harbors several paralogous Sec7 genes that encode members of three distinct subfamilies of the Sec7 superfamily of Guanine nucleotide exchange factors. Among them are proteins of the GBF/BIG family present in all eukaryotes. The third subfamily represented with three members in D. discoideum is the cytohesin family that has been thought to be metazoan specific. Cytohesins are characterized by a Sec7 PH tandem domain and have roles in cell adhesion and migration. PRINCIPAL FINDINGS: Dictyostelium SecG exhibits highest homologies to the cytohesins. It harbors at its amino terminus several ankyrin repeats that are followed by the Sec7 PH tandem domain. Mutants lacking SecG show reduced cell-substratum adhesion whereas cell-cell adhesion that is important for development is not affected. Accordingly, multicellular development proceeds normally in the mutant. During chemotaxis secG(- cells elongate and migrate in a directed fashion towards cAMP, however speed is moderately reduced. SIGNIFICANCE: The data indicate that SecG is a relevant factor for cell-substrate adhesion and reveal the basic function of a cytohesin in a lower eukaryote.

  6. Knots in homology spheres which have simple knot Floer homology are trivial

    OpenAIRE

    Eftekhary, Eaman

    2010-01-01

    We show that if K is a non-trivial knot inside a homology sphere X, the rank of the knot Floer homology group associated with K is strictly bigger than the rank of the Heegaard Floer homology group associated with X.

  7. DNA Sequence Alignment during Homologous Recombination.

    Science.gov (United States)

    Greene, Eric C

    2016-05-27

    Homologous recombination allows for the regulated exchange of genetic information between two different DNA molecules of identical or nearly identical sequence composition, and is a major pathway for the repair of double-stranded DNA breaks. A key facet of homologous recombination is the ability of recombination proteins to perfectly align the damaged DNA with homologous sequence located elsewhere in the genome. This reaction is referred to as the homology search and is akin to the target searches conducted by many different DNA-binding proteins. Here I briefly highlight early investigations into the homology search mechanism, and then describe more recent research. Based on these studies, I summarize a model that includes a combination of intersegmental transfer, short-distance one-dimensional sliding, and length-specific microhomology recognition to efficiently align DNA sequences during the homology search. I also suggest some future directions to help further our understanding of the homology search. Where appropriate, I direct the reader to other recent reviews describing various issues related to homologous recombination.

  8. Homology in classical and molecular biology.

    Science.gov (United States)

    Patterson, C

    1988-11-01

    Hypotheses of homology are the basis of comparative morphology and comparative molecular biology. The kinds of homologous and nonhomologous relations in classical and molecular biology are explored through the three tests that may be applied to a hypothesis of homology: congruence, conjunction, and similarity. The same three tests apply in molecular comparisons and in morphology, and in each field they differentiate eight kinds of relation. These various relations are discussed and compared. The unit or standard of comparison differs in morphology and in molecular biology; in morphology it is the adult or life cycle, but with molecules it is the haploid genome. In morphology the congruence test is decisive in separating homology and nonhomology, whereas with molecular sequence data similarity is the decisive test. Consequences of this difference are that the boundary between homology and nonhomology is not the same in molecular biology as in morphology, that homology and synapomorphy can be equated in morphology but not in all molecular comparisons, and that there is no detected molecular equivalent of convergence. Since molecular homology may reflect either species phylogeny or gene phylogeny, there are more kinds of homologous relation between molecular sequences than in morphology. The terms paraxenology and plerology are proposed for two of these kinds--respectively, the consequence of multiple xenology and of gene conversion.

  9. DNA Sequence Alignment during Homologous Recombination*

    Science.gov (United States)

    Greene, Eric C.

    2016-01-01

    Homologous recombination allows for the regulated exchange of genetic information between two different DNA molecules of identical or nearly identical sequence composition, and is a major pathway for the repair of double-stranded DNA breaks. A key facet of homologous recombination is the ability of recombination proteins to perfectly align the damaged DNA with homologous sequence located elsewhere in the genome. This reaction is referred to as the homology search and is akin to the target searches conducted by many different DNA-binding proteins. Here I briefly highlight early investigations into the homology search mechanism, and then describe more recent research. Based on these studies, I summarize a model that includes a combination of intersegmental transfer, short-distance one-dimensional sliding, and length-specific microhomology recognition to efficiently align DNA sequences during the homology search. I also suggest some future directions to help further our understanding of the homology search. Where appropriate, I direct the reader to other recent reviews describing various issues related to homologous recombination. PMID:27129270

  10. Why do bacteria engage in homologous recombination?

    NARCIS (Netherlands)

    Vos, M.

    2009-01-01

    Microbiologists have long recognized that the uptake and incorporation of homologous DNA from outside the cell is a common feature of bacteria, with important implications for their evolution. However, the exact reasons why bacteria engage in homologous recombination remain elusive. This Opinion

  11. Why do bacteria engage in homologous recombination?

    NARCIS (Netherlands)

    Vos, M.

    2009-01-01

    Microbiologists have long recognized that the uptake and incorporation of homologous DNA from outside the cell is a common feature of bacteria, with important implications for their evolution. However, the exact reasons why bacteria engage in homologous recombination remain elusive. This Opinion art

  12. Synthetic Homology in Homotopy Type Theory

    OpenAIRE

    Graham, Robert

    2017-01-01

    This paper defines homology in homotopy type theory, in the process stable homotopy groups are also defined. Previous research in synthetic homotopy theory is relied on, in particular the definition of cohomology. This work lays the foundation for a computer checked construction of homology.

  13. GENE SEQUENCE HOMOLOGY OF CHEMOKINES ACROSS SPECIES

    Science.gov (United States)

    The abundance of expressed gene and protein sequences available in the biological information databases facilitates comparison of protein homologies. A high degree of sequence similarity typically implies homology regarding structure and function and may provide clues to antibody cross-react...

  14. Traces of differential forms and Hochschild homology

    CERN Document Server

    Hübl, Reinhold

    1989-01-01

    This monograph provides an introduction to, as well as a unification and extension of the published work and some unpublished ideas of J. Lipman and E. Kunz about traces of differential forms and their relations to duality theory for projective morphisms. The approach uses Hochschild-homology, the definition of which is extended to the category of topological algebras. Many results for Hochschild-homology of commutative algebras also hold for Hochschild-homology of topological algebras. In particular, after introducing an appropriate notion of completion of differential algebras, one gets a natural transformation between differential forms and Hochschild-homology of topological algebras. Traces of differential forms are of interest to everyone working with duality theory and residue symbols. Hochschild-homology is a useful tool in many areas of k-theory. The treatment is fairly elementary and requires only little knowledge in commutative algebra and algebraic geometry.

  15. Investigations of homologous recombination pathways and their regulation.

    Science.gov (United States)

    Daley, James M; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick

    2013-12-13

    The DNA double-strand break (DSB), arising from exposure to ionizing radiation or various chemotherapeutic agents or from replication fork collapse, is among the most dangerous of chromosomal lesions. DSBs are highly cytotoxic and can lead to translocations, deletions, duplications, or mutations if mishandled. DSBs are eliminated by either homologous recombination (HR), which uses a homologous template to guide accurate repair, or by nonhomologous end joining (NHEJ), which simply rejoins the two broken ends after damaged nucleotides have been removed. HR generates error-free repair products and is also required for generating chromosome arm crossovers between homologous chromosomes in meiotic cells. The HR reaction includes several distinct steps: resection of DNA ends, homologous DNA pairing, DNA synthesis, and processing of HR intermediates. Each occurs in a highly regulated fashion utilizing multiple protein factors. These steps are being elucidated using a combination of genetic tools, cell-based assays, and in vitro reconstitution with highly purified HR proteins. In this review, we summarize contributions from our laboratory at Yale University in understanding HR mechanisms in eukaryotic cells.

  16. Homology--history of a concept.

    Science.gov (United States)

    Panchen, A L

    1999-01-01

    The concept of homology is traceable to Aristotle, but Belon's comparison in 1555 of a human skeleton with that of a bird expressed it overtly. Before the late 18th century, the dominant view of the pattern of organisms was the scala naturae--even Linnaeus with his divergent hierarchical classification did not necessarily see the resulting taxonomic pattern as a natural phenomenon. The divergent hierarchy, rather than the acceptance of phylogeny, was the necessary spur to discussion of homology and the concept of analogy. Lamarck, despite his proposal of evolution, attributed homology to his escalator naturae and analogy to convergent acquired characters. Significantly, it was the concept of serial homology that emerged at the end of the 18th century, although comparison between organisms became popular soon after, and was boosted by the famous Cuvier/Geoffroy Saint-Hilaire debate of the 1830s. The concepts of homology and analogy were well understood by the pre- (or anti-) evolutionary comparative anatomists before the general acceptance of phylogeny, and they were defined by Owen in 1843. The acceptance of evolution led to the idea that homology should be defined by common ancestry, and to the confusion between definition and explanation. The term 'homoplasy', introduced by Lankester in 1870, also arose from a phylogenetic explanation of homology.

  17. Hidden torsion, 3-manifolds, and homology cobordism

    CERN Document Server

    Cha, Jae Choon

    2011-01-01

    This paper continues our exploration of homology cobordism of 3-manifolds using our recent results on Cheeger-Gromov rho-invariants associated to amenable representations. We introduce a new type of torsion in 3-manifold groups we call hidden torsion, and an algebraic approximation we call local hidden torsion. We construct infinitely many hyperbolic 3-manifolds which have local hidden torsion in the transfinite lower central subgroup. By realizing Cheeger-Gromov invariants over amenable groups, we show that our hyperbolic 3-manifolds are not pairwise homology cobordant, yet remain indistinguishable by any prior known homology cobordism invariants.

  18. Threading homology through algebra selected patterns

    CERN Document Server

    Boffi, Giandomenico

    2006-01-01

    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

  19. Precise genome editing by homologous recombination.

    Science.gov (United States)

    Hoshijima, K; Jurynec, M J; Grunwald, D J

    2016-01-01

    Simple and efficient methods are presented for creating precise modifications of the zebrafish genome. Edited alleles are generated by homologous recombination between the host genome and double-stranded DNA (dsDNA) donor molecules, stimulated by the induction of double-strand breaks at targeted loci in the host genome. Because several kilobase-long tracts of sequence can be exchanged, multiple genome modifications can be generated simultaneously at a single locus. Methods are described for creating: (1) alleles with simple sequence changes or in-frame additions, (2) knockin/knockout alleles that express a reporter protein from an endogenous locus, and (3) conditional alleles in which exons are flanked by recombinogenic loxP sites. Significantly, our approach to genome editing allows the incorporation of a linked reporter gene into the donor sequences so that successfully edited alleles can be identified by virtue of expression of the reporter. Factors affecting the efficiency of genome editing are discussed, including the finding that dsDNA products of I-SceI meganuclease enzyme digestion are particularly effective as donor molecules for gene-editing events. Reagents and procedures are described for accomplishing efficient genome editing in the zebrafish.

  20. Pleckstrin homology domains and the cytoskeleton.

    Science.gov (United States)

    Lemmon, Mark A; Ferguson, Kathryn M; Abrams, Charles S

    2002-02-20

    Pleckstrin homology (PH) domains are 100-120 amino acid protein modules best known for their ability to bind phosphoinositides. All possess an identical core beta-sandwich fold and display marked electrostatic sidedness. The binding site for phosphoinositides lies in the center of the positively charged face. In some cases this binding site is well defined, allowing highly specific and strong ligand binding. In several of these cases the PH domains specifically recognize 3-phosphorylated phosphoinositides, allowing them to drive membrane recruitment in response to phosphatidylinositol 3-kinase activation. Examples of these PH domain-containing proteins include certain Dbl family guanine nucleotide exchange factors, protein kinase B, PhdA, and pleckstrin-2. PH domain-mediated membrane recruitment of these proteins contributes to regulated actin assembly and cell polarization. Many other PH domain-containing cytoskeletal proteins, such as spectrin, have PH domains that bind weakly, and to all phosphoinositides. In these cases, the individual phosphoinositide interactions may not be sufficient for membrane association, but appear to require self-assembly of their host protein and/or cooperation with other anchoring motifs within the same molecule to drive membrane attachment.

  1. The homologous recombination system of Ustilago maydis.

    Science.gov (United States)

    Holloman, William K; Schirawski, Jan; Holliday, Robin

    2008-08-01

    Homologous recombination is a high fidelity, template-dependent process that is used in repair of damaged DNA, recovery of broken replication forks, and disjunction of homologous chromosomes in meiosis. Much of what is known about recombination genes and mechanisms comes from studies on baker's yeast. Ustilago maydis, a basidiomycete fungus, is distant evolutionarily from baker's yeast and so offers the possibility of gaining insight into recombination from an alternative perspective. Here we have surveyed the genome of U. maydis to determine the composition of its homologous recombination system. Compared to baker's yeast, there are fundamental differences in the function as well as in the repertoire of dedicated components. These include the use of a BRCA2 homolog and its modifier Dss1 rather than Rad52 as a mediator of Rad51, the presence of only a single Rad51 paralog, and the absence of Dmc1 and auxiliary meiotic proteins.

  2. Dualities in Persistent (Co)Homology

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-16

    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.

  3. INVHOGEN: a database of homologous invertebrate genes

    OpenAIRE

    Paulsen, Ingo; von Haeseler, Arndt

    2005-01-01

    Classification of proteins into families of homologous sequences constitutes the basis of functional analysis or of evolutionary studies. Here we present INVertebrate HOmologous GENes (INVHOGEN), a database combining the available invertebrate protein genes from UniProt (consisting of Swiss-Prot and TrEMBL) into gene families. For each family INVHOGEN provides a multiple protein alignment, a maximum likelihood based phylogenetic tree and taxonomic information about the sequences. It is possib...

  4. Dualities in Persistent (Co)Homology

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-16

    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.

  5. The homologous recombination system of Ustilago maydis

    OpenAIRE

    Holloman, William K.; Schirawski, Jan; Holliday, Robin

    2008-01-01

    Homologous recombination is a high fidelity, template-dependent process that is used in repair of damaged DNA, recovery of broken replication forks, and disjunction of homologous chromosomes in meiosis. Much of what is known about recombination genes and mechanisms comes from studies on baker's yeast. Ustilago maydis, a basidiomycete fungus, is distant evolutionarily from baker's yeast and so offers the possibility of gaining insight into recombination from an alternative perspective. Here we...

  6. A Khovanov Type Link Homology with Geometric Interpretation

    Institute of Scientific and Technical Information of China (English)

    Mei Li ZHANG; Feng Chun LEI

    2016-01-01

    We study a Khovanov type homology close to the original Khovanov homology theory from Frobenius system. The homology is an invariant for oriented links up to isotopy by applying a tautological functor on the geometric complex. The homology has also geometric descriptions by introducing the genus generating operations. We prove that Jones Polynomial is equal to a suitable Euler characteristic of the homology groups. As an application, we compute the homology groups of (2, k)-torus knots for every k∈N.

  7. Homolog pairing and segregation in Drosophila meiosis.

    Science.gov (United States)

    McKee, B D

    2009-01-01

    Pairing of homologous chromosomes is fundamental to their reliable segregation during meiosis I and thus underlies sexual reproduction. In most eukaryotes homolog pairing is confined to prophase of meiosis I and is accompanied by frequent exchanges, known as crossovers, between homologous chromatids. Crossovers give rise to chiasmata, stable interhomolog connectors that are required for bipolar orientation (orientation to opposite poles) of homologs during meiosis I. Drosophila is unique among model eukaryotes in exhibiting regular homolog pairing in mitotic as well as meiotic cells. I review the results of recent molecular studies of pairing in both mitosis and meiosis in Drosophila. These studies show that homolog pairing is continuous between pre-meiotic mitosis and meiosis but that pairing frequencies and patterns are altered during the mitotic-meiotic transition. They also show that, with the exception of X-Y pairing in male meiosis, which is mediated specifically by the 240-bp rDNA spacer repeats, chromosome pairing is not restricted to specific sites in either mitosis or meiosis. Instead, virtually all chromosome regions, both heterochromatic and euchromatic, exhibit autonomous pairing capacity. Mutations that reduce the frequencies of both mitotic and meiotic pairing have been recently described, but no mutations that abolish pairing completely have been discovered, and the genetic control of pairing in Drosophila remains to be elucidated.

  8. On the hodological criterion for homology.

    Science.gov (United States)

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

    2015-01-01

    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.

  9. On the hodological criterion for homology

    Science.gov (United States)

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

    2015-01-01

    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

  10. Investigating homology between proteins using energetic profiles.

    Directory of Open Access Journals (Sweden)

    James O Wrabl

    2010-03-01

    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

  11. On the hodological criterion for homology

    Directory of Open Access Journals (Sweden)

    Macarena eFaunes

    2015-06-01

    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. Homologous Recombination in Protozoan Parasites and Recombinase Inhibitors.

    Science.gov (United States)

    Kelso, Andrew A; Waldvogel, Sarah M; Luthman, Adam J; Sehorn, Michael G

    2017-01-01

    Homologous recombination (HR) is a DNA double-strand break (DSB) repair pathway that utilizes a homologous template to fully repair the damaged DNA. HR is critical to maintain genome stability and to ensure genetic diversity during meiosis. A specialized class of enzymes known as recombinases facilitate the exchange of genetic information between sister chromatids or homologous chromosomes with the help of numerous protein accessory factors. The majority of the HR machinery is highly conserved among eukaryotes. In many protozoan parasites, HR is an essential DSB repair pathway that allows these organisms to adapt to environmental conditions and evade host immune systems through genetic recombination. Therefore, small molecule inhibitors, capable of disrupting HR in protozoan parasites, represent potential therapeutic options. A number of small molecule inhibitors were identified that disrupt the activities of the human recombinase RAD51. Recent studies have examined the effect of two of these molecules on the Entamoeba recombinases. Here, we discuss the current understandings of HR in the protozoan parasites Trypanosoma, Leishmania, Plasmodium, and Entamoeba, and we review the small molecule inhibitors known to disrupt human RAD51 activity.

  13. Homologous recombination in DNA repair and DNA damage tolerance

    Institute of Scientific and Technical Information of China (English)

    Xuan Li; Wolf-Dietrich Heyer

    2008-01-01

    Homologous recombination (HR) comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks (DSBs) and interstrand crosslinks (ICLs). In addition, recombination provides critical sup-port for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR: homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modaUties of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.

  14. On the Mechanism of Homology Search by RecA Protein Filaments.

    Science.gov (United States)

    Kochugaeva, Maria P; Shvets, Alexey A; Kolomeisky, Anatoly B

    2017-03-14

    Genetic stability is a key factor in maintaining, survival, and reproduction of biological cells. It relies on many processes, but one of the most important is a homologous recombination, in which the repair of breaks in double-stranded DNA molecules is taking place with a help of several specific proteins. In bacteria, this task is accomplished by RecA proteins that are active as nucleoprotein filaments formed on single-stranded segments of DNA. A critical step in the homologous recombination is a search for a corresponding homologous region on DNA, which is called a homology search. Recent single-molecule experiments clarified some aspects of this process, but its molecular mechanisms remain not well understood. We developed a quantitative theoretical approach to analyze the homology search. It is based on a discrete-state stochastic model that takes into account the most relevant physical-chemical processes in the system. Using a method of first-passage processes, a full dynamic description of the homology search is presented. It is found that the search dynamics depends on the degree of extension of DNA molecules and on the size of RecA nucleoprotein filaments, in agreement with experimental single-molecule measurements of DNA pairing by RecA proteins. Our theoretical calculations, supported by extensive Monte Carlo computer simulations, provide a molecular description of the mechanisms of the homology search. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  15. Hyper(co)homology for exact left covariant functors and a homology theory for topological spaces

    Science.gov (United States)

    Sklyarenko, E. G.

    1995-06-01

    Contents Introduction §1. Strong cohomology of dual complexes §2. Hyperhomology §3. Examples §4. Typical limit relations for Steenrod-Sitnikov homology §5. The strong homology of topological spaces §6. On the special position held by singular theory Bibliography

  16. Borel-Moore homology and cap product operations

    OpenAIRE

    Hanamura, Masaki

    2016-01-01

    We show that, for a simplicial complex, the supported cap product operation on Borel-Moore homology coincides with the supported cap product on simplicial homology. For this purpose we introduce the supported cap product for locally finite singular homology, and compare the cap product on the three homology theories.

  17. INVHOGEN: a database of homologous invertebrate genes.

    Science.gov (United States)

    Paulsen, Ingo; von Haeseler, Arndt

    2006-01-01

    Classification of proteins into families of homologous sequences constitutes the basis of functional analysis or of evolutionary studies. Here we present INVertebrate HOmologous GENes (INVHOGEN), a database combining the available invertebrate protein genes from UniProt (consisting of Swiss-Prot and TrEMBL) into gene families. For each family INVHOGEN provides a multiple protein alignment, a maximum likelihood based phylogenetic tree and taxonomic information about the sequences. It is possible to download the corresponding GenBank flatfiles, the alignment and the tree in Newick format. Sequences and related information have been structured in an ACNUC database under a client/server architecture. Thus, complex selections can be performed. An external graphical tool (FamFetch) allows access to the data to evaluate homology relationships between genes and distinguish orthologous from paralogous sequences. Thus, INVHOGEN complements the well-known HOVERGEN database. The databank is available at http://www.bi.uni-duesseldorf.de/~invhogen/invhogen.html.

  18. Crystal structure of an archaeal actin homolog.

    Science.gov (United States)

    Roeben, Annette; Kofler, Christine; Nagy, István; Nickell, Stephan; Hartl, F Ulrich; Bracher, Andreas

    2006-04-21

    Prokaryotic homologs of the eukaryotic structural protein actin, such as MreB and ParM, have been implicated in determination of bacterial cell shape, and in the segregation of genomic and plasmid DNA. In contrast to these bacterial actin homologs, little is known about the archaeal counterparts. As a first step, we expressed a predicted actin homolog of the thermophilic archaeon Thermoplasma acidophilum, Ta0583, and determined its crystal structure at 2.1A resolution. Ta0583 is expressed as a soluble protein in T.acidophilum and is an active ATPase at physiological temperature. In vitro, Ta0583 forms sheets with spacings resembling the crystal lattice, indicating an inherent propensity to form filamentous structures. The fold of Ta0583 contains the core structure of actin and clearly belongs to the actin/Hsp70 superfamily of ATPases. Ta0583 is approximately equidistant from actin and MreB on the structural level, and combines features from both eubacterial actin homologs, MreB and ParM. The structure of Ta0583 co-crystallized with ADP indicates that the nucleotide binds at the interface between the subdomains of Ta0583 in a manner similar to that of actin. However, the conformation of the nucleotide observed in complex with Ta0583 clearly differs from that in complex with actin, but closely resembles the conformation of ParM-bound nucleotide. On the basis of sequence and structural homology, we suggest that Ta0583 derives from a ParM-like actin homolog that was once encoded by a plasmid and was transferred into a common ancestor of Thermoplasma and Ferroplasma. Intriguingly, both genera are characterized by the lack of a cell wall, and therefore Ta0583 could have a function in cellular organization.

  19. Homological Algebra of Semimodules and Semicontramodules

    CERN Document Server

    Positselski, Leonid

    2010-01-01

    This is a monograph in semi-infinite homological algebra, concentrated mostly on the semi-infinite theory of associative algebraic structures, but including also some material on the semi-infinite homology and cohomology of Lie algebras and topological groups. The main objects of study are the double-sided derived functors SemiExt and SemiTor, and the phenomenon of comodule-contramodule correspondence, connecting them with the more conventional, one-sided Ext and CtrTor. Contramodules, introduced originally by Eilenberg and Moore in 1960's but almost forgotten for four decades, play a very pro

  20. Relative Derived Equivalences and Relative Homological Dimensions

    Institute of Scientific and Technical Information of China (English)

    Sheng Yong PAN

    2016-01-01

    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.

  1. Homological and homotopical Dehn functions are different

    CERN Document Server

    Abrams, Aaron; Dani, Pallavi; Young, Robert

    2012-01-01

    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.

  2. New mesogenic homologous series of -methylcinnamates

    Indian Academy of Sciences (India)

    R A Vora; A K Prajapati

    2001-04-01

    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.

  3. Homology and cohomology of Rees semigroup algebras

    DEFF Research Database (Denmark)

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

    2011-01-01

    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....

  4. Change of gene structure and function by non-homologous end-joining, homologous recombination, and transposition of DNA.

    Science.gov (United States)

    Goettel, Wolfgang; Messing, Joachim

    2009-06-01

    An important objective in genome research is to relate genome structure to gene function. Sequence comparisons among orthologous and paralogous genes and their allelic variants can reveal sequences of functional significance. Here, we describe a 379-kb region on chromosome 1 of maize that enables us to reconstruct chromosome breakage, transposition, non-homologous end-joining, and homologous recombination events. Such a high-density composition of various mechanisms in a small chromosomal interval exemplifies the evolution of gene regulation and allelic diversity in general. It also illustrates the evolutionary pace of changes in plants, where many of the above mechanisms are of somatic origin. In contrast to animals, somatic alterations can easily be transmitted through meiosis because the germline in plants is contiguous to somatic tissue, permitting the recovery of such chromosomal rearrangements. The analyzed region contains the P1-wr allele, a variant of the genetically well-defined p1 gene, which encodes a Myb-like transcriptional activator in maize. The P1-wr allele consists of eleven nearly perfect P1-wr 12-kb repeats that are arranged in a tandem head-to-tail array. Although a technical challenge to sequence such a structure by shotgun sequencing, we overcame this problem by subcloning each repeat and ordering them based on nucleotide variations. These polymorphisms were also critical for recombination and expression analysis in presence and absence of the trans-acting epigenetic factor Ufo1. Interestingly, chimeras of the p1 and p2 genes, p2/p1 and p1/p2, are framing the P1-wr cluster. Reconstruction of sequence amplification steps at the p locus showed the evolution from a single Myb-homolog to the multi-gene P1-wr cluster. It also demonstrates how non-homologous end-joining can create novel gene fusions. Comparisons to orthologous regions in sorghum and rice also indicate a greater instability of the maize genome, probably due to diploidization

  5. Archaeal Tuc1/Ncs6 homolog required for wobble uridine tRNA thiolation is associated with ubiquitin-proteasome, translation, and RNA processing system homologs.

    Directory of Open Access Journals (Sweden)

    Nikita E Chavarria

    Full Text Available While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6 and ubiquitin-related modifier-1 (Urm1 are important in the 2-thiolation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U at wobble uridines of tRNAs in eukaryotes, the biocatalytic roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax volcanii that is essential for maintaining cellular pools of thiolated tRNA(LysUUU and for growth at high temperature. When purified from Hfx. volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1 enzyme homolog of archaea (UbaA was required for this covalent modification. Non-covalent protein partners that specifically associated with NcsA were also identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN-A/1, translation elongation factor aEF-1α and a β-CASP ribonuclease homolog of the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1. Together, our study reveals that NcsA is essential for growth at high temperature, required for formation of thiolated tRNA(LysUUU and intimately linked to homologs of ubiquitin-proteasome, translation and RNA processing systems.

  6. Seiberg-Witten-Floer Theory for Homology 3-Spheres

    CERN Document Server

    Wang, B L

    1996-01-01

    We give the definition of the Seiberg-Witten-Floer homology group for a homology 3-sphere. Its Euler characteristic number is a Casson-type invariant. For a four-manifold with boundary a homology sphere, a relative Seiberg-Witten invariant is defined taking values in the Seiberg-Witten-Floer homology group, these relative Seiberg-Witten invariants are applied to certain homology spheres bounding Stein surfaces.

  7. Competition between replicative and translesion polymerases during homologous recombination repair in Drosophila.

    Directory of Open Access Journals (Sweden)

    Daniel P Kane

    Full Text Available In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis.

  8. Homological Perturbation Theory and Mirror Symmetry

    Institute of Scientific and Technical Information of China (English)

    Jian ZHOU

    2003-01-01

    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.

  9. Homological stability for unordered configuration spaces

    DEFF Research Database (Denmark)

    Randal-Williams, Oscar

    2013-01-01

    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...

  10. Khovanov homology for virtual tangles and applications

    DEFF Research Database (Denmark)

    Tubbenhauer, Daniel

    We extend the cobordism based categorification of the virtual Jones polynomial to virtual tangles. This extension is combinatorial and has semi-local properties. We use the semi-local property to prove an applications, i.e. we give a discussion of Lee's degeneration of virtual homology....

  11. Persistent homology in graph power filtrations.

    Science.gov (United States)

    Parks, Allen D; Marchette, David J

    2016-10-01

    The persistence of homological features in simplicial complex representations of big datasets in R (n) resulting from Vietoris-Rips or Čech filtrations is commonly used to probe the topological structure of such datasets. In this paper, the notion of homological persistence in simplicial complexes obtained from power filtrations of graphs is introduced. Specifically, the rth complex, r ≥ 1, in such a power filtration is the clique complex of the rth power G(r) of a simple graph G. Because the graph distance in G is the relevant proximity parameter, unlike a Euclidean filtration of a dataset where regional scale differences can be an issue, persistence in power filtrations provides a scale-free insight into the topology of G. It is shown that for a power filtration of G, the girth of G defines an r range over which the homology of the complexes in the filtration are guaranteed to persist in all dimensions. The role of chordal graphs as trivial homology delimiters in power filtrations is also discussed and the related notions of 'persistent triviality', 'transient noise' and 'persistent periodicity' in power filtrations are introduced.

  12. Homology stability for the general linear group

    NARCIS (Netherlands)

    Maazen, Hendrik

    1979-01-01

    This thesis studies the homology stability problem for general linear groups over Euclidean rings and over subrings of the field of rational numbers. Affine linear groups, acting on affine space rather than linear space, are also considered. In order to get stability results one establishes that cer

  13. Cell biology of homologous recombination in yeast

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  14. Threading homology through algebra selected patterns

    CERN Document Server

    Boffi, Giandomenico

    2006-01-01

    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.

  15. Gorenstein Homological Dimensions and Change of Rings

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan YANG

    2012-01-01

    In this paper,we shall be concerned with what happens of Gorenstein homological dimensions when certain modifications are made to a ring. The five structural operations addressed later are the formation of excellent extensions,localizations,Morita equivalences,polynomial extensions and power series extensions.

  16. Homological stability for unordered configuration spaces

    DEFF Research Database (Denmark)

    Randal-Williams, Oscar

    2013-01-01

    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...

  17. Persistent Homology for Random Fields and Complexes

    CERN Document Server

    Adler, Robert J; Borman, Matthew S; Subag, Eliran; Weinberger, Shmuel

    2010-01-01

    We discuss and review recent developments in the area of applied algebraic topology, such as persistent homology and barcodes. In particular, we discuss how these are related to understanding more about manifold learning from random point cloud data, the algebraic structure of simplicial complexes determined by random vertices, and, in most detail, the algebraic topology of the excursion sets of random fields.

  18. Homology stability for the general linear group

    NARCIS (Netherlands)

    Maazen, Hendrik

    1979-01-01

    This thesis studies the homology stability problem for general linear groups over Euclidean rings and over subrings of the field of rational numbers. Affine linear groups, acting on affine space rather than linear space, are also considered. In order to get stability results one establishes that

  19. Khovanov homology for virtual tangles and applications

    DEFF Research Database (Denmark)

    Tubbenhauer, Daniel

    We extend the cobordism based categorification of the virtual Jones polynomial to virtual tangles. This extension is combinatorial and has semi-local properties. We use the semi-local property to prove an applications, i.e. we give a discussion of Lee's degeneration of virtual homology....

  20. Safety and efficacy of cryopreserved homologous veins for venous reconstruction in pancreatoduodenectomy.

    Science.gov (United States)

    Yamamoto, Masaki; Akamatsu, Nobuhisa; Aoki, Taku; Sakamoto, Yoshihiro; Tamura, Sumihito; Hasegawa, Kiyoshi; Kokudo, Norihiro

    2017-02-01

    There are several techniques for reconstructing the portal vein-superior mesenteric vein during pancreatoduodenectomy. The aim of the present study was to present our results with portal vein-superior mesenteric vein reconstruction using cryopreserved homologous veins during pancreatoduodenectomy for patients with pancreatic head cancer. Patients who underwent pancreatoduodenectomy for pancreatic head cancer were reviewed retrospectively. In patients with portal vein-superior mesenteric vein resection, the detailed method of reconstruction and clinical outcomes were reviewed. Clinical characteristics, patient survival, and portal vein-superior mesenteric vein patency were compared between those with and without homologous vein grafts. Factors affecting the patency of reconstructed veins were assessed by univariate analysis. Among 144 patients undergoing pancreatoduodenectomy, portal vein-superior mesenteric vein resection was performed in 36 patients (25%); 18 (50%) underwent reconstruction with homologous veins, and the other 18 (50%) underwent reconstruction without homologous veins. The extent of portal vein-superior mesenteric vein involvement, operative time, duration of clamping of portal vein-superior mesenteric vein, intraoperative blood loss, and length of the venous resection were greater (P ≤ .013 each) in those with homologous vein grafts. There was no significant difference in postoperative morbidity/mortality, patient survival, or portal vein-superior mesenteric vein patency. The 1- and 2-year overall patency of portal vein-superior mesenteric vein was 76% and 71%, respectively, while the 2-year patencies were 67% and 67% in those with homologous veins and 87% and 73% in those without homologous veins without difference between the groups. Circumferential resection and pathologic portal vein-superior mesenteric vein involvement were associated with the patency of the reconstructed vein (P = .002 and P = .028, resp). Use of homologous venous

  1. 自身免疫性感音神经性聋患者候选基因——凝血因子C同源物突变筛查%A candidate gene screening of coagulation factor C homology in patients with autoimmune sensorineural hearing loss

    Institute of Scientific and Technical Information of China (English)

    孙勍; 于飞; 刘新; 康东洋; 张昕; 戴朴; 袁慧军; 韩东一

    2008-01-01

    目的 通过对22例自身免疫性感音神经性聋(autoimmune sensorineural hearing loss,ASNHL)患者进行凝血因子C同源物基因(coagulation factor C homology,COCH)全序列分析,探索自身免疫性感音神经性聋与COCH突变的相关性.方法 应用聚合酶链反应(PCR)产物直接测序方法对22例自身免疫性感音神经性聋患者进行COCH全序列分析.结果 在22例自身免疫性感音神经性聋病例中未发现COCH突变和多态.结论 初步探索了ASNHL与COCH突变的相关性,未发现COCH突变和多态,还需进一步收集临床病例来证实.

  2. Relative K-homology and normal operators

    DEFF Research Database (Denmark)

    Manuilov, Vladimir; Thomsen, Klaus

    2009-01-01

    Let $A$ be a $C^*$-algebra, $J \\subset A$ a $C^*$-subalgebra, and let $B$ be a stable $C^*$-algebra. Under modest assumptions we organize invertible $C^*$-extensions of $A$ by $B$ that are trivial when restricted onto $J$ to become a group $\\mathrm{Ext}_J^{-1}(A,B)$, which can be computed by a six......-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....

  3. Homologous pairing in stretched supercoiled DNA

    Science.gov (United States)

    Strick, T. R.; Croquette, V.; Bensimon, D.

    1998-01-01

    By using elastic measurements on single DNA molecules, we show that stretching a negatively supercoiled DNA activates homologous pairing in physiological conditions. These experiments indicate that a stretched unwound DNA locally denatures to alleviate the force-driven increase in torsional stress. This is detected by hybridization with 1 kb of homologous single-stranded DNA probes. The stretching force involved (≈2 pN) is small compared with those typically developed by molecular motors, suggesting that this process may be relevant to DNA processing in vivo. We used this technique to monitor the progressive denaturation of DNA as it is unwound and found that distinct, stable denaturation bubbles formed, beginning in A+T-rich regions. PMID:9724746

  4. Homological mirror symmetry and tropical geometry

    CERN Document Server

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

    2014-01-01

    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...

  5. Translated points and Rabinowitz Floer homology

    CERN Document Server

    Albers, Peter

    2011-01-01

    We prove that if a contact manifold admits an exact filling then every local contactomorphism isotopic to the identity admits a translated point in the interior of its support, in the sense of Sandon [San11b]. In addition we prove that if the Rabinowitz Floer homology of the filling is non-zero then every contactomorphism isotopic to the identity admits a translated point, and if the Rabinowitz Floer homology of the filling is infinite dimensional then every contactmorphism isotopic to the identity has either infinitely many translated points, or a translated point on a closed leaf. Moreover if the contact manifold has dimension greater than or equal to 3, the latter option generically doesn't happen. Finally, we prove that a generic contactomorphism on $\\mathbb{R}^{2n+1}$ has infinitely many geometrically distinct iterated translated points all of which lie in the interior of its support.

  6. Nash equilibria via duality and homological selection

    Indian Academy of Sciences (India)

    Arnab Basu; Samik Basu; Mahan MJ

    2014-11-01

    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.

  7. Homological Methods in Equations of Mathematical Physics

    OpenAIRE

    Krasil'shchik, Joseph; Verbovetsky, Alexander

    1998-01-01

    These lecture notes are a systematic and self-contained exposition of the cohomological theories naturally related to partial differential equations: the Vinogradov C-spectral sequence and the C-cohomology, including the formulation in terms of the horizontal (characteristic) cohomology. Applications to computing invariants of differential equations are discussed. The lectures contain necessary introductory material on the geometric theory of differential equations and homological algebra.

  8. Homology and phylogeny and their automated inference

    Science.gov (United States)

    Fuellen, Georg

    2008-06-01

    The analysis of the ever-increasing amount of biological and biomedical data can be pushed forward by comparing the data within and among species. For example, an integrative analysis of data from the genome sequencing projects for various species traces the evolution of the genomes and identifies conserved and innovative parts. Here, I review the foundations and advantages of this “historical” approach and evaluate recent attempts at automating such analyses. Biological data is comparable if a common origin exists (homology), as is the case for members of a gene family originating via duplication of an ancestral gene. If the family has relatives in other species, we can assume that the ancestral gene was present in the ancestral species from which all the other species evolved. In particular, describing the relationships among the duplicated biological sequences found in the various species is often possible by a phylogeny, which is more informative than homology statements. Detecting and elaborating on common origins may answer how certain biological sequences developed, and predict what sequences are in a particular species and what their function is. Such knowledge transfer from sequences in one species to the homologous sequences of the other is based on the principle of ‘my closest relative looks and behaves like I do’, often referred to as ‘guilt by association’. To enable knowledge transfer on a large scale, several automated ‘phylogenomics pipelines’ have been developed in recent years, and seven of these will be described and compared. Overall, the examples in this review demonstrate that homology and phylogeny analyses, done on a large (and automated) scale, can give insights into function in biology and biomedicine.

  9. Dental homologies in lamniform sharks (Chondrichthyes: Elasmobranchii).

    Science.gov (United States)

    Shimada, Kenshu

    2002-01-01

    The dentitions of lamniform sharks are said to exhibit a unique heterodonty called the "lamnoid tooth pattern." The presence of an inflated hollow "dental bulla" on each jaw cartilage allows the recognition of homologous teeth across most modern macrophagous lamniforms based on topographic correspondence through the "similarity test." In most macrophagous lamniforms, three tooth rows are supported by the upper dental bulla: two rows of large anterior teeth followed by a row of small intermediate teeth. The lower tooth row occluding between the two rows of upper anterior teeth is the first lower anterior tooth row. Like the first and second lower anterior tooth rows, the third lower tooth row is supported by the dental bulla and may be called the first lower intermediate tooth row. The lower intermediate tooth row occludes between the first and second upper lateral tooth rows situated distal to the upper dental bulla, and the rest of the upper and lower tooth rows, all called lateral tooth rows, occlude alternately. Tooth symmetry cannot be used to identify their dental homology. The presence of dental bullae can be regarded as a synapomorphy of Lamniformes and this character is more definable than the "lamnoid tooth pattern." The formation of the tooth pattern appears to be related to the evolution of dental bullae. This study constitutes the first demonstration of supraspecific tooth-to-tooth dental homologies in nonmammalian vertebrates.

  10. Homology among divergent Paleozoic tetrapod clades.

    Science.gov (United States)

    Carroll, R L

    1999-01-01

    A stringent definition of homology is necessary to establish phylogenetic relationships among Paleozoic amphibians. Many derived characters exhibited by divergent clades of Carboniferous lepospondyls resemble those achieved convergently among Cenozoic squamates that have elongate bodies and reduced limbs, and by lineages of modern amphibians that have undergone miniaturization. Incongruent character distribution, poorly resolved cladograms and functionally improbable character transformations determined by phylogenetic analysis suggest that convergence was also common among Paleozoic amphibians with a skull length under 3 cm, including lepospondyls, early amniotes and the putative ancestors of modern amphibians. For this reason, it is injudicious to equate apparent synapomorphy (perceived common presence of a particular derived character in two putative sister-taxa) with strict homology of phylogenetic origin. Identification of homology by the similarity of structure, anatomical position and pattern of development is insufficient to establish the synapomorphy of bone and limb loss or precocial ossification of vertebral centra, which are common among small Paleozoic amphibians. The only way in which synapomorphies can be established definitively is through the discovery and recognition of the trait in question in basal members of each of the clades under study, and in their immediate common ancestors.

  11. Irradiated homologous costal cartilage for augmentation rhinoplasty

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-10-01

    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.

  12. Note on homological modeling of the electric circuits

    OpenAIRE

    2014-01-01

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

  13. Homology and ontogeny: pattern and process in comparative developmental biology.

    Science.gov (United States)

    Scholtz, Gerhard

    2005-11-01

    In this article the interface between development and homology is discussed. Development is here interpreted as a sequence of evolutionarily independent stages. Any approach stressing the importance of specific developmental stages is rejected. A homology definition is favoured which includes similarity, and complexity serves as a test for homology. Complexity is seen as the possibility of subdividing a character into evolutionarily independent corresponding substructures. Topology as a test for homology is critically discussed because corresponding positions are not necessarily indicative of homology. Complexity can be used twofold for homology assessments of development: either stages or processes of development are homologized. These two approaches must not be con-flated. This distinction leads to the conclusion that there is no ontogenetic homology "criterion".

  14. HomologMiner: looking for homologous genomic groups in whole genomes.

    Science.gov (United States)

    Hou, Minmei; Berman, Piotr; Hsu, Chih-Hao; Harris, Robert S

    2007-04-15

    Complex genomes contain numerous repeated sequences, and genomic duplication is believed to be a main evolutionary mechanism to obtain new functions. Several tools are available for de novo repeat sequence identification, and many approaches exist for clustering homologous protein sequences. We present an efficient new approach to identify and cluster homologous DNA sequences with high accuracy at the level of whole genomes, excluding low-complexity repeats, tandem repeats and annotated interspersed repeats. We also determine the boundaries of each group member so that it closely represents a biological unit, e.g. a complete gene, or a partial gene coding a protein domain. We developed a program called HomologMiner to identify homologous groups applicable to genome sequences that have been properly marked for low-complexity repeats and annotated interspersed repeats. We applied it to the whole genomes of human (hg17), macaque (rheMac2) and mouse (mm8). Groups obtained include gene families (e.g. olfactory receptor gene family, zinc finger families), unannotated interspersed repeats and additional homologous groups that resulted from recent segmental duplications. Our program incorporates several new methods: a new abstract definition of consistent duplicate units, a new criterion to remove moderately frequent tandem repeats, and new algorithmic techniques. We also provide preliminary analysis of the output on the three genomes mentioned above, and show several applications including identifying boundaries of tandem gene clusters and novel interspersed repeat families. All programs and datasets are downloadable from www.bx.psu.edu/miller_lab.

  15. Persistent homology analysis of protein structure, flexibility and folding

    Science.gov (United States)

    Xia, Kelin; Wei, Guo-Wei

    2014-01-01

    Proteins are the most important biomolecules for living organisms. The understanding of protein structure, function, dynamics and transport is one of most challenging tasks in biological science. In the present work, persistent homology is, for the first time, introduced for extracting molecular topological fingerprints (MTFs) based on the persistence of molecular topological invariants. MTFs are utilized for protein characterization, identification and classification. The method of slicing is proposed to track the geometric origin of protein topological invariants. Both all-atom and coarse-grained representations of MTFs are constructed. A new cutoff-like filtration is proposed to shed light on the optimal cutoff distance in elastic network models. Based on the correlation between protein compactness, rigidity and connectivity, we propose an accumulated bar length generated from persistent topological invariants for the quantitative modeling of protein flexibility. To this end, a correlation matrix based filtration is developed. This approach gives rise to an accurate prediction of the optimal characteristic distance used in protein B-factor analysis. Finally, MTFs are employed to characterize protein topological evolution during protein folding and quantitatively predict the protein folding stability. An excellent consistence between our persistent homology prediction and molecular dynamics simulation is found. This work reveals the topology-function relationship of proteins. PMID:24902720

  16. Deletion of a KU80 homolog enhances homologous recombination in the thermotolerant yeast Kluyveromyces marxianus.

    Science.gov (United States)

    Choo, Jin Ho; Han, Changpyo; Kim, Jae-Young; Kang, Hyun Ah

    2014-10-01

    Targeted gene replacement in the thermotolerant yeast Kluyveromyces marxianus KCTC 17555 has been hampered by its propensity to non-homologous end joining (NHEJ). To enhance homologous recombination (HR) by blocking NHEJ, we identified and disrupted the K. marxianus KU80 gene. The ku80 deletion mutant strain (Kmku80∆) of K. marxianus KCTC 17555 did not show apparent growth defects under several conditions with the exception of exposure to tunicamycin. The targeted disruption of the three model genes, KmLEU2, KmPDC1, and KmPDC5, was increased by 13-70 % in Kmku80∆, although the efficiency was greatly affected by the length of the homologous flanking fragments. In contrast, the double HR frequency was 0-13.7 % in the wild-type strain even with flanking fragments 1 kb long. Therefore, Kmku80∆ promises to be a useful recipient strain for targeted gene manipulation.

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

    CERN Document Server

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

    2015-01-01

    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.

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

    Science.gov (United States)

    Takamiya, Kazunori; Yamamoto, Keisuke; 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.

  19. Exponential growth of colored HOMFLY-PT homology

    CERN Document Server

    Wedrich, Paul

    2016-01-01

    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.

  20. Change of gene structure and function by non-homologous end-joining, homologous recombination, and transposition of DNA.

    Directory of Open Access Journals (Sweden)

    Wolfgang Goettel

    2009-06-01

    Full Text Available An important objective in genome research is to relate genome structure to gene function. Sequence comparisons among orthologous and paralogous genes and their allelic variants can reveal sequences of functional significance. Here, we describe a 379-kb region on chromosome 1 of maize that enables us to reconstruct chromosome breakage, transposition, non-homologous end-joining, and homologous recombination events. Such a high-density composition of various mechanisms in a small chromosomal interval exemplifies the evolution of gene regulation and allelic diversity in general. It also illustrates the evolutionary pace of changes in plants, where many of the above mechanisms are of somatic origin. In contrast to animals, somatic alterations can easily be transmitted through meiosis because the germline in plants is contiguous to somatic tissue, permitting the recovery of such chromosomal rearrangements. The analyzed region contains the P1-wr allele, a variant of the genetically well-defined p1 gene, which encodes a Myb-like transcriptional activator in maize. The P1-wr allele consists of eleven nearly perfect P1-wr 12-kb repeats that are arranged in a tandem head-to-tail array. Although a technical challenge to sequence such a structure by shotgun sequencing, we overcame this problem by subcloning each repeat and ordering them based on nucleotide variations. These polymorphisms were also critical for recombination and expression analysis in presence and absence of the trans-acting epigenetic factor Ufo1. Interestingly, chimeras of the p1 and p2 genes, p2/p1 and p1/p2, are framing the P1-wr cluster. Reconstruction of sequence amplification steps at the p locus showed the evolution from a single Myb-homolog to the multi-gene P1-wr cluster. It also demonstrates how non-homologous end-joining can create novel gene fusions. Comparisons to orthologous regions in sorghum and rice also indicate a greater instability of the maize genome, probably due to

  1. PRIMO: An Interactive Homology Modeling Pipeline

    Science.gov (United States)

    Glenister, Michael

    2016-01-01

    The development of automated servers to predict the three-dimensional structure of proteins has seen much progress over the years. These servers make calculations simpler, but largely exclude users from the process. In this study, we present the PRotein Interactive MOdeling (PRIMO) pipeline for homology modeling of protein monomers. The pipeline eases the multi-step modeling process, and reduces the workload required by the user, while still allowing engagement from the user during every step. Default parameters are given for each step, which can either be modified or supplemented with additional external input. PRIMO has been designed for users of varying levels of experience with homology modeling. The pipeline incorporates a user-friendly interface that makes it easy to alter parameters used during modeling. During each stage of the modeling process, the site provides suggestions for novice users to improve the quality of their models. PRIMO provides functionality that allows users to also model ligands and ions in complex with their protein targets. Herein, we assess the accuracy of the fully automated capabilities of the server, including a comparative analysis of the available alignment programs, as well as of the refinement levels used during modeling. The tests presented here demonstrate the reliability of the PRIMO server when producing a large number of protein models. While PRIMO does focus on user involvement in the homology modeling process, the results indicate that in the presence of suitable templates, good quality models can be produced even without user intervention. This gives an idea of the base level accuracy of PRIMO, which users can improve upon by adjusting parameters in their modeling runs. The accuracy of PRIMO’s automated scripts is being continuously evaluated by the CAMEO (Continuous Automated Model EvaluatiOn) project. The PRIMO site is free for non-commercial use and can be accessed at https://primo.rubi.ru.ac.za/. PMID:27855192

  2. PRIMO: An Interactive Homology Modeling Pipeline.

    Science.gov (United States)

    Hatherley, Rowan; Brown, David K; Glenister, Michael; Tastan Bishop, Özlem

    2016-01-01

    The development of automated servers to predict the three-dimensional structure of proteins has seen much progress over the years. These servers make calculations simpler, but largely exclude users from the process. In this study, we present the PRotein Interactive MOdeling (PRIMO) pipeline for homology modeling of protein monomers. The pipeline eases the multi-step modeling process, and reduces the workload required by the user, while still allowing engagement from the user during every step. Default parameters are given for each step, which can either be modified or supplemented with additional external input. PRIMO has been designed for users of varying levels of experience with homology modeling. The pipeline incorporates a user-friendly interface that makes it easy to alter parameters used during modeling. During each stage of the modeling process, the site provides suggestions for novice users to improve the quality of their models. PRIMO provides functionality that allows users to also model ligands and ions in complex with their protein targets. Herein, we assess the accuracy of the fully automated capabilities of the server, including a comparative analysis of the available alignment programs, as well as of the refinement levels used during modeling. The tests presented here demonstrate the reliability of the PRIMO server when producing a large number of protein models. While PRIMO does focus on user involvement in the homology modeling process, the results indicate that in the presence of suitable templates, good quality models can be produced even without user intervention. This gives an idea of the base level accuracy of PRIMO, which users can improve upon by adjusting parameters in their modeling runs. The accuracy of PRIMO's automated scripts is being continuously evaluated by the CAMEO (Continuous Automated Model EvaluatiOn) project. The PRIMO site is free for non-commercial use and can be accessed at https://primo.rubi.ru.ac.za/.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Didelot, Xavier; Méric, Guillaume; Falush, Daniel; Darling, Aaron E

    2012-06-19

    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. 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. 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 therefore provide additional evidence to explain the

  5. Periodic cyclic homology of affine Hecke algebras

    CERN Document Server

    Solleveld, Maarten

    2009-01-01

    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

  6. Railway vehicle performance optimisation using virtual homologation

    Science.gov (United States)

    Magalhães, H.; Madeira, J. F. A.; Ambrósio, J.; Pombo, J.

    2016-09-01

    Unlike regular automotive vehicles, which are designed to travel in different types of roads, railway vehicles travel mostly in the same route during their life cycle. To accept the operation of a railway vehicle in a particular network, a homologation process is required according to local standard regulations. In Europe, the standards EN 14363 and UIC 518, which are used for railway vehicle acceptance, require on-track tests and/or numerical simulations. An important advantage of using virtual homologation is the reduction of the high costs associated with on-track tests by studying the railway vehicle performance in different operation conditions. This work proposes a methodology for the improvement of railway vehicle design with the objective of its operation in selected railway tracks by using optimisation. The analyses required for the vehicle improvement are performed under control of the optimisation method global and local optimisation using direct search. To quantify the performance of the vehicle, a new objective function is proposed, which includes: a Dynamic Performance Index, defined as a weighted sum of the indices obtained from the virtual homologation process; the non-compensated acceleration, which is related to the operational velocity; and a penalty associated with cases where the vehicle presents an unacceptable dynamic behaviour according to the standards. Thus, the optimisation process intends not only to improve the quality of the vehicle in terms of running safety and ride quality, but also to increase the vehicle availability via the reduction of the time for a journey while ensuring its operational acceptance under the standards. The design variables include the suspension characteristics and the operational velocity of the vehicle, which are allowed to vary in an acceptable range of variation. The results of the optimisation lead to a global minimum of the objective function in which the suspensions characteristics of the vehicle are

  7. Identification of plant microRNA homologs.

    Science.gov (United States)

    Dezulian, Tobias; Remmert, Michael; Palatnik, Javier F; Weigel, Detlef; Huson, Daniel H

    2006-02-01

    MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that regulate gene and protein expression in plants and animals. MiRNAs have so far been identified mostly by specific cloning of small RNA molecules, complemented by computational methods. We present a computational identification approach that is able to identify candidate miRNA homologs in any set of sequences, given a query miRNA. The approach is based on a sequence similarity search step followed by a set of structural filters.

  8. Detailed assessment of homology detection using different substitution matrices

    Institute of Scientific and Technical Information of China (English)

    LI Jing; WANG Wei

    2006-01-01

    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.

  9. Resonance for loop homology of spheres

    CERN Document Server

    Hingston, Nancy

    2011-01-01

    A Riemannian or Finsler metric on a compact manifold M gives rise to a length function on the free loop space \\Lambda M, whose critical points are the closed geodesics in the given metric. If X is a homology class on \\Lambda M, the minimax critical level cr(X) is a critical value. Let M be a sphere of dimension >2, and fix a metric g and a coefficient field G. We prove that the limit as deg(X) goes to infinity of cr(X)/deg(X) exists. We call this limit the "global mean frequency" of M. As a consequence we derive resonance statements for closed geodesics on spheres; in particular either all homology on \\Lambda M of sufficiently high degreee lies hanging on closed geodesics whose mean frequency (average index / length) equals the global mean frequency, or there is a sequence of infinitely many closed geodesics whose mean frequencies converge to the global mean frequency. The proof uses the Chas-Sullivan product and results of Goresky-Hingston [GH].

  10. MYB3Rs, plant homologs of Myb oncoproteins, control cell cycle-regulated transcription and form DREAM-like complexes.

    Science.gov (United States)

    Kobayashi, Kosuke; Suzuki, Toshiya; Iwata, Eriko; Magyar, Zoltán; Bögre, László; Ito, Masaki

    2015-01-01

    Plant MYB3R transcription factors, homologous to Myb oncoproteins, regulate the genes expressed at G2 and M phases in the cell cycle. Recent studies showed that MYB3Rs constitute multiprotein complexes that may correspond to animal complexes known as DREAM or dREAM. Discovery of the putative homologous complex in plants uncovered their significant varieties in structure, function, dynamics, and heterogeneity, providing insight into conserved and diversified aspects of cell cycle-regulated gene transcription.

  11. MYB3Rs, plant homologs of Myb oncoproteins, control cell cycle-regulated transcription and form DREAM-like complexes

    OpenAIRE

    Kobayashi, Kosuke; Suzuki, Toshiya; Iwata, Eriko; Magyar, Zoltán; Bögre, László; Ito, Masaki

    2015-01-01

    Plant MYB3R transcription factors, homologous to Myb oncoproteins, regulate the genes expressed at G2 and M phases in the cell cycle. Recent studies showed that MYB3Rs constitute multiprotein complexes that may correspond to animal complexes known as DREAM or dREAM. Discovery of the putative homologous complex in plants uncovered their significant varieties in structure, function, dynamics, and heterogeneity, providing insight into conserved and diversified aspects of cell cycle-regulated gen...

  12. Should nucleotide sequence analyzing computer algorithms always extend homologies by extending homologies?

    Science.gov (United States)

    Burnett, L; Basten, A; Hensley, W J

    1986-01-10

    Most computer algorithms used for comparing or aligning nucleotide sequences rely on the premise that the best way to extend a homology between the two sequences is to select a match rather than a mismatch. We have tested this assumption and found that it is not always valid.

  13. Hotspots of homologous recombination in the human genome: not all homologous sequences are equal.

    Science.gov (United States)

    Lupski, James R

    2004-01-01

    Homologous recombination between alleles or non-allelic paralogous sequences does not occur uniformly but is concentrated in 'hotspots' with high recombination rates. Recent studies of these hotspots show that they do not share common sequence motifs, but they do have other features in common.

  14. Hotspots of homologous recombination in the human genome: not all homologous sequences are equal

    OpenAIRE

    Lupski, James R

    2004-01-01

    Homologous recombination between alleles or non-allelic paralogous sequences does not occur uniformly but is concentrated in 'hotspots' with high recombination rates. Recent studies of these hotspots show that they do not share common sequence motifs, but they do have other features in common.

  15. Recombination-Independent Recognition of DNA Homology for Repeat-Induced Point Mutation (RIP Is Modulated by the Underlying Nucleotide Sequence.

    Directory of Open Access Journals (Sweden)

    Eugene Gladyshev

    2016-05-01

    Full Text Available Haploid germline nuclei of many filamentous fungi have the capacity to detect homologous nucleotide sequences present on the same or different chromosomes. Once recognized, such sequences can undergo cytosine methylation or cytosine-to-thymine mutation specifically over the extent of shared homology. In Neurospora crassa this process is known as Repeat-Induced Point mutation (RIP. Previously, we showed that RIP did not require MEI-3, the only RecA homolog in Neurospora, and that it could detect homologous trinucleotides interspersed with a matching periodicity of 11 or 12 base-pairs along participating chromosomal segments. This pattern was consistent with a mechanism of homology recognition that involved direct interactions between co-aligned double-stranded (ds DNA molecules, where sequence-specific dsDNA/dsDNA contacts could be established using no more than one triplet per turn. In the present study we have further explored the DNA sequence requirements for RIP. In our previous work, interspersed homologies were always examined in the context of a relatively long adjoining region of perfect homology. Using a new repeat system lacking this strong interaction, we now show that interspersed homologies with overall sequence identity of only 36% can be efficiently detected by RIP in the absence of any perfect homology. Furthermore, in this new system, where the total amount of homology is near the critical threshold required for RIP, the nucleotide composition of participating DNA molecules is identified as an important factor. Our results specifically pinpoint the triplet 5'-GAC-3' as a particularly efficient unit of homology recognition. Finally, we present experimental evidence that the process of homology sensing can be uncoupled from the downstream mutation. Taken together, our results advance the notion that sequence information can be compared directly between double-stranded DNA molecules during RIP and, potentially, in other processes

  16. Recombination-Independent Recognition of DNA Homology for Repeat-Induced Point Mutation (RIP) Is Modulated by the Underlying Nucleotide Sequence.

    Science.gov (United States)

    Gladyshev, Eugene; Kleckner, Nancy

    2016-05-01

    Haploid germline nuclei of many filamentous fungi have the capacity to detect homologous nucleotide sequences present on the same or different chromosomes. Once recognized, such sequences can undergo cytosine methylation or cytosine-to-thymine mutation specifically over the extent of shared homology. In Neurospora crassa this process is known as Repeat-Induced Point mutation (RIP). Previously, we showed that RIP did not require MEI-3, the only RecA homolog in Neurospora, and that it could detect homologous trinucleotides interspersed with a matching periodicity of 11 or 12 base-pairs along participating chromosomal segments. This pattern was consistent with a mechanism of homology recognition that involved direct interactions between co-aligned double-stranded (ds) DNA molecules, where sequence-specific dsDNA/dsDNA contacts could be established using no more than one triplet per turn. In the present study we have further explored the DNA sequence requirements for RIP. In our previous work, interspersed homologies were always examined in the context of a relatively long adjoining region of perfect homology. Using a new repeat system lacking this strong interaction, we now show that interspersed homologies with overall sequence identity of only 36% can be efficiently detected by RIP in the absence of any perfect homology. Furthermore, in this new system, where the total amount of homology is near the critical threshold required for RIP, the nucleotide composition of participating DNA molecules is identified as an important factor. Our results specifically pinpoint the triplet 5'-GAC-3' as a particularly efficient unit of homology recognition. Finally, we present experimental evidence that the process of homology sensing can be uncoupled from the downstream mutation. Taken together, our results advance the notion that sequence information can be compared directly between double-stranded DNA molecules during RIP and, potentially, in other processes where homologous

  17. Homologous Recombination—Experimental Systems, Analysis and Significance

    Science.gov (United States)

    Kuzminov, Andrei

    2014-01-01

    Homologous recombination is the most complex of all recombination events that shape genomes and produce material for evolution. Homologous recombination events are exchanges between DNA molecules in the lengthy regions of shared identity, catalyzed by a group of dedicated enzymes. There is a variety of experimental systems in E. coli and Salmonella to detect homologous recombination events of several different kinds. Genetic analysis of homologous recombination reveals three separate phases of this process: pre-synapsis (the early phase), synapsis (homologous strand exchange) and post-synapsis (the late phase). In E. coli, there are at least two independent pathway of the early phase and at least two independent pathways of the late phase. All this complexity is incongruent with the originally ascribed role of homologous recombination as accelerator of genome evolution: there is simply not enough duplication and repetition in enterobacterial genomes for homologous recombination to have a detectable evolutionary role, and therefore not enough selection to maintain such a complexity. At the same time, the mechanisms of homologous recombination are uniquely suited for repair of complex DNA lesions called chromosomal lesions. In fact, the two major classes of chromosomal lesions are recognized and processed by the two individual pathways at the early phase of homologous recombination. It follows, therefore, that homologous recombination events are occasional reflections of the continual recombinational repair, made possible in cases of natural or artificial genome redundancy. PMID:26442506

  18. Increased homologous integration frequency in Yarrowia lipolytica strains defective in non-homologous end-joining.

    Science.gov (United States)

    Kretzschmar, Anne; Otto, Christina; Holz, Martina; Werner, Severine; Hübner, Linda; Barth, Gerold

    2013-05-01

    The ascomycetous yeast Yarrowia lipolytica has been established as model system for studies of several research topics as well as for biotechnological processes in the last two decades. However, frequency of heterologous recombination is high in this yeast species, and so knockouts of genes are laborious to achieve. Therefore, the aim of this study was to check whether a reduction of non-homologous end-joining (NHEJ) of double strand breaks (DSB) results in a strong increase of proportion of homologous recombinants. The Ku70-Ku80 heterodimer is known as an essential protein complex of the NHEJ. We show that deletion of YlKU70 and/or YlKU80 results in an increase of the rate of transformants with homologous recombination (HR) up to 85 % in each case. However, it never reaches near 100 % of HR in any case as described for some other yeast. Furthermore, we demonstrated that growth of Δylku strains was similar to that of the wild-type strain. In addition, no differences were detected between the Δylku strains and the parent strain in respect to sensitivity to the mutagenic agent EMS as well as to the antibiotics hygromycin, bleomycin and nourseothricin. However, Δylku70 and Δylku80 strain showed a slightly higher sensitivity against UV rays. Thus, the new constructed Δylku strains are attractive recipient strains for homologous integration of DNA fragments and a valuable tool for directed knockouts of genes. Nevertheless, our data suggest the existence of another system of non-homologous recombination what may be subject of further investigation.

  19. Histone deacetylase inhibitors selectively target homology dependent DNA repair defective cells and elevate non-homologous endjoining activity.

    Directory of Open Access Journals (Sweden)

    Stephanie Smith

    Full Text Available BACKGROUND: We have previously used the ATAD5-luciferase high-throughput screening assay to identify genotoxic compounds with potential chemotherapeutic capabilities. The successful identification of known genotoxic agents, including the histone deacetylase inhibitor (HDACi trichostatin A (TSA, confirmed the specificity of the screen since TSA has been widely studied for its ability to cause apoptosis in cancer cells. Because many cancers have acquired mutations in DNA damage checkpoints or repair pathways, we hypothesized that these cancers may be susceptible to treatments that target compensatory pathways. Here, we used a panel of isogenic chicken DT40 B lymphocyte mutant and human cell lines to investigate the ability of TSA to define selective pathways that promote HDACi toxicity. RESULTS: HDACi induced a DNA damage response and reduced viability in all repair deficient DT40 mutants although ATM-nulls were least affected. The most dramatic sensitivity was observed in mutants lacking the homology dependent repair (HDR factor BLM or the non-homologous end-joining (NHEJ and HDR factors, KU/RAD54, suggesting an involvement of either HDR or NHEJ in HDACi-induced cell death. To extend these findings, we measured the frequencies of HDR and NHEJ after HDACi treatment and monitored viability in human cell lines comparably deficient in HDR or NHEJ. Although no difference in HDR frequency was observed between HDACi treated and untreated cells, HDR-defective human cell lines were clearly more sensitive than wild type. Unexpectedly, cells treated with HDACis showed a significantly elevated NHEJ frequency. CONCLUSIONS: HDACi targeting drugs induced significant increases in NHEJ activity in human cell lines but did not alter HDR frequency. Moreover, HDR is required for cellular resistance to HDACi therapy; therefore, NHEJ does not appear to be a critical axis for HDACi resistance. Rather, HDACi compounds induced DNA damage, most likely double strand breaks

  20. [Contemporary concepts of homology in biology (a theoretical review)].

    Science.gov (United States)

    Pavlinov, I Ia

    2011-01-01

    A brief review of the contemporary theoretical concepts of homology being developed basically in systematics and phylogenetics as well as in developmental biology is presented. Ontologically, both homology and analogy represent a kind of correspondence considered from the standpoint of nominalism, realism, and conceptualism. According to their nominalistic treatment, both are described by a set-theory approximation which makes them classes (in the logical sense). The realistic treatment provides their holistic view according to which a homologue is an anatomical or evolutionary singular while analogue remains a class. The conceptualistic treatment means that there are real (objective) correspondences existing among real (objective) entities while fixation of any of them is based on certain theoretical presumptions adopted by a researcher; homology as a natural kind (including homeostatic property cluster) seems to be most consistent with such a treatment. Realistic view of homology makes it "absolute", while two others make discrimination of homology and analogy strictly relative. Two basic general homology concepts have been developed in recent literature--taxic and transformational ones; the first considers respective correspondences as structure relations, the second as process relations. The taxic homology is nearly the same as classical typological one (Owen), while transformational homology unites all its phylogenetic, ontogenetic (developmental) and transformation-typological definitions. Process-structuralistic approach seems to unite both taxic and transformational ones. The latter makes it possible to apply general homology concept not only to structures but to processes as well. It is stressed that homology is not identical to the similarity, the latter being just the means for revealing the former. Some closer consideration is given to phylogenetic, ontogenetic and genetic treatments of homology; significant uncertainty is shown to exist between them

  1. Homological mirror symmetry. New developments and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Kapustin, Anton [California Inst. of Tech., Pasadena, CA (United States); Kreuzer, Maximilian [Technische Univ., Vienna (Austria). Inst. fuer Theoretische Physik; Schlesinger, Karl-Georg (eds.) [Vienna Univ. (Austria). Inst. fuer Theoretische Physik

    2009-07-01

    Homological Mirror Symmetry, the study of dualities of certain quantum field theories in a mathematically rigorous form, has developed into a flourishing subject on its own over the past years. The present volume bridges a gap in the literature by providing a set of lectures and reviews that both introduce and representatively review the state-of-the art in the field from different perspectives. With contributions by K. Fukaya, M. Herbst, K. Hori, M. Huang, A. Kapustin, L. Katzarkov, A. Klemm, M. Kontsevich, D. Page, S. Quackenbush, E. Sharpe, P. Seidel, I. Smith and Y. Soibelman, this volume will be a reference on the topic for everyone starting to work or actively working on mathematical aspects of quantum field theory. (orig.)

  2. Chatter detection in turning using persistent homology

    Science.gov (United States)

    Khasawneh, Firas A.; Munch, Elizabeth

    2016-03-01

    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.

  3. Towards Stratification Learning through Homology Inference

    CERN Document Server

    Bendich, Paul; Wang, Bei

    2010-01-01

    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.

  4. Role of discs large homolog 5

    Institute of Scientific and Technical Information of China (English)

    Frauke Friedrichs; Monika Stoll

    2006-01-01

    In 2004, an association of genetic variation in the discs large homolog 5 (DLG5) gene with inflammatory bowel disease (IBD) was described in two large European study samples[1]. The initial report of DLG5 as a novel IBD susceptibility gene sparked a multitude of studies investigating its effect on CD and IBD, respectively,leading to controversial findings and ongoing discussions concerning the validity of the initial association finding and its role in the aetiology of Crohn disease. This review aims to summarize the current state of knowledge and to place the reported findings in the context of current concepts of complex diseases. This includes aspects of statistical power, phenotype differences and genetic heterogeneity between different populations as well as gene-gene and gene-environment interactions.

  5. How homologous recombination maintains telomere integrity.

    Science.gov (United States)

    Tacconi, Eliana M C; Tarsounas, Madalena

    2015-06-01

    Telomeres protect the ends of linear chromosomes against loss of genetic information and inappropriate processing as damaged DNA and are therefore crucial to the maintenance of chromosome integrity. In addition to providing a pathway for genome-wide DNA repair, homologous recombination (HR) plays a key role in telomere replication and capping. Consistent with this, the genomic instability characteristic of HR-deficient cells and tumours is driven in part by telomere dysfunction. Here, we discuss the mechanisms by which HR modulates the response to intrinsic cellular challenges that arise during telomere replication, as well as its impact on the assembly of telomere protective structures. How normal and tumour cells differ in their ability to maintain telomeres is deeply relevant to the search for treatments that would selectively eliminate cells whose capacity for HR-mediated repair has been compromised.

  6. [Homology and carbapenemase gene in Acinetobacter baumannii].

    Science.gov (United States)

    Yan, Qun; Deng, Shuang; Li, Hongling; Zou, Mingxiang

    2012-11-01

    To study the antibiotic resistance evolution, homology, phenotypes and genotypes of carbapenemase in Acinetobacter baumannii from clinical isolates. A total of 72 strains of Acinetobacter baumannii were isolated from Xiangya Hospital of Central South University from March to May 2012. Antimicrobial susceptibility test was carried out by automatic microorganism clinical analytical system VITEK-II. The homology of the 72 strains was analyzed by enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Modified Hodge test was used to screen carbapenemases of the strains. Carbapenemase genes blaOXA-23, blaOXA-40 and blaOXA-58 were also amplified and sequenced. The 72 strains of Acinetobacter baumannii remained sensitive to cefoperazone/sulbactam (resistance rate 8.33%), followed by Amikacin. Otherwise, they were resistant to most of the antimicrobial agents (resistance rate more than 70%). The 72 strains were identified as 7 epidemic clones, A-G, by means of ERIC-PCR and the phylogenetic relationship among D, E, F and G was very close, suggesting a nosocomial infection possibility. Totally 56 strains produced carbapenemase; 61 strains were positive for carbapenemase gene blaOXA-23 and 1 strain positive for blaOXA-58. All strains were negative for carbapenemase gene blaOXA-40. Acinetobacter baumannii strains isolated clinically are resistant to most of the antimicrobial agents and nosocomial infection had been observed. Most of the strains produce carbapenemase, among which, blaOXA-23 gene is the main carbapenemase gene. blaOXA-58 gene exists in the Acinetobacter baumannii isolates from Hunan Province.

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

    Directory of Open Access Journals (Sweden)

    Didelot Xavier

    2012-06-01

    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

  8. RPA homologs and ssDNA processing during meiotic recombination

    OpenAIRE

    Ribeiro, Jonathan; Abby, Emilie; Livera, Gabriel; Martini, Emmanuelle

    2015-01-01

    Meiotic homologous recombination is a specialized process that involves homologous chromosome pairing and strand exchange to guarantee proper chromosome segregation and genetic diversity. The formation and repair of DNA double-strand breaks (DSBs) during meiotic recombination differs from those during mitotic recombination in that the homologous chromosome rather than the sister chromatid is the preferred repair template. The processing of single-stranded DNA (ssDNA) formed on intermediate re...

  9. Heteromorphic Sex Chromosomes: Navigating Meiosis without a Homologous Partner

    OpenAIRE

    Checchi, Paula M.; Engebrecht, JoAnne

    2011-01-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have ...

  10. Benchmarking the next generation of homology inference tools

    OpenAIRE

    Saripella, Ganapathi Varma; Sonnhammer, Erik L.L.; Forslund, Kristoffer

    2016-01-01

    Motivation: Over the last decades, vast numbers of sequences were deposited in public databases. Bioinformatics tools allow homology and consequently functional inference for these sequences. New profile-based homology search tools have been introduced, allowing reliable detection of remote homologs, but have not been systematically benchmarked. To provide such a comparison, which can guide bioinformatics workflows, we extend and apply our previously developed benchmark approach to evaluate t...

  11. A sign assignment in totally twisted Khovanov homology

    OpenAIRE

    Manion, Andrew

    2011-01-01

    We lift the characteristic-2 totally twisted Khovanov homology of Roberts and Jaeger to a theory with integer coefficients. The result is a complex computing reduced odd Khovanov homology for knots. This complex is equivalent to a spanning-tree complex whose differential is explicit modulo a sign ambiguity coming from the need to choose a sign assignment in the definition of odd Khovanov homology.

  12. [Homologous recombination among bacterial genomes: the measurement and identification].

    Science.gov (United States)

    Xianwei, Yang; Ruifu, Yang; Yujun, Cui

    2016-02-01

    Homologous recombination is one of important sources in shaping the bacterial population diversity, which disrupts the clonal relationship among different lineages through horizontal transferring of DNA-segments. As consequence of blurring the vertical inheritance signals, the homologous recombination raises difficulties in phylogenetic analysis and reconstruction of population structure. Here we discuss the impacts of homologous recombination in inferring phylogenetic relationship among bacterial isolates, and summarize the tools and models separately used in recombination measurement and identification. We also highlight the merits and drawbacks of various approaches, aiming to assist in the practical application for the analysis of homologous recombination in bacterial evolution research.

  13. On the digital homology groups of digital images

    CERN Document Server

    Lee, Dae-Woong

    2011-01-01

    In this article we study the digital homology groups of digital images which are based on the singular homology groups of topological spaces in algebraic topology. Specifically, we define a digitally standard $n$-simplex, a digitally singular $n$-simplex, and the digital homology groups of digital images with $k$-adjacency relations. We then construct a covariant functor from a category of digital images and digitally continuous functions to the one of abelian groups and group homomorphisms, and investigate some fundamental and interesting properties of digital homology groups of digital images, such as the digital version of the dimension axiom which is one of the Eilenberg-Steenrod axioms.

  14. A geometric model for Hochschild homology of Soergel bimodules

    DEFF Research Database (Denmark)

    Webster, Ben; Williamson, Geordie

    2008-01-01

    An important step in the calculation of the triply graded link homology of Khovanov and Rozansky is the determination of the Hochschild homology of Soergel bimodules for SL(n). We present a geometric model for this Hochschild homology for any simple group G, as B–equivariant intersection cohomology...... of B×B–orbit closures in G. We show that, in type A, these orbit closures are equivariantly formal for the conjugation B–action. We use this fact to show that, in the case where the corresponding orbit closure is smooth, this Hochschild homology is an exterior algebra over a polynomial ring...

  15. The cytogenetics of homologous chromosome pairing in meiosis in plants.

    Science.gov (United States)

    Bozza, C G; Pawlowski, W P

    2008-01-01

    Three activities hallmark meiotic cell division: homologous chromosome pairing, synapsis, and recombination. Recombination and synapsis are well-studied but homologous pairing still holds many black boxes. In the past several years, many studies in plants have yielded insights into the mechanisms of chromosome pairing interactions. Research in several plant species showed the importance of telomere clustering on the nuclear envelope (telomere bouquet formation) in facilitating alignment of homologous chromosomes. Homologous pairing was also shown to be tied to the early stages of recombination by mutant analyses in Arabidopsis and maize. In contrast, little is known about the mechanisms that guide homolog interaction after their rough alignment by the bouquet and before the close-range recombination-dependent homology search. The relatively large and complex genomes of plants may require additional mechanisms, not needed in small genome eukaryotes, to distinguish between local homology of duplicated genes or transposable elements and global chromosomal homology. Plants provide an excellent large genome model for the study of homologous pairing and dissection of this process. 2008 S. Karger AG, Basel

  16. DNA-Pairing and Annealing Processes in Homologous Recombination and Homology-Directed Repair

    Science.gov (United States)

    Morrical, Scott W.

    2015-01-01

    The formation of heteroduplex DNA is a central step in the exchange of DNA sequences via homologous recombination, and in the accurate repair of broken chromosomes via homology-directed repair pathways. In cells, heteroduplex DNA largely arises through the activities of recombination proteins that promote DNA-pairing and annealing reactions. Classes of proteins involved in pairing and annealing include RecA-family DNA-pairing proteins, single-stranded DNA (ssDNA)-binding proteins, recombination mediator proteins, annealing proteins, and nucleases. This review explores the properties of these pairing and annealing proteins, and highlights their roles in complex recombination processes including the double Holliday junction (DhJ) formation, synthesis-dependent strand annealing, and single-strand annealing pathways—DNA transactions that are critical both for genome stability in individual organisms and for the evolution of species. PMID:25646379

  17. Audiological and vestibular evaluation of new coagulation factor C homology mutation carriers in a Chinese family%中国一家系凝血因子C同源物基因新突变携带者听力学及前庭功能特点

    Institute of Scientific and Technical Information of China (English)

    孙勍; 张昕; 刘新; 戴朴; 袁慧军; 韩东一; 谢溯江; 丰雷; 王玉凤; 许剑; 仇春燕; 陈艾婷; 冀飞; 康东洋

    2007-01-01

    目的 分析携带凝血因子C同源物(coagulation factor C homology,COCH)基因新突变的中国常染色体显性遗传非综合征型聋(autosomal dominant non-syndromic sensorineural hearing loss,DFNA)9家系成员的听力学及前庭功能特点.方法 对家系成员进行纯音测听、听性脑干反应、耳蜗电图等听力学及计算机动态姿势描记、前庭诱发性肌源性电位、视眼动、前庭眼动等前庭功能检查.结果 听力学检查提示该家系患者20~50岁出现以高频下降为主的进行性感音神经性聋,60~70岁进展为重至极重度全频听力损失.前庭功能检查提示随意抽取的家系中耳聋患者计算机动态姿势描记、视眼动、温度试验正常;前庭诱发性肌源性电位检查提示耳聋患者耳石功能异常;速度阶梯试验时间常数异常、正弦谐波试验增益和相位异常,提示耳聋患者水平半规管功能减弱.结论 中国DFNA9家系的所有耳聋患者均无前庭功能损害的主诉,通过详尽的前庭功能检查提示位于COCH非胶原结构糖蛋白A型2结构域上的突变所导致的前庭功能损害明显轻于位于LCCL结构域上的突变.中国DFNA9家系的临床资料分析首次表明DFNA9存在基因型和表现型的相关性.

  18. Involvement of Caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining.

    Directory of Open Access Journals (Sweden)

    Hua Zhu

    Full Text Available BACKGROUND: Caveolin-1 (Cav-1, the major component of caveolae, is a 21-24 kDa integral membrane protein that interacts with a number of signaling molecules. By acting as a scaffolding protein, Cav-1 plays crucial roles in the regulation of various physiologic and patho-physiologic processes including oncogenic transformation and tumorigenesis, and tumor invasion and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we sought to explore the role of Cav-1 in response to DNA damage and the mechanism involved. We found that the level of Cav-1 was up-regulated rapidly in cells treated with ionizing radiation. The up-regulation of Cav-1 following DNA damage occurred only in cells expressing endogenous Cav-1, and was associated with the activation of DNA damage response pathways. Furthermore, we demonstrated that the expression of Cav-1 protected cells against DNA damage through modulating the activities of both the homologous recombination (HR and non-homologous end joining (NHEJ repair systems, as evidenced by the inhibitory effects of the Cav-1-targeted siRNA on cell survival, HR frequency, phosphorylation of DNA-dependent protein kinase (DNA-PK, and nuclear translocation of epidermal growth factor receptor (EGFR following DNA damage, and by the stimulatory effect of the forced expression of Cav-1 on NHEJ frequency. CONCLUSION/SIGNIFICANCE: Our results indicate that Cav-1 may play a critical role in sensing genotoxic stress and in orchestrating the response of cells to DNA damage through regulating the important molecules involved in maintaining genomic integrity.

  19. Complete Cohomologies and Some Homological Invariants

    Institute of Scientific and Technical Information of China (English)

    Javad Asadollahi; Shokrollah Salarian

    2007-01-01

    There is a complete cohomology theory developed over a commutative noetherian ring in which injectives take the role of projectives in Vogel's construction of complete cohomology theory. We study the interaction between this complete cohomology, that is referred to as I-complete cohomology, and Vogel's one and give some sufficient conditions for their equivalence. Using I-complete functors, we assign a new homological invariant to any finitely generated module over an arbitrary commutative noetherian local ring,that would generalize Auslander's delta invariant. We generalize the results about the δ-invariant to arbitrary rings and give a sufficient condition for the vanishing of this new invariant. We also introduce an analogue of the notion of the index of a Gorenstein local ring, introduced by Auslander, for arbitrary local rings and study its behavior under flat extensions of local rings. Finally, we study the connection between the index and Loewy length of a local ring and generalize the main result of [11] to arbitrary rings.

  20. Altering symplectic manifolds by homologous recombination

    CERN Document Server

    Abouzaid, Mohammed

    2010-01-01

    We use symplectic cohomology to study the non-uniqueness of symplectic structures on the smooth manifolds underlying affine varieties. Starting with a Lefschetz fibration on such a variety and a finite set of primes, the main new tool is a method, which we call homologous recombination, for constructing a Lefschetz fibration whose total space is smoothly equivalent to the original variety, but for which symplectic cohomology with coefficients in the given set of primes vanishes (there is also a simpler version that kills symplectic cohomology completely). Rather than relying on a geometric analysis of periodic orbits of a flow, the computation of symplectic cohomology depends on describing the Fukaya category associated to the new fibration. As a consequence we use a result of McLean to prove, for example, that an affine variety of real dimension greater than or equal to 4 supports infinitely many different (Wein)stein structures of finite type, and, assuming a mild cohomological condition, uncountably many d...

  1. The Causes of Quasi-homologous CMEs

    Science.gov (United States)

    Liu, Lijuan; Wang, Yuming; Liu, Rui; Zhou, Zhenjun; Temmer, M.; Thalmann, J. K.; Liu, Jiajia; Liu, Kai; Shen, Chenglong; Zhang, Quanhao; Veronig, A. M.

    2017-08-01

    In this paper, we identified the magnetic source locations of 142 quasi-homologous (QH) coronal mass ejections (CMEs), of which 121 are from solar cycle (SC) 23 and 21 from SC 24. Among those CMEs, 63% originated from the same source location as their predecessor (defined as S-type), while 37% originated from a different location within the same active region as their predecessor (defined as D-type). Their distinctly different waiting time distributions, peaking around 7.5 and 1.5 hr for S- and D-type CMEs, suggest that they might involve different physical mechanisms with different characteristic timescales. Through detailed analysis based on nonlinear force-free coronal magnetic field modeling of two exemplary cases, we propose that the S-type QH CMES might involve a recurring energy release process from the same source location (by magnetic free energy replenishment), whereas the D-type QH CMEs can happen when a flux tube system is disturbed by a nearby CME.

  2. Regulation of homologous recombination at telomeres in budding yeast

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Lisby, Michael

    2010-01-01

    Homologous recombination is suppressed at normal length telomere sequences. In contrast, telomere recombination is allowed when telomeres erode in the absence of telomerase activity or as a consequence of nucleolytic degradation or incomplete replication. Here, we review the mechanisms...... that contribute to regulating mitotic homologous recombination at telomeres and the role of these mechanisms in signalling short telomeres in the budding yeast Saccharomyces cerevisiae....

  3. CBH1 homologs and varian CBH1 cellulase

    Energy Technology Data Exchange (ETDEWEB)

    Goedegebuur, Frits; Gualfetti, Peter; Mitchinson, Colin; Neefe, Paulien

    2014-07-01

    Disclosed are a number of homologs and variants of Hypocrea jecorina Cel7A (formerly Trichoderma reesei cellobiohydrolase I or CBH1), nucleic acids encoding the same and methods for producing the same. The homologs and variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted and/or deleted.

  4. CBH1 homologs and varian CBH1 cellulase

    Science.gov (United States)

    Goedegebuur, Frits; Gualfetti, Peter; Mitchinson, Colin; Neefe, Paulien

    2014-07-01

    Disclosed are a number of homologs and variants of Hypocrea jecorina Cel7A (formerly Trichoderma reesei cellobiohydrolase I or CBH1), nucleic acids encoding the same and methods for producing the same. The homologs and variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted and/or deleted.

  5. Dynamic protein assemblies in homologous recombination with single DNA molecules

    NARCIS (Netherlands)

    van der Heijden, A.H.

    2007-01-01

    What happens when your DNA breaks? This thesis describes experimental work on the single-molecule level focusing on the interaction between DNA and DNA-repair proteins, in particular bacterial RecA and human Rad51, involved in homologous recombination. Homologous recombination and its central event

  6. [DNA homology in various strains of nitrogen-fixing bacteria].

    Science.gov (United States)

    Vardevanian, P O; Minasbekian, L A; Parsadanian, M A

    2000-01-01

    Melting temperature and GC content were evaluated for DNA of some nitrogen-fixing bacteria of Rhizobium leguminosarum and Onobrychis spp. (Adans). The degree of homology between strains of the same species was determined. A combination of thermal denaturing and molecular hybridization can serve as a rapid test for evaluating the genome homology of the organisms compared.

  7. About the globular homology of higher dimensional automata

    OpenAIRE

    Gaucher, Philippe

    2000-01-01

    We introduce a new simplicial nerve of higher dimensional automata whose homology groups yield a new definition of the globular homology. With this new definition, the drawbacks noticed with the construction of math.CT/9902151 disappear. Moreover the important morphisms which associate to every globe its corresponding branching area and merging area of execution paths become morphisms of simplicial sets.

  8. Computability of Homology for Compact Absolute Neighbourhood Retracts

    NARCIS (Netherlands)

    P.J. Collins (Pieter); A. Bauer; P. Hertling; K.-I. Ko

    2009-01-01

    textabstractIn this note we discuss the information needed to compute the homology groups of a topological space. We argue that the natural class of spaces to consider are the compact absolute neighbourhood retracts, since for these spaces the homology groups are finite. We show that we need to

  9. Molecular Phylogenetics and the Perennial Problem of Homology.

    Science.gov (United States)

    Inkpen, S Andrew; Doolittle, W Ford

    2016-12-01

    The concept of homology has a long history, during much of which the issue has been how to reconcile similarity and common descent when these are not coextensive. Although thinking molecular phylogeneticists have learned not to say "percent homology," the problems are deeper than that and unresolved.

  10. The tedious task of finding homologous noncoding RNA genes

    DEFF Research Database (Denmark)

    Menzel, Karl Peter; Gorodkin, Jan; Stadler, Peter F

    2009-01-01

    : BLAST still works better or equally good as other methods unless extensive expert knowledge on the RNA family is included. However, when good curated data are available the recent development yields further improvements in finding remote homologs. Homology search beyond the reach of BLAST hence...

  11. Remarks on Khovanov Homology and the Potts Model

    CERN Document Server

    Kauffman, Louis H

    2009-01-01

    This paper is about Khovanov homology and its relationships with statistical mechanics models such as the Ising model and the Potts model. The paper gives a relatively self-contained introduction to Khovanov homology, and also to a reformulation of the Potts model in terms of a bracket state sum expansion on a knot diagram K(G) related to a planar graph G via the medial construction. We consider the original Khovanov homology and also the homology defined by Stosic via the dichromatic polynomial, and examine those values of the Potts model where the partition function can be expressed in terms of homological Euler characteristics. These points occur at imaginary temperature, and consequences of this phenomenon will be studied in subsequent work. This paper is dedicated to Oleg Viro on his 60-th birthday.

  12. Refinement of protein structure homology models via long, all-atom molecular dynamics simulations.

    Science.gov (United States)

    Raval, Alpan; Piana, Stefano; Eastwood, Michael P; Dror, Ron O; Shaw, David E

    2012-08-01

    Accurate computational prediction of protein structure represents a longstanding challenge in molecular biology and structure-based drug design. Although homology modeling techniques are widely used to produce low-resolution models, refining these models to high resolution has proven difficult. With long enough simulations and sufficiently accurate force fields, molecular dynamics (MD) simulations should in principle allow such refinement, but efforts to refine homology models using MD have for the most part yielded disappointing results. It has thus far been unclear whether MD-based refinement is limited primarily by accessible simulation timescales, force field accuracy, or both. Here, we examine MD as a technique for homology model refinement using all-atom simulations, each at least 100 μs long-more than 100 times longer than previous refinement simulations-and a physics-based force field that was recently shown to successfully fold a structurally diverse set of fast-folding proteins. In MD simulations of 24 proteins chosen from the refinement category of recent Critical Assessment of Structure Prediction (CASP) experiments, we find that in most cases, simulations initiated from homology models drift away from the native structure. Comparison with simulations initiated from the native structure suggests that force field accuracy is the primary factor limiting MD-based refinement. This problem can be mitigated to some extent by restricting sampling to the neighborhood of the initial model, leading to structural improvement that, while limited, is roughly comparable to the leading alternative methods.

  13. A recurrent translocation is mediated by homologous recombination between HERV-H elements

    Directory of Open Access Journals (Sweden)

    Hermetz Karen E

    2012-01-01

    Full Text Available Abstract Background Chromosome rearrangements are caused by many mutational mechanisms; of these, recurrent rearrangements can be particularly informative for teasing apart DNA sequence-specific factors. Some recurrent translocations are mediated by homologous recombination between large blocks of segmental duplications on different chromosomes. Here we describe a recurrent unbalanced translocation casued by recombination between shorter homologous regions on chromosomes 4 and 18 in two unrelated children with intellectual disability. Results Array CGH resolved the breakpoints of the 6.97-Megabase (Mb loss of 18q and the 7.30-Mb gain of 4q. Sequencing across the translocation breakpoints revealed that both translocations occurred between 92%-identical human endogenous retrovirus (HERV elements in the same orientation on chromosomes 4 and 18. In addition, we find sequence variation in the chromosome 4 HERV that makes one allele more like the chromosome 18 HERV. Conclusions Homologous recombination between HERVs on the same chromosome is known to cause chromosome deletions, but this is the first report of interchromosomal HERV-HERV recombination leading to a translocation. It is possible that normal sequence variation in substrates of non-allelic homologous recombination (NAHR affects the alignment of recombining segments and influences the propensity to chromosome rearrangement.

  14. In vivo importance of homologous recombination DNA repair for mouse neural stem and progenitor cells.

    Directory of Open Access Journals (Sweden)

    Laure Rousseau

    Full Text Available We characterized the in vivo importance of the homologous recombination factor RAD54 for the developing mouse brain cortex in normal conditions or after ionizing radiation exposure. Contrary to numerous homologous recombination genes, Rad54 disruption did not impact the cortical development without exogenous stress, but it dramatically enhanced the radiation sensitivity of neural stem and progenitor cells. This resulted in the death of all cells irradiated during S or G2, whereas the viability of cells irradiated in G1 or G0 was not affected by Rad54 disruption. Apoptosis occurred after long arrests at intra-S and G2/M checkpoints. This concerned every type of neural stem and progenitor cells, showing that the importance of Rad54 for radiation response was linked to the cell cycle phase at the time of irradiation and not to the differentiation state. In the developing brain, RAD54-dependent homologous recombination appeared absolutely required for the repair of damages induced by ionizing radiation during S and G2 phases, but not for the repair of endogenous damages in normal conditions. Altogether our data support the existence of RAD54-dependent and -independent homologous recombination pathways.

  15. Possible cause of lack of positive samples on homologous blood transfusion.

    Science.gov (United States)

    Krotov, Grigory; Nikitina, Maria; Rodchenkov, Grigory

    2014-01-01

    Homologous blood transfusion is a prohibited method of blood manipulation that can be used to increase the number of erythrocytes circulating in the blood stream resulting in an increased oxygen transport capacity. In doping controls, homologous blood transfusions are determined by means of a procedure based on the detection of red blood cell phenotypes by flow cytometry. In the past six years, no adverse analytical findings concerning homologous blood transfusions were reported. One explanation for that phenomenon, assuming that athletes have not completely given up this kind of manipulation, would be a more careful selection of potential donors. If such a donor has the same set of minor erythrocyte antigens as the recipient, the established methodology to detect homologous transfusion would fail. We have hypothesized that any athlete can be a potential donor for teammates with the same RhD factor and AB0 blood group. Having analyzed the phenotype of erythrocytes of 535 Russian athletes in various endurance sports, several pairs of athletes with the same phenotype were observed. Based on the frequency of occurrence of red blood cell antigens, the theoretical probability of finding a donor within a team with exactly the same phenotype was calculated, and the existing number of occurrences where two individuals share the same phenotype in the same sport was in fact five times higher than the theoretical probability. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Dynamics of Homology Searching During Gene Conversion in Saccharomyces cerevisiae Revealed by Donor Competition

    Science.gov (United States)

    Coïc, Eric; Martin, Joshua; Ryu, Taehyun; Tay, Sue Yen; Kondev, Jané; Haber, James E.

    2011-01-01

    One of the least understood aspects of homologous recombination is the process by which the ends of a double-strand break (DSB) search the entire genome for homologous templates that can be used to repair the break. We took advantage of the natural competition between the alternative donors HML and HMR employed during HO endonuclease-induced switching of the budding yeast MAT locus. The strong mating-type-dependent bias in the choice of the donors is enforced by the recombination enhancer (RE), which lies 17 kb proximal to HML. We investigated factors that improve the use of the disfavored donor. We show that the normal heterochromatic state of the donors does not impair donor usage, as donor choice is not affected by removing this epigenetic silencing. In contrast, increasing the length of homology shared by the disfavored donor increases its use. This result shows that donor choice is not irrevocable and implies that there are several encounters between the DSB ends and even the favored donor before recombination is accomplished. The increase by adding more homology is not linear; these results can be explained by a thermodynamic model that determines the energy cost of using one donor over the other. An important inference from this analysis is that when HML is favored as the donor, RE causes a reduction in its effective genomic distance from MAT from 200 kb to ∼20 kb, which we hypothesize occurs after the DSB is created, by epigenetic chromatin modifications around MAT. PMID:21954161

  17. Minimum length of direct repeat sequences required for efficient homologous recombination induced by zinc finger nuclease in yeast.

    Science.gov (United States)

    Ren, ChongHua; Yan, Qiang; Zhang, ZhiYing

    2014-10-01

    Zinc finger nuclease (ZFN) technology is a powerful molecular tool for targeted genome modifications and genetic engineering. However, screening for specific ZFs and validation of ZFN activity are labor intensive and time consuming. We previously designed a yeast-based ZFN screening and validation system by inserting a ZFN binding site flanked by a 164 bp direct repeat sequence into the middle of a Gal4 transcription factor, disrupting the open reading frame of the yeast Gal4 gene. Expression of the ZFN causes a double stranded break at its binding site, which promotes the cellular DNA repair system to restore expression of a functional Gal transcriptional factor via homologous recombination. Expression of Gal4 transcription factor leads to activation of three reporter genes in an AH109 yeast two-hybrid strain. However, the 164 bp direct repeat appears to generate spontaneous homologous recombination frequently, resulting in many false positive ZFNs. To overcome this, a series of DNA fragments of various lengths from 10 to 150 bp with 10 bp increase each and 164 bp direct repeats flanking the ZFN binding site were designed and constructed. The results demonstrated that the minimum length required for ZFN-induced homologous recombination was 30 bp, which almost eliminated spontaneous recombination. Using the 30 bp direct repeat sequence, ZFN could efficiently induce homologous recombination, while false positive ZFNs resulting from spontaneous homologous recombination were minimized. Thus, this study provided a simple, fast and sensitive ZFN screening and activity validation system in yeast.

  18. Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1.

    Science.gov (United States)

    Machida, Shinichi; Takaku, Motoki; Ikura, Masae; Sun, Jiying; Suzuki, Hidekazu; Kobayashi, Wataru; Kinomura, Aiko; Osakabe, Akihisa; Tachiwana, Hiroaki; Horikoshi, Yasunori; Fukuto, Atsuhiko; Matsuda, Ryo; Ura, Kiyoe; Tashiro, Satoshi; Ikura, Tsuyoshi; Kurumizaka, Hitoshi

    2014-05-06

    Homologous recombination plays essential roles in mitotic DNA double strand break (DSB) repair and meiotic genetic recombination. In eukaryotes, RAD51 promotes the central homologous-pairing step during homologous recombination, but is not sufficient to overcome the reaction barrier imposed by nucleosomes. RAD54, a member of the ATP-dependent nucleosome remodeling factor family, is required to promote the RAD51-mediated homologous pairing in nucleosomal DNA. In higher eukaryotes, most nucleosomes form higher-ordered chromatin containing the linker histone H1. However, the mechanism by which RAD51/RAD54-mediated homologous pairing occurs in higher-ordered chromatin has not been elucidated. In this study, we found that a histone chaperone, Nap1, accumulates on DSB sites in human cells, and DSB repair is substantially decreased in Nap1-knockdown cells. We determined that Nap1 binds to RAD54, enhances the RAD54-mediated nucleosome remodeling by evicting histone H1, and eventually stimulates the RAD51-mediated homologous pairing in higher-ordered chromatin containing histone H1.

  19. Peridinialean dinoflagellate plate patterns, labels and homologies

    Science.gov (United States)

    Edwards, L.E.

    1990-01-01

    Tabulation patterns for peridinialean dinoflagellate thecae and cysts have been traditionally expressed using a plate labelling system described by C.A. Kofoid in the early 1900's. This system can obscure dinoflagellate plate homologies and has not always been strictly applied. The plate-labelling system presented here introduces new series labels but incorporates key features and ideas from the more recently proposed systems of G.L. Eaton and F.J.R. Taylor, as modified by W.R. Evitt. Plate-series recognition begins with the cingulum (C-series) and proceeds from the cingulum toward the apex for the three series of the epitheca/epicyst and proceeds from the cingulum toward the antapex for the two series of the hypotheca/hypocyst. The epithecal/epicystal model consists of eight plates that touch the anterior margin of the cingulum (E-series: plates E1-E7, ES), seven plates toward the apex that touch the E-series plates (M-series: R, M1-M6), and up to seven plates near the apex that do not touch E-series plates (D-series: Dp-Dv). The hypothecal/hypocystal model consists of eight plates that touch the posterior margin of the cingulum (H-series: H1-H6,HR,HS) and three plates toward the antapex (T1-T3). Epithecal/epicystal tabulation patterns come in both 8- and 7- models, corresponding to eight and seven plates, respectively, in the E-series. Hypothecal/hypocystal tabulation patterns also come in both 8- and 7-models, corresponding to eight and seven plates, respectively, in the H-series. By convention, the 7-model epitheca/epicyst has no plates E1 and M1; the 7-model hypotheca/hypocyst has no plate H6. Within an 8-model or 7-model, the system emphasizes plates that are presumed to be homologous by giving them identical labels. I introduce the adjectives "monothigmate", "dithigmate," and "trithigmate" to designate plates touching one, two, and three plates, respectively, of the adjacent series. The term "thigmation" applies to the analysis of plate contacts between

  20. Productive homologous and non-homologous recombination of hepatitis C virus in cell culture

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Galli, Andrea; Li, Yi-Ping

    2013-01-01

    . In addition, recombination is an important regulatory mechanism of cytopathogenicity for the related pestiviruses. Here we describe recombination of HCV RNA in cell culture leading to production of infectious virus. Initially, hepatoma cells were co-transfected with a replicating JFH1ΔE1E2 genome (genotype 2a......) lacking functional envelope genes and strain J6 (2a), which has functional envelope genes but does not replicate in culture. After an initial decrease in the number of HCV positive cells, infection spread after 13-36 days. Sequencing of recovered viruses revealed non-homologous recombinants with J6...

  1. A role for the p53 tumour suppressor in regulating the balance between homologous recombination and non-homologous end joining.

    Science.gov (United States)

    Moureau, Sylvie; Luessing, Janna; Harte, Emma Christina; Voisin, Muriel; Lowndes, Noel Francis

    2016-09-01

    Loss of p53, a transcription factor activated by cellular stress, is a frequent event in cancer. The role of p53 in tumour suppression is largely attributed to cell fate decisions. Here, we provide evidence supporting a novel role for p53 in the regulation of DNA double-strand break (DSB) repair pathway choice. 53BP1, another tumour suppressor, was initially identified as p53 Binding Protein 1, and has been shown to inhibit DNA end resection, thereby stimulating non-homologous end joining (NHEJ). Yet another tumour suppressor, BRCA1, reciprocally promotes end resection and homologous recombination (HR). Here, we show that in both human and mouse cells, the absence of p53 results in impaired 53BP1 focal recruitment to sites of DNA damage induced by ionizing radiation. This effect is largely independent of cell cycle phase and the extent of DNA damage. In p53-deficient cells, diminished localization of 53BP1 is accompanied by a reciprocal increase in BRCA1 recruitment to DSBs. Consistent with these findings, we demonstrate that DSB repair via NHEJ is abrogated, while repair via homology-directed repair (HDR) is stimulated. Overall, we propose that in addition to its role as an 'effector' protein in the DNA damage response, p53 plays a role in the regulation of DSB repair pathway choice. © 2016 The Authors.

  2. Relative rates of homologous and nonhomologous recombination in transfected DNA.

    Science.gov (United States)

    Roth, D B; Wilson, J H

    1985-05-01

    Both homologous and nonhomologous recombination events occur at high efficiency in DNA molecules transfected into mammalian cells. Both types of recombination occur with similar overall efficiencies, as measured by an endpoint assay, but their relative rates are unknown. In this communication, we measure the relative rates of homologous and nonhomologous recombination in DNA transfected into monkey cells. This measurement is made by using a linear simian virus 40 genome that contains a 131-base-pair duplication at its termini. Once inside the cell, this molecule must circularize to initiate lytic infection. Circularization can occur either by direct, nonhomologous end-joining or by homologous recombination within the duplicated region. Although the products of the two recombination pathways are different, they are equally infectious. Since homologous and nonhomologous recombination processes are competing for the same substrate, the relative amounts of the products of each pathway should reflect the relative rates of homologous and nonhomologous recombination. Analysis of individual recombinant genomes from 164 plaques indicates that the rate of circularization by nonhomologous recombination is 2- to 3-fold higher than the rate of homologous recombination. The assay system described here may prove to be useful for testing procedures designed to influence the relative rates of homologous and nonhomologous recombination.

  3. Homologous recombination in bovine pestiviruses. Phylogenetic and statistic evidence.

    Science.gov (United States)

    Jones, Leandro Roberto; Weber, E Laura

    2004-12-01

    Bovine pestiviruses (Bovine Viral Diarrea Virus 1 (BVDV 1) and Bovine Viral Diarrea Virus 2 (BVDV 2)) belong to the genus Pestivirus (Flaviviridae), which is composed of positive stranded RNA viruses causing significant economic losses world-wide. We used phylogenetic and bootstrap analyses to systematically scan alignments of previously sequenced genomes in order to explore further the evolutionary mechanisms responsible for variation in the virus. Previously published data suggested that homologous crossover might be one of the mechanisms responsible for the genomic rearrangements observed in cytopathic (cp) strains of bovine pestiviruses. Nevertheless, homologous recombination involves not just homologous crossovers, but also replacement of a homologous region of the acceptor RNA. Furthermore, cytopathic strains represent dead paths in evolution, since they are isolated exclusively from the fatal cases of mucosal disease. Herein, we report evidence of homologous inter-genotype recombination in the genome of a non-cytopathic (ncp) strain of Bovine Viral Diarrea Virus 1, the type species of the genus Pestivirus. We also show that intra-genotype homologous recombination might be a common phenomenon in both species of Pestivirus. This evidence demonstrates that homologous recombination contribute to the diversification of bovine pestiviruses in nature. Implications for virus evolution, taxonomy and phylogenetics are discussed.

  4. Deep homology in the age of next-generation sequencing.

    Science.gov (United States)

    Tschopp, Patrick; Tabin, Clifford J

    2017-02-05

    The principle of homology is central to conceptualizing the comparative aspects of morphological evolution. The distinctions between homologous or non-homologous structures have become blurred, however, as modern evolutionary developmental biology (evo-devo) has shown that novel features often result from modification of pre-existing developmental modules, rather than arising completely de novo. With this realization in mind, the term 'deep homology' was coined, in recognition of the remarkably conserved gene expression during the development of certain animal structures that would not be considered homologous by previous strict definitions. At its core, it can help to formulate an understanding of deeper layers of ontogenetic conservation for anatomical features that lack any clear phylogenetic continuity. Here, we review deep homology and related concepts in the context of a gene expression-based homology discussion. We then focus on how these conceptual frameworks have profited from the recent rise of high-throughput next-generation sequencing. These techniques have greatly expanded the range of organisms amenable to such studies. Moreover, they helped to elevate the traditional gene-by-gene comparison to a transcriptome-wide level. We will end with an outlook on the next challenges in the field and how technological advances might provide exciting new strategies to tackle these questions.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'. © 2016 The Author(s).

  5. The history of the homology concept and the "Phylogenetisches Symposium".

    Science.gov (United States)

    Hossfeld, Uwe; Olsson, Lennart

    2005-11-01

    The homology concept has had a long and varied history, starting out as a geometrical term in ancient Greece. Here we describe briefly how a typological use of homology to designate organs and body parts in the same position anatomically in different organisms was changed by Darwin's theory of evolution into a phylogenetic concept. We try to indicate the diversity of opinions on how to define and test for homology that has prevailed historically, before the important books by Hennig (1950. Grundzüge einer Theorie der Phylogenetischen Systematik. Deutscher Zentralverlag, Berlin) and Remane (1952. Die Grundlagen des Natürlichen Systems, der Vergleichenden Anatomie und der Phylogenetik. Geest & Portig, Leipzig) brought more rigor into both the debate on homology and into the usage of the term homology among systematists. Homology as a theme has recurred repeatedly throughout the history of the "Phylogenetisches Symposium" and we give a very brief overview of the different aspects of homology that have been discussed at specific symposia over the last 48 years. We also honour the fact that the 2004 symposium was held in Jena by pointing to the roles played by biologists active in Jena, such as Ernst Haeckel and Carl Gegenbaur, in starting the development towards a homology concept concordant with an evolutionary world view. As historians of biology, we emphasize the importance of major treatises on homology and its history that may be little read by systematists active today, and have sometimes also received less attention by historians of biology than they deserve. Prominent among these are the works of Dietrich Starck, who also happened to be both a student, and later a benefactor, of systematics at Jena University.

  6. Benchmarking the next generation of homology inference tools.

    Science.gov (United States)

    Saripella, Ganapathi Varma; Sonnhammer, Erik L L; Forslund, Kristoffer

    2016-09-01

    Over the last decades, vast numbers of sequences were deposited in public databases. Bioinformatics tools allow homology and consequently functional inference for these sequences. New profile-based homology search tools have been introduced, allowing reliable detection of remote homologs, but have not been systematically benchmarked. To provide such a comparison, which can guide bioinformatics workflows, we extend and apply our previously developed benchmark approach to evaluate the 'next generation' of profile-based approaches, including CS-BLAST, HHSEARCH and PHMMER, in comparison with the non-profile based search tools NCBI-BLAST, USEARCH, UBLAST and FASTA. We generated challenging benchmark datasets based on protein domain architectures within either the PFAM + Clan, SCOP/Superfamily or CATH/Gene3D domain definition schemes. From each dataset, homologous and non-homologous protein pairs were aligned using each tool, and standard performance metrics calculated. We further measured congruence of domain architecture assignments in the three domain databases. CSBLAST and PHMMER had overall highest accuracy. FASTA, UBLAST and USEARCH showed large trade-offs of accuracy for speed optimization. Profile methods are superior at inferring remote homologs but the difference in accuracy between methods is relatively small. PHMMER and CSBLAST stand out with the highest accuracy, yet still at a reasonable computational cost. Additionally, we show that less than 0.1% of Swiss-Prot protein pairs considered homologous by one database are considered non-homologous by another, implying that these classifications represent equivalent underlying biological phenomena, differing mostly in coverage and granularity. Benchmark datasets and all scripts are placed at (http://sonnhammer.org/download/Homology_benchmark). forslund@embl.de Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  7. Arabidopsis RAD51C gene is important for homologous recombination in meiosis and mitosis.

    Science.gov (United States)

    Abe, Kiyomi; Osakabe, Keishi; Nakayama, Shigeki; Endo, Masaki; Tagiri, Akemi; Todoriki, Setsuko; Ichikawa, Hiroaki; Toki, Seiichi

    2005-10-01

    Rad51 is a homolog of the bacterial RecA recombinase, and a key factor in homologous recombination in eukaryotes. Rad51 paralogs have been identified from yeast to vertebrates. Rad51 paralogs are thought to play an important role in the assembly or stabilization of Rad51 that promotes homologous pairing and strand exchange reactions. We previously characterized two RAD51 paralogous genes in Arabidopsis (Arabidopsis thaliana) named AtRAD51C and AtXRCC3, which are homologs of human RAD51C and XRCC3, respectively, and described the interaction of their products in a yeast two-hybrid system. Recent studies showed the involvement of AtXrcc3 in DNA repair and functional role in meiosis. To determine the role of RAD51C in meiotic and mitotic recombination in higher plants, we characterized a T-DNA insertion mutant of AtRAD51C. Although the atrad51C mutant grew normally during vegetative developmental stage, the mutant produced aborted siliques, and their anthers did not contain mature pollen grains. Crossing of the mutant with wild-type plants showed defective male and female gametogeneses as evidenced by lack of seed production. Furthermore, meiosis was severely disturbed in the mutant. The atrad51C mutant also showed increased sensitivity to gamma-irradiation and cisplatin, which are known to induce double-strand DNA breaks. The efficiency of homologous recombination in somatic cells in the mutant was markedly reduced relative to that in wild-type plants.

  8. Dynamics and impact of homologous recombination on the evolution of Legionella pneumophila.

    Science.gov (United States)

    David, Sophia; Sánchez-Busó, Leonor; Harris, Simon R; Marttinen, Pekka; Rusniok, Christophe; Buchrieser, Carmen; Harrison, Timothy G; Parkhill, Julian

    2017-06-01

    Legionella pneumophila is an environmental bacterium and the causative agent of Legionnaires' disease. Previous genomic studies have shown that recombination accounts for a high proportion (>96%) of diversity within several major disease-associated sequence types (STs) of L. pneumophila. This suggests that recombination represents a potentially important force shaping adaptation and virulence. Despite this, little is known about the biological effects of recombination in L. pneumophila, particularly with regards to homologous recombination (whereby genes are replaced with alternative allelic variants). Using newly available population genomic data, we have disentangled events arising from homologous and non-homologous recombination in six major disease-associated STs of L. pneumophila (subsp. pneumophila), and subsequently performed a detailed characterisation of the dynamics and impact of homologous recombination. We identified genomic "hotspots" of homologous recombination that include regions containing outer membrane proteins, the lipopolysaccharide (LPS) region and Dot/Icm effectors, which provide interesting clues to the selection pressures faced by L. pneumophila. Inference of the origin of the recombined regions showed that isolates have most frequently imported DNA from isolates belonging to their own clade, but also occasionally from other major clades of the same subspecies. This supports the hypothesis that the possibility for horizontal exchange of new adaptations between major clades of the subspecies may have been a critical factor in the recent emergence of several clinically important STs from diverse genomic backgrounds. However, acquisition of recombined regions from another subspecies, L. pneumophila subsp. fraseri, was rarely observed, suggesting the existence of a recombination barrier and/or the possibility of ongoing speciation between the two subspecies. Finally, we suggest that multi-fragment recombination may occur in L. pneumophila

  9. Cyclic structures in algebraic (co)homology theories

    CERN Document Server

    Kowalzig, Niels

    2010-01-01

    This note discusses the cyclic cohomology of a left Hopf algebroid ($\\times_A$-Hopf algebra) with coefficients in a right module-left comodule, defined using a straightforward generalisation of the original operators given by Connes and Moscovici for Hopf algebras. Lie-Rinehart homology is a special case of this theory. A generalisation of cyclic duality that makes sense for arbitrary para-cyclic objects yields a dual homology theory. The twisted cyclic homology of an associative algebra provides an example of this dual theory that uses coefficients that are not necessarily stable anti Yetter-Drinfel'd modules.

  10. The tedious task of finding homologous noncoding RNA genes

    DEFF Research Database (Denmark)

    Menzel, Karl Peter; Gorodkin, Jan; Stadler, Peter F

    2009-01-01

    User-driven in silico RNA homology search is still a nontrivial task. In part, this is the consequence of a limited precision of the computational tools in spite of recent exciting progress in this area, and to a certain extent, computational costs are still problematic in practice. An important......: BLAST still works better or equally good as other methods unless extensive expert knowledge on the RNA family is included. However, when good curated data are available the recent development yields further improvements in finding remote homologs. Homology search beyond the reach of BLAST hence...

  11. Importing the homology concept from biology into developmental psychology.

    Science.gov (United States)

    Moore, David S

    2013-01-01

    To help introduce the idea of homology into developmental psychology, this article presents some of the concepts, distinctions, and guidelines biologists and philosophers of biology have devised to study homology. Some unresolved issues related to this idea are considered as well. Because homology reflects continuity across time, developmental scientists should find this concept to be useful in the study of psychological/behavioral development, just as biologists have found it essential in the study of the evolution and development of morphological and other characteristics.

  12. Tomato FRUITFULL homologs regulate fruit ripening via ethylene biosynthesis.

    Science.gov (United States)

    Shima, Yoko; Fujisawa, Masaki; Kitagawa, Mamiko; Nakano, Toshitsugu; Kimbara, Junji; Nakamura, Nobutaka; Shiina, Takeo; Sugiyama, Junichi; Nakamura, Toshihide; Kasumi, Takafumi; Ito, Yasuhiro

    2014-01-01

    Certain MADS-box transcription factors play central roles in regulating fruit ripening. RIPENING INHIBITOR (RIN), a tomato MADS-domain protein, acts as a global regulator of ripening, affecting the climacteric rise of ethylene, pigmentation changes, and fruit softening. Previously, we showed that two MADS-domain proteins, the FRUITFULL homologs FUL1 and FUL2, form complexes with RIN. Here, we characterized the FUL1/FUL2 loss-of-function phenotype in co-suppressed plants. The transgenic plants produced ripening-defective fruits accumulating little or no lycopene. Unlike a previous study on FUL1/FUL2 suppressed tomatoes, our transgenic fruits showed very low levels of ethylene production, and this was associated with suppression of the genes for 1-aminocyclopropane-1-carboxylic acid synthase, a rate-limiting enzyme in ethylene synthesis. FUL1/FUL2 suppression also caused the fruit to soften in a manner independent of ripening, possibly due to reduced cuticle thickness in the peel of the suppressed tomatoes.

  13. Transcription-coupled homologous recombination after oxidative damage.

    Science.gov (United States)

    Wei, Leizhen; Levine, Arthur Samuel; Lan, Li

    2016-08-01

    Oxidative DNA damage induces genomic instability and may lead to mutagenesis and carcinogenesis. As severe blockades to RNA polymerase II (RNA POLII) during transcription, oxidative DNA damage and the associated DNA strand breaks have a profoundly deleterious impact on cell survival. To protect the integrity of coding regions, high fidelity DNA repair at a transcriptionally active site in non-dividing somatic cells, (i.e., terminally differentiated and quiescent/G0 cells) is necessary to maintain the sequence integrity of transcribed regions. Recent studies indicate that an RNA-templated, transcription-associated recombination mechanism is important to protect coding regions from DNA damage-induced genomic instability. Here, we describe the discovery that G1/G0 cells exhibit Cockayne syndrome (CS) B (CSB)-dependent assembly of homologous recombination (HR) factors at double strand break (DSB) sites within actively transcribed regions. This discovery is a challenge to the current dogma that HR occurs only in S/G2 cells where undamaged sister chromatids are available as donor templates.

  14. A conserved role for p48 homologs in protecting dopaminergic neurons from oxidative stress.

    Directory of Open Access Journals (Sweden)

    Peter Bou Dib

    2014-10-01

    Full Text Available Parkinson's disease (PD is the most common neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA neurons. Both environmental and genetic factors are thought to contribute to the pathogenesis of PD. Although several genes linked to rare familial PD have been identified, endogenous risk factors for sporadic PD, which account for the majority of PD cases, remain largely unknown. Genome-wide association studies have identified many single nucleotide polymorphisms associated with sporadic PD in neurodevelopmental genes including the transcription factor p48/ptf1a. Here we investigate whether p48 plays a role in the survival of DA neurons in Drosophila melanogaster and Caenorhabditis elegans. We show that a Drosophila p48 homolog, 48-related-2 (Fer2, is expressed in and required for the development and survival of DA neurons in the protocerebral anterior medial (PAM cluster. Loss of Fer2 expression in adulthood causes progressive PAM neuron degeneration in aging flies along with mitochondrial dysfunction and elevated reactive oxygen species (ROS production, leading to the progressive locomotor deficits. The oxidative stress challenge upregulates Fer2 expression and exacerbates the PAM neuron degeneration in Fer2 loss-of-function mutants. hlh-13, the worm homolog of p48, is also expressed in DA neurons. Unlike the fly counterpart, hlh-13 loss-of-function does not impair development or survival of DA neurons under normal growth conditions. Yet, similar to Fer2, hlh-13 expression is upregulated upon an acute oxidative challenge and is required for the survival of DA neurons under oxidative stress in adult worms. Taken together, our results indicate that p48 homologs share a role in protecting DA neurons from oxidative stress and degeneration, and suggest that loss-of-function of p48 homologs in flies and worms provides novel tools to study gene-environmental interactions affecting DA neuron survival.

  15. Recombination, Pairing, and Synapsis of Homologs during Meiosis

    Science.gov (United States)

    Zickler, Denise; Kleckner, Nancy

    2015-01-01

    Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships. PMID:25986558

  16. Recombination, Pairing, and Synapsis of Homologs during Meiosis.

    Science.gov (United States)

    Zickler, Denise; Kleckner, Nancy

    2015-05-18

    Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships.

  17. Seiberg-Witten-Floer Homology and Gluing Formulae

    Institute of Scientific and Technical Information of China (English)

    Alan L. CAREY; Bai Ling WANG

    2003-01-01

    This paper gives a detailed construction of Seiberg-Witten-Floer homology for a closed oriented 3-manifold with a non-torsion Spinc structure. Gluing formulae for certain 4-dimensional manifolds splitting along an embedded 3-manifold are obtained.

  18. Homology of normal chains and cohomology of charges

    CERN Document Server

    Pauw, Th De; Pfeffer, W F

    2017-01-01

    The authors consider a category of pairs of compact metric spaces and Lipschitz maps where the pairs satisfy a linearly isoperimetric condition related to the solvability of the Plateau problem with partially free boundary. It includes properly all pairs of compact Lipschitz neighborhood retracts of a large class of Banach spaces. On this category the authors define homology and cohomology functors with real coefficients which satisfy the Eilenberg-Steenrod axioms, but reflect the metric properties of the underlying spaces. As an example they show that the zero-dimensional homology of a space in our category is trivial if and only if the space is path connected by arcs of finite length. The homology and cohomology of a pair are, respectively, locally convex and Banach spaces that are in duality. Ignoring the topological structures, the homology and cohomology extend to all pairs of compact metric spaces. For locally acyclic spaces, the authors establish a natural isomorphism between their cohomology and the �...

  19. Homological Dimensions of the Extension Algebras of Monomial Algebras

    Institute of Scientific and Technical Information of China (English)

    Hong Bo SHI

    2015-01-01

    The main objective of this paper is to study the dimension trees and further the homo-logical dimensions of the extension algebras — dual and trivially twisted extensions — with a unified combinatorial approach using the two combinatorial algorithms — Topdown and Bottomup. We first present a more complete and clearer picture of a dimension tree, with which we are then able, on the one hand, to sharpen some results obtained before and furthermore reveal a few more hidden sub-tle homological phenomenons of or connections between the involved algebras; on the other hand, to provide two more effi cient combinatorial algorithms for computing dimension trees, and consequently the homological dimensions as an application. We believe that the more refined complete structural information on dimension trees will be useful to study other homological properties of this class of extension algebras.

  20. Frequency of nonallelic homologous recombination is correlated with length of homology: evidence that ectopic synapsis precedes ectopic crossing-over.

    Science.gov (United States)

    Liu, Pengfei; Lacaria, Melanie; Zhang, Feng; Withers, Marjorie; Hastings, P J; Lupski, James R

    2011-10-07

    Genomic disorders constitute a class of diseases that are associated with DNA rearrangements resulting from region-specific genome instability, that is, genome architecture incites genome instability. Nonallelic homologous recombination (NAHR) or crossing-over in meiosis between sequences that are not in allelic positions (i.e., paralogous sequences) can result in recurrent deletions or duplications causing genomic disorders. Previous studies of NAHR have focused on description of the phenomenon, but it remains unclear how NAHR occurs during meiosis and what factors determine its frequency. Here we assembled two patient cohorts with reciprocal genomic disorders; deletion associated Smith-Magenis syndrome and duplication associated Potocki-Lupski syndrome. By assessing the full spectrum of rearrangement types from the two cohorts, we find that complex rearrangements (those with more than one breakpoint) are more prevalent in copy-number gains (17.7%) than in copy-number losses (2.3%); an observation that supports a role for replicative mechanisms in complex rearrangement formation. Interestingly, for NAHR-mediated recurrent rearrangements, we show that crossover frequency is positively associated with the flanking low-copy repeat (LCR) length and inversely influenced by the inter-LCR distance. To explain this, we propose that the probability of ectopic chromosome synapsis increases with increased LCR length, and that ectopic synapsis is a necessary precursor to ectopic crossing-over. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. A definition of graph homology and graph K-theory of algebras

    OpenAIRE

    Movshev, M. V.

    1999-01-01

    We introduce and study elementary properties of graph homology of algebras. This new homology theory shares many features of cyclic and Hochschild homology. We also define a graph K-theory together with an analog of Chern character.

  2. Continuation homomorphism in Rabinowitz Floer homology for symplectic deformations

    CERN Document Server

    Bae, Youngjin

    2010-01-01

    Will Merry computed Rabinowitz Floer homology above Mane's critical value in terms of loop space homology by establishing an Abbondandolo-Schwarz short exact sequence. The purpose of this article is to provide an alternative proof of Merry's result. We construct a continuation homomorphism for symplectic deformations which enables us to reduce the computation to the untwisted case. Our construction takes advantage of a special version of the isoperimetric inequality which above Mane's critical value holds true.

  3. On homological stability for configuration spaces on closed background manifolds

    OpenAIRE

    Cantero, Federico; Palmer, Martin

    2014-01-01

    We introduce a new map between configuration spaces of points in a background manifold - the replication map - and prove that it is a homology isomorphism in a range with certain coefficients. This is particularly of interest when the background manifold is closed, in which case the classical stabilisation map does not exist. We then establish conditions on the manifold and on the coefficients under which homological stability holds for configuration spaces on closed manifolds. These conditio...

  4. Spectral Invariants in Rabinowitz Floer homology and Global Hamiltonian perturbations

    CERN Document Server

    Albers, Peter

    2010-01-01

    Spectral invariant were introduced in Hamiltonian Floer homology by Viterbo, Oh, and Schwarz. We extend this concept to Rabinowitz Floer homology. As an application we derive new quantitative existence results for leaf-wise intersections. The importance of spectral invariants for the presented application is that spectral invariants allow us to derive existence of critical points of the Rabinowitz action functional even in degenerate situations where the functional is not Morse.

  5. Relative rates of homologous and nonhomologous recombination in transfected DNA.

    OpenAIRE

    Roth, D B; Wilson, J H

    1985-01-01

    Both homologous and nonhomologous recombination events occur at high efficiency in DNA molecules transfected into mammalian cells. Both types of recombination occur with similar overall efficiencies, as measured by an endpoint assay, but their relative rates are unknown. In this communication, we measure the relative rates of homologous and nonhomologous recombination in DNA transfected into monkey cells. This measurement is made by using a linear simian virus 40 genome that contains a 131-ba...

  6. MRFalign: protein homology detection through alignment of Markov random fields.

    Science.gov (United States)

    Ma, Jianzhu; Wang, Sheng; Wang, Zhiyong; Xu, Jinbo

    2014-03-01

    Sequence-based protein homology detection has been extensively studied and so far the most sensitive method is based upon comparison of protein sequence profiles, which are derived from multiple sequence alignment (MSA) of sequence homologs in a protein family. A sequence profile is usually represented as a position-specific scoring matrix (PSSM) or an HMM (Hidden Markov Model) and accordingly PSSM-PSSM or HMM-HMM comparison is used for homolog detection. This paper presents a new homology detection method MRFalign, consisting of three key components: 1) a Markov Random Fields (MRF) representation of a protein family; 2) a scoring function measuring similarity of two MRFs; and 3) an efficient ADMM (Alternating Direction Method of Multipliers) algorithm aligning two MRFs. Compared to HMM that can only model very short-range residue correlation, MRFs can model long-range residue interaction pattern and thus, encode information for the global 3D structure of a protein family. Consequently, MRF-MRF comparison for remote homology detection shall be much more sensitive than HMM-HMM or PSSM-PSSM comparison. Experiments confirm that MRFalign outperforms several popular HMM or PSSM-based methods in terms of both alignment accuracy and remote homology detection and that MRFalign works particularly well for mainly beta proteins. For example, tested on the benchmark SCOP40 (8353 proteins) for homology detection, PSSM-PSSM and HMM-HMM succeed on 48% and 52% of proteins, respectively, at superfamily level, and on 15% and 27% of proteins, respectively, at fold level. In contrast, MRFalign succeeds on 57.3% and 42.5% of proteins at superfamily and fold level, respectively. This study implies that long-range residue interaction patterns are very helpful for sequence-based homology detection. The software is available for download at http://raptorx.uchicago.edu/download/. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.

  7. Pairs of periodic orbits with fixed homology difference

    DEFF Research Database (Denmark)

    Risager, Morten S.; Sharp, Richard

    2010-01-01

    We obtain an asymptotic formula for the number of pairs of closed orbits of a  weak-mixing transitive Anosov ¿ow whose homology classes have a ¿xed di¿erence.......We obtain an asymptotic formula for the number of pairs of closed orbits of a  weak-mixing transitive Anosov ¿ow whose homology classes have a ¿xed di¿erence....

  8. Rational equivariant K-homology of low dimensional groups

    CERN Document Server

    Lafont, Jean-François; Sánchez-García, Rubén J

    2011-01-01

    We consider groups G which have a cocompact, 3-manifold model for the classifying space \\underline{E}G. We provide an algorithm for computing the rationalized equivariant K-homology of \\underline{E}G. Under the additional hypothesis that the quotient 3-orbifold \\underline{E}G/G is geometrizable, the rationalized K-homology groups coincide with the rationalized K-theory of the reduced C*-algebra of G. We illustrate our algorithm on some concrete examples.

  9. Metagenomic gene annotation by a homology-independent approach

    Energy Technology Data Exchange (ETDEWEB)

    Froula, Jeff; Zhang, Tao; Salmeen, Annette; Hess, Matthias; Kerfeld, Cheryl A.; Wang, Zhong; Du, Changbin

    2011-06-02

    Fully understanding the genetic potential of a microbial community requires functional annotation of all the genes it encodes. The recently developed deep metagenome sequencing approach has enabled rapid identification of millions of genes from a complex microbial community without cultivation. Current homology-based gene annotation fails to detect distantly-related or structural homologs. Furthermore, homology searches with millions of genes are very computational intensive. To overcome these limitations, we developed rhModeller, a homology-independent software pipeline to efficiently annotate genes from metagenomic sequencing projects. Using cellulases and carbonic anhydrases as two independent test cases, we demonstrated that rhModeller is much faster than HMMER but with comparable accuracy, at 94.5percent and 99.9percent accuracy, respectively. More importantly, rhModeller has the ability to detect novel proteins that do not share significant homology to any known protein families. As {approx}50percent of the 2 million genes derived from the cow rumen metagenome failed to be annotated based on sequence homology, we tested whether rhModeller could be used to annotate these genes. Preliminary results suggest that rhModeller is robust in the presence of missense and frameshift mutations, two common errors in metagenomic genes. Applying the pipeline to the cow rumen genes identified 4,990 novel cellulases candidates and 8,196 novel carbonic anhydrase candidates.In summary, we expect rhModeller to dramatically increase the speed and quality of metagnomic gene annotation.

  10. Homology-dependent gene silencing and host defense in plants.

    Science.gov (United States)

    Matzke, Marjori A; Aufsatz, Werner; Kanno, Tatsuo; Mette, M Florian; Matzke, Antonius J M

    2002-01-01

    Analyses of transgene silencing phenomena in plants and other organisms have revealed the existence of epigenetic silencing mechanisms that are based on recognition of nucleic acid sequence homology at either the DNA or RNA level. Common triggers of homology-dependent gene silencing include inverted DNA repeats and double-stranded RNA, a versatile silencing molecule that can induce both degradation of homologous RNA in the cytoplasm and methylation of homologous DNA sequences in the nucleus. Inverted repeats might be frequently associated with silencing because they can potentially interact in cis and in trans to trigger DNA methylation via homologous DNA pairing, or they can be transcribed to produce double-stranded RNA. Homology-dependent gene silencing mechanisms are ideally suited for countering natural parasitic sequences such as transposable elements and viruses, which are usually present in multiple copies and/or produce double-stranded RNA during replication. These silencing mechanisms can thus be regarded as host defense strategies to foreign or invasive nucleic acids. The high content of transposable elements and, in some cases, endogenous viruses in many plant genomes suggests that host defenses do not always prevail over invasive sequences. During evolution, slightly faulty genome defense responses probably allowed transposable elements and viral sequences to accumulate gradually in host chromosomes and to invade host genes. Possible beneficial consequences of this "foreign" DNA buildup include the establishment of genome defense-derived epigenetic control mechanisms for regulating host gene expression and acquired hereditary immunity to some viruses.

  11. The Ku70/80 ring in Non-Homologous End-Joining

    DEFF Research Database (Denmark)

    Kragelund, Birthe Brandt; Weterings, Eric; Hartmann-Petersen, Rasmus;

    2016-01-01

    Non-homologous end-joining (NHEJ) is an essential DNA double strand break repair pathway during all cell cycle stages. Deficiency in NHEJ factors can lead to accumulation of unrepaired DNA breaks or faulty DNA repair, which may ultimately result in cell death, senescence or carcinogenesis. The Ku70....../80 heterodimer is a key-player in the NHEJ pathway and binds to DNA termini with high affinity, where it helps to protect DNA ends from degradation and to recruit other NHEJ factors required for repair. The mechanism of Ku70/80 detachment from the DNA helix after completion of DNA repair is incompletely...

  12. Implication of RuvABC and RecG in homologous recombination in Streptomyces ambofaciens.

    Science.gov (United States)

    Hoff, Grégory; Bertrand, Claire; Piotrowski, Emilie; Thibessard, Annabelle; Leblond, Pierre

    2017-01-01

    Most bacterial organisms rely on homologous recombination to repair DNA double-strand breaks and for the post-replicative repair of DNA single-strand gaps. Homologous recombination can be divided into three steps: (i) a pre-synaptic step in which the DNA 3'-OH ends are processed, (ii) a recA-dependent synaptic step allowing the invasion of an intact copy and the formation of Holliday junctions, and (iii) a post-synaptic step consisting of migration and resolution of these junctions. Currently, little is known about factors involved in homologous recombination, especially for the post-synaptic step. In Escherichia coli, branch migration and resolution are performed by the RuvABC complex, but could also rely on the RecG helicase in a redundant manner. In this study, we show that recG and ruvABC are well-conserved among Streptomyces. ΔruvABC, ΔrecG and ΔruvABC ΔrecG mutant strains were constructed. ΔruvABC ΔrecG is only slightly affected by exposure to DNA damage (UV). We also show that conjugational recombination decreases in the absence of RuvABC and RecG, but that intra-chromosomal recombination is not affected. These data suggest that RuvABC and RecG are indeed involved in homologous recombination in Streptomyces ambofaciens and that alternative factors are able to take over Holliday junction in Streptomyces. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  13. Change of gene structure and function by non-homologous end-joining, homologous recombination, and transposition of DNA.

    OpenAIRE

    Wolfgang Goettel; Joachim Messing

    2009-01-01

    An important objective in genome research is to relate genome structure to gene function. Sequence comparisons among orthologous and paralogous genes and their allelic variants can reveal sequences of functional significance. Here, we describe a 379-kb region on chromosome 1 of maize that enables us to reconstruct chromosome breakage, transposition, non-homologous end-joining, and homologous recombination events. Such a high-density composition of various mechanisms in a small chromosomal int...

  14. Multiscale analysis of nonlinear systems using computational homology

    Energy Technology Data Exchange (ETDEWEB)

    Konstantin Mischaikow; Michael Schatz; William Kalies; Thomas Wanner

    2010-05-24

    This is a collaborative project between the principal investigators. However, as is to be expected, different PIs have greater focus on different aspects of the project. This report lists these major directions of research which were pursued during the funding period: (1) Computational Homology in Fluids - For the computational homology effort in thermal convection, the focus of the work during the first two years of the funding period included: (1) A clear demonstration that homology can sensitively detect the presence or absence of an important flow symmetry, (2) An investigation of homology as a probe for flow dynamics, and (3) The construction of a new convection apparatus for probing the effects of large-aspect-ratio. (2) Computational Homology in Cardiac Dynamics - We have initiated an effort to test the use of homology in characterizing data from both laboratory experiments and numerical simulations of arrhythmia in the heart. Recently, the use of high speed, high sensitivity digital imaging in conjunction with voltage sensitive fluorescent dyes has enabled researchers to visualize electrical activity on the surface of cardiac tissue, both in vitro and in vivo. (3) Magnetohydrodynamics - A new research direction is to use computational homology to analyze results of large scale simulations of 2D turbulence in the presence of magnetic fields. Such simulations are relevant to the dynamics of black hole accretion disks. The complex flow patterns from simulations exhibit strong qualitative changes as a function of magnetic field strength. Efforts to characterize the pattern changes using Fourier methods and wavelet analysis have been unsuccessful. (4) Granular Flow - two experts in the area of granular media are studying 2D model experiments of earthquake dynamics where the stress fields can be measured; these stress fields from complex patterns of 'force chains' that may be amenable to analysis using computational homology. (5) Microstructure

  15. Multiscale analysis of nonlinear systems using computational homology

    Energy Technology Data Exchange (ETDEWEB)

    Konstantin Mischaikow, Rutgers University/Georgia Institute of Technology, Michael Schatz, Georgia Institute of Technology, William Kalies, Florida Atlantic University, Thomas Wanner,George Mason University

    2010-05-19

    This is a collaborative project between the principal investigators. However, as is to be expected, different PIs have greater focus on different aspects of the project. This report lists these major directions of research which were pursued during the funding period: (1) Computational Homology in Fluids - For the computational homology effort in thermal convection, the focus of the work during the first two years of the funding period included: (1) A clear demonstration that homology can sensitively detect the presence or absence of an important flow symmetry, (2) An investigation of homology as a probe for flow dynamics, and (3) The construction of a new convection apparatus for probing the effects of large-aspect-ratio. (2) Computational Homology in Cardiac Dynamics - We have initiated an effort to test the use of homology in characterizing data from both laboratory experiments and numerical simulations of arrhythmia in the heart. Recently, the use of high speed, high sensitivity digital imaging in conjunction with voltage sensitive fluorescent dyes has enabled researchers to visualize electrical activity on the surface of cardiac tissue, both in vitro and in vivo. (3) Magnetohydrodynamics - A new research direction is to use computational homology to analyze results of large scale simulations of 2D turbulence in the presence of magnetic fields. Such simulations are relevant to the dynamics of black hole accretion disks. The complex flow patterns from simulations exhibit strong qualitative changes as a function of magnetic field strength. Efforts to characterize the pattern changes using Fourier methods and wavelet analysis have been unsuccessful. (4) Granular Flow - two experts in the area of granular media are studying 2D model experiments of earthquake dynamics where the stress fields can be measured; these stress fields from complex patterns of 'force chains' that may be amenable to analysis using computational homology. (5) Microstructure

  16. PDBalert: automatic, recurrent remote homology tracking and protein structure prediction

    Directory of Open Access Journals (Sweden)

    Söding Johannes

    2008-11-01

    Full Text Available Abstract Background During the last years, methods for remote homology detection have grown more and more sensitive and reliable. Automatic structure prediction servers relying on these methods can generate useful 3D models even below 20% sequence identity between the protein of interest and the known structure (template. When no homologs can be found in the protein structure database (PDB, the user would need to rerun the same search at regular intervals in order to make timely use of a template once it becomes available. Results PDBalert is a web-based automatic system that sends an email alert as soon as a structure with homology to a protein in the user's watch list is released to the PDB database or appears among the sequences on hold. The mail contains links to the search results and to an automatically generated 3D homology model. The sequence search is performed with the same software as used by the very sensitive and reliable remote homology detection server HHpred, which is based on pairwise comparison of Hidden Markov models. Conclusion PDBalert will accelerate the information flow from the PDB database to all those who can profit from the newly released protein structures for predicting the 3D structure or function of their proteins of interest.

  17. DNA sequence alignment by microhomology sampling during homologous recombination.

    Science.gov (United States)

    Qi, Zhi; Redding, Sy; Lee, Ja Yil; Gibb, Bryan; Kwon, YoungHo; Niu, Hengyao; Gaines, William A; Sung, Patrick; Greene, Eric C

    2015-02-26

    Homologous recombination (HR) mediates the exchange of genetic information between sister or homologous chromatids. During HR, members of the RecA/Rad51 family of recombinases must somehow search through vast quantities of DNA sequence to align and pair single-strand DNA (ssDNA) with a homologous double-strand DNA (dsDNA) template. Here, we use single-molecule imaging to visualize Rad51 as it aligns and pairs homologous DNA sequences in real time. We show that Rad51 uses a length-based recognition mechanism while interrogating dsDNA, enabling robust kinetic selection of 8-nucleotide (nt) tracts of microhomology, which kinetically confines the search to sites with a high probability of being a homologous target. Successful pairing with a ninth nucleotide coincides with an additional reduction in binding free energy, and subsequent strand exchange occurs in precise 3-nt steps, reflecting the base triplet organization of the presynaptic complex. These findings provide crucial new insights into the physical and evolutionary underpinnings of DNA recombination. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Homologous recombination is required for recovery from oxidative DNA damage.

    Science.gov (United States)

    Hayashi, Michio; Umezu, Keiko

    2017-04-03

    We have been studying the genetic events, including chromosome loss, chromosome rearrangements and intragenic point mutations, that are responsible for the deletion of a URA3 marker in a loss of heterozygosity (LOH) assay in the yeast Saccharomycess cerevisiae. With this assay, we previously showed that homologous recombination plays an important role in genome maintenance in response to DNA lesions that occur spontaneously in normally growing cells. Here, to investigate DNA lesions capable of triggering homologous recombination, we examined the effects of oxidative stress, a prominent cause of endogenous DNA damage, on LOH events. Treatment of log-phase cells with H2O2 first caused growth arrest and then, during the subsequent recovery, chromosome loss and various chromosome rearrangements were induced more than 10-fold. Further analysis of the rearrangements showed that gene conversion was strongly induced, approximately 100 times more frequently than in untreated cells. Consistent with these results, two diploid strains deficient for homologous recombination, rad52Δ/rad52Δ and rad51Δ/rad51Δ, were sensitive to H2O2 treatment. In addition, chromosome DNA breaks were detected in H2O2-treated cells using pulsed-field gel electrophoresis. Altogether, these results suggest that oxidative stress induced recombinogenic lesions on chromosomes, which then triggered homologous recombination leading to chromosome rearrangements, and that this response contributed to the survival of cells afflicted by oxidative DNA damage. We therefore conclude that homologous recombination is required for the recovery of cells from oxidative stress.

  19. Single-Stranded DNA Curtains for Studying Homologous Recombination.

    Science.gov (United States)

    Ma, C J; Steinfeld, J B; Greene, E C

    2017-01-01

    Homologous recombination is an important pathway involved in the repair of double-stranded DNA breaks. Genetic studies form the foundation of our knowledge on homologous recombination. Significant progress has also been made toward understanding the biochemical and biophysical properties of the proteins, complexes, and reaction intermediates involved in this essential DNA repair pathway. However, heterogeneous or transient recombination intermediates remain extremely difficult to assess through traditional ensemble methods, leaving an incomplete mechanistic picture of many steps that take place during homologous recombination. To help overcome some of these limitations, we have established DNA curtain methodologies as an experimental platform for studying homologous DNA recombination in real-time at the single-molecule level. Here, we present a detailed overview describing the preparation and use of single-stranded DNA curtains in applications related to the study of homologous DNA recombination with emphasis on recent work related to the study of the eukaryotic recombinase Rad51. © 2017 Elsevier Inc. All rights reserved.

  20. Primary homologies of the circumorbital bones of snakes.

    Science.gov (United States)

    Palci, Alessandro; Caldwell, Michael W

    2013-09-01

    Some snakes have two circumorbital ossifications that in the current literature are usually referred to as the postorbital and supraorbital. We review the arguments that have been proposed to justify this interpretation and provide counter-arguments that reject those conjectures of primary homology based on the observation of 32 species of lizards and 81 species of snakes (both extant and fossil). We present similarity arguments, both topological and structural, for reinterpretation of the primary homologies of the dorsal and posterior orbital ossifications of snakes. Applying the test of similarity, we conclude that the posterior orbital ossification of snakes is topologically consistent as the homolog of the lacertilian jugal, and that the dorsal orbital ossification present in some snakes (e.g., pythons, Loxocemus, and Calabaria) is the homolog of the lacertilian postfrontal. We therefore propose that the terms postorbital and supraorbital should be abandoned as reference language for the circumorbital bones of snakes, and be replaced with the terms jugal and postfrontal, respectively. The primary homology claim for the snake "postorbital" fails the test of similarity, while the term "supraorbital" is an unnecessary and inaccurate application of the concept of a neomorphic ossification, for an element that passes the test of similarity as a postfrontal. This reinterpretation of the circumorbital bones of snakes is bound to have important repercussions for future phylogenetic analyses and consequently for our understanding of the origin and evolution of snakes.

  1. RecA filament sliding on DNA facilitates homology search

    Science.gov (United States)

    Ragunathan, Kaushik; Liu, Cheng; Ha, Taekjip

    2012-01-01

    During homologous recombination, RecA forms a helical filament on a single stranded (ss) DNA that searches for a homologous double stranded (ds) DNA and catalyzes the exchange of complementary base pairs to form a new heteroduplex. Using single molecule fluorescence imaging tools with high spatiotemporal resolution we characterized the encounter complex between the RecA filament and dsDNA. We present evidence in support of the ‘sliding model’ wherein a RecA filament diffuses along a dsDNA track. We further show that homology can be detected during sliding. Sliding occurs with a diffusion coefficient of approximately 8000 bp2/s allowing the filament to sample several hundred base pairs before dissociation. Modeling suggests that sliding can accelerate homology search by as much as 200 fold. Homology recognition can occur for as few as 6 nt of complementary basepairs with the recognition efficiency increasing for higher complementarity. Our data represents the first example of a DNA bound multi-protein complex which can slide along another DNA to facilitate target search. DOI: http://dx.doi.org/10.7554/eLife.00067.001 PMID:23240082

  2. Homology Modeling a Fast Tool for Drug Discovery: Current Perspectives

    Science.gov (United States)

    Vyas, V. K.; Ukawala, R. D.; Ghate, M.; Chintha, C.

    2012-01-01

    Major goal of structural biology involve formation of protein-ligand complexes; in which the protein molecules act energetically in the course of binding. Therefore, perceptive of protein-ligand interaction will be very important for structure based drug design. Lack of knowledge of 3D structures has hindered efforts to understand the binding specificities of ligands with protein. With increasing in modeling software and the growing number of known protein structures, homology modeling is rapidly becoming the method of choice for obtaining 3D coordinates of proteins. Homology modeling is a representation of the similarity of environmental residues at topologically corresponding positions in the reference proteins. In the absence of experimental data, model building on the basis of a known 3D structure of a homologous protein is at present the only reliable method to obtain the structural information. Knowledge of the 3D structures of proteins provides invaluable insights into the molecular basis of their functions. The recent advances in homology modeling, particularly in detecting and aligning sequences with template structures, distant homologues, modeling of loops and side chains as well as detecting errors in a model contributed to consistent prediction of protein structure, which was not possible even several years ago. This review focused on the features and a role of homology modeling in predicting protein structure and described current developments in this field with victorious applications at the different stages of the drug design and discovery. PMID:23204616

  3. The OGCleaner: filtering false-positive homology clusters.

    Science.gov (United States)

    Fujimoto, M Stanley; Suvorov, Anton; Jensen, Nicholas O; Clement, Mark J; Snell, Quinn; Bybee, Seth M

    2017-01-01

    Detecting homologous sequences in organisms is an essential step in protein structure and function prediction, gene annotation and phylogenetic tree construction. Heuristic methods are often employed for quality control of putative homology clusters. These heuristics, however, usually only apply to pairwise sequence comparison and do not examine clusters as a whole. We present the Orthology Group Cleaner (the OGCleaner), a tool designed for filtering putative orthology groups as homology or non-homology clusters by considering all sequences in a cluster. The OGCleaner relies on high-quality orthologous groups identified in OrthoDB to train machine learning algorithms that are able to distinguish between true-positive and false-positive homology groups. This package aims to improve the quality of phylogenetic tree construction especially in instances of lower-quality transcriptome assemblies. https://github.com/byucsl/ogcleaner CONTACT: sfujimoto@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Double-stranded DNA homology produces a physical signature

    Science.gov (United States)

    Wang, Xing; Zhang, Xiaoping; Mao, Chengde; Seeman, Nadrian C.

    2010-01-01

    DNA is found in the cell largely as a negatively supercoiled molecule. This high-energy form of the genetic material can engender sequence-dependent structures, such as cruciforms, Z-DNA, or H-DNA, even though they are not favored by conventional conditions in relaxed DNA. A key feature of DNA in living systems is the presence of homology. We have sought homology-dependent structural phenomena based on topological relaxation. Using two-dimensional electrophoresis, we demonstrate a structural transition in supercoiled plasmid molecules containing homologous segments. Atomic force microscopy (AFM) reveals a dumbbell structure in molecules whose linking difference is beyond the transition point. The position of the dumbbell shaft is a function of the site of homology, and its extent is proportional to the linking difference. Second-site-reversion electrophoresis data support the notion that the shaft contains PX-DNA. Predicted cross-linking patterns generated in vivo suggest that homology-dependent structures can occur within the cell. PMID:20616051

  5. WeederH: an algorithm for finding conserved regulatory motifs and regions in homologous sequences

    Directory of Open Access Journals (Sweden)

    Pesole Graziano

    2007-02-01

    Full Text Available Abstract Background This work addresses the problem of detecting conserved transcription factor binding sites and in general regulatory regions through the analysis of sequences from homologous genes, an approach that is becoming more and more widely used given the ever increasing amount of genomic data available. Results We present an algorithm that identifies conserved transcription factor binding sites in a given sequence by comparing it to one or more homologs, adapting a framework we previously introduced for the discovery of sites in sequences from co-regulated genes. Differently from the most commonly used methods, the approach we present does not need or compute an alignment of the sequences investigated, nor resorts to descriptors of the binding specificity of known transcription factors. The main novel idea we introduce is a relative measure of conservation, assuming that true functional elements should present a higher level of conservation with respect to the rest of the sequence surrounding them. We present tests where we applied the algorithm to the identification of conserved annotated sites in homologous promoters, as well as in distal regions like enhancers. Conclusion Results of the tests show how the algorithm can provide fast and reliable predictions of conserved transcription factor binding sites regulating the transcription of a gene, with better performances than other available methods for the same task. We also show examples on how the algorithm can be successfully employed when promoter annotations of the genes investigated are missing, or when regulatory sites and regions are located far away from the genes.

  6. Nascent DNA synthesis during homologous recombination is synergistically promoted by the rad51 recombinase and DNA homology.

    Science.gov (United States)

    Mundia, Maureen M; Desai, Vatsal; Magwood, Alissa C; Baker, Mark D

    2014-05-01

    In this study, we exploited a plasmid-based assay that detects the new DNA synthesis (3' extension) that accompanies Rad51-mediated homology searching and strand invasion steps of homologous recombination to investigate the interplay between Rad51 concentration and homology length. Mouse hybridoma cells that express endogenous levels of Rad51 display an approximate linear increase in the frequency of 3' extension for homology lengths of 500 bp to 2 kb. At values below ∼500 bp, the frequency of 3' extension declines markedly, suggesting that this might represent the minimal efficient processing segment for 3' extension. Overexpression of wild-type Rad51 stimulated the frequency of 3' extension by ∼3-fold for homology lengths homology was >2 kb, 3' extension frequency increased by as much as 10-fold. Excess wild-type Rad51 did not increase the average 3' extension tract length. Analysis of cell lines expressing N-terminally FLAG-tagged Rad51 polymerization mutants F86E, A89E, or F86E/A89E established that the 3' extension process requires Rad51 polymerization activity. Mouse hybridoma cells that have reduced Brca2 (Breast cancer susceptibility 2) due to stable expression of small interfering RNA show a significant reduction in 3' extension efficiency; expression of wild-type human BRCA2, but not a BRCA2 variant devoid of BRC repeats 1-8, rescues the 3' extension defect in these cells. Our results suggest that increased Rad51 concentration and homology length interact synergistically to promote 3' extension, presumably as a result of enhanced Brca2-mediated Rad51 polymerization.

  7. Functional analysis of Vibrio vulnificus RND efflux pumps homologous to Vibrio cholerae VexAB and VexCD, and to Escherichia coli AcrAB.

    Science.gov (United States)

    Lee, Seunghwa; Yeom, Ji-Hyun; Seo, Sojin; Lee, Minho; Kim, Sarang; Bae, Jeehyeon; Lee, Kangseok; Hwang, Jihwan

    2015-04-01

    Resistance-nodulation-division (RND) efflux pumps are associated with multidrug resistance in many gram-negative pathogens. The genome of Vibrio vulnificus encodes 11 putative RND pumps homologous to those of Vibrio cholerae and Escherichia coli. In this study, we analyzed three putative RND efflux pumps, showing homology to V. cholerae VexAB and VexCD and to E. coli AcrAB, for their functional roles in multidrug resistance of V. vulnificus. Deletion of the vexAB homolog resulted in increased susceptibility of V. vulnificus to bile acid, acriflavine, ethidium bromide, and erythromycin, whereas deletion of acrAB homologs rendered V. vulnificus more susceptible to acriflavine only. Deletion of vexCD had no effect on susceptibility of V. vulnificus to these chemicals. Upon exposure to these antibacterial chemicals, expression of tolCV1 and tolCV2, which are putative outer membrane factors of RND efflux pumps, was induced, whereas expression levels of vexAB, vexCD, and acrAB homologs were not significantly changed. Our results show that the V. vulnificus homologs of VexAB largely contributed to in vitro antimicrobial resistance with a broad substrate specificity that was partially redundant with the AcrAB pump homologs.

  8. Differential forms on singular varieties and cyclic homology

    CERN Document Server

    Brasselet, J P; Brasselet, Jean-Paul; Legrand, André

    1996-01-01

    A classical result of A. Connes asserts that the Frechet algebra of smooth functions on a smooth compact manifold X provides, by a purely algebraic procedure, the de Rham cohomology of X. Namely the procedure uses Hochschild and cyclic homology of this algebra. In the situation of a Thom-Mather stratified variety, we construct a Frechet algebra of functions on the regular part and a module of poles along the singular part. We associate to these objects a complex of differential forms and an Hochschild complex, on the regular part, both with poles along the singular part. The de Rham cohomology of the first complex and the cylic homology of the second one are related to the intersection homology of the variety, the corresponding perversity is determined by the orders of poles.

  9. Nasal pungency, odor, and eye irritation thresholds for homologous acetates.

    Science.gov (United States)

    Cometto-Muñiz, J E; Cain, W S

    1991-08-01

    We measured detection thresholds for nasal pungency (in anosmics), odor (in normosmics) and eye irritation employing a homologous series of acetates: methyl through octyl acetate, decyl and dodecyl acetate. All anosmics reliably detected the series up to heptyl acetate. Only the anosmics without smell since birth (congenital) reliably detected octyl acetate, and only one congenital anosmic detected decyl and dodecyl acetate. Anosmics who lost smell from head trauma proved to be selectively less sensitive. As expected, odor thresholds lay well below pungency thresholds. Eye irritation thresholds for selected acetates came close to nasal pungency thresholds. All three types of thresholds decreased logarithmically with carbon chain length, as previously seen with homologous alcohols and as seen in narcotic and toxic phenomena. Results imply that nasal pungency for these stimuli rests upon a physical, rather than chemical, interaction with susceptible mucosal structures. When expressed as thermodynamic activity, nasal pungency thresholds remain remarkably constant within and across the homologous series of acetates and alcohols.

  10. Homology groups for particles on one-connected graphs

    Science.gov (United States)

    MaciÄ Żek, Tomasz; Sawicki, Adam

    2017-06-01

    We present a mathematical framework for describing the topology of configuration spaces for particles on one-connected graphs. In particular, we compute the homology groups over integers for different classes of one-connected graphs. Our approach is based on some fundamental combinatorial properties of the configuration spaces, Mayer-Vietoris sequences for different parts of configuration spaces, and some limited use of discrete Morse theory. As one of the results, we derive the closed-form formulae for ranks of the homology groups for indistinguishable particles on tree graphs. We also give a detailed discussion of the second homology group of the configuration space of both distinguishable and indistinguishable particles. Our motivation is the search for new kinds of quantum statistics.

  11. Quantization of gauge fields, graph polynomials and graph homology

    Energy Technology Data Exchange (ETDEWEB)

    Kreimer, Dirk, E-mail: kreimer@physik.hu-berlin.de [Humboldt University, 10099 Berlin (Germany); Sars, Matthias [Humboldt University, 10099 Berlin (Germany); Suijlekom, Walter D. van [Radboud University Nijmegen, 6525 AJ Nijmegen (Netherlands)

    2013-09-15

    We review quantization of gauge fields using algebraic properties of 3-regular graphs. We derive the Feynman integrand at n loops for a non-abelian gauge theory quantized in a covariant gauge from scalar integrands for connected 3-regular graphs, obtained from the two Symanzik polynomials. The transition to the full gauge theory amplitude is obtained by the use of a third, new, graph polynomial, the corolla polynomial. This implies effectively a covariant quantization without ghosts, where all the relevant signs of the ghost sector are incorporated in a double complex furnished by the corolla polynomial–we call it cycle homology–and by graph homology. -- Highlights: •We derive gauge theory Feynman from scalar field theory with 3-valent vertices. •We clarify the role of graph homology and cycle homology. •We use parametric renormalization and the new corolla polynomial.

  12. Homologous flares and the evolution of NOAA Active Region 2372

    Science.gov (United States)

    Strong, K. T.; Smith, J. B., Jr.; Mccabe, M. K.; Machado, M. E.; Saba, J. L. R.; Simnett, G. M.

    1984-01-01

    A detailed record of the evolution of NOAA Active Region 2372 has been compiled by the FBS Homology Study Group. It was one of the most prolific flare-producing regions observed by SMM. The flares occurred in distinct stages which corresponded to particular evolutionary phases in the development of the active region magnetic field. By comparison with a similar but less productive active region, it is found that the activity seems to be related to the magnetic complexity of the region and the amount of shear in the field. Further, the soft X-ray emission in the quiescent active region is related to its flare rate. Within the broader definition of homology adopted, there was a degree of homology between the events within each stage of evolution of AR2372.

  13. Bacterial actin and tubulin homologs in cell growth and division.

    Science.gov (United States)

    Busiek, Kimberly K; Margolin, William

    2015-03-16

    In contrast to the elaborate cytoskeletal machines harbored by eukaryotic cells, such as mitotic spindles, cytoskeletal structures detectable by typical negative stain electron microscopy are generally absent from bacterial cells. As a result, for decades it was thought that bacteria lacked cytoskeletal machines. Revolutions in genomics and fluorescence microscopy have confirmed the existence not only of smaller-scale cytoskeletal structures in bacteria, but also of widespread functional homologs of eukaryotic cytoskeletal proteins. The presence of actin, tubulin, and intermediate filament homologs in these relatively simple cells suggests that primitive cytoskeletons first arose in bacteria. In bacteria such as Escherichia coli, homologs of tubulin and actin directly interact with each other and are crucial for coordinating cell growth and division. The function and direct interactions between these proteins will be the focus of this review.

  14. Remote homology and the functions of metagenomic dark matter.

    Science.gov (United States)

    Lobb, Briallen; Kurtz, Daniel A; Moreno-Hagelsieb, Gabriel; Doxey, Andrew C

    2015-01-01

    Predicted open reading frames (ORFs) that lack detectable homology to known proteins are termed ORFans. Despite their prevalence in metagenomes, the extent to which ORFans encode real proteins, the degree to which they can be annotated, and their functional contributions, remain unclear. To gain insights into these questions, we applied sensitive remote-homology detection methods to functionally analyze ORFans from soil, marine, and human gut metagenome collections. ORFans were identified, clustered into sequence families, and annotated through profile-profile comparison to proteins of known structure. We found that a considerable number of metagenomic ORFans (73,896 of 484,121, 15.3%) exhibit significant remote homology to structurally characterized proteins, providing a means for ORFan functional profiling. The extent of detected remote homology far exceeds that obtained for artificial protein families (1.4%). As expected for real genes, the predicted functions of ORFans are significantly similar to the functions of their gene neighbors (p homology searches, ORFans show biologically intriguing differences. Many ORFan-enriched functions are virus-related and tend to reflect biological processes associated with extreme sequence diversity. Each environment also possesses a large number of unique ORFan families and functions, including some known to play important community roles such as gut microbial polysaccharide digestion. Lastly, ORFans are a valuable resource for finding novel enzymes of interest, as we demonstrate through the identification of hundreds of novel ORFan metalloproteases that all possess a signature catalytic motif despite a general lack of similarity to known proteins. Our ORFan functional predictions are a valuable resource for discovering novel protein families and exploring the boundaries of protein sequence space. All remote homology predictions are available at http://doxey.uwaterloo.ca/ORFans.

  15. RNA Structural Homology Search with a Succinct Stochastic Grammar Model

    Institute of Scientific and Technical Information of China (English)

    Ying-Lei Song; Ji-Zhen Zhao; Chun-Mei Liu; Kan Liu; Russell Malmberg; Li-Ming Cai

    2005-01-01

    An increasing number of structural homology search tools, mostly based on profile stochastic context-free grammars (SCFGs) have been recently developed for the non-coding RNA gene identification. SCFGs can include statistical biases that often occur in RNA sequences, necessary to profile specific RNA structures for structural homology search. In this paper, a succinct stochastic grammar model is introduced for RNA that has competitive search effectiveness. More importantly, the profiling model can be easily extended to include pseudoknots, structures that are beyond the capability of profile SCFGs. In addition, the model allows heuristics to be exploited, resulting in a significant speed-up for the CYK algorithm-based search.

  16. Ganea Term for Homology of Leibniz n-Algebras

    Institute of Scientific and Technical Information of China (English)

    J.M. Casas

    2005-01-01

    We extend the five-term exact sequence of homology with trivial coefficients of Leibniz n-algebras nH L1 ( K ) → nH L1 (L) → M → nH L0( K ) → nH L0( L ) → 0 associated to a central extension of Leibniz n-algebras 0 → M →K → L → 0 by means of a sixth term which is a generalization of the Ganea term for homology of Leibniz algebras. We use this sequence in order to analyze several questions related with the centre and central extensions of a Leibniz n-algebra.

  17. Homological unimodularity and Calabi-Yau condition for Poisson algebras

    Science.gov (United States)

    Lü, Jiafeng; Wang, Xingting; Zhuang, Guangbin

    2017-09-01

    In this paper, we show that the twisted Poincaré duality between Poisson homology and cohomology can be derived from the Serre invertible bimodule. This gives another definition of a unimodular Poisson algebra in terms of its Poisson Picard group. We also achieve twisted Poincaré duality for Hochschild (co)homology of Poisson bimodules using rigid dualizing complex. For a smooth Poisson affine variety with the trivial canonical bundle, we prove that its enveloping algebra is a Calabi-Yau algebra if the Poisson structure is unimodular.

  18. Khovanov-Rozansky Graph Homology and Composition Product

    DEFF Research Database (Denmark)

    Wagner, Emmanuel

    2008-01-01

    In analogy with a recursive formula for the HOMFLY-PT polynomial of links given by Jaeger, we give a recursive formula for the graph polynomial introduced by Kauffman and Vogel. We show how this formula extends to the Khovanov–Rozansky graph homology.......In analogy with a recursive formula for the HOMFLY-PT polynomial of links given by Jaeger, we give a recursive formula for the graph polynomial introduced by Kauffman and Vogel. We show how this formula extends to the Khovanov–Rozansky graph homology....

  19. Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Glenn M Manthey

    Full Text Available Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs, such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA. Among the factors important for translocation formation by SSA is the central mismatch repair (MMR and homologous recombination (HR factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage.

  20. Does distant homology with Evf reveal a lipid binding site in Bacillus thuringiensis cytolytic toxins?

    Science.gov (United States)

    Rigden, Daniel J

    2009-05-19

    The Cry and Cyt classes of insecticidal toxins derived from the sporulating bacterium Bacillus thuringiensis are valuable substitutes for synthetic pesticides in agricultural contexts. Crystal structures and many biochemical data have provided insights into their molecular mechanisms, generally thought to involve oligomerization and pore formation, but have not localised the site on Cyt toxins responsible for selective binding of phospholipids containing unsaturated fatty acids. Here, distant homology between the structure of Cyt toxins and Erwinia virulence factor (Evf) is demonstrated which, along with sequence conservation analysis, allows a putative lipid binding site to be localised in the toxins.

  1. Targeting of human aFGF gene into silkworm,Bombyx mori L. through homologous recombination

    Institute of Scientific and Technical Information of China (English)

    吴小锋; 曹翠平

    2004-01-01

    The long-arm and short-arm genes of fibroin light chain (L-chain) of silkworm, Bombyx Mori L., and the gene of human acidic fibroblast growth factor were cloned respectively and subsequently inserted into a transfer vector pVL 1392 used as a tool to target the L-chain region of the silkworm genome. Genomic DNA from their offsprings was extracted and the expected targeting was detected using polymerase chain reaction and DNA sequencing, as well as protein analysis. The results showed that positive events occurred and that the FGF gene was integrated into the L-chain locus through homologous recombination.

  2. Targeting of human aFGF gene into silkworm, Bombyx mori L.Through homologous recombination

    Institute of Scientific and Technical Information of China (English)

    吴小锋; 曹翠平

    2004-01-01

    The long-arm and short-arm genes of fibroin light chain (L-chain) of silkworm, Bombyx Mori L., and the gene of human acidic fibroblast growth factor were cloned respectively and subsequently inserted into a transfer vector pVL1392 used as a tool to target the L-chain region of the silkworm genome. Genomic DNA from their offsprings was extracted and the expected targeting was detected using polymerase chain reaction and DNA sequencing, as well as protein analysis. The results showed that positive events occurred and that the FGF gene was integrated into the L-chain locus through homologous recombination.

  3. Using genetic networks and homology to understand the evolution of phenotypic traits.

    Science.gov (United States)

    McCune, Amy R; Schimenti, John C

    2012-03-01

    Homology can have different meanings for different kinds of biologists. A phylogenetic view holds that homology, defined by common ancestry, is rigorously identified through phylogenetic analysis. Such homologies are taxic homologies (=synapomorphies). A second interpretation, "biological homology" emphasizes common ancestry through the continuity of genetic information underlying phenotypic traits, and is favored by some developmental geneticists. A third kind of homology, deep homology, was recently defined as "the sharing of the genetic regulatory apparatus used to build morphologically and phylogenetically disparate features." Here we explain the commonality among these three versions of homology. We argue that biological homology, as evidenced by a conserved gene regulatory network giving a trait its "essential identity" (a Character Identity Network or "ChIN") must also be a taxic homology. In cases where a phenotypic trait has been modified over the course of evolution such that homology (taxic) is obscured (e.g. jaws are modified gill arches), a shared underlying ChIN provides evidence of this transformation. Deep homologies, where molecular and cellular components of a phenotypic trait precede the trait itself (are phylogenetically deep relative to the trait), are also taxic homologies, undisguised. Deep homologies inspire particular interest for understanding the evolutionary assembly of phenotypic traits. Mapping these deeply homologous building blocks on a phylogeny reveals the sequential steps leading to the origin of phenotypic novelties. Finally, we discuss how new genomic technologies will revolutionize the comparative genomic study of non-model organisms in a phylogenetic context, necessary to understand the evolution of phenotypic traits.

  4. ATM release at resected double-strand breaks provides heterochromatin reconstitution to facilitate homologous recombination.

    Directory of Open Access Journals (Sweden)

    Verena Geuting

    Full Text Available Non-homologous end-joining (NHEJ and homologous recombination (HR represent the two main pathways for repairing DNA double-strand breaks (DSBs. During the G2 phase of the mammalian cell cycle, both processes can operate and chromatin structure is one important factor which determines DSB repair pathway choice. ATM facilitates the repair of heterochromatic DSBs by phosphorylating and inactivating the heterochromatin building factor KAP-1, leading to local chromatin relaxation. Here, we show that ATM accumulation and activity is strongly diminished at DSBs undergoing end-resection during HR. Such DSBs remain unrepaired in cells devoid of the HR factors BRCA2, XRCC3 or RAD51. Strikingly, depletion of KAP-1 or expression of phospho-mimic KAP-1 allows repair of resected DSBs in the absence of BRCA2, XRCC3 or RAD51 by an erroneous PARP-dependent alt-NHEJ process. We suggest that DSBs in heterochromatin elicit initial local heterochromatin relaxation which is reversed during HR due to the release of ATM from resection break ends. The restored heterochromatic structure facilitates HR and prevents usage of error-prone alternative processes.

  5. Homology and K-theory of the Bianchi groups

    CERN Document Server

    Rahm, Alexander D

    2011-01-01

    We reveal a correspondence between the homological torsion of the Bianchi groups and new geometric invariants, which are effectively computable thanks to their action on hyperbolic space. We use it to explicitly compute their integral group homology and equivariant K-homology. By the Baum/Connes conjecture, which holds for the Bianchi groups, we obtain the K-theory of their reduced C\\ast -algebras in terms of isomorphic images of the computed K-homology. We further find an application to Chen/Ruan orbifold cohomology. Nous mettons en \\'evidence une correspondance entre la torsion homologique des groupes de Bianchi et de nouveaux invariants g\\'eom\\'etriques, calculables gr\\^ace \\'a leur action sur l'espace hyperbolique. Nous l'utilisons pour calculer explicitement leur homologie de groupe \\'a coefficients entiers et leur K-homologie \\'equivariante. En cons\\'equence de la conjecture de Baum/Connes, qui est v\\'erifi\\'ee pour ces groupes, nous obtenons la K-th\\'eorie de leurs C\\ast-alg\\'ebres r\\'eduites en termes...

  6. Action of the cork twist on Floer homology

    CERN Document Server

    Akbulut, Selman

    2011-01-01

    We utilize the Ozsvath-Szabo contact invariant to detect the action of involutions on certain homology spheres that are surgeries on symmetric links, generalizing a previous result of Akbulut and Durusoy. Potentially this may be useful to detect different smooth structures on 4-manifolds by cork twisting operation.

  7. Isolation and characterization of an AGAMOUS homolog from Fraxinus pennsylvanica

    Science.gov (United States)

    Ningxia Du; Paula M. Pijut

    2010-01-01

    An AGAMOUS homolog (FpAG) was isolated from green ash (Fraxinus pennsylvanica) using a reverse transcriptase polymerase chain reaction method. Southern blot analysis indicated that FpAG was present as a single-copy sequence in the genome of green ash. RNA accumulated in the reproductive tissues (female...

  8. Disruption of an ADE6 Homolog of Ustilago maydis

    Science.gov (United States)

    Ustilago maydis secretes iron-binding compounds during times of iron depletion. A putative homolog of the Sacharromyces cereviseae ADE6 and Escherichia coli purL genes was identified near a multigenic complex, which contains two genes sid1 and sid2 involved in a siderophore biosynthetic pathway. The...

  9. O-minimal homotopy and generalized (co)homology

    CERN Document Server

    Piȩkosz, Artur

    2008-01-01

    This article gives a version of the homotopy theory (giving also generalized homology and cohomology theories), developed by H. Delfs and M. Knebusch in the semialgebraic case, extended to regular paracompact locally definable spaces and weakly definable spaces over a model R of an o-minimal theory T extending RCF, with some restrictions on T.

  10. Discovery of eight novel divergent homologs expressed in cattle placenta.

    Science.gov (United States)

    Larson, Joshua H; Kumar, Charu G; Everts, Robin E; Green, Cheryl A; Everts-van der Wind, Annelie; Band, Mark R; Lewin, Harris A

    2006-05-16

    Ten divergent homologs were identified using a subtractive bioinformatic analysis of 12,614 cattle placenta expressed sequence tags followed by comparative, evolutionary, and gene expression studies. Among the 10 divergent homologs, 8 have not been identified previously. These were named as follows: cattle cerebrum and skeletal muscle-specific transcript 1 (CSSMST1), cattle intestine-specific transcript 1 (CIST1), hepatitis A virus cellular receptor 1 amino-terminal domain-containing protein (HAVCRNDP), prolactin-related proteins 8, 9, and 11 (PRP8, PRP9, and PRP11, respectively) and secreted and transmembrane protein 1A and 1B (SECTM1A and SECTM1B, respectively). In addition, two previously known divergent genes were identified, trophoblast Kunitz domain protein 1 (TKDP1) and a new splice variant of TKDP4. Nucleotide substitution analysis provided evidence for positive selection in members of the PRP gene family, SECTM1A and SECTM1B. Gene expression profiles, motif predictions, and annotations of homologous sequences indicate immunological and reproductive functions of the divergent homologs. The genes identified in this study are thus of evolutionary and physiological importance and may have a role in placental adaptations.

  11. Non-homologous end joining: emerging themes and unanswered questions

    OpenAIRE

    Radhakrishnan, Sarvan Kumar; Jette, Nicholas; Lees-Miller, Susan P.

    2014-01-01

    Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing radiation induced DNA double strand breaks in human cells. Here, we discuss current insights into the mechanism of NHEJ and the interplay between NHEJ and other pathways for repair of IR-induced DNA damage.

  12. Monitoring homologous recombination in rice (Oryza sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Yang Zhuanying; Tang Li [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China); Li Meiru [South China Botanic Garden, Chinese Academy of Sciences, Guangzhou 510650 (China); Chen Lei; Xu Jie [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China); Wu Goujiang [South China Botanic Garden, Chinese Academy of Sciences, Guangzhou 510650 (China); Li Hongqing, E-mail: hqli@scnu.edu.cn [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China)

    2010-09-10

    Here we describe a system to assay homologous recombination during the complete life cycle of rice (Oryza sativa L.). Rice plants were transformed with two copies of non-functional GUS reporter overlap fragments as recombination substrate. Recombination was observed in all plant organs examined, from the seed stage until the flowering stage of somatic plant development. Embryogenic cells exhibited the highest recombination ability with an average of 3 x 10{sup -5} recombination events per genome, which is about 10-fold of that observed in root cells, and two orders of that observed in leaf cells. Histological analysis revealed that recombination events occurred in diverse cell types, but preferentially in cells with small size. Examples of this included embryogenic cells in callus, phloem cells in the leaf vein, and cells located in the root apical meristem. Steady state RNA analysis revealed that the expression levels of rice Rad51 homologs are positively correlated with increased recombination rates in embryogenic calli, roots and anthers. Finally, radiation treatment of plantlets from distinct recombination lines increased the recombination frequency to different extents. These results showed that homologous recombination frequency can be effectively measured in rice using a transgene reporter assay. This system will facilitate the study of DNA damage signaling and homologous recombination in rice, a model monocot.

  13. Real bundle gerbes, orientifolds and twisted KR-homology

    CERN Document Server

    Hekmati, Pedram; Szabo, Richard J; Vozzo, Raymond F

    2016-01-01

    We introduce a notion of Real bundle gerbes on manifolds equipped with an involution. We elucidate their relation to Jandl gerbes and prove that they are classified by their Real Dixmier-Douady class in Grothendieck's equivariant sheaf cohomology. We show that the Grothendieck group of Real bundle gerbe modules is isomorphic to twisted KR-theory for a torsion Real Dixmier-Douady class. Building on the Baum-Douglas model for K-homology and the orientifold construction in string theory, we introduce geometric cycles for twisted KR-homology groups using Real bundle gerbe modules. We prove that this defines a real-oriented generalised homology theory dual to twisted KR-theory for Real closed manifolds, and more generally for Real finite CW-complexes, for any Real Dixmier-Douady class. This is achieved by defining an explicit natural transformation to analytic twisted KR-homology and proving that it is an isomorphism. Our constructions give a new framework for the classification of orientifolds in string theory, p...

  14. Characterization and expression pattern of the novel MIA homolog TANGO.

    Science.gov (United States)

    Bosserhoff, A K; Moser, M; Buettner, R

    2004-07-01

    A novel human gene, TANGO, encoding a MIA ('melanoma inhibitory activity') homologous protein was identified by a gene bank search. TANGO, together with the homologous genes MIA, OTOR (FPD, MIAL) and MIA2 define a novel gene family sharing important structural features, significant homology at both the nucleotide and protein level, and similar genomic organization. The four members share 34-45% amino acid identity and 47-59% cDNA sequence identity. TANGO encodes a mature protein of 103 amino acids in addition to a hydrophobic secretory signal sequence. Sequence homology confirms the highly conserved SH3 structure present also in MIA, OTOR and MIA2. Thus, it appears that there are a number of extracellular proteins with SH3-fold like structures. Interestingly, in situ hybridization, RT-PCR and Northern Blots revealed very broad TANGO expression patterns in contrast to the highly restricted expression patterns previously determined for the other members of the MIA gene family. The only cells lacking TANGO expression are cells belonging to the hematopoetic system. High levels of TANGO expression were observed both during embryogenesis and in adult tissues.

  15. Annotating Simplices with a Homology Basis and Its Applications

    CERN Document Server

    Busaryev, Oleksiy; Chen, Chao; Dey, Tamal K; Wang, Yusu

    2011-01-01

    Let $K$ be a simplicial complex and $g$ the rank of its $p$-th homology group $H_p(K)$ defined with $Z_2$ coefficients. We show that we can compute a basis $H$ of $H_p(K)$ and annotate each $p$-simplex of $K$ with a binary vector of length $g$ with the following property: the annotations, summed over all $p$-simplices in any $p$-cycle $z$, provide the coordinate vector of the homology class $[z]$ in the basis $H$. The basis and the annotations for all simplices can be computed in $O(n^{\\omega})$ time, where $n$ is the size of $K$ and $\\omega<2.376$ is a quantity so that two $n\\times n$ matrices can be multiplied in $O(n^{\\omega})$ time. The pre-computation of annotations permits answering queries about the independence or the triviality of $p$-cycles efficiently. Using annotations of edges in 2-complexes, we derive better algorithms for computing optimal basis and optimal homologous cycles in 1-dimensional homology. Specifically, for computing an optimal basis of $H_1(K)$, we improve the time complexity kn...

  16. Homology of classical groups and K-theory

    NARCIS (Netherlands)

    Mirzaii, B.

    2004-01-01

    The study of the homology groups of classical group over a ring R with coefficient A, where A is a commutative ring with trivial group action, seems important, notably because of their close relation to algebraic and Hermitian Ktheory and their appearance in the study of scissors congruence of polyh

  17. Protein homology reveals new targets for bioactive small molecules.

    Science.gov (United States)

    Gfeller, David; Zoete, Vincent

    2015-08-15

    The functional impact of small molecules is increasingly being assessed in different eukaryotic species through large-scale phenotypic screening initiatives. Identifying the targets of these molecules is crucial to mechanistically understand their function and uncover new therapeutically relevant modes of action. However, despite extensive work carried out in model organisms and human, it is still unclear to what extent one can use information obtained in one species to make predictions in other species. Here, for the first time, we explore and validate at a large scale the use of protein homology relationships to predict the targets of small molecules across different species. Our results show that exploiting target homology can significantly improve the predictions, especially for molecules experimentally tested in other species. Interestingly, when considering separately orthology and paralogy relationships, we observe that mapping small molecule interactions among orthologs improves prediction accuracy, while including paralogs does not improve and even sometimes worsens the prediction accuracy. Overall, our results provide a novel approach to integrate chemical screening results across multiple species and highlight the promises and remaining challenges of using protein homology for small molecule target identification. Homology-based predictions can be tested on our website http://www.swisstargetprediction.ch. david.gfeller@unil.ch or vincent.zoete@isb-sib.ch. Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Using intron position conservation for homology-based gene prediction.

    Science.gov (United States)

    Keilwagen, Jens; Wenk, Michael; Erickson, Jessica L; Schattat, Martin H; Grau, Jan; Hartung, Frank

    2016-05-19

    Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest.Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the-art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well.Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Homology of the open moduli space of curves

    DEFF Research Database (Denmark)

    Madsen, Ib Henning

    2012-01-01

    This is a survey on the proof of a generalized version of the Mumford conjecture obtained in joint work with M. Weiss stating that a certain map between some classifying spaces which a priori have different natures induces an isomorphism at the level of integral homology. We also discuss our proof...

  20. A homology theory for étale groupoids

    NARCIS (Netherlands)

    Crainic, M.; Moerdijk, I.

    1998-01-01

    Etale groupoids arise naturally as models for leaf spaces of foliations for orbifolds and for orbit spaces of discrete group actions In this paper we introduce a sheaf homology theory for etale groupoids We prove its invariance under Morita equivalence as well as Verdier duality between Haeiger

  1. Homology of classical groups and K-theory

    NARCIS (Netherlands)

    Mirzaii, B.

    2004-01-01

    The study of the homology groups of classical group over a ring R with coefficient A, where A is a commutative ring with trivial group action, seems important, notably because of their close relation to algebraic and Hermitian Ktheory and their appearance in the study of scissors congruence of

  2. Multiresolution persistent homology for excessively large biomolecular datasets

    Science.gov (United States)

    Xia, Kelin; Zhao, Zhixiong; Wei, Guo-Wei

    2015-01-01

    Although persistent homology has emerged as a promising tool for the topological simplification of complex data, it is computationally intractable for large datasets. We introduce multiresolution persistent homology to handle excessively large datasets. We match the resolution with the scale of interest so as to represent large scale datasets with appropriate resolution. We utilize flexibility-rigidity index to access the topological connectivity of the data set and define a rigidity density for the filtration analysis. By appropriately tuning the resolution of the rigidity density, we are able to focus the topological lens on the scale of interest. The proposed multiresolution topological analysis is validated by a hexagonal fractal image which has three distinct scales. We further demonstrate the proposed method for extracting topological fingerprints from DNA molecules. In particular, the topological persistence of a virus capsid with 273 780 atoms is successfully analyzed which would otherwise be inaccessible to the normal point cloud method and unreliable by using coarse-grained multiscale persistent homology. The proposed method has also been successfully applied to the protein domain classification, which is the first time that persistent homology is used for practical protein domain analysis, to our knowledge. The proposed multiresolution topological method has potential applications in arbitrary data sets, such as social networks, biological networks, and graphs. PMID:26450288

  3. Reducing dimensionality in remote homology detection using predicted contact maps.

    Science.gov (United States)

    Bedoya, Oscar; Tischer, Irene

    2015-04-01

    In this paper, a new method for remote protein homology detection is presented. Most discriminative methods concatenate the values extracted from physicochemical properties to build a model that separates homolog and non-homolog examples. Each discriminative method uses a specific strategy to represent the information extracted from the protein sequence and a different number of indices. After the vector representation is achieved, support vector machines (SVM) are usually used. Most classification techniques are not suitable in remote homology detection because they do not address high dimensional datasets. In this paper, we propose a method that reduces the high dimensionality of the vector representation using models that are defined at the 3D level. Next, the models are mapped from the protein primary sequence. The new method, called remote-C3D, is presented and tested on the SCOP 1.53 and SCOP 1.55 datasets. The remote-C3D method achieves a higher accuracy than the composition-based methods and a comparable performance with profile-based methods. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Homology modeling: an important tool for the drug discovery.

    Science.gov (United States)

    França, Tanos Celmar Costa

    2015-01-01

    In the last decades, homology modeling has become a popular tool to access theoretical three-dimensional (3D) structures of molecular targets. So far several 3D models of proteins have been built by this technique and used in a great diversity of structural biology studies. But are those models consistent enough with experimental structures to make this technique an effective and reliable tool for drug discovery? Here we present, briefly, the fundamentals and current state-of-the-art of the homology modeling techniques used to build 3D structures of molecular targets, which experimental structures are not available in databases, and list some of the more important works, using this technique, available in literature today. In many cases those studies have afforded successful models for the drug design of more selective agonists/antagonists to the molecular targets in focus and guided promising experimental works, proving that, when the appropriate templates are available, useful models can be built using some of the several software available today for this purpose. Limitations of the experimental techniques used to solve 3D structures allied to constant improvements in the homology modeling software will maintain the need for theoretical models, establishing the homology modeling as a fundamental tool for the drug discovery.

  5. Multiresolution persistent homology for excessively large biomolecular datasets

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Kelin; Zhao, Zhixiong [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Wei, Guo-Wei, E-mail: wei@math.msu.edu [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824 (United States)

    2015-10-07

    Although persistent homology has emerged as a promising tool for the topological simplification of complex data, it is computationally intractable for large datasets. We introduce multiresolution persistent homology to handle excessively large datasets. We match the resolution with the scale of interest so as to represent large scale datasets with appropriate resolution. We utilize flexibility-rigidity index to access the topological connectivity of the data set and define a rigidity density for the filtration analysis. By appropriately tuning the resolution of the rigidity density, we are able to focus the topological lens on the scale of interest. The proposed multiresolution topological analysis is validated by a hexagonal fractal image which has three distinct scales. We further demonstrate the proposed method for extracting topological fingerprints from DNA molecules. In particular, the topological persistence of a virus capsid with 273 780 atoms is successfully analyzed which would otherwise be inaccessible to the normal point cloud method and unreliable by using coarse-grained multiscale persistent homology. The proposed method has also been successfully applied to the protein domain classification, which is the first time that persistent homology is used for practical protein domain analysis, to our knowledge. The proposed multiresolution topological method has potential applications in arbitrary data sets, such as social networks, biological networks, and graphs.

  6. Homology and the optimization of DNA sequence data

    Science.gov (United States)

    Wheeler, W.

    2001-01-01

    Three methods of nucleotide character analysis are discussed. Their implications for molecular sequence homology and phylogenetic analysis are compared. The criterion of inter-data set congruence, both character based and topological, are applied to two data sets to elucidate and potentially discriminate among these parsimony-based ideas. c2001 The Willi Hennig Society.

  7. Homolog-specific PCR primer design for profiling splice variants.

    Science.gov (United States)

    Srivastava, Gyan Prakash; Hanumappa, Mamatha; Kushwaha, Garima; Nguyen, Henry T; Xu, Dong

    2011-05-01

    To study functional diversity of proteins encoded from a single gene, it is important to distinguish the expression levels among the alternatively spliced variants. A variant-specific primer pair is required to amplify each alternatively spliced variant individually. For this purpose, we developed a new feature, homolog-specific primer design (HSPD), in our high-throughput primer and probe design software tool, PRIMEGENS-v2. The algorithm uses a de novo approach to design primers without any prior information of splice variants or close homologs for an input query sequence. It not only designs primer pairs but also finds potential isoforms and homologs of the input sequence. Efficiency of this algorithm was tested for several gene families in soybean. A total of 187 primer pairs were tested under five different abiotic stress conditions with three replications at three time points. Results indicate a high success rate of primer design. Some primer pairs designed were able to amplify all splice variants of a gene. Furthermore, by utilizing combinations within the same multiplex pool, we were able to uniquely amplify a specific variant or duplicate gene. Our method can also be used to design PCR primers to specifically amplify homologs in the same gene family. PRIMEGENS-v2 is available at: http://primegens.org.

  8. K-homology and index theory on contact manifolds

    CERN Document Server

    Baum, Paul F

    2011-01-01

    Let X be a closed connected contact manifold. On X there is a naturally arising class of hypoelliptic (but not elliptic) operators which are Fredholm. In this paper we solve the index problem for this class of operators. The solution is achieved by combining Van Erp's earlier partial result with the Baum-Douglas isomorphism of analytic and geometric K-homology.

  9. Illustrating and homology modeling the proteins of the Zika virus

    Science.gov (United States)

    Ekins, Sean; Liebler, John; Neves, Bruno J.; Lewis, Warren G.; Coffee, Megan; Bienstock, Rachelle; Southan, Christopher; Andrade, Carolina H.

    2016-01-01

    The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening. PMID:27746901

  10. Single-stranded heteroduplex intermediates in λ Red homologous recombination

    Directory of Open Access Journals (Sweden)

    Zhang Youming

    2010-07-01

    Full Text Available Abstract Background The Red proteins of lambda phage mediate probably the simplest and most efficient homologous recombination reactions yet described. However the mechanism of dsDNA recombination remains undefined. Results Here we show that the Red proteins can act via full length single stranded intermediates to establish single stranded heteroduplexes at the replication fork. We created asymmetrically digestible dsDNA substrates by exploiting the fact that Redα exonuclease activity requires a 5' phosphorylated end, or is blocked by phosphothioates. Using these substrates, we found that the most efficient configuration for dsDNA recombination occurred when the strand that can prime Okazaki-like synthesis contained both homology regions on the same ssDNA molecule. Furthermore, we show that Red recombination requires replication of the target molecule. Conclusions Hence we propose a new model for dsDNA recombination, termed 'beta' recombination, based on the formation of ssDNA heteroduplexes at the replication fork. Implications of the model were tested using (i an in situ assay for recombination, which showed that recombination generated mixed wild type and recombinant colonies; and (ii the predicted asymmetries of the homology arms, which showed that recombination is more sensitive to non-homologies attached to 5' than 3' ends. Whereas beta recombination can generate deletions in target BACs of at least 50 kb at about the same efficiency as small deletions, the converse event of insertion is very sensitive to increasing size. Insertions up to 3 kb are most efficiently achieved using beta recombination, however at greater sizes, an alternative Red-mediated mechanism(s appears to be equally efficient. These findings define a new intermediate in homologous recombination, which also has practical implications for recombineering with the Red proteins.

  11. Remote homology and the functions of metagenomic dark matter

    Directory of Open Access Journals (Sweden)

    Briallen eLobb

    2015-07-01

    Full Text Available Predicted open reading frames (ORFs that lack detectable homology to known proteins are termed ORFans. Despite their prevalence in metagenomes, the extent to which ORFans encode real proteins, the degree to which they can be annotated, and their functional contributions, remain unclear. To gain insights into these questions, we applied sensitive remote-homology detection methods to functionally analyze ORFans from soil, marine, and human gut metagenome collections. ORFans were identified, clustered into sequence families, and annotated through profile-profile comparison to proteins of known structure.We found that a considerable number of metagenomic ORFans (73,896 of 484,121, 15.3% exhibit significant remote homology to structurally characterized proteins, providing a means for ORFan functional profiling. The extent of detected remote homology significantly exceeds that obtained for artificial protein families (1.4%. In addition, predicted ORFan functions show significant functional consistency with their gene neighbors (p < 0.001 as expected for real genes. Compared to genes annotated through standard homology searches, ORFans have intriguing functional differences such as an enrichment of virus-related functions and biological processes associated with extreme sequence diversity. Each environment also possesses many unique ORFan families that likely play important community roles such as identified ORFan polysaccharide degradation genes unique to the human gut metagenome. Lastly, ORFans are a valuable resource for finding novel enzymes of interest, as we demonstrate by identifying hundreds of ORFan metalloproteases that conserve a catalytic site despite a lack of overall sequence similarity to known proteins. Our ORFan functional predictions are a valuable resource for discovering novel protein families and exploring the boundaries of protein sequence space. Our resource of annotated metagenomic ORFans is available at http://doxey.uwaterloo.ca.

  12. Illustrating and homology modeling the proteins of the Zika virus.

    Science.gov (United States)

    Ekins, Sean; Liebler, John; Neves, Bruno J; Lewis, Warren G; Coffee, Megan; Bienstock, Rachelle; Southan, Christopher; Andrade, Carolina H

    2016-01-01

    The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening.

  13. Khovanov-Rozansky homology via Cohen-Macaulay approximations and Soergel bimodules

    CERN Document Server

    Becker, Hanno

    2011-01-01

    This is the author's diploma thesis. We describe a simplification in the construction of Khovanov-Rozansky's categorification of quantum sl(n) link homology using the theory of maximal Cohen-Macaulay modules over hypersurface singularities and the combinatorics of Soergel bimodules. More precisely, we show that the matrix factorizations associated to basic MOY-graphs equal Cohen-Macaulay approximations of certain Soergel bimodules, and prove that taking Cohen-Macaulay approximation commutes with tensor products as long as the MOY-graph under consideration does not possess oriented cycles. It follows that the matrix factorization associated to a MOY-braid equals the Cohen-Macaulay approximation of the Soergel bimodule corresponding to the endofunctor on BGG-category O associated to the braid by Mazorchuk and Stroppel. This reduces certain computations in the category of matrix factorizations to known combinatorics of the Hecke-algebra. Finally, we describe braid closure as some kind of Hochschild cohomology an...

  14. The Transcriptional Coregulator LEUNIG_HOMOLOG Inhibits Light-Dependent Seed Germination in Arabidopsis.

    Science.gov (United States)

    Lee, Nayoung; Park, Jeongmoo; Kim, Keunhwa; Choi, Giltsu

    2015-08-01

    PHYTOCHROME-INTERACTING FACTOR1 (PIF1) is a basic helix-loop-helix transcription factor that inhibits light-dependent seed germination in Arabidopsis thaliana. However, it remains unclear whether PIF1 requires other factors to regulate its direct targets. Here, we demonstrate that LEUNIG_HOMOLOG (LUH), a Groucho family transcriptional corepressor, binds to PIF1 and coregulates its targets. Not only are the transcriptional profiles of the luh and pif1 mutants remarkably similar, more than 80% of the seeds of both genotypes germinate in the dark. We show by chromatin immunoprecipitation that LUH binds a subset of PIF1 targets in a partially PIF1-dependent manner. Unexpectedly, we found LUH binds and coregulates not only PIF1-activated targets but also PIF1-repressed targets. Together, our results indicate LUH functions with PIF1 as a transcriptional coregulator to inhibit seed germination.

  15. Alleles of the homologous recombination gene, RAD59, identify multiple responses to disrupted DNA replication in Saccharomyces cerevisiae.

    Science.gov (United States)

    Liddell, Lauren C; Manthey, Glenn M; Owens, Shannon N; Fu, Becky X H; Bailis, Adam M

    2013-10-14

    of Rad52 with double-strand breaks, suggesting that this may be essential for rescuing replication lesions in rad27 mutant cells. The rad59-K174A and rad59-F180A alleles may fractionally reduce this same function, which proportionally reduced repair of replication lesions by homologous recombination and growth rate. In contrast, rad59-Y92A stimulates homologous recombination, perhaps by affecting association of replication lesions with the Rad51 recombinase. This suggests that Rad59 influences the rescue of replication lesions by multiple recombination factors.

  16. Meiotic crossover control by concerted action of Rad51-Dmc1 in homolog template bias and robust homeostatic regulation.

    Directory of Open Access Journals (Sweden)

    Jessica P Lao

    Full Text Available During meiosis, repair of programmed DNA double-strand breaks (DSBs by recombination promotes pairing of homologous chromosomes and their connection by crossovers. Two DNA strand-exchange proteins, Rad51 and Dmc1, are required for meiotic recombination in many organisms. Studies in budding yeast imply that Rad51 acts to regulate Dmc1's strand exchange activity, while its own exchange activity is inhibited. However, in a dmc1 mutant, elimination of inhibitory factor, Hed1, activates Rad51's strand exchange activity and results in high levels of recombination without participation of Dmc1. Here we show that Rad51-mediated meiotic recombination is not subject to regulatory processes associated with high-fidelity chromosome segregation. These include homolog bias, a process that directs strand exchange between homologs rather than sister chromatids. Furthermore, activation of Rad51 does not effectively substitute for Dmc1's chromosome pairing activity, nor does it ensure formation of the obligate crossovers required for accurate homolog segregation. We further show that Dmc1's dominance in promoting strand exchange between homologs involves repression of Rad51's strand-exchange activity. This function of Dmc1 is independent of Hed1, but requires the meiotic kinase, Mek1. Hed1 makes a relatively minor contribution to homolog bias, but nonetheless this is important for normal morphogenesis of synaptonemal complexes and efficient crossing-over especially when DSB numbers are decreased. Super-resolution microscopy shows that Dmc1 also acts to organize discrete complexes of a Mek1 partner protein, Red1, into clusters along lateral elements of synaptonemal complexes; this activity may also contribute to homolog bias. Finally, we show that when interhomolog bias is defective, recombination is buffered by two feedback processes, one that increases the fraction of events that yields crossovers, and a second that we propose involves additional DSB formation

  17. Monitoring homology search during DNA double-strand break repair in vivo.

    Science.gov (United States)

    Renkawitz, Jörg; Lademann, Claudio A; Kalocsay, Marian; Jentsch, Stefan

    2013-04-25

    Homologous recombination (HR) is crucial for genetic exchange and accurate repair of DNA double-strand breaks and is pivotal for genome integrity. HR uses homologous sequences for repair, but how homology search, the exploration of the genome for homologous DNA sequences, is conducted in the nucleus remains poorly understood. Here, we use time-resolved chromatin immunoprecipitations of repair proteins to monitor homology search in vivo. We found that homology search proceeds by a probing mechanism, which commences around the break and samples preferentially on the broken chromosome. However, elements thought to instruct chromosome loops mediate homology search shortcuts, and centromeres, which cluster within the nucleus, may facilitate homology search on other chromosomes. Our study thus reveals crucial parameters for homology search in vivo and emphasizes the importance of linear distance, chromosome architecture, and proximity for recombination efficiency. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. A HOMOLOGOUS GENE-REPORTER SYSTEM FOR THE BASIDIOMYCETE SCHIZOPHYLLUM-COMMUNE BASED ON INTERNALLY DELETED HOMOLOGOUS GENES

    NARCIS (Netherlands)

    SCHUREN, FHJ; HARMSEN, MC; WESSELS, JGH

    Problems encountered in our attempts to achieve expression of heterologous genes, driven by ascomycetous regulatory sequences, in homobasidiomycetes led us to develop a gene-reporter system based on the expression of homologous genes in Schizophyllum commune. Internal deletions were made in the

  19. COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.

    Science.gov (United States)

    Lemmens, Bennie B L G; Johnson, Nicholas M; Tijsterman, Marcel

    2013-01-01

    Successful completion of meiosis requires the induction and faithful repair of DNA double-strand breaks (DSBs). DSBs can be repaired via homologous recombination (HR) or non-homologous end joining (NHEJ), yet only repair via HR can generate the interhomolog crossovers (COs) needed for meiotic chromosome segregation. Here we identify COM-1, the homolog of CtIP/Sae2/Ctp1, as a crucial regulator of DSB repair pathway choice during Caenorhabditis elegans gametogenesis. COM-1-deficient germ cells repair meiotic DSBs via the error-prone pathway NHEJ, resulting in a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. In contrast to its yeast counterparts, COM-1 is not required for Spo11 removal and initiation of meiotic DSB repair, but instead promotes meiotic recombination by counteracting the NHEJ complex Ku. In fact, animals defective for both COM-1 and Ku are viable and proficient in CO formation. Further genetic dissection revealed that COM-1 acts parallel to the nuclease EXO-1 to promote interhomolog HR at early pachytene stage of meiotic prophase and thereby safeguards timely CO formation. Both of these nucleases, however, are dispensable for RAD-51 recruitment at late pachytene stage, when homolog-independent repair pathways predominate, suggesting further redundancy and/or temporal regulation of DNA end resection during meiotic prophase. Collectively, our results uncover the potentially lethal properties of NHEJ during meiosis and identify a critical role for COM-1 in NHEJ inhibition and CO assurance in germ cells.

  20. COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.

    Directory of Open Access Journals (Sweden)

    Bennie B L G Lemmens

    Full Text Available Successful completion of meiosis requires the induction and faithful repair of DNA double-strand breaks (DSBs. DSBs can be repaired via homologous recombination (HR or non-homologous end joining (NHEJ, yet only repair via HR can generate the interhomolog crossovers (COs needed for meiotic chromosome segregation. Here we identify COM-1, the homolog of CtIP/Sae2/Ctp1, as a crucial regulator of DSB repair pathway choice during Caenorhabditis elegans gametogenesis. COM-1-deficient germ cells repair meiotic DSBs via the error-prone pathway NHEJ, resulting in a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. In contrast to its yeast counterparts, COM-1 is not required for Spo11 removal and initiation of meiotic DSB repair, but instead promotes meiotic recombination by counteracting the NHEJ complex Ku. In fact, animals defective for both COM-1 and Ku are viable and proficient in CO formation. Further genetic dissection revealed that COM-1 acts parallel to the nuclease EXO-1 to promote interhomolog HR at early pachytene stage of meiotic prophase and thereby safeguards timely CO formation. Both of these nucleases, however, are dispensable for RAD-51 recruitment at late pachytene stage, when homolog-independent repair pathways predominate, suggesting further redundancy and/or temporal regulation of DNA end resection during meiotic prophase. Collectively, our results uncover the potentially lethal properties of NHEJ during meiosis and identify a critical role for COM-1 in NHEJ inhibition and CO assurance in germ cells.

  1. [Rule of homology and morbid anatomy (author's transl)].

    Science.gov (United States)

    Doerr, W

    1979-07-27

    1. According to J.W. Goethe, morphology is a theory of evolution, H. Braus defined it as a theory of historic incidents, and according to D. Starck morphology is the role of shapes of the organisms. 2. The term homology was coined by morphologic researchers. Of course, it is used nowadays also in mathematics, chemistry, and linguistics and other logic matters. 3. Homologies have a special position in Goethe's work on the theory of types. Goethe's morphologic research and Schiller's aesthetic speculations are considered to be the origin of a 'typologic point of view.' 4. Coherences of Platon's theory of ideas and Goethe's theory of types are scrutinized. The theory of shapes ('Gestalt theory') is inconceivable without Platon's theory, and scientic morphology is inconceivable without shapes, either, and according to C. v. Ehrenfels "Gestaltphilosophie" could not exist without the shapes of Platon's theory. 5. It is shown that without Gestalt philosophy one cannot comprehend the following coherences: Gestalt (shape) as an idea, idea as a type of Goethe's rule, type as an element of the theory of homologies and even of constitution. 6. Homology will be constituted using certain criterions: a) detection of an equal descent, b) equal position of organismic structures in individuals, c) evidence of interpositions, and d) certain qualities of parts which are compared with each other. Homologous structures may be dissimilar in their architecture. 7. The term homology is explained a) by giving an analysis of morphologic and teratologic lines, b) by scrutinizing froms of symmetry, and c) by presenting the histopathology of topographical diverse but according to the morphogenetic mode coinciding tumours which are resembling each other in their microscopic patterns. 8. The application of the rule of homology in the morphologic investigation of diseases proves to be a) valuable from a heuristic point of view, b) an instrument of communication to characterize comparable matters

  2. Identification of genes that promote or antagonize somatic homolog pairing using a high-throughput FISH-based screen.

    Directory of Open Access Journals (Sweden)

    Eric F Joyce

    Full Text Available The pairing of homologous chromosomes is a fundamental feature of the meiotic cell. In addition, a number of species exhibit homolog pairing in nonmeiotic, somatic cells as well, with evidence for its impact on both gene regulation and double-strand break (DSB repair. An extreme example of somatic pairing can be observed in Drosophila melanogaster, where homologous chromosomes remain aligned throughout most of development. However, our understanding of the mechanism of somatic homolog pairing remains unclear, as only a few genes have been implicated in this process. In this study, we introduce a novel high-throughput fluorescent in situ hybridization (FISH technology that enabled us to conduct a genome-wide RNAi screen for factors involved in the robust somatic pairing observed in Drosophila. We identified both candidate "pairing promoting genes" and candidate "anti-pairing genes," providing evidence that pairing is a dynamic process that can be both enhanced and antagonized. Many of the genes found to be important for promoting pairing are highly enriched for functions associated with mitotic cell division, suggesting a genetic framework for a long-standing link between chromosome dynamics during mitosis and nuclear organization during interphase. In contrast, several of the candidate anti-pairing genes have known interphase functions associated with S-phase progression, DNA replication, and chromatin compaction, including several components of the condensin II complex. In combination with a variety of secondary assays, these results provide insights into the mechanism and dynamics of somatic pairing.

  3. Transcriptional coactivator CIITA, a functional homolog of TAF1, has kinase activity.

    Science.gov (United States)

    Soe, Katherine C; Devaiah, Ballachanda N; Singer, Dinah S

    2013-11-01

    The Major Histocompatibility Complex (MHC) class II transactivator (CIITA) mediates activated immune responses and its deficiency results in the Type II Bare Lymphocyte Syndrome. CIITA is a transcriptional co-activator that regulates γ-interferon-activated transcription of MHC class I and class II genes. It is also a functional homolog of TAF1, a component of the general transcription factor complex TFIID. TAF1 and CIITA both possess intrinsic acetyltransferase (AT) activity that is required for transcription initiation. In response to induction by γ-interferon, CIITA and it's AT activity bypass the requirement for TAF1 AT activity. TAF1 also has kinase activity that is essential for its function. However, no similar activity has been identified for CIITA thus far. Here we report that CIITA, like TAF1, is a serine-threonine kinase. Its substrate specificity parallels, but does not duplicate, that of TAF1 in phosphorylating the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF and histone H2B. Like TAF1, CIITA autophosphorylates, affecting its interaction with TAF7. Additionally, CIITA phosphorylates histone H2B at Ser36, a target of TAF1 that is required for transcription during cell cycle progression and stress response. However, unlike TAF1, CIITA also phosphorylates all the other histones. The identification of this novel kinase activity of CIITA further clarifies its role as a functional homolog of TAF1 which may operate during stress and γ-IFN activated MHC gene transcription.

  4. Hochschild homology, global dimension, and truncated oriented cycles

    CERN Document Server

    Han, Yang

    2010-01-01

    It is shown that a bounded quiver algebra having a 2-truncated oriented cycle is of infinite Hochschild homology dimension and global dimension, which generalizes a result of Solotar and Vigu\\'{e}-Poirrier to nonlocal ungraded algebras having a 2-truncated oriented cycle of arbitrary length. Therefore, a bounded quiver algebra of finite global dimension has no 2-truncated oriented cycles. Note that the well-known "no loops conjecture", which has been proved to be true already, says that a bounded quiver algebra of finite global dimension has no loops, i.e., truncated oriented cycles of length 1. Moreover, it is shown that a monomial algebra having a truncated oriented cycle is of infinite Hochschild homology dimension and global dimension. Consequently, a monomial algebra of finite global dimension has no truncated oriented cycles.

  5. Homology and isomorphism: Bourdieu in conversation with New Institutionalism.

    Science.gov (United States)

    Wang, Yingyao

    2016-06-01

    Bourdieusian Field Theory (BFT) provided decisive inspiration for the early conceptual formulation of New Institutionalism (NI). This paper attempts to reinvigorate the stalled intellectual dialogue between NI and BFT by comparing NI's concept of isomorphism with BFT's notion of homology. I argue that Bourdieu's understanding of domination-oriented social action, transposable habitus, and a non-linear causality, embodied in his neglected concept of homology, provides an alternative theorization of field-level convergence to New Institutionalism's central idea of institutional isomorphism. To showcase how BFT can be useful for organizational research, I postulate a habitus-informed and field-conditioned theory of transference to enrich NI's spin-off thesis of 'diffusion'. I propose that while NI can benefit from BFT's potential of bringing social structure back into organizational research, BFT can enrich its social analysis by borrowing from NI's elaboration of the symbolic system of organizations.

  6. Molecular evolution of a Drosophila homolog of human BRCA2.

    Science.gov (United States)

    Bennett, Sarah M; Noor, Mohamed A F

    2009-11-01

    The human cancer susceptibility gene, BRCA2, functions in double-strand break repair by homologous recombination, and it appears to function via interaction of a repetitive region ("BRC repeats") with RAD-51. A putatively simpler homolog, dmbrca2, was identified in Drosophila melanogaster recently and also affects mitotic and meiotic double-strand break repair. In this study, we examined patterns of repeat variation both within Drosophila pseudoobscura and among available Drosophila genome sequences. We identified extensive variation within and among closely related Drosophila species in BRC repeat number, to the extent that variation within this genus recapitulates the extent of variation found across the entire animal kingdom. We describe patterns of evolution across species by documenting recent repeat expansions (sometimes in tandem arrays) and homogenizations within available genome sequences. Overall, we have documented patterns and modes of evolution in a new model system of a gene which is important to human health.

  7. Botulinum neurotoxin homologs in non-Clostridium species.

    Science.gov (United States)

    Mansfield, Michael J; Adams, Jeremy B; Doxey, Andrew C

    2015-01-30

    Clostridial neurotoxins (CNTs) are the deadliest toxins known and the causative agents of botulism and tetanus. Despite their structural and functional complexity, no CNT homologs are currently known outside Clostridium. Here, we report the first homologs of Clostridium CNTs within the genome of the rice fermentation organism Weissella oryzae SG25. One gene in W. oryzae S25 encodes a protein with a four-domain architecture and HExxH protease motif common to botulinum neurotoxins (BoNTs). An adjacent gene with partial similarity to CNTs is also present, and both genes seem to have been laterally transferred into the W. oryzae genome from an unknown source. Identification of mobile, CNT-related genes outside of Clostridium has implications for our understanding of the evolution of this important toxin family. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Phenylbutyrate inhibits homologous recombination induced by camptothecin and methyl methanesulfonate

    DEFF Research Database (Denmark)

    Kaiser, Gitte Schalck; Germann, Susanne Manuela; Westergaard, Tine

    2011-01-01

    (CPT) and the alkylating agent methyl methanesulfonate (MMS) is blocked by sodium phenylbutyrate (PBA) in the budding yeast Saccharomyces cerevisiae. In particular, PBA suppresses CPT- and MMS-induced genetic recombination as well as DNA double-strand break repair during mating-type interconversion....... Treatment with PBA is accompanied by a dramatic reduction in histone H4 lysine 8 acetylation. Live cell imaging of homologous recombination proteins indicates that repair of CPT-induced DNA damage is redirected to a non-recombinogenic pathway in the presence of PBA without loss in cell viability......Homologous recombination is accompanied by extensive changes to chromatin organization at the site of DNA damage. Some of these changes are mediated through acetylation/deacetylation of histones. Here, we show that recombinational repair of DNA damage induced by the anti-cancer drug camptothecin...

  9. Homology Parameters for Large Axisymmetric Shaped Dual-Reflector Antennas

    Science.gov (United States)

    Ban, You; Duan, Baoyan; Wang, Congsi; Wang, Wei; Feng, Shufei; Xiang, Binbin

    2017-05-01

    We extend the concept of best-fitting paraboloids for large single and dual reflectors with conic-section surfaces to best-fit shaped surface for large dual reflectors shaped for uniform amplitude distribution. The point focus of the paraboloidal main reflector is replaced by focal lines for the main reflector and the primary subreflector focus, whereas the secondary subreflector point focus at the feed is kept. The reflector surfaces are shaped, and all rays from the main-reflector aperture to the feed meet an equal-path-length condition. This condition may be represented by a set of "homology parameters" determined by a least-squares method. Finally, we calculate the homology parameters and the root mean square of surface errors for an 8-m dual-reflector system including gravity effects for the antenna pointed toward zenith and the horizon.

  10. DEK is required for homologous recombination repair of DNA breaks

    DEFF Research Database (Denmark)

    Smith, Eric A; Gole, Boris; Willis, Nicholas A

    2017-01-01

    -deficiency phenotypes were thought to arise from a moderate attenuation of non-homologous end joining (NHEJ) repair, the role of DEK in DNA repair remains incompletely understood. We present new evidence demonstrating the observed decrease in NHEJ is insufficient to impact immunoglobulin class switching in DEK knockout...... mice. Furthermore, DEK knockout cells were sensitive to apoptosis with NHEJ inhibition. Thus, we hypothesized DEK plays additional roles in homologous recombination (HR). Using episomal and integrated reporters, we demonstrate that HR repair of conventional DSBs is severely compromised in DEK...... filament formation, stability, or function. These findings define DEK as an important and multifunctional mediator of HR, and establish a synthetic lethal relationship between DEK loss and NHEJ inhibition....

  11. The endless tale of non-homologous end-joining.

    Science.gov (United States)

    Weterings, Eric; Chen, David J

    2008-01-01

    DNA double-strand breaks (DSBs) are introduced in cells by ionizing radiation and reactive oxygen species. In addition, they are commonly generated during V(D)J recombination, an essential aspect of the developing immune system. Failure to effectively repair these DSBs can result in chromosome breakage, cell death, onset of cancer, and defects in the immune system of higher vertebrates. Fortunately, all mammalian cells possess two enzymatic pathways that mediate the repair of DSBs: homologous recombination and non-homologous end-joining (NHEJ). The NHEJ process utilizes enzymes that capture both ends of the broken DNA molecule, bring them together in a synaptic DNA-protein complex, and finally repair the DNA break. In this review, all the known enzymes that play a role in the NHEJ process are discussed and a working model for the co-operation of these enzymes during DSB repair is presented.

  12. The endless tale of non-homologous end-joining

    Institute of Scientific and Technical Information of China (English)

    Eric Weterings; David J Chen

    2008-01-01

    DNA double-strand breaks (DSBs) are introduced in cells by ionizing radiation and reactive oxygen species. In addi-tion, they are commonly generated during V(D)J recombination, an essential aspect of the developing immune system. Failure to effectively repair these DSBs can result in chromosome breakage, cell death, onset of cancer, and defects in the immune system of higher vertebrates. Fortunately, all mammalian cells possess two enzymatic pathways that mediate the repair of DSBs: homologous recombination and non-homologous end-joining (NHEJ). The NHEJ process utilizes enzymes that capture both ends of the broken DNA molecule, bring them together in a synaptic DNA-protein complex, and finally repair the DNA break. In this review, all the known enzymes that play a role in the NHEJ process are discussed and a working model for the co-operation of these enzymes during DSB repair is presented.

  13. Back-Translation for Discovering Distant Protein Homologies

    Science.gov (United States)

    Gîrdea, Marta; Noé, Laurent; Kucherov, Gregory

    Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins’ common origin. Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level. To cope with this situation, we propose a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences. We design a dynamic programming alignment algorithm over memory-efficient graph representations of the complete set of putative DNA sequences of each protein, with the goal of determining the two putative DNA sequences which have the best scoring alignment under a powerful scoring system designed to reflect the most probable evolutionary process. This allows us to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.

  14. Levels of homology and the problem of neocortex.

    Science.gov (United States)

    Dugas-Ford, Jennifer; Ragsdale, Clifton W

    2015-07-08

    The neocortex is found only in mammals, and the fossil record is silent on how this soft tissue evolved. Understanding neocortex evolution thus devolves to a search for candidate homologous neocortex traits in the extant nonmammalian amniotes. The difficulty is that homology is based on similarity, and the six-layered neocortex structure could hardly be more dissimilar in appearance from the nuclear organization that is so conspicuous in the dorsal telencephalon of birds and other reptiles. Recent molecular data have, however, provided new support for one prominent hypothesis, based on neuronal circuits, that proposes the principal neocortical input and output cell types are a conserved feature of amniote dorsal telencephalon. Many puzzles remain, the greatest being understanding the selective pressures and molecular mechanisms that underlie such tremendous morphological variation in telencephalon structure.

  15. Homology, similarity, and identity in peptide epitope immunodefinition.

    Science.gov (United States)

    Kanduc, Darja

    2012-08-01

    The tendency to use the terms homology, similarity, and identity interchangeably persists in comparative biology. When translated to immunology, overlapping the concepts of homology, similarity, and identity complicates the exact definition of the self-nonself dichotomy and, in particular, affects immunopeptidomics, an emerging field aimed at cataloging and distinguishing immunoreactive peptide epitopes from silent nonreactive amino acid sequences. The definition of similar/dissimilar peptides in immunology is discussed with special attention to the analysis of immunological (dis)similarity between two or more protein sequences that equates to measuring sequence similarity with the use of a proper measurement unit such as a length determinant. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  16. Guidelines for Homology Modeling of Dopamine, Norepinephrine, and Serotonin Transporters.

    Science.gov (United States)

    Haddad, Yazan; Heger, Zbynek; Adam, Vojtech

    2016-11-16

    The human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT) are carriers of neurotransmitters and targets for many drugs. Pioneering works in the past three years to elucidate experimental models of the Drosophila dDAT and human hSERT structures will rapidly impact the field of neuroscience. Here, we evaluated automated homology-based human models of these transporters, employing systematic physics-based, knowledge-based, and empirical-based check. Modeling guidelines were conveyed with attention to the central binding site (S1), secondary binding site (S2), and the extracellular loops EL2 and EL4. Application of new experimental models (dDAT and hSERT) will improve the accuracy of homology models, previously utilizing prokaryotic leucine transporter (LeuT) structure, and provide better predictions of ligand interactions, which is required for understanding of cellular mechanisms and for development of novel therapeutics.

  17. Cosmetic Surgery in Integral Homology $L$-Spaces

    CERN Document Server

    Wu, Zhongtao

    2009-01-01

    Let $K$ be a non-trivial knot in $S^3$, and let $r$ and $r'$ be two distinct rational numbers of same sign, allowing $r$ to be infinite; we prove that there is no orientation-preserving homeomorphism between the manifolds $S^3_r(K)$ and $S^3_{r'}(K)$. We further generalize this uniqueness result to knots in arbitrary integral homology L-spaces.

  18. [An homologous recombination strategy to directly clone mammalian telemeres

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-01

    We have pursued three goals over the past year. The first involved determining whether the HARY vector could be used for homologous integration in the human genome. The second was to ascertain whether inserted sequences could be amplified in preference to the endogenous DHFR genes. The third was to determine if the HARY insertion could provide an anchor point for long range restriction mapping. The progress in each goal is described.

  19. A New Homologous Series of Lanthanum Copper Oxides

    NARCIS (Netherlands)

    Cava, R.J.; Siegrist, T.; Hessen, B.; Krajewski, J.J.; Peck, Jr.; Batlogg, B.; Tagaki, H.; Waszczak, J.V.; Schneemeyer, L.F.; Zandbergen, H.W.

    1991-01-01

    We report the synthesis and structural characterization of a new homologous series of lanthanum cuprates, with the formula La4+4nCu8+2nO14+8n . The n = 2 and n = 3 members, La2Cu2O5 and La8Cu7O19 , synthesized in the bulk, are stable in very narrow temperature ranges in air and oxygen. The n = 4 mem

  20. A Smale Type Result and Applications to Contact Homology

    Directory of Open Access Journals (Sweden)

    Vittorio Martino

    2014-12-01

    Full Text Available In this note we will show that the injection of a suitable subspace of the space of Legendrian loops into the full loop space is an S1-equivariant homotopy equivalence. Moreover, since the smaller space is the space of variations of a given action functional, we will compute the relative Contact Homology of a family of tight contact forms on the three-dimensional torus.

  1. A novel homologous model for noninvasive monitoring of endometriosis progression.

    Science.gov (United States)

    Ferrero, Hortensia; Buigues, Anna; Martínez, Jessica; Simón, Carlos; Pellicer, Antonio; Gómez, Raúl

    2017-02-01

    To date, several groups have generated homologous models of endometriosis through the implantation of endometrial tissue fluorescently labeled by green fluorescent protein (GFP) or tissue from luciferase-expressing transgenic mice into recipient animals, enabling noninvasive monitoring of lesion signal. These models present an advantage over endpoint models, but some limitations persist; use of transgenic mice is laborious and expensive, and GFP presents poor tissue penetration due to the relatively short emission wavelength. For this reason, a homologous mouse model of endometriosis that allows in vivo monitoring of generated lesions over time and mimics human lesions in recipient mice would be most desirable. In this regard, using C57BL/6 and B6N-Tyrc-Brd/BrdCrCrl mice, we optimized a decidualization protocol to obtain large volumes of decidual endometrium and mimic human lesions. Subsequently, to obtain a more robust and reliable noninvasive monitoring of lesions, we used the fluorescent reporter mCherry, which presents deeper tissue penetration and higher photostability, showing that endometrial tissue was properly labeled with 1 × 108 PFU/mL mCherry adenoviral vectors. mCherry-labeled endometriotic tissue was implanted in recipient mice, generating lesions that displayed characteristics typical of human endometriotic lesions, such as epithelial cells forming glands, local inflammation, collagen deposits, and new vessel formation. In vivo monitoring demonstrated that subcutaneous implantation on ventral abdomen of recipient mice provided the most intense and reliable signal for noninvasive lesion monitoring over a period of at least 20 days. This homologous model improves upon previously reported models of endometriosis and provides opportunities to study mechanism underlying endometriotic lesion growth and progression. We created a cost-effective but accurate homologous mouse model of endometriosis that allows the study of growth and progression of

  2. GHOSTM: a GPU-accelerated homology search tool for metagenomics.

    Directory of Open Access Journals (Sweden)

    Shuji Suzuki

    Full Text Available BACKGROUND: A large number of sensitive homology searches are required for mapping DNA sequence fragments to known protein sequences in public and private databases during metagenomic analysis. BLAST is currently used for this purpose, but its calculation speed is insufficient, especially for analyzing the large quantities of sequence data obtained from a next-generation sequencer. However, faster search tools, such as BLAT, do not have sufficient search sensitivity for metagenomic analysis. Thus, a sensitive and efficient homology search tool is in high demand for this type of analysis. METHODOLOGY/PRINCIPAL FINDINGS: We developed a new, highly efficient homology search algorithm suitable for graphics processing unit (GPU calculations that was implemented as a GPU system that we called GHOSTM. The system first searches for candidate alignment positions for a sequence from the database using pre-calculated indexes and then calculates local alignments around the candidate positions before calculating alignment scores. We implemented both of these processes on GPUs. The system achieved calculation speeds that were 130 and 407 times faster than BLAST with 1 GPU and 4 GPUs, respectively. The system also showed higher search sensitivity and had a calculation speed that was 4 and 15 times faster than BLAT with 1 GPU and 4 GPUs. CONCLUSIONS: We developed a GPU-optimized algorithm to perform sensitive sequence homology searches and implemented the system as GHOSTM. Currently, sequencing technology continues to improve, and sequencers are increasingly producing larger and larger quantities of data. This explosion of sequence data makes computational analysis with contemporary tools more difficult. We developed GHOSTM, which is a cost-efficient tool, and offer this tool as a potential solution to this problem.

  3. Protein Identification Pipeline for the Homology Driven Proteomics

    Science.gov (United States)

    Junqueira, Magno; Spirin, Victor; Balbuena, Tiago Santana; Thomas, Henrik; Adzhubei, Ivan; Sunyaev, Shamil; Shevchenko, Andrej

    2008-01-01

    Homology-driven proteomics is a major tool to characterize proteomes of organisms with unsequenced genomes. This paper addresses practical aspects of automated homology–driven protein identifications by LC-MS/MS on a hybrid LTQ Orbitrap mass spectrometer. All essential software elements supporting the presented pipeline are either hosted at the publicly accessible web server, or are available for free download. PMID:18639657

  4. The evolution of function within the Nudix homology clan.

    Science.gov (United States)

    Srouji, John R; Xu, Anting; Park, Annsea; Kirsch, Jack F; Brenner, Steven E

    2017-05-01

    The Nudix homology clan encompasses over 80,000 protein domains from all three domains of life, defined by homology to each other. Proteins with a domain from this clan fall into four general functional classes: pyrophosphohydrolases, isopentenyl diphosphate isomerases (IDIs), adenine/guanine mismatch-specific adenine glycosylases (A/G-specific adenine glycosylases), and nonenzymatic activities such as protein/protein interaction and transcriptional regulation. The largest group, pyrophosphohydrolases, encompasses more than 100 distinct hydrolase specificities. To understand the evolution of this vast number of activities, we assembled and analyzed experimental and structural data for 205 Nudix proteins collected from the literature. We corrected erroneous functions or provided more appropriate descriptions for 53 annotations described in the Gene Ontology Annotation database in this family, and propose 275 new experimentally-based annotations. We manually constructed a structure-guided sequence alignment of 78 Nudix proteins. Using the structural alignment as a seed, we then made an alignment of 347 "select" Nudix homology domains, curated from structurally determined, functionally characterized, or phylogenetically important Nudix domains. Based on our review of Nudix pyrophosphohydrolase structures and specificities, we further analyzed a loop region downstream of the Nudix hydrolase motif previously shown to contact the substrate molecule and possess known functional motifs. This loop region provides a potential structural basis for the functional radiation and evolution of substrate specificity within the hydrolase family. Finally, phylogenetic analyses of the 347 select protein domains and of the complete Nudix homology clan revealed general monophyly with regard to function and a few instances of probable homoplasy. Proteins 2017; 85:775-811. © 2016 Wiley Periodicals, Inc. © 2016 The Authors. Wiley Periodicals, Inc.

  5. FastBLAST: homology relationships for millions of proteins.

    Directory of Open Access Journals (Sweden)

    Morgan N Price

    Full Text Available BACKGROUND: All-versus-all BLAST, which searches for homologous pairs of sequences in a database of proteins, is used to identify potential orthologs, to find new protein families, and to provide rapid access to these homology relationships. As DNA sequencing accelerates and data sets grow, all-versus-all BLAST has become computationally demanding. METHODOLOGY/PRINCIPAL FINDINGS: We present FastBLAST, a heuristic replacement for all-versus-all BLAST that relies on alignments of proteins to known families, obtained from tools such as PSI-BLAST and HMMer. FastBLAST avoids most of the work of all-versus-all BLAST by taking advantage of these alignments and by clustering similar sequences. FastBLAST runs in two stages: the first stage identifies additional families and aligns them, and the second stage quickly identifies the homologs of a query sequence, based on the alignments of the families, before generating pairwise alignments. On 6.53 million proteins from the non-redundant Genbank database ("NR", FastBLAST identifies new families 25 times faster than all-versus-all BLAST. Once the first stage is completed, FastBLAST identifies homologs for the average query in less than 5 seconds (8.6 times faster than BLAST and gives nearly identical results. For hits above 70 bits, FastBLAST identifies 98% of the top 3,250 hits per query. CONCLUSIONS/SIGNIFICANCE: FastBLAST enables research groups that do not have supercomputers to analyze large protein sequence data sets. FastBLAST is open source software and is available at http://microbesonline.org/fastblast.

  6. TALEN-mediated homologous recombination in Daphnia magna.

    Science.gov (United States)

    Nakanishi, Takashi; Kato, Yasuhiko; Matsuura, Tomoaki; Watanabe, Hajime

    2015-12-17

    Transcription Activator-Like Effector Nucleases (TALENs) offer versatile tools to engineer endogenous genomic loci in various organisms. We established a homologous recombination (HR)-based knock-in using TALEN in the crustacean Daphnia magna, a model for ecological and toxicological genomics. We constructed TALENs and designed the 67 bp donor insert targeting a point deletion in the eyeless mutant that shows eye deformities. Co-injection of the TALEN mRNA with donor DNA into eggs led to the precise integration of the donor insert in the germ line, which recovered eye deformities in offspring. The frequency of HR events in the germ line was 2% by using both plasmid and single strand oligo DNA with 1.5 kb and 80 nt homology to the target. Deficiency of ligase 4 involved in non-homologous end joining repair did not increase the HR efficiency. Our data represent efficient HR-based knock-in by TALENs in D. magna, which is a promising tool to understand Daphnia gene functions.

  7. Xenogeneic homologous genes, molecular evolution and cancer therapy

    Institute of Scientific and Technical Information of China (English)

    田聆; 魏于全

    2001-01-01

    Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.

  8. Ocular toxicity of benzalkonium chloride homologs compared with their mixtures.

    Science.gov (United States)

    Okahara, Akihiko; Tanioka, Hidetoshi; Takada, Koichi; Kawazu, Kouichi

    2013-12-01

    This study was performed to assess the in vivo ocular toxicity of benzalkonium chloride (BAK) homologs compared with commercially available BAK (BAK mixture) and to assess the ocular toxicity of BAK homolog after repeated ocular application. Rabbit eyes were examined by ophthalmology and scanning electron microscopy (SEM) after 10 applications of BAK homologs with C12 (C12-BAK) and C14 (C14-BAK) alkyl chain lengths and a BAK mixture at concentrations of 0.001% (w/v), 0.003% (w/v), 0.005% (w/v), 0.01% (w/v) and 0.03% (w/v). The ocular toxicity of C12-BAK to rabbit eyes was examined by ophthalmology and histopathology after repeated ocular application for 39 weeks. In addition, the antimicrobial activities of C12-BAK and C14-BAK against A. niger, S. aureus and P. aeruginosa were assessed. Ocular toxicity of C12-BAK was less than those of the BAK mixture and C14-BAK. No ocular toxicity was noted after ocular application of 0.01% C12-BAK to rabbits for 39 weeks. C12-BAK showed antimicrobial activities at a concentration of 0.003%. These results suggest that the use of C12-BAK to replace BAK mixture as a preservative in ophthalmic solutions should be considered in order to reduce the incidence of the corneal epithelial cell injury induced clinically by BAK.

  9. Three-Dimensional Modeling of Quasi-Homologous Solar Jets

    Science.gov (United States)

    Pariat, E.; Antiochos, S. K.; DeVore, C. R.

    2010-01-01

    Recent solar observations (e.g., obtained with Hinode and STEREO) have revealed that coronal jets are a more frequent phenomenon than previously believed. This higher frequency results, in part, from the fact that jets exhibit a homologous behavior: successive jets recur at the same location with similar morphological features. We present the results of three-dimensional (31)) numerical simulations of our model for coronal jets. This study demonstrates the ability of the model to generate recurrent 3D untwisting quasi-homologous jets when a stress is constantly applied at the photospheric boundary. The homology results from the property of the 3D null-point system to relax to a state topologically similar to its initial configuration. In addition, we find two distinct regimes of reconnection in the simulations: an impulsive 3D mode involving a helical rotating current sheet that generates the jet, and a quasi-steady mode that occurs in a 2D-like current sheet located along the fan between the sheared spines. We argue that these different regimes can explain the observed link between jets and plumes.

  10. Accelerated homologous recombination and subsequent genome modification in Drosophila

    Science.gov (United States)

    Baena-Lopez, Luis Alberto; Alexandre, Cyrille; Mitchell, Alice; Pasakarnis, Laurynas; Vincent, Jean-Paul

    2013-01-01

    Gene targeting by ‘ends-out’ homologous recombination enables the deletion of genomic sequences and concurrent introduction of exogenous DNA with base-pair precision without sequence constraint. In Drosophila, this powerful technique has remained laborious and hence seldom implemented. We describe a targeting vector and protocols that achieve this at high frequency and with very few false positives in Drosophila, either with a two-generation crossing scheme or by direct injection in embryos. The frequency of injection-mediated gene targeting can be further increased with CRISPR-induced double-strand breaks within the region to be deleted, thus making homologous recombination almost as easy as conventional transgenesis. Our targeting vector replaces genomic sequences with a multifunctional fragment comprising an easy-to-select genetic marker, a fluorescent reporter, as well as an attP site, which acts as a landing platform for reintegration vectors. These vectors allow the insertion of a variety of transcription reporters or cDNAs to express tagged or mutant isoforms at endogenous levels. In addition, they pave the way for difficult experiments such as tissue-specific allele switching and functional analysis in post-mitotic or polyploid cells. Therefore, our method retains the advantages of homologous recombination while capitalising on the mutagenic power of CRISPR. PMID:24154526

  11. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens

    Directory of Open Access Journals (Sweden)

    Shinji Amari

    2013-01-01

    Full Text Available The three-dimensional (3D structures of human leukocyte antigen (HLA molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  12. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens.

    Science.gov (United States)

    Amari, Shinji; Kataoka, Ryoichi; Ikegami, Takashi; Hirayama, Noriaki

    2013-01-01

    The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  13. Two pathways of homologous recombination in Trypanosoma brucei.

    Science.gov (United States)

    Conway, Colin; Proudfoot, Chris; Burton, Peter; Barry, J David; McCulloch, Richard

    2002-09-01

    African trypanosomes are unicellular parasites that use DNA recombination to evade the mammalian immune response. They do this in a process called antigenic variation, in which the parasites periodically switch the expression of VSG genes that encode distinct Variant Surface Glycoprotein coats. Recombination is used to move new VSG genes into specialised bloodstream VSG transcription sites. Genetic and molecular evidence has suggested that antigenic variation uses homologous recombination, but the detailed reaction pathways are not understood. In this study, we examine the recombination pathways used by trypanosomes to integrate transformed DNA into their genome, and show that they possess at least two pathways of homologous recombination. The primary mechanism is dependent upon RAD51, but a subsidiary pathway exists that is RAD51-independent. Both pathways contribute to antigenic variation. We show that the RAD51-independent pathway is capable of recombining DNA substrates with very short lengths of sequence homology and in some cases aberrant recombination reactions can be detected using such microhomologies.

  14. Heteromorphic sex chromosomes: navigating meiosis without a homologous partner.

    Science.gov (United States)

    Checchi, Paula M; Engebrecht, Joanne

    2011-09-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have been modified in many different ways to ensure segregation of heteromorphic sex chromosomes at the first meiotic division. Additionally, an almost universal feature of heteromorphic sex chromosomes during meiosis is transcriptional silencing, or meiotic sex chromosome inactivation, an essential process proposed to prevent expression of genes deleterious to meiosis in the heterogametic sex as well as to shield unpaired sex chromosomes from recognition by meiotic checkpoints. Comparative analyses of the meiotic behavior of sex chromosomes in nematodes, mammals, and birds reveal important conserved features as well as provide insight into sex chromosome evolution. Copyright © 2011 Wiley-Liss, Inc.

  15. Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily.

    Science.gov (United States)

    Lenoir, Marc; Kufareva, Irina; Abagyan, Ruben; Overduin, Michael

    2015-10-23

    The human genome encodes about 285 proteins that contain at least one annotated pleckstrin homology (PH) domain. As the first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes. PH domains constitute one of the largest protein superfamilies, and have diverged to regulate many different signaling proteins and modules such as Dbl homology (DH) and Tec homology (TH) domains. The ligands of approximately 70 PH domains have been validated by binding assays and complexed structures, allowing meaningful extrapolation across the entire superfamily. Here the Membrane Optimal Docking Area (MODA) program is used at a genome-wide level to identify all membrane docking PH structures and map their lipid-binding determinants. In addition to the linear sequence motifs which are employed for phosphoinositide recognition, the three dimensional structural features that allow peripheral membrane domains to approach and insert into the bilayer are pinpointed and can be predicted ab initio. The analysis shows that conserved structural surfaces distinguish which PH domains associate with membrane from those that do not. Moreover, the results indicate that lipid-binding PH domains can be classified into different functional subgroups based on the type of membrane insertion elements they project towards the bilayer.

  16. Persistent homology for the quantitative prediction of fullerene stability.

    Science.gov (United States)

    Xia, Kelin; Feng, Xin; Tong, Yiying; Wei, Guo Wei

    2015-03-05

    Persistent homology is a relatively new tool often used for qualitative analysis of intrinsic topological features in images and data originated from scientific and engineering applications. In this article, we report novel quantitative predictions of the energy and stability of fullerene molecules, the very first attempt in using persistent homology in this context. The ground-state structures of a series of small fullerene molecules are first investigated with the standard Vietoris-Rips complex. We decipher all the barcodes, including both short-lived local bars and long-lived global bars arising from topological invariants, and associate them with fullerene structural details. Using accumulated bar lengths, we build quantitative models to correlate local and global Betti-2 bars, respectively with the heat of formation and total curvature energies of fullerenes. It is found that the heat of formation energy is related to the local hexagonal cavities of small fullerenes, while the total curvature energies of fullerene isomers are associated with their sphericities, which are measured by the lengths of their long-lived Betti-2 bars. Excellent correlation coefficients (>0.94) between persistent homology predictions and those of quantum or curvature analysis have been observed. A correlation matrix based filtration is introduced to further verify our findings. © 2014 Wiley Periodicals, Inc.

  17. Remote homology detection incorporating the context of physicochemical properties.

    Science.gov (United States)

    Bedoya, Oscar; Tischer, Irene

    2014-02-01

    A new method for remote protein homology detection, called support vector machine incorporating the context of physicochemical properties (SVM-CP), is presented. Recent discriminative methods are based on concatenating information extracted from each protein by considering several physicochemical properties. We show that there are physicochemical properties that reflect the functional or structural characteristics of each specific protein family, but there are also some physicochemical properties that affect the accuracy of the classification techniques. The research highlights the importance of the selection of physicochemical properties in remote homology detection. Most of the methods slide a window over every protein sequence to extract physicochemical information. This extraction is usually performed by giving the same importance to every value in the window, i.e., averaging the physicochemical values in the observation window. SVM-CP takes into account that every residue in a sliding window has a different weight, which reflects the importance or contribution to the representative value of the window. The SVM-CP method reaches a receiver operating characteristic (ROC) score of 0.93462, which is the highest value for a remote homology detection method based on the sequence composition information. © 2013 Published by Elsevier Ltd.

  18. Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily

    Directory of Open Access Journals (Sweden)

    Marc Lenoir

    2015-10-01

    Full Text Available The human genome encodes about 285 proteins that contain at least one annotated pleckstrin homology (PH domain. As the first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes. PH domains constitute one of the largest protein superfamilies, and have diverged to regulate many different signaling proteins and modules such as Dbl homology (DH and Tec homology (TH domains. The ligands of approximately 70 PH domains have been validated by binding assays and complexed structures, allowing meaningful extrapolation across the entire superfamily. Here the Membrane Optimal Docking Area (MODA program is used at a genome-wide level to identify all membrane docking PH structures and map their lipid-binding determinants. In addition to the linear sequence motifs which are employed for phosphoinositide recognition, the three dimensional structural features that allow peripheral membrane domains to approach and insert into the bilayer are pinpointed and can be predicted ab initio. The analysis shows that conserved structural surfaces distinguish which PH domains associate with membrane from those that do not. Moreover, the results indicate that lipid-binding PH domains can be classified into different functional subgroups based on the type of membrane insertion elements they project towards the bilayer.

  19. A Minimal Rac Activation Domain in the Unconventional Guanine Nucleotide Exchange Factor Dock180†

    OpenAIRE

    Xin WU; Ramachandran, Sekar; Cerione, Richard A.; Erickson, Jon W.

    2011-01-01

    Guanine nucleotide exchange factors (GEFs) activate Rho GTPases by catalyzing the exchange of bound GDP for GTP, thereby resulting in downstream effector recognition. Two metazoan families of GEFs have been described: Dbl-GEF family members that share conserved Dbl homology (DH) and Pleckstrin homology (PH) domains and the more recently described Dock180 family members that share little sequence homology with the Dbl family and are characterized by conserved Dock homology regions 1 and 2 (DHR...

  20. Cohesin Is limiting for the suppression of DNA damage-induced recombination between homologous chromosomes.

    Directory of Open Access Journals (Sweden)

    Shay Covo

    2010-07-01

    Full Text Available Double-strand break (DSB repair through homologous recombination (HR is an evolutionarily conserved process that is generally error-free. The risk to genome stability posed by nonallelic recombination or loss-of-heterozygosity could be reduced by confining HR to sister chromatids, thereby preventing recombination between homologous chromosomes. Here we show that the sister chromatid cohesion complex (cohesin is a limiting factor in the control of DSB repair and genome stability and that it suppresses DNA damage-induced interactions between homologues. We developed a gene dosage system in tetraploid yeast to address limitations on various essential components in DSB repair and HR. Unlike RAD50 and RAD51, which play a direct role in HR, a 4-fold reduction in the number of essential MCD1 sister chromatid cohesion subunit genes affected survival of gamma-irradiated G(2/M cells. The decreased survival reflected a reduction in DSB repair. Importantly, HR between homologous chromosomes was strongly increased by ionizing radiation in G(2/M cells with a single copy of MCD1 or SMC3 even at radiation doses where survival was high and DSB repair was efficient. The increased recombination also extended to nonlethal doses of UV, which did not induce DSBs. The DNA damage-induced recombinants in G(2/M cells included crossovers. Thus, the cohesin complex has a dual role in protecting chromosome integrity: it promotes DSB repair and recombination between sister chromatids, and it suppresses damage-induced recombination between homologues. The effects of limited amounts of Mcd1and Smc3 indicate that small changes in cohesin levels may increase the risk of genome instability, which may lead to genetic diseases and cancer.

  1. Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance.

    Directory of Open Access Journals (Sweden)

    Vlad C Seitan

    2006-07-01

    Full Text Available Saccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside certain fungi. Some metazoan orthologs of Scc2 were initially identified as developmental gene regulators, such as Drosophila Nipped-B, a regulator of cut and Ultrabithorax, and delangin, a protein mutant in Cornelia de Lange syndrome. We show that delangin and Nipped-B bind previously unstudied human and fly orthologs of Caenorhabditis elegans MAU-2, a non-axis-specific guidance factor for migrating cells and axons. PSI-BLAST shows that Scc4 is evolutionarily related to metazoan MAU-2 sequences, with the greatest homology evident in a short N-terminal domain, and protein-protein interaction studies map the site of interaction between delangin and human MAU-2 to the N-terminal regions of both proteins. Short interfering RNA knockdown of human MAU-2 in HeLa cells resulted in precocious sister chromatid separation and in impaired loading of cohesin onto chromatin, indicating that it is functionally related to Scc4, and RNAi analyses show that MAU-2 regulates chromosome segregation in C. elegans embryos. Using antisense morpholino oligonucleotides to knock down Xenopus tropicalis delangin or MAU-2 in early embryos produced similar patterns of retarded growth and developmental defects. Our data show that sister chromatid cohesion in metazoans involves the formation of a complex similar to the Scc2-Scc4 interaction in the budding yeast. The very high degree of sequence conservation between Scc4 homologs in complex metazoans is consistent with increased selection pressure to conserve additional essential functions, such as regulation of cell and axon migration during development.

  2. Functional connection between Rad51 and PML in homology-directed repair.

    Directory of Open Access Journals (Sweden)

    Sergei Boichuk

    Full Text Available The promyelocytic leukemia protein (PML is a tumor suppressor critical for formation of nuclear bodies (NBs performing important functions in transcription, apoptosis, DNA repair and antiviral responses. Earlier studies demonstrated that simian virus 40 (SV40 initiates replication near PML NBs. Here we show that PML knockdown inhibits viral replication in vivo, thus indicating a positive role of PML early in infection. SV40 large T antigen (LT induces DNA damage and, consequently, nuclear foci of the key homologous recombination repair protein Rad51 that colocalize with PML. PML depletion abrogates LT-induced Rad51 foci. LT may target PML NBs to gain access to DNA repair factors like Rad51 that are required for viral replication. We have used the SV40 model to gain insight to DNA repair events involving PML. Strikingly, even in normal cells devoid of viral oncoproteins, PML is found to be instrumental for foci of Rad51, Mre11 and BRCA1, as well as homology-directed repair after double-strand break (DSB induction. Following LT expression or external DNA damage, PML associates with Rad51. PML depletion also causes a loss of RPA foci following γ-irradiation, suggesting that PML is required for processing of DSBs. Immunofluorescent detection of incorporated BrdU without prior denaturation indicates a failure to generate ssDNA foci in PML knockdown cells upon γ-irradiation. Consistent with the lack of RPA and BrdU foci, γ-irradiation fails to induce Chk1 activation, when PML is depleted. Taken together, we have discovered a novel functional connection between PML and the homologous recombination-mediated repair machinery, which might contribute to PML tumor suppressor activity.

  3. An active site homology model of phenylalanine ammonia-lyase from Petroselinum crispum.

    Science.gov (United States)

    Röther, Dagmar; Poppe, László; Morlock, Gaby; Viergutz, Sandra; Rétey, János

    2002-06-01

    The plant enzyme phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) shows homology to histidine ammonia-lyase (HAL) whose structure has been solved by X-ray crystallography. Based on amino-acid sequence alignment of the two enzymes, mutagenesis was performed on amino-acid residues that were identical or similar to the active site residues in HAL to gain insight into the importance of this residues in PAL for substrate binding or catalysis. We mutated the following amino-acid residues: S203, R354, Y110, Y351, N260, Q348, F400, Q488 and L138. Determination of the kinetic constants of the overexpressed and purified enzymes revealed that mutagenesis led in each case to diminished activity. Mutants S203A, R354A and Y351F showed a decrease in kcat by factors of 435, 130 and 235, respectively. Mutants F400A, Q488A and L138H showed a 345-, 615- and 14-fold lower kcat, respectively. The greatest loss of activity occurred in the PAL mutants N260A, Q348A and Y110F, which were 2700, 2370 and 75 000 times less active than wild-type PAL. To elucidate the possible function of the mutated amino-acid residues in PAL we built a homology model of PAL based on structural data of HAL and mutagenesis experiments with PAL. The homology model of PAL showed that the active site of PAL resembles the active site of HAL. This allowed us to propose possible roles for the corresponding residues in PAL catalysis.

  4. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  5. A homolog of Drosophila grainy head is essential for epidermal integrity in mice.

    Science.gov (United States)

    Ting, Stephen B; Caddy, Jacinta; Hislop, Nikki; Wilanowski, Tomasz; Auden, Alana; Zhao, Lin-Lin; Ellis, Sarah; Kaur, Pritinder; Uchida, Yoshikazu; Holleran, Walter M; Elias, Peter M; Cunningham, John M; Jane, Stephen M

    2005-04-15

    The Drosophila cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor grainy head, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.

  6. Bacterial and Fungal Pattern Recognition Receptors in Homologous Innate Signaling Pathways of Insects and Mammals

    Directory of Open Access Journals (Sweden)

    Bethany A Stokes

    2015-01-01

    Full Text Available In response to bacterial and fungal infections in insects and mammals, distinct families of innate immune pattern recognition receptors initiate highly complex intracellular signaling cascades. Those cascades induce a variety of immune functions that restrain the spread of microbes in the host. Insect and mammalian innate immune receptors include molecules that recognize conserved microbial molecular patterns. Innate immune recognition leads to the recruitment of adaptor molecules forming multi-protein complexes that include kinases, transcription factors and other regulatory molecules. Innate immune signaling cascades induce the expression of genes encoding antimicrobial peptides and other key factors that mount and regulate the immune response against microbial challenge. In this review, we summarize our current understanding of the bacterial and fungal pattern recognition receptors for homologous innate signaling pathways of insects and mammals in an effort to provide a framework for future studies.

  7. Silencing the lettuce homologs of small rubber particle protein does not influence natural rubber biosynthesis in lettuce (Lactuca sativa).

    Science.gov (United States)

    Chakrabarty, Romit; Qu, Yang; Ro, Dae-Kyun

    2015-05-01

    Natural rubber, cis-1,4-polyisoprene, is an important raw material in chemical industries, but its biosynthetic mechanism remains elusive. Natural rubber is known to be synthesized in rubber particles suspended in laticifer cells in the Brazilian rubber tree (Hevea brasiliensis). In the rubber tree, rubber elongation factor (REF) and its homolog, small rubber particle protein (SRPP), were found to be the most abundant proteins in rubber particles, and they have been implicated in natural rubber biosynthesis. As lettuce (Lactuca sativa) can synthesize natural rubber, we utilized this annual, transformable plant to examine in planta roles of the lettuce REF/SRPP homologs by RNA interference. Among eight lettuce REF/SRPP homologs identified, transcripts of two genes (LsSRPP4 and LsSRPP8) accounted for more than 90% of total transcripts of REF/SRPP homologs in lettuce latex. LsSRPP4 displays a typical primary protein sequence as other REF/SRPP, while LsSRPP8 is twice as long as LsSRPP4. These two major LsSRPP transcripts were individually and simultaneously silenced by RNA interference, and relative abundance, polymer molecular weight, and polydispersity of natural rubber were analyzed from the LsSRPP4- and LsSRPP8-silenced transgenic lettuce. Despite previous data suggesting the implications of REF/SRPP in natural rubber biosynthesis, qualitative and quantitative alterations of natural rubber could not be observed in transgenic lettuce lines. It is concluded that lettuce REF/SRPP homologs are not critically important proteins in natural rubber biosynthesis in lettuce. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Identification of viruses and viroids by next-generation sequencing and homology-dependent and homology-independent algorithms.

    Science.gov (United States)

    Wu, Qingfa; Ding, Shou-Wei; Zhang, Yongjiang; Zhu, Shuifang

    2015-01-01

    A fast, accurate, and full indexing of viruses and viroids in a sample for the inspection and quarantine services and disease management is desirable but was unrealistic until recently. This article reviews the rapid and exciting recent progress in the use of next-generation sequencing (NGS) technologies for the identification of viruses and viroids in plants. A total of four viroids/viroid-like RNAs and 49 new plant RNA and DNA viruses from 18 known or unassigned virus families have been identified from plants since 2009. A comparison of enrichment strategies reveals that full indexing of RNA and DNA viruses as well as viroids in a plant sample at single-nucleotide resolution is made possible by one NGS run of total small RNAs, followed by data mining with homology-dependent and homology-independent computational algorithms. Major challenges in the application of NGS technologies to pathogen discovery are discussed.

  9. The third homology of the special linear group of a field

    CERN Document Server

    Hutchinson, Kevin

    2008-01-01

    We prove that for any infinite field homology stability for the third integral homology of the special linear groups $SL(n,F)$ begins at $n=3$. When $n=2$ the cokernel of the map from the third homology of $SL(2,F)$ to the third homology of $SL(3,F)$ is naturally isomorphic to the square of Milnor $K_3$. We discuss applications to the indecomposable $K_3$ of the field and to Milnor-Witt K-theory.

  10. The third homology of the special linear group of a field

    OpenAIRE

    Hutchinson, Kevin; Tao, Liqun

    2009-01-01

    We prove that for any infinite field homology stability for the third integral homology of the special linear groups $SL(n,F)$ begins at $n=3$. When $n=2$ the cokernel of the map from the third homology of $SL(2,F)$ to the third homology of $SL(3,F)$ is naturally isomorphic to the square of Milnor $K_3$. We discuss applications to the indecomposable $K_3$ of the field and to Milnor-Witt K-theory.

  11. Genetic selection and DNA sequences of 4.5S RNA homologs

    DEFF Research Database (Denmark)

    Brown, S; Thon, G; Tolentino, E

    1989-01-01

    A general strategy for cloning the functional homologs of an Escherichia coli gene was used to clone homologs of 4.5S RNA from other bacteria. The genes encoding these homologs were selected by their ability to complement a deletion of the gene for 4.5S RNA. DNA sequences of the regions encoding...

  12. On mathematical arbitrariness of some papers on the potential homologous linear rule investigation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The history of homologous linear rule investigation is reviewed simply. The author puts forward a problem worth paying attention to in the recent potential homologous linear rule investigation, especially some mistakes made in these investigations on mathematical foundations. The author also exposes the mathematical arbitrariness of some papers on their potential homologous linear rule investigation.

  13. Equidistribution of geodesics on homology classes and analogues for free groups

    DEFF Research Database (Denmark)

    Petridis, Y.N.; Risager, Morten

    2005-01-01

    We investigate how often geodesics have homology in a fixed set of the homology lattice of a compact Riemann surface. We prove that closed geodesics are equidistributed on a random set of homology classes and certain arithmetic sets. We explain the analogues for free groups, conjugacy classes...

  14. DNA end resection controls the balance between homologous and illegitimate recombination in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Siniša Ivanković

    Full Text Available Even a partial loss of function of human RecQ helicase analogs causes adverse effects such as a cancer-prone Werner, Bloom or Rothmund-Thompson syndrome, whereas a complete RecQ deficiency in Escherichia coli is not deleterious for a cell. We show that this puzzling difference is due to different mechanisms of DNA double strand break (DSB resection in E. coli and humans. Coupled helicase and RecA loading activities of RecBCD enzyme, which is found exclusively in bacteria, are shown to be responsible for channeling recombinogenic 3' ending tails toward productive, homologous and away from nonproductive, aberrant recombination events. On the other hand, in recB1080/recB1067 mutants, lacking RecBCD's RecA loading activity while preserving its helicase activity, DSB resection is mechanistically more alike that in eukaryotes (by its uncoupling from a recombinase polymerization step, and remarkably, the role of RecQ also becomes akin of its eukaryotic counterparts in a way of promoting homologous and suppressing illegitimate recombination. The sickly phenotype of recB1080 recQ mutant was further exacerbated by inactivation of an exonuclease I, which degrades the unwound 3' tail. The respective recB1080 recQ xonA mutant showed poor viability, DNA repair and homologous recombination deficiency, and very increased illegitimate recombination. These findings demonstrate that the metabolism of the 3' ending overhang is a decisive factor in tuning the balance of homologous and illegitimate recombination in E. coli, thus highlighting the importance of regulating DSB resection for preserving genome integrity. recB mutants used in this study, showing pronounced RecQ helicase and exonuclease I dependence, make up a suitable model system for studying mechanisms of DSB resection in bacteria. Also, these mutants might be useful for investigating functions of the conserved RecQ helicase family members, and congruently serve as a simpler, more defined model system

  15. Paracoccus denitrificans possesses two BioR homologs having a role in regulation of biotin metabolism.

    Science.gov (United States)

    Feng, Youjun; Kumar, Ritesh; Ravcheev, Dmitry A; Zhang, Huimin

    2015-08-01

    Recently, we determined that BioR, the GntR family of transcription factor, acts as a repressor for biotin metabolism exclusively distributed in certain species of α-proteobacteria, including the zoonotic agent Brucella melitensis and the plant pathogen Agrobacterium tumefaciens. However, the scenario is unusual in Paracoccus denitrificans, another closely related member of the same phylum α-proteobacteria featuring with denitrification. Not only does it encode two BioR homologs Pden_1431 and Pden_2922 (designated as BioR1 and BioR2, respectively), but also has six predictive BioR-recognizable sites (the two bioR homolog each has one site, whereas the two bio operons (bioBFDAGC and bioYB) each contains two tandem BioR boxes). It raised the possibility that unexpected complexity is present in BioR-mediated biotin regulation. Here we report that this is the case. The identity of the purified BioR proteins (BioR1 and BioR2) was confirmed with LC-QToF-MS. Phylogenetic analyses combined with GC percentage raised a possibility that the bioR2 gene might be acquired by horizontal gene transfer. Gel shift assays revealed that the predicted BioR-binding sites are functional for the two BioR homologs, in much similarity to the scenario seen with the BioR site of A. tumefaciens bioBFDAZ. Using the A. tumefaciens reporter system carrying a plasmid-borne LacZ fusion, we revealed that the two homologs of P. denitrificans BioR are functional repressors for biotin metabolism. As anticipated, not only does the addition of exogenous biotin stimulate efficiently the expression of bioYB operon encoding biotin transport/uptake system BioY, but also inhibits the transcription of the bioBFDAGC operon resembling the de novo biotin synthetic pathway. EMSA-based screening failed to demonstrate that the biotin-related metabolite is involved in BioR-DNA interplay, which is consistent with our former observation with Brucella BioR. Our finding defined a complex regulatory network for biotin

  16. Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain.

    Science.gov (United States)

    Russo, C; Gao, Y; Mancini, P; Vanni, C; Porotto, M; Falasca, M; Torrisi, M R; Zheng, Y; Eva, A

    2001-06-01

    The Dbl family guanine nucleotide exchange factors (GEFs) contain a region of sequence similarity consisting of a catalytic Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. PH domains are involved in the regulated targeting of signaling molecules to plasma membranes by protein-protein and/or protein-lipid interactions. Here we show that Dbl PH domain binding to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-triphosphate results in the inhibition of Dbl GEF activity on Rho family GTPase Cdc42. Phosphatidylinositol 4,5-bisphosphate binding to the PH domain significantly inhibits the Cdc42 interactive activity of the DH domain suggesting that the DH domain is subjected to the PH domain modulation under the influence of phosphoinositides (PIPs). We generated Dbl mutants unable to interact with PIPs. These mutants retained GEF activity on Cdc42 in the presence of PIPs and showed a markedly enhanced activating potential for both Cdc42 and RhoA in vivo while displaying decreased cellular transforming activity. Immunofluorescence analysis of NIH3T3 transfectants revealed that whereas the PH domain localizes to actin stress fibers and plasma membrane, the PH mutants are no longer detectable on the plasma membrane. These results suggest that modulation of PIPs in both the GEF catalytic activity and the targeting to plasma membrane determines the outcome of the biologic activity of Dbl.

  17. Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch in allelic gene expression

    Science.gov (United States)

    Stratigi, Kalliopi; Kapsetaki, Manouela; Aivaliotis, Michalis; Town, Terrence; Flavell, Richard A.; Spilianakis, Charalampos G.

    2015-01-01

    Physiological processes rely on the regulation of total mRNA levels in a cell. In diploid organisms, the transcriptional activation of one or both alleles of a gene may involve trans-allelic interactions that provide a tight spatial and temporal level of gene expression regulation. The mechanisms underlying such interactions still remain poorly understood. Here, we demonstrate that lipopolysaccharide stimulation of murine macrophages rapidly resulted in the actin-mediated and transient homologous spatial proximity of Tnfα alleles, which was necessary for the mono- to biallelic switch in gene expression. We identified two new complementary long noncoding RNAs transcribed from the TNFα locus and showed that their knockdown had opposite effects in Tnfα spatial proximity and allelic expression. Moreover, the observed spatial proximity of Tnfα alleles depended on pyruvate kinase muscle isoform 2 (PKM2) and T-helper-inducing POZ-Krüppel-like factor (ThPOK). This study suggests a role for lncRNAs in the regulation of somatic homologous spatial proximity and allelic expression control necessary for fine-tuning mammalian immune responses. PMID:25770217

  18. Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs

    Directory of Open Access Journals (Sweden)

    Teiji Sawa

    2016-10-01

    Full Text Available Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species (Ps. fluorescens, Ps. lundensis, Ps. weihenstephanensis, Ps. marginalis, Ps. rhodesiae, Ps. synxantha, Ps. libanensis, Ps. extremaustralis, Ps. veronii, Ps. simiae, Ps. trivialis, Ps. tolaasii, Ps. orientalis, Ps. taetrolens, Ps. syringae, Ps. viridiflava, and Ps. cannabina and 8 Gram-negative bacteria from three other genera (Photorhabdus, Aeromonas, and Paludibacterium. In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin.

  19. Pea VEGETATIVE2 Is an FD Homolog That Is Essential for Flowering and Compound Inflorescence Development.

    Science.gov (United States)

    Sussmilch, Frances C; Berbel, Ana; Hecht, Valérie; Vander Schoor, Jacqueline K; Ferrándiz, Cristina; Madueño, Francisco; Weller, James L

    2015-04-01

    As knowledge of the gene networks regulating inflorescence development in Arabidopsis thaliana improves, the current challenge is to characterize this system in different groups of crop species with different inflorescence architecture. Pea (Pisum sativum) has served as a model for development of the compound raceme, characteristic of many legume species, and in this study, we characterize the pea VEGETATIVE2 (VEG2) locus, showing that it is critical for regulation of flowering and inflorescence development and identifying it as a homolog of the bZIP transcription factor FD. Through detailed phenotypic characterizations of veg2 mutants, expression analyses, and the use of protein-protein interaction assays, we find that VEG2 has important roles during each stage of development of the pea compound inflorescence. Our results suggest that VEG2 acts in conjunction with multiple FLOWERING LOCUS T (FT) proteins to regulate expression of downstream target genes, including TERMINAL FLOWER1, LEAFY, and MADS box homologs, and to facilitate cross-regulation within the FT gene family. These findings further extend our understanding of the mechanisms underlying compound inflorescence development in pea and may have wider implications for future manipulation of inflorescence architecture in related legume crop species.

  20. What Evidence Is There for the Homology of Protein-Protein Interactions?

    Science.gov (United States)

    Lewis, Anna C. F.; Jones, Nick S.; Porter, Mason A.; Deane, Charlotte M.

    2012-01-01

    The notion that sequence homology implies functional similarity underlies much of computational biology. In the case of protein-protein interactions, an interaction can be inferred between two proteins on the basis that sequence-similar proteins have been observed to interact. The use of transferred interactions is common, but the legitimacy of such inferred interactions is not clear. Here we investigate transferred interactions and whether data incompleteness explains the lack of evidence found for them. Using definitions of homology associated with functional annotation transfer, we estimate that conservation rates of interactions are low even after taking interactome incompleteness into account. For example, at a blastp -value threshold of , we estimate the conservation rate to be about between S. cerevisiae and H. sapiens. Our method also produces estimates of interactome sizes (which are similar to those previously proposed). Using our estimates of interaction conservation we estimate the rate at which protein-protein interactions are lost across species. To our knowledge, this is the first such study based on large-scale data. Previous work has suggested that interactions transferred within species are more reliable than interactions transferred across species. By controlling for factors that are specific to within-species interaction prediction, we propose that the transfer of interactions within species might be less reliable than transfers between species. Protein-protein interactions appear to be very rarely conserved unless very high sequence similarity is observed. Consequently, inferred interactions should be used with care. PMID:23028270

  1. Construction of SMART cDNA Library of Sheep Ovary and Identification of Candidate Gene by Homologous Cloning

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The cDNA library of an ovary from Small Tail Han sheep before estrus was constructed by switching mechanism at 5' end of RNA transcript (SMART) approach. This library had a plaque titer of 1 × 109pfu mL-1 and a 96% recombinant ratio of which the fragment length of inserted average eDNA sequences was 1.0 kb. Based on bioinformatics analysis of the sequences, we obtained 338 expressed sequence tags (ESTs) from 380 cDNA clones which indicated 191 contigs. These contigs consist of 89 unmatched ESTs, 9 homologous known genes in sheep, and 93 homologous sequences in species of mouse, bovine, and human beings, including 19 sequences expressed in the ovary or follicle and 14 unknown sequences.Several candidate genes associated with sheep reproduction trait such as epidermal growth factor (EGF), estrogen receptor (ESR), Inhibin, follicle stimulating hormone receptor (FSHR), prostaglandin (PG), and transforming growth factor-β (TGF-β) were identified and the homologous were cloned from this library, which will contribute to compile expression profies and find the major genes of prolificacy of Small Tail Han sheep.

  2. Suppressor of fusion, a Fusarium oxysporum homolog of Ndt80, is required for nutrient-dependent regulation of anastomosis.

    Science.gov (United States)

    Shahi, Shermineh; Fokkens, Like; Houterman, Petra M; Rep, Martijn

    2016-10-01

    Heterokaryon formation is an essential step in asexual recombination in Fusarium oxysporum. Filamentous fungi have an elaborate nonself recognition machinery to prevent formation and proliferation of heterokaryotic cells, called heterokaryon incompatibility (HI). In F. oxysporum the regulation of this machinery is not well understood. In Neurospora crassa, Vib-1, a putative transcription factor of the p53-like Ndt80 family of transcription factors, has been identified as global regulator of HI. In this study we investigated the role of the F. oxysporum homolog of Vib-1, called Suf, in vegetative hyphal and conidial anastomosis tube (CAT) fusion and HI. We identified a novel function for an Ndt80 homolog as a nutrient-dependent regulator of anastomosis. Strains carrying the SUF deletion mutation display a hyper-fusion phenotype during vegetative growth as well as germling development. In addition, conidial paring of incompatible SUF deletion strains led to more heterokaryon formation, which is independent of suppression of HI. Our data provides further proof for the divergence in the functions of different members Ndt80 family. We propose that Ndt80 homologs mediate responses to nutrient quality and quantity, with specific responses varying between species.

  3. MutS2 Promotes Homologous Recombination in Bacillus subtilis.

    Science.gov (United States)

    Burby, Peter E; Simmons, Lyle A

    2017-01-15

    Bacterial MutS proteins are subdivided into two families, MutS1 and MutS2. MutS1 family members recognize DNA replication errors during their participation in the well-characterized mismatch repair (MMR) pathway. In contrast to the well-described function of MutS1, the function of MutS2 in bacteria has remained less clear. In Helicobacter pylori and Thermus thermophilus, MutS2 has been shown to suppress homologous recombination. The role of MutS2 is unknown in the Gram-positive bacterium Bacillus subtilis In this work, we investigated the contribution of MutS2 to maintaining genome integrity in B. subtilis We found that deletion of mutS2 renders B. subtilis sensitive to the natural antibiotic mitomycin C (MMC), which requires homologous recombination for repair. We demonstrate that the C-terminal small MutS-related (Smr) domain is necessary but not sufficient for tolerance to MMC. Further, we developed a CRISPR/Cas9 genome editing system to test if the inducible prophage PBSX was the underlying cause of the observed MMC sensitivity. Genetic analysis revealed that MMC sensitivity was dependent on recombination and not on nucleotide excision repair or a symptom of prophage PBSX replication and cell lysis. We found that deletion of mutS2 resulted in decreased transformation efficiency using both plasmid and chromosomal DNA. Further, deletion of mutS2 in a strain lacking the Holliday junction endonuclease gene recU resulted in increased MMC sensitivity and decreased transformation efficiency, suggesting that MutS2 could function redundantly with RecU. Together, our results support a model where B. subtilis MutS2 helps to promote homologous recombination, demonstrating a new function for bacterial MutS2. Cells contain pathways that promote or inhibit recombination. MutS2 homologs are Smr-endonuclease domain-containing proteins that have been shown to function in antirecombination in some bacteria. We present evidence that B. subtilis MutS2 promotes recombination

  4. Homology modeling and validation of SAS2271 transcriptional regulator of AraC family in Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Money Gupta

    2013-02-01

    Full Text Available Objective: To predict three dimensional structure of AraC Family transcription regulator protein in staphylococcus aureus involved in causing virulence. Methods: Evolutionary dynamics of S. aureus reveled that several mutations preceding virulence lead to truncated proteins that plays an important role in virulence. The Structural templates are identified using homology search and then homology modelling is used to get the 3-D structure of the protein. Results: The 3-D structure of SAS2271 transcriptional factor of AraC family in MSSA476 strain of S. aureus was modelled and validated using the Ramachandran plot. Conclusions: The knowledge of 3-D structure of the protein will be helpful in identifying its biochemical function along with its regulatory mechanism in causing virulence.

  5. PCR mutagenesis identifies a polymerase-binding sequence of sigma 54 that includes a sigma 70 homology region.

    Science.gov (United States)

    Tintut, Y; Gralla, J D

    1995-10-01

    Sigma 54 is a minor bacterial sigma factor that is not a member of the sigma 70 family of proteins but binds the same core RNA polymerase. Previously, we identified a region of sigma 54 that is important for binding core polymerase. In this work, PCR mutagenesis was used to identify specific amino acids important for this binding. The results show that important residues are clustered most closely in a short sequence that was previously speculated to be potentially homologous to a sequence in sigma 70. The mutagenesis also identifies important residues in the flanking hydrophobic-acidic region of sigma 54, which is absent in sigma 70. Overall, the data indicate that sigma 54 binds core polymerase through a sequence homologous to that of sigma 70 but in addition uses unique motifs to modify this interaction.

  6. The Tomato FRUITFULL Homologs TDR4/FUL1 and MBP7/FUL2 Regulate Ethylene-Independent Aspects of Fruit Ripening

    NARCIS (Netherlands)

    Bemer, M.; Karlova, R.B.; Ballester, A.R.; Tikunov, Y.M.; Bovy, A.G.; Wolters-Arts, M.; Barros Rossetto, de P.; Angenent, G.C.; Maagd, de R.A.

    2012-01-01

    Tomato (Solanum lycopersicum) contains two close homologs of the Arabidopsis thaliana MADS domain transcription factor FRUITFULL (FUL), FUL1 (previously called TDR4) and FUL2 (previously MBP7). Both proteins interact with the ripening regulator RIPENING INHIBITOR (RIN) and are expressed during fruit

  7. μ-Opioid receptor desensitization: homologous or heterologous?

    Science.gov (United States)

    Llorente, Javier; Lowe, Janet D; Sanderson, Helen S; Tsisanova, Elena; Kelly, Eamonn; Henderson, Graeme; Bailey, Chris P

    2012-12-01

    There is considerable controversy over whether μ-opioid receptor (MOPr) desensitization is homologous or heterologous and over the mechanisms underlying such desensitization. In different cell types MOPr desensitization has been reported to involve receptor phosphorylation by various kinases, including G-protein-coupled receptor kinases (GRKs), second messenger and other kinases as well as perturbation of the MOPr effector pathway by GRK sequestration of G protein βγ subunits or ion channel modulation. Here we report that in brainstem locus coeruleus (LC) neurons prepared from relatively mature rats (5-8 weeks old) rapid MOPr desensitization induced by the high-efficacy opioid peptides methionine enkephalin and DAMGO was homologous and not heterologous to α(2)-adrenoceptors and somatostatin SST(2) receptors. Given that these receptors all couple through G proteins to the same set of G-protein inwardly rectifying (GIRK) channels it is unlikely therefore that in mature neurons MOPr desensitization involves G protein βγ subunit sequestration or ion channel modulation. In contrast, in slices from immature animals (less than postnatal day 20), MOPr desensitization was observed to be heterologous and could be downstream of the receptor. Heterologous MOPr desensitization was not dependent on protein kinase C or c-Jun N-terminal kinase activity, but the change from heterologous to homologous desensitization with age was correlated with a decrease in the expression levels of GRK2 in the LC and other brain regions. The observation that the mechanisms underlying MOPr desensitization change with neuronal development is important when extrapolating to the mature brain results obtained from experiments on expression systems, cell lines and immature neuronal preparations.

  8. A procedure for identifying homologous alternative splicing events

    Directory of Open Access Journals (Sweden)

    Orozco Modesto

    2007-07-01

    Full Text Available Abstract Background The study of the functional role of alternative splice isoforms of a gene is a very active area of research in biology. The difficulty of the experimental approach (in particular, in its high-throughput version leaves ample room for the development of bioinformatics tools that can provide a useful first picture of the problem. Among the possible approaches, one of the simplest is to follow classical protein function annotation protocols and annotate target alternative splice events with the information available from conserved events in other species. However, the application of this protocol requires a procedure capable of recognising such events. Here we present a simple but accurate method developed for this purpose. Results We have developed a method for identifying homologous, or equivalent, alternative splicing events, based on the combined use of neural networks and sequence searches. The procedure comprises four steps: (i BLAST search for homologues of the two isoforms defining the target alternative splicing event; (ii construction of all possible candidate events; (iii scoring of the latter with a series of neural networks; and (iv filtering of the results. When tested in a set of 473 manually annotated pairs of homologous events, our method showed a good performance, with an accuracy of 0.99, a precision of 0.98 and a sensitivity of 0.93. When no candidates were available, the specificity of our method varied between 0.81 and 0.91. Conclusion The method described in this article allows the identification of homologous alternative splicing events, with a good success rate, indicating that such method could be used for the development of functional annotation of alternative splice isoforms.

  9. Cell cycle-dependent control of homologous recombination.

    Science.gov (United States)

    Zhao, Xin; Wei, Chengwen; Li, Jingjing; Xing, Poyuan; Li, Jingyao; Zheng, Sihao; Chen, Xuefeng

    2017-08-01

    DNA double-strand breaks (DSBs) are among the most deleterious type of DNA lesions threatening genome integrity. Homologous recombination (HR) and non-homologous end joining (NHEJ) are two major pathways to repair DSBs. HR requires a homologous template to direct DNA repair, and is generally recognized as a high-fidelity pathway. In contrast, NHEJ directly seals broken ends, but the repair product is often accompanied by sequence alterations. The choice of repair pathways is strictly controlled by the cell cycle. The occurrence of HR is restricted to late S to G2 phases while NHEJ operates predominantly in G1 phase, although it can act throughout most of the cell cycle. Deregulation of repair pathway choice can result in genotoxic consequences associated with cancers. How the cell cycle regulates the choice of HR and NHEJ has been extensively studied in the past decade. In this review, we will focus on the current progresses on how HR is controlled by the cell cycle in both Saccharomyces cerevisiae and mammals. Particular attention will be given to how cyclin-dependent kinases modulate DSB end resection, DNA damage checkpoint signaling, repair and processing of recombination intermediates. In addition, we will discuss recent findings on how HR is repressed in G1 and M phases by the cell cycle. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. The PIKE homolog Centaurin gamma regulates developmental timing in Drosophila.

    Science.gov (United States)

    Gündner, Anna Lisa; Hahn, Ines; Sendscheid, Oliver; Aberle, Hermann; Hoch, Michael

    2014-01-01

    Phosphoinositide-3-kinase enhancer (PIKE) proteins encoded by the PIKE/CENTG1 gene are members of the gamma subgroup of the Centaurin superfamily of small GTPases. They are characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH) domain, a GTPase-activating (GAP) domain, Ankyrin repeats as well as an intrinsic GTPase domain. In mammals, three PIKE isoforms with variations in protein structure and subcellular localization are encoded by the PIKE locus. PIKE inactivation in mice results in a broad range of defects, including neuronal cell death during brain development and misregulation of mammary gland development. PIKE -/- mutant mice are smaller, contain less white adipose tissue, and show insulin resistance due to misregulation of AMP-activated protein kinase (AMPK) and insulin receptor/Akt signaling. here, we have studied the role of PIKE proteins in metabolic regulation in the fly. We show that the Drosophila PIKE homolog, ceng1A, encodes functional GTPases whose internal GAP domains catalyze their GTPase activity. To elucidate the biological function of ceng1A in flies, we introduced a deletion in the ceng1A gene by homologous recombination that removes all predicted functional PIKE domains. We found that homozygous ceng1A mutant animals survive to adulthood. In contrast to PIKE -/- mouse mutants, genetic ablation of Drosophila ceng1A does not result in growth defects or weight reduction. Although metabolic pathways such as insulin signaling, sensitivity towards starvation and mobilization of lipids under high fed conditions are not perturbed in ceng1A mutants, homozygous ceng1A mutants show a prolonged development in second instar larval stage, leading to a late onset of pupariation. In line with these results we found that expression of ecdysone inducible genes is reduced in ceng1A mutants. Together, we propose a novel role for Drosophila Ceng1A in regulating ecdysone signaling-dependent second to third instar

  11. The PIKE homolog Centaurin gamma regulates developmental timing in Drosophila.

    Directory of Open Access Journals (Sweden)

    Anna Lisa Gündner

    Full Text Available Phosphoinositide-3-kinase enhancer (PIKE proteins encoded by the PIKE/CENTG1 gene are members of the gamma subgroup of the Centaurin superfamily of small GTPases. They are characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH domain, a GTPase-activating (GAP domain, Ankyrin repeats as well as an intrinsic GTPase domain. In mammals, three PIKE isoforms with variations in protein structure and subcellular localization are encoded by the PIKE locus. PIKE inactivation in mice results in a broad range of defects, including neuronal cell death during brain development and misregulation of mammary gland development. PIKE -/- mutant mice are smaller, contain less white adipose tissue, and show insulin resistance due to misregulation of AMP-activated protein kinase (AMPK and insulin receptor/Akt signaling. here, we have studied the role of PIKE proteins in metabolic regulation in the fly. We show that the Drosophila PIKE homolog, ceng1A, encodes functional GTPases whose internal GAP domains catalyze their GTPase activity. To elucidate the biological function of ceng1A in flies, we introduced a deletion in the ceng1A gene by homologous recombination that removes all predicted functional PIKE domains. We found that homozygous ceng1A mutant animals survive to adulthood. In contrast to PIKE -/- mouse mutants, genetic ablation of Drosophila ceng1A does not result in growth defects or weight reduction. Although metabolic pathways such as insulin signaling, sensitivity towards starvation and mobilization of lipids under high fed conditions are not perturbed in ceng1A mutants, homozygous ceng1A mutants show a prolonged development in second instar larval stage, leading to a late onset of pupariation. In line with these results we found that expression of ecdysone inducible genes is reduced in ceng1A mutants. Together, we propose a novel role for Drosophila Ceng1A in regulating ecdysone signaling-dependent second to

  12. Building multiclass classifiers for remote homology detection and fold recognition

    Directory of Open Access Journals (Sweden)

    Karypis George

    2006-10-01

    Full Text Available Abstract Background Protein remote homology detection and fold recognition are central problems in computational biology. Supervised learning algorithms based on support vector machines are currently one of the most effective methods for solving these problems. These methods are primarily used to solve binary classification problems and they have not been extensively used to solve the more general multiclass remote homology prediction and fold recognition problems. Results We present a comprehensive evaluation of a number of methods for building SVM-based multiclass classification schemes in the context of the SCOP protein classification. These methods include schemes that directly build an SVM-based multiclass model, schemes that employ a second-level learning approach to combine the predictions generated by a set of binary SVM-based classifiers, and schemes that build and combine binary classifiers for various levels of the SCOP hierarchy beyond those defining the target classes. Conclusion Analyzing the performance achieved by the different approaches on four different datasets we show that most of the proposed multiclass SVM-based classification approaches are quite effective in solving the remote homology prediction and fold recognition problems and that the schemes that use predictions from binary models constructed for ancestral categories within the SCOP hierarchy tend to not only lead to lower error rates but also reduce the number of errors in which a superfamily is assigned to an entirely different fold and a fold is predicted as being from a different SCOP class. Our results also show that the limited size of the training data makes it hard to learn complex second-level models, and that models of moderate complexity lead to consistently better results.

  13. The eIF4G–homolog p97 can activate translation independent of caspase cleavage

    OpenAIRE

    Nousch, Marco; Reed, Victoria; Bryson-Richardson, Robert J.; Currie, Peter D.; Preiss, Thomas

    2007-01-01

    The eukaryotic initiation factor (eIF) 4G family plays a central role during translation initiation, bridging between the 5′ and 3′ ends of the mRNA via its N-terminal third while recruiting other factors and ribosomes through its central and C-terminal third. The protein p97/NAT1/DAP5 is homologous to the central and C-terminal thirds of eIF4G. p97 has long been considered to be a translational repressor under normal cellular conditions. Further, caspase cleavage liberates a p86 fragment tha...

  14. The growth rate of symplectic homology and affine varieties

    CERN Document Server

    McLean, Mark

    2010-01-01

    We will show that the cotangent bundle of an integrally hyperbolic manifold is not symplectomorphic to any smooth affine variety. We will also show that the unit cotangent bundle of such a manifold is not Stein fillable by a Stein domain whose completion is symplectomorphic to a smooth affine variety. For instance, these results hold when our manifolds are simply connected with at least one Betti number greater than the corresponding Betti number of the n torus. We use an invariant called the growth rate of symplectic homology to prove this result.

  15. Identification of rodent homologs of hepatitis C virus and pegiviruses

    DEFF Research Database (Denmark)

    Kapoor, Amit; Simmonds, Peter; Scheel, Troels K H

    2013-01-01

    Flaviviridae. The genetic diversity of the rodent hepaciviruses exceeded that observed for hepaciviruses infecting either humans or non-primates, leading to new insights into the origin, evolution, and host range of hepaciviruses. The presence of genes, encoded proteins, and translation elements homologous......-like viruses were found in deer mice (Peromyscus maniculatus), a small rodent used in laboratories to study viruses, including hantaviruses. We also identified pegiviruses in rodents that are distinct from the pegiviruses found in primates, bats, and horses. These novel viruses may enable the development...

  16. The colocalization transition of homologous chromosomes at meiosis

    Science.gov (United States)

    Nicodemi, Mario; Panning, Barbara; Prisco, Antonella

    2008-06-01

    Meiosis is the specialized cell division required in sexual reproduction. During its early stages, in the mother cell nucleus, homologous chromosomes recognize each other and colocalize in a crucial step that remains one of the most mysterious of meiosis. Starting from recent discoveries on the system molecular components and interactions, we discuss a statistical mechanics model of chromosome early pairing. Binding molecules mediate long-distance interaction of special DNA recognition sequences and, if their concentration exceeds a critical threshold, they induce a spontaneous colocalization transition of chromosomes, otherwise independently diffusing.

  17. The Non-Homologous Nature of Solar Diameter Variations

    CERN Document Server

    Sofia, S; Demarque, P; Li, L; Thuillier, G; Sofia, Sabatino; Basu, Sarbani; Demarque, Pierre; Li, Linghuai; Thuillier, Gerard

    2005-01-01

    We show in this paper that the changes of the solar diameter in response to variations of large scale magnetic fields and turbulence are not homologous. For the best current model, the variation at the photospheric level is over 1000 times larger than the variation at a depth of 5 Mm, which is about the level at which f-mode solar oscillations determine diameter variations. This model is supported by observations that indicate larger diameter changes for high degree f-modes than for low degree f-modes, since energy of the former are concentrated at shallower layers than the latter.

  18. Building Multiclass Classifiers for Remote Homology Detection and Fold Recognition

    Science.gov (United States)

    2006-04-05

    NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS...are thoroughly evaluated for both remote homology prediction and fold recognition using four differ- ent datasets derived from Astral [5]. Our...function may not be the most appropriate as it may lead to models where 5 Table 1: Dataset Statistics. Statistic DS1 DS2 DS3 DS4 ASTRAL filtering 90% 40% 25

  19. Seamless gene tagging by endonuclease-driven homologous recombination.

    Directory of Open Access Journals (Sweden)

    Anton Khmelinskii

    Full Text Available Gene tagging facilitates systematic genomic and proteomic analyses but chromosomal tagging typically disrupts gene regulatory sequences. Here we describe a seamless gene tagging approach that preserves endogenous gene regulation and is potentially applicable in any species with efficient DNA double-strand break repair by homologous recombination. We implement seamless tagging in Saccharomyces cerevisiae and demonstrate its application for protein tagging while preserving simultaneously upstream and downstream gene regulatory elements. Seamless tagging is compatible with high-throughput strain construction using synthetic genetic arrays (SGA, enables functional analysis of transcription antisense to open reading frames and should facilitate systematic and minimally-invasive analysis of gene functions.

  20. Drosophila homolog of the murine Int-1 protooncogene.

    OpenAIRE

    1988-01-01

    We have isolated phage clones from Drosophila melanogaster genomic and cDNA libraries containing a sequence homologous to the murine Int-1 protooncogene. The Drosophila gene is represented by a single locus at position 28A1-2 on chromosome 2. The gene is expressed as a 2.9-kilobase-long polyadenylylated mRNA in embryo, larval, and pupal stages. It is hardly detectable in adult flies. The longest open reading frame of the cDNA clone corresponds to a protein 469 amino acids long. Alignment of t...

  1. Parallel Computation of Persistent Homology using the Blowup Complex

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Ryan [Stanford Univ., CA (United States); Morozov, Dmitriy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-04-27

    We describe a parallel algorithm that computes persistent homology, an algebraic descriptor of a filtered topological space. Our algorithm is distinguished by operating on a spatial decomposition of the domain, as opposed to a decomposition with respect to the filtration. We rely on a classical construction, called the Mayer--Vietoris blowup complex, to glue global topological information about a space from its disjoint subsets. We introduce an efficient algorithm to perform this gluing operation, which may be of independent interest, and describe how to process the domain hierarchically. We report on a set of experiments that help assess the strengths and identify the limitations of our method.

  2. Relative Binding Free Energy Calculations Applied to Protein Homology Models.

    Science.gov (United States)

    Cappel, Daniel; Hall, Michelle Lynn; Lenselink, Eelke B; Beuming, Thijs; Qi, Jun; Bradner, James; Sherman, Woody

    2016-12-27

    A significant challenge and potential high-value application of computer-aided drug design is the accurate prediction of protein-ligand binding affinities. Free energy perturbation (FEP) using molecular dynamics (MD) sampling is among the most suitable approaches to achieve accurate binding free energy predictions, due to the rigorous statistical framework of the methodology, correct representation of the energetics, and thorough treatment of the important degrees of freedom in the system (including explicit waters). Recent advances in sampling methods and force fields coupled with vast increases in computational resources have made FEP a viable technology to drive hit-to-lead and lead optimization, allowing for more efficient cycles of medicinal chemistry and the possibility to explore much larger chemical spaces. However, previous FEP applications have focused on systems with high-resolution crystal structures of the target as starting points-something that is not always available in drug discovery projects. As such, the ability to apply FEP on homology models would greatly expand the domain of applicability of FEP in drug discovery. In this work we apply a particular implementation of FEP, called FEP+, on congeneric ligand series binding to four diverse targets: a kinase (Tyk2), an epigenetic bromodomain (BRD4), a transmembrane GPCR (A2A), and a protein-protein interaction interface (BCL-2 family protein MCL-1). We apply FEP+ using both crystal structures and homology models as starting points and find that the performance using homology models is generally on a par with the results when using crystal structures. The robustness of the calculations to structural variations in the input models can likely be attributed to the conformational sampling in the molecular dynamics simulations, which allows the modeled receptor to adapt to the "real" conformation for each ligand in the series. This work exemplifies the advantages of using all-atom simulation methods with

  3. Addressing inaccuracies in BLOSUM computation improves homology search performance.

    Science.gov (United States)

    Hess, Martin; Keul, Frank; Goesele, Michael; Hamacher, Kay

    2016-04-27

    BLOSUM matrices belong to the most commonly used substitution matrix series for protein homology search and sequence alignments since their publication in 1992. In 2008, Styczynski et al. discovered miscalculations in the clustering step of the matrix computation. Still, the RBLOSUM64 matrix based on the corrected BLOSUM code was reported to perform worse at a statistically significant level than the BLOSUM62. Here, we present a further correction of the (R)BLOSUM code and provide a thorough performance analysis of BLOSUM-, RBLOSUM- and the newly derived CorBLOSUM-type matrices. Thereby, we assess homology search performance of these matrix-types derived from three different BLOCKS databases on all versions of the ASTRAL20, ASTRAL40 and ASTRAL70 subsets resulting in 51 different benchmarks in total. Our analysis is focused on two of the most popular BLOSUM matrices - BLOSUM50 and BLOSUM62. Our study shows that fixing small errors in the BLOSUM code results in substantially different substitution matrices with a beneficial influence on homology search performance when compared to the original matrices. The CorBLOSUM matrices introduced here performed at least as good as their BLOSUM counterparts in ∼75 % of all test cases. On up-to-date ASTRAL databases BLOSUM matrices were even outperformed by CorBLOSUM matrices in more than 86 % of the times. In contrast to the study by Styczynski et al., the tested RBLOSUM matrices also outperformed the corresponding BLOSUM matrices in most of the cases. Comparing the CorBLOSUM with the RBLOSUM matrices revealed no general performance advantages for either on older ASTRAL releases. On up-to-date ASTRAL databases however CorBLOSUM matrices performed better than their RBLOSUM counterparts in ∼74 % of the test cases. Our results imply that CorBLOSUM type matrices outperform the BLOSUM matrices on a statistically significant level in most of the cases, especially on up-to-date databases such as ASTRAL ≥2.01. Additionally, Cor

  4. A spectral sequence in odd Khovanov homology (Eine Spektralsequenz in ungerader Khovanov-Homologie)

    CERN Document Server

    Beier, Simon

    2011-01-01

    Ozsvath, Rasmussen and Szabo constructed odd Khovanov homology. It is a link invariant which has the same reduction modulo 2 as (even) Khovanov homology. Szabo introduced a spectral sequence with mod 2 coefficients from mod 2 Khovanov homology to another link homology. He got his spectral sequence from a chain complex with a filtration. We give an integral lift of Szabo's complex, that provides a spectral sequence from odd Khovanov homology to a link homology, from which one can get Szabo's link homology with the Universal Coefficient Theorem. Szabo has constructed such a lift independently, but has not yet published it. This is my master thesis which I wrote under supervision of Thomas Schick at Georg August University G\\"ottingen in summer 2011. It is in German. I will publish a reworked version in English later.

  5. Discovery of a Homolog of Siderophilin in a Plant

    Institute of Scientific and Technical Information of China (English)

    Yun-Biao FEI; Peng-Xiu CAO; Su-Qin GAO; Ling-Bo WEI; Bin WANG

    2005-01-01

    Members belonging to the siderophilin family are iron-binding and iron-transporting proteins,which includes transferrin and lactoferrin. They have only been found in animals previously. If siderophilin could be found in and isolated from a plant, its production and subsequent extensive application could be increased. The present study is the first to report the discovery of a homolog of siderophilin in a plant. In order to purify antifreeze proteins from Ammopiptanthus mongolicus (Maxim.) Cheng f., the authors processed the proteins from the leaves using techniques such as column chromatography using DEAE-Cellulose-52, gel filtration via Sephacryl S-100 HR medium, hydrophobic interaction chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mass spectroscopy was performed on the three proteins purified and the sequence of one of the proteins (containing 32 amino acids) was found to have 97%homology with the corresponding part of one type of human lactoferrin. Moreover, one of the two peptides belongs to an iron-binding domain. So, it is possible that siderophilin also exists in plants and plays a role as an antibacterial and antifungal, among other actions.

  6. Nasal pungency and odor of homologous aldehydes and carboxylic acids.

    Science.gov (United States)

    Cometto-Muñiz, J E; Cain, W S; Abraham, M H

    1998-01-01

    Airborne substances can stimulate both the olfactory and the trigeminal nerve in the nose, giving rise to odor and pungent (irritant) sensations, respectively. Nose, eye, and throat irritation constitute common adverse effects in indoor environments. We measured odor and nasal pungency thresholds for homologous aliphatic aldehydes (butanal through octanal) and carboxylic acids (formic, acetic, butanoic, hexanoic, and octanoic). Nasal pungency was measured in subjects lacking olfaction (i.e., anosmics) to avoid odor biases. Similar to other homologous series, odor and pungency thresholds declined (i.e., sensory potency increased) with increasing carbon chain length. A previously derived quantitative structure-activity relationship (QSAR) based on solvation energies predicted all nasal pungency thresholds, except for acetic acid, implying that a key step in the mechanism for threshold pungency involves transfer of the inhaled substance from the vapor phase to the receptive biological phase. In contrast, acetic acid - with a pungency threshold lower than predicted - is likely to produce threshold pungency through direct chemical reaction with the mucosa. Both in the series studied here and in those studied previously, we reach a member at longer chain-lengths beyond which pungency fades. The evidence suggests a biological cut-off, presumably based upon molecular size, across the various series.

  7. Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination

    Directory of Open Access Journals (Sweden)

    Kritika Hanamshet

    2016-09-01

    Full Text Available Homologous recombination (HR plays an important role in maintaining genomic integrity. It is responsible for repair of the most harmful DNA lesions, DNA double-strand breaks and inter-strand DNA cross-links. HR function is also essential for proper segregation of homologous chromosomes in meiosis, maintenance of telomeres, and resolving stalled replication forks. Defects in HR often lead to genetic diseases and cancer. Rad52 is one of the key HR proteins, which is evolutionarily conserved from yeast to humans. In yeast, Rad52 is important for most HR events; Rad52 mutations disrupt repair of DNA double-strand breaks and targeted DNA integration. Surprisingly, in mammals, Rad52 knockouts showed no significant DNA repair or recombination phenotype. However, recent work demonstrated that mutations in human RAD52 are synthetically lethal with mutations in several other HR proteins including BRCA1 and BRCA2. These new findings indicate an important backup role for Rad52, which complements the main HR mechanism in mammals. In this review, we focus on the Rad52 activities and functions in HR and the possibility of using human RAD52 as therapeutic target in BRCA1 and BRCA2-deficient familial breast cancer and ovarian cancer.

  8. Flexible mapping of homology onto structure with Homolmapper

    Directory of Open Access Journals (Sweden)

    Lagarias J Clark

    2007-04-01

    Full Text Available Abstract Background Over the past decade, a number of tools have emerged for the examination of homology relationships among protein sequences in a structural context. Most recent software implementations for such analysis are tied to specific molecular viewing programs, which can be problematic for collaborations involving multiple viewing environments. Incorporation into larger packages also adds complications for users interested in adding their own scoring schemes or in analyzing proteins incorporating unusual amino acid residues such as selenocysteine. Results We describe homolmapper, a command-line application for mapping information from a multiple protein sequence alignment onto a protein structure for analysis in the viewing software of the user's choice. Homolmapper is small (under 250 K for the application itself and is written in Python to ensure portability. It is released for non-commercial use under a modified University of California BSD license. Homolmapper permits facile import of additional scoring schemes and can incorporate arbitrary additional amino acids to allow handling of residues such as selenocysteine or pyrrolysine. Homolmapper also provides tools for defining and analyzing subfamilies relative to a larger alignment, for mutual information analysis, and for rapidly visualizing the locations of mutations and multi-residue motifs. Conclusion Homolmapper is a useful tool for analysis of homology relationships among proteins in a structural context. There is also extensive, example-driven documentation available. More information about homolmapper is available at http://www.mcb.ucdavis.edu/faculty-labs/lagarias/homolmapper_home/homolmapper%20web%20page.htm.

  9. Bloom Syndrome Helicase Promotes Meiotic Crossover Patterning and Homolog Disjunction.

    Science.gov (United States)

    Hatkevich, Talia; Kohl, Kathryn P; McMahan, Susan; Hartmann, Michaelyn A; Williams, Andrew M; Sekelsky, Jeff

    2017-01-09

    In most sexually reproducing organisms, crossover formation between homologous chromosomes is necessary for proper chromosome disjunction during meiosis I. During meiotic recombination, a subset of programmed DNA double-strand breaks (DSBs) are repaired as crossovers, with the remainder becoming noncrossovers [1]. Whether a repair intermediate is designated to become a crossover is a highly regulated decision that integrates several crossover patterning processes, both along chromosome arms (interference and the centromere effect) and between chromosomes (crossover assurance) [2]. Because the mechanisms that generate crossover patterning have remained elusive for over a century, it has been difficult to assess the relationship between crossover patterning and meiotic chromosome behavior. We show here that meiotic crossover patterning is lost in Drosophila melanogaster mutants that lack the Bloom syndrome helicase. In the absence of interference and the centromere effect, crossovers are distributed more uniformly along chromosomes. Crossovers even occur on the small chromosome 4, which normally never has meiotic crossovers [3]. Regulated distribution of crossovers between chromosome pairs is also lost, resulting in an elevated frequency of homologs that do not receive a crossover, which in turn leads to elevated nondisjunction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. On discrete symmetries and torsion homology in F-theory

    Energy Technology Data Exchange (ETDEWEB)

    Mayrhofer, Christoph [Arnold-Sommerfeld-Center, Ludwig-Maximilians-Universität München,München (Germany); Palti, Eran; Till, Oskar; Weigand, Timo [Institut für Theoretische Physik, Ruprecht-Karls-Universität Heidelberg,Heidelberg (Germany)

    2015-06-04

    We study the relation between discrete gauge symmetries in F-theory compactifications and torsion homology on the associated Calabi-Yau manifold. Focusing on the simplest example of a ℤ{sub 2} symmetry, we show that there are two physically distinct ways that such a discrete gauge symmetry can arise. First, compactifications of M-Theory on Calabi-Yau threefolds which support a genus-one fibration with a bi-section are known to be dual to six-dimensional F-theory vacua with a ℤ{sub 2} gauge symmetry. We show that the resulting five-dimensional theories do not have a ℤ{sub 2} symmetry but that the latter emerges only in the F-theory decompactification limit. Accordingly the genus-one fibred Calabi-Yau manifolds do not exhibit torsion in homology. Associated to the bi-section fibration is a Jacobian fibration which does support a section. Compactifying on these related but distinct varieties does lead to a ℤ{sub 2} symmetry in five dimensions and, accordingly, we find explicitly an associated torsion cycle. We identify the expected particle and membrane system of the discrete symmetry in terms of wrapped M2 and M5 branes and present a field-theory description of the physics for both cases in terms of circle reductions of six-dimensional theories. Our results and methods generalise straightforwardly to larger discrete symmetries and to four-dimensional compactifications.

  11. CRISPR/Cas9 Genome Editing in Caenorhabditis elegans: Evaluation of Templates for Homology-Mediated Repair and Knock-Ins by Homology-Independent DNA Repair.

    Science.gov (United States)

    Katic, Iskra; Xu, Lan; Ciosk, Rafal

    2015-06-03

    Precise genome editing by the Cas9 nuclease depends on exogenously provided templates for homologous recombination. Here, we compare oligonucleotides with short homology and circular DNA molecules with extensive homology to genomic targets as templates for homology-based repair of CRISPR/Cas9 induced double-strand breaks. We find oligonucleotides to be templates of choice for introducing small sequence changes into the genome based on editing efficiency and ease of use. We show that polarity of oligonucleotide templates greatly affects repair efficiency: oligonucleotides in the sense orientation with respect to the target gene are better templates. In addition, combining a gene loss-of-function phenotype screen with detection of integrated fluorescent markers, we demonstrate that targeted knock-ins in Caenorhabditis elegans also can be achieved by homology-independent repair. Copyright © 2015 Katic et al.

  12. Homological Mirror Symmetry for Calabi-Yau hypersurfaces in projective space

    CERN Document Server

    Sheridan, Nicholas

    2011-01-01

    We prove Homological Mirror Symmetry for a smooth d-dimensional Calabi-Yau hypersurface in projective space, for any d > 2 (for example, d = 3 is the quintic three-fold). The main techniques involved in the proof are: the construction of an immersed Lagrangian sphere in the `d-dimensional pair of pants'; the introduction of the `relative Fukaya category', and an understanding of its grading structure; a description of the behaviour of this category with respect to branched covers (via an `orbifold' Fukaya category); a Morse-Bott model for the relative Fukaya category that allows one to make explicit computations; and the introduction of certain graded categories of matrix factorizations mirror to the relative Fukaya category.

  13. No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

    Institute of Scientific and Technical Information of China (English)

    Lynette S Phillips; Cheryl L Thompson; Alona Merkulova; Sarah J Plummer; Thomas C Tucker; Graham Casey; Li Li

    2009-01-01

    AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based casecontrol study of incident colon cancer individuals ( n = 421) and controls ( n = 483) aged ≥ 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. RESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors ( P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene.

  14. Separation and PurificationHomologous Compounds byof Dodecanedioic Acid from Its Falling Film Crystallization

    Institute of Scientific and Technical Information of China (English)

    李裕; 刘有智; 齐雪琴

    2004-01-01

    Separation and purification of dodecanedioic acid (DDDA) from its homologous compounds were studied experimentally by falling film crystallization (FFC). The influences of various operation parameters, including crystallizing time, flow rate of melt and temperature of glycerine bath, on purity of DDDA and crystallizing rate were investigated. Over 99% (by mole) DDDA was obtained for a feed composition of 96% (by mole). The main factors affecting the separation efficiency are flow rate of melt and temperature of glycerine bath. The crystallizing layer of DDDA was further purified by sweating and blasting. A set of optimized operation data are provided for better understanding the mechanism of heat and mass transfer in FFC, and for further industrial application of DDDA purification process.

  15. LEDGF (p75) promotes DNA-end resection and homologous recombination

    DEFF Research Database (Denmark)

    Daugaard, Mads; Baude, Annika; Fugger, Kasper

    2012-01-01

    ) by the homologous recombination repair pathway. Depletion of LEDGF impairs the recruitment of C-terminal binding protein interacting protein (CtIP) to DNA DSBs and the subsequent CtIP-dependent DNA-end resection. LEDGF is constitutively associated with chromatin through its Pro-Trp-Trp-Pro (PWWP) domain that binds......Lens epithelium-derived growth factor p75 splice variant (LEDGF) is a chromatin-binding protein known for its antiapoptotic activity and ability to direct human immunodeficiency virus into active transcription units. Here we show that LEDGF promotes the repair of DNA double-strand breaks (DSBs...... preferentially to epigenetic methyl-lysine histone markers characteristic of active transcription units. LEDGF binds CtIP in a DNA damage-dependent manner, thereby enhancing its tethering to the active chromatin and facilitating its access to DNA DSBs. These data highlight the role of PWWP-domain proteins in DNA...

  16. Context-dependent dual role of SKI8 homologs in mRNA synthesis and turnover.

    Directory of Open Access Journals (Sweden)

    Eavan Dorcey

    Full Text Available Eukaryotic mRNA transcription and turnover is controlled by an enzymatic machinery that includes RNA polymerase II and the 3' to 5' exosome. The activity of these protein complexes is modulated by additional factors, such as the nuclear RNA polymerase II-associated factor 1 (Paf1c and the cytoplasmic Superkiller (SKI complex, respectively. Their components are conserved across uni- as well as multi-cellular organisms, including yeast, Arabidopsis, and humans. Among them, SKI8 displays multiple facets on top of its cytoplasmic role in the SKI complex. For instance, nuclear yeast ScSKI8 has an additional function in meiotic recombination, whereas nuclear human hSKI8 (unlike ScSKI8 associates with Paf1c. The Arabidopsis SKI8 homolog VERNALIZATION INDEPENDENT 3 (VIP3 has been found in Paf1c as well; however, whether it also has a role in the SKI complex remains obscure so far. We found that transgenic VIP3-GFP, which complements a novel vip3 mutant allele, localizes to both nucleus and cytoplasm. Consistently, biochemical analyses suggest that VIP3-GFP associates with the SKI complex. A role of VIP3 in the turnover of nuclear encoded mRNAs is supported by random-primed RNA sequencing of wild-type and vip3 seedlings, which indicates mRNA stabilization in vip3. Another SKI subunit homolog mutant, ski2, displays a dwarf phenotype similar to vip3. However, unlike vip3, it displays neither early flowering nor flower development phenotypes, suggesting that the latter reflect VIP3's role in Paf1c. Surprisingly then, transgenic ScSKI8 rescued all aspects of the vip3 phenotype, suggesting that the dual role of SKI8 depends on species-specific cellular context.

  17. Homologous recombination and non-homologous end-joining repair pathways in bovine embryos with different developmental competence

    Energy Technology Data Exchange (ETDEWEB)

    Henrique Barreta, Marcos [Universidade Federal de Santa Catarina, Campus Universitario de Curitibanos, Curitibanos, SC (Brazil); Laboratorio de Biotecnologia e Reproducao Animal-BioRep, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Garziera Gasperin, Bernardo; Braga Rissi, Vitor; Cesaro, Matheus Pedrotti de [Laboratorio de Biotecnologia e Reproducao Animal-BioRep, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Ferreira, Rogerio [Centro de Educacao Superior do Oeste-Universidade do Estado de Santa Catarina, Chapeco, SC (Brazil); Oliveira, Joao Francisco de; Goncalves, Paulo Bayard Dias [Laboratorio de Biotecnologia e Reproducao Animal-BioRep, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Bordignon, Vilceu, E-mail: vilceu.bordignon@mcgill.ca [Department of Animal Science, McGill University, Ste-Anne-De-Bellevue, QC (Canada)

    2012-10-01

    This study investigated the expression of genes controlling homologous recombination (HR), and non-homologous end-joining (NHEJ) DNA-repair pathways in bovine embryos of different developmental potential. It also evaluated whether bovine embryos can respond to DNA double-strand breaks (DSBs) induced with ultraviolet irradiation by regulating expression of genes involved in HR and NHEJ repair pathways. Embryos with high, intermediate or low developmental competence were selected based on the cleavage time after in vitro insemination and were removed from in vitro culture before (36 h), during (72 h) and after (96 h) the expected period of embryonic genome activation. All studied genes were expressed before, during and after the genome activation period regardless the developmental competence of the embryos. Higher mRNA expression of 53BP1 and RAD52 was found before genome activation in embryos with low developmental competence. Expression of 53BP1, RAD51 and KU70 was downregulated at 72 h and upregulated at 168 h post-insemination in response to DSBs induced by ultraviolet irradiation. In conclusion, important genes controlling HR and NHEJ DNA-repair pathways are expressed in bovine embryos, however genes participating in these pathways are only regulated after the period of embryo genome activation in response to ultraviolet-induced DSBs.

  18. Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance

    Science.gov (United States)

    Jagut, Marlène; Hamminger, Patricia; Woglar, Alexander; Millonigg, Sophia; Paulin, Luis; Mikl, Martin; Dello Stritto, Maria Rosaria; Tang, Lois; Habacher, Cornelia; Tam, Angela; Gallach, Miguel; von Haeseler, Arndt; Villeneuve, Anne M.; Jantsch, Verena

    2016-01-01

    During the first meiotic division, crossovers (COs) between homologous chromosomes ensure their correct segregation. COs are produced by homologous recombination (HR)-mediated repair of programmed DNA double strand breaks (DSBs). As more DSBs are induced than COs, mechanisms are required to establish a regulated number of COs and to repair remaining intermediates as non-crossovers (NCOs). We show that the Caenorhabditis elegans RMI1 homolog-1 (RMH-1) functions during meiosis to promote both CO and NCO HR at appropriate chromosomal sites. RMH-1 accumulates at CO sites, dependent on known pro-CO factors, and acts to promote CO designation and enforce the CO outcome of HR-intermediate resolution. RMH-1 also localizes at NCO sites and functions in parallel with SMC-5 to antagonize excess HR-based connections between chromosomes. Moreover, RMH-1 also has a major role in channeling DSBs into an NCO HR outcome near the centers of chromosomes, thereby ensuring that COs form predominantly at off-center positions. PMID:27011106

  19. Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance.

    Science.gov (United States)

    Jagut, Marlène; Hamminger, Patricia; Woglar, Alexander; Millonigg, Sophia; Paulin, Luis; Mikl, Martin; Dello Stritto, Maria Rosaria; Tang, Lois; Habacher, Cornelia; Tam, Angela; Gallach, Miguel; von Haeseler, Arndt; Villeneuve, Anne M; Jantsch, Verena

    2016-03-01

    During the first meiotic division, crossovers (COs) between homologous chromosomes ensure their correct segregation. COs are produced by homologous recombination (HR)-mediated repair of programmed DNA double strand breaks (DSBs). As more DSBs are induced than COs, mechanisms are required to establish a regulated number of COs and to repair remaining intermediates as non-crossovers (NCOs). We show that the Caenorhabditis elegans RMI1 homolog-1 (RMH-1) functions during meiosis to promote both CO and NCO HR at appropriate chromosomal sites. RMH-1 accumulates at CO sites, dependent on known pro-CO factors, and acts to promote CO designation and enforce the CO outcome of HR-intermediate resolution. RMH-1 also localizes at NCO sites and functions in parallel with SMC-5 to antagonize excess HR-based connections between chromosomes. Moreover, RMH-1 also has a major role in channeling DSBs into an NCO HR outcome near the centers of chromosomes, thereby ensuring that COs form predominantly at off-center positions.

  20. A conserved hydrophobic surface of the LARG pleckstrin homology domain is critical for RhoA activation in cells.

    Science.gov (United States)

    Aittaleb, Mohamed; Gao, Guang; Evelyn, Chris R; Neubig, Richard R; Tesmer, John J G

    2009-11-01

    Leukemia associated Rho guanine nucleotide exchange factor (LARG) activates RhoA in response to signals received by specific classes of cell surface receptors. The catalytic core of LARG is a Dbl homology (DH) domain whose activity is modulated by an adjacent pleckstrin homology (PH) domain. In this study, we used a transcriptional assay and confocal microscopy to examine the roles of several novel structural features of the LARG DH/PH domains, including a conserved and exposed hydrophobic patch on the PH domain that mediates protein-protein interactions in crystal structures of LARG and its close homolog PDZ-RhoGEF. Mutation of the hydrophobic patch has no effect on nucleotide exchange activity in vitro, but abolished the ability of LARG to activate RhoA and to induce stress fiber formation in cultured cells. The activity of these mutants could be rescued by fusion with exogenous membrane-targeting domains. However, because membrane recruitment by activated G alpha(13) subunits was not sufficient to rescue activity of a hydrophobic patch mutant, the LARG PH domain cannot solely contribute to membrane targeting. Instead, it seems likely that the domain is involved in regulatory interactions with other proteins near the membrane surface. We also show that the hydrophobic patch of the PH domain is likely important for the activity of all Lbc subfamily RhoGEFs.