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Sample records for replication bir occurs

  1. No evidence for 'break-induced replication' in a higher plant – but break-induced conversion may occur

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    Ingo eSchubert

    2011-04-01

    Full Text Available ‘Break-induced replication’ (BIR is considered as one way to repair DNA double-strand breaks (DSBs. BIR is defined as replication of the proximal break-ends up to the end of the broken chromosome using an undamaged homologous double-stranded template and mimicking a non-reciprocal translocation. This phenomenon was detected by genetic experiments in yeast. BIR is assumed to occur also in mammals, but experimental evidence is not yet at hand. We have studied chromosomes of the field bean, Vicia faba L., as to the occurrence of BIR after DSB induction during S and G2 phase. Simultaneous incorporation of the base analogue ethynyldeoxyuridine (EdU revealed no chromosomal replication pattern indicative of BIR. Thus, if occurring at all, BIR does not play a major role for DSB repair in higher plants with large chromosome arms. However, the frequency of interstitial asymmetric EdU incorporation within heterochromatic regions, visible on metaphase chromosomes, increased after chromosome breakage during S and G2 phase. Such asymmetric labelling could be interpreted as conservative replication up to the next replicon, circumventing a DSB and yielding an interstitial conversion-like event.

  2. Global profiling of DNA replication timing and efficiency reveals that efficient replication/firing occurs late during S-phase in S. pombe.

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    Majid Eshaghi

    Full Text Available BACKGROUND: During S. pombe S-phase, initiation of DNA replication occurs at multiple sites (origins that are enriched with AT-rich sequences, at various times. Current studies of genome-wide DNA replication profiles have focused on the DNA replication timing and origin location. However, the replication and/or firing efficiency of the individual origins on the genomic scale remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using the genome-wide ORF-specific DNA microarray analysis, we show that in S. pombe, individual origins fire with varying efficiencies and at different times during S-phase. The increase in DNA copy number plotted as a function of time is approximated to the near-sigmoidal model, when considering the replication start and end timings at individual loci in cells released from HU-arrest. Replication efficiencies differ from origin to origin, depending on the origin's firing efficiency. We have found that DNA replication is inefficient early in S-phase, due to inefficient firing at origins. Efficient replication occurs later, attributed to efficient but late-firing origins. Furthermore, profiles of replication timing in cds1Delta cells are abnormal, due to the failure in resuming replication at the collapsed forks. The majority of the inefficient origins, but not the efficient ones, are found to fire in cds1Delta cells after HU removal, owing to the firing at the remaining unused (inefficient origins during HU treatment. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that efficient DNA replication/firing occurs late in S-phase progression in cells after HU removal, due to efficient late-firing origins. Additionally, checkpoint kinase Cds1p is required for maintaining the efficient replication/firing late in S-phase. We further propose that efficient late-firing origins are essential for ensuring completion of DNA duplication by the end of S-phase.

  3. Melon necrotic spot virus Replication Occurs in Association with Altered Mitochondria.

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    Gómez-Aix, Cristina; García-García, María; Aranda, Miguel A; Sánchez-Pina, María Amelia

    2015-04-01

    Melon necrotic spot virus (MNSV) (genus Carmovirus, family Tombusviridae) is a single-stranded, positive-sense RNA virus that has become an experimental model for the analysis of cell-to-cell virus movement and translation of uncapped viral RNAs, whereas little is known about its replication. Analysis of the cytopathology after MNSV infection showed the specific presence of modified organelles that resemble mitochondria. Immunolocalization of the glycine decarboxylase complex (GDC) P protein in these organelles confirmed their mitochondrial origin. In situ hybridization and immunolocalization experiments showed the specific localization of positive-sense viral RNA, capsid protein (CP), and double-stranded (ds)RNA in these organelles meaning that replication of the virus takes place in association with them. The three-dimensional reconstructions of the altered mitochondria showed the presence of large, interconnected, internal dilations which appeared to be linked to the outside cytoplasmic environment through pores and/or complex structures, and with lipid bodies. Transient expression of MNSV p29 revealed that its specific target is mitochondria. Our data document the extensive reorganization of host mitochondria induced by MNSV, which provides a protected environment to viral replication, and show that the MNSV p29 protein is the primary determinant of this effect in the host.

  4. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks

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    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia

    2016-01-01

    Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depl...

  5. Gorunmezler Dunyasinda Bir Ali

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    Erdem Özkara

    2007-04-01

    Full Text Available Bu kaçıncı denemem bilmiyorum, ama yazamıyorum bir türlü... Nasıl yazacağımı bilemiyorum ama yazmam gerekiyor. Çünkü O’nu tanıma şansına sahip olduğum için kendimi borçlu hissediyorum. O’nu bilmeyenlere anlatmam gerekiyor. Hani derler ya iyi insanların ardından “Bir yıldız daha kaydı bu dünyadan” diye. Ali Abi yalnızca “iyi” değildi aynı zamanda “asil” idi. Hayata karşı bakışı ve kendisini bekleyen ölümü çok iyi bildiği halde ölüme karşı mağrur ve metanetli duruşu ile gerçekten bize zarafeti gösterdi. John Mc Creery’nin sözü hislerimi anlatıyor: “Ölüm yoktur! Yıldızlar başka bir kıyıda doğmak için batarlar.” Evet Ali Yemişcigil artık başka bir boyutta, dün gece bir yıldız daha kaydı bu dünyadan ve başka bir yerde belki de “görünmezler dünyasında” parlayacak yeniden... Ve kalanlar; metanetli ailesi, üzerine titrediği ailesi, başta sevgili eşi Lale Abla, kızı Serra, oğlu Sefa, annesi, kardeşleri, yakınları, bizler... Onu yakından tanıyanlar olarak gerçekten çok acı çekiyoruz şu anda ama bir yandan da onun yaşama bakışını ve güzelliğini gördüğümüz için de şanslıyız aslında. I Iayat yolculuğunda kaç kişinin yolu böyle bir “Ali insan” ile kesişebilir, kaçımız böyle bir bilgeye rastlayabiliriz? Adının anlamını taşıyordu kişiliğiyle; “yüce” idi. İki gün sonra doğum günü, kırk beş yaşını bitirecekti, sürpriz doğum günü planlarken, sıkça verdiği mesajı bir daha hatırlatarak son dersi verdi Ali Abi; “Carpe diem-Anı yaşa, geleceği planlama, çünkü düşündüğün gibi olmayabilir” derdi hep. Haklısın Abi olmuyormuş, bir kere daha haklısın, maalesef... O’nu genç yaşta kaybettiğimiz için üzgünüz ama her anını dolu dolu yaşamaya çalıştığı hayatıyla kimilerinin 80 yıla sığdıramadıklarını yapabildi ve bu yönüyle örnek oldu. Martin Luther King

  6. Bir Kartagener Sendromu Olgusu

    OpenAIRE

    Mıkla, Şerare; Aydın, Ahmet; Birtane, Nügürt; Çam, Halit; Fıçıcıoğlu, Can; Yılmazer, Sema; Akaslan, İlhan

    2014-01-01

    Bu makalede immobil silya sendromu situs inversus totalis Kartagener sendromu tanısı konulan 4 yaşında erkek hasta sunulmuştur Bronş silyasında ultrastrüktürel incelemesinde iç ve veya dış dynein kollarında tam ya da kısmi defektler saptanmıştır Olgunun bir özelliği de Kartagener sendromunda şimdiye kadar bildirilmemiş olan malrotasyon anomalisine sahip olmasıdır Anahtar kelimeler: İmmobil Silya Sendromu Kartagener Sendromu Malrotasyon

  7. Characterization of large deletions occurring during a single round of retrovirus vector replication: novel deletion mechanism involving errors in strand transfer.

    OpenAIRE

    Pulsinelli, G A; Temin, H M

    1991-01-01

    Retroviruses mutate at a high rate during replication. We used a spleen necrosis virus-based vector system and helper cell line to characterize mutations occurring during a single round of retrovirus replication. The vector used, JD216HyNeo, codes for two drug resistance genes, hygromycin resistance (hygro) and neomycin resistance (neo). The downstream neo gene is expressed only when a mutation alleviates a block to splicing which is located in the upstream hygro gene. The mutations allowing ...

  8. Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse

    Science.gov (United States)

    Nguyen, Michael O; Jalan, Manisha; Morrow, Carl A; Osman, Fekret; Whitby, Matthew C

    2015-01-01

    The completion of genome duplication during the cell cycle is threatened by the presence of replication fork barriers (RFBs). Following collision with a RFB, replication proteins can dissociate from the stalled fork (fork collapse) rendering it incapable of further DNA synthesis unless recombination intervenes to restart replication. We use time-lapse microscopy and genetic assays to show that recombination is initiated within ∼10 min of replication fork blockage at a site-specific barrier in fission yeast, leading to a restarted fork within ∼60 min, which is only prevented/curtailed by the arrival of the opposing replication fork. The restarted fork is susceptible to further collapse causing hyper-recombination downstream of the barrier. Surprisingly, in our system fork restart is unnecessary for maintaining cell viability. Seemingly, the risk of failing to complete replication prior to mitosis is sufficient to warrant the induction of recombination even though it can cause deleterious genetic change. DOI: http://dx.doi.org/10.7554/eLife.04539.001 PMID:25806683

  9. Replication-Coupled PCNA Unloading by the Elg1 Complex Occurs Genome-wide and Requires Okazaki Fragment Ligation

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    Takashi Kubota

    2015-08-01

    Full Text Available The sliding clamp PCNA is a crucial component of the DNA replication machinery. Timely PCNA loading and unloading are central for genome integrity and must be strictly coordinated with other DNA processing steps during replication. Here, we show that the S. cerevisiae Elg1 replication factor C-like complex (Elg1-RLC unloads PCNA genome-wide following Okazaki fragment ligation. In the absence of Elg1, PCNA is retained on chromosomes in the wake of replication forks, rather than at specific sites. Degradation of the Okazaki fragment ligase Cdc9 leads to PCNA accumulation on chromatin, similar to the accumulation caused by lack of Elg1. We demonstrate that Okazaki fragment ligation is the critical prerequisite for PCNA unloading, since Chlorella virus DNA ligase can substitute for Cdc9 in yeast and simultaneously promotes PCNA unloading. Our results suggest that Elg1-RLC acts as a general PCNA unloader and is dependent upon DNA ligation during chromosome replication.

  10. A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication.

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    Peng, Jinyu; Ao, Zhujun; Matthews, Chris; Wang, Xiaoxia; Ramdahin, Sue; Chen, Xi; Li, Junhua; Chen, Liyu; He, Jianmei; Ball, Blake; Fowke, Keith; Plummer, Frank; Embree, Joanne; Yao, Xiaojian

    2013-08-23

    The human immunodeficiency virus type 1 (HIV-1) Vif protein counteracts the antiviral activity of the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of proteins by targeting the proteins for degradation through the ubiquitin-proteasome pathway. Previous mutagenic studies have shown that multiple domains of Vif are required for interacting with APOBEC3G proteins and the proteasome pathway. However, very few mutagenesis and functional analyses of patient-derived Vif proteins have been conducted. In this study, we amplified and cloned the HIV-1 vif genes from the peripheral blood mononuclear cells (PBMCs) of five HIV-1-infected individuals in Nairobi and further tested the impact of the genes on anti-A3G activity and HIV-1 replication. The gene sequence analysis revealed high genetic variation of vif genes from different HIV-1-infected individuals. Interestingly, the Vif proteins derived from two of the three long-term survivors (LTSs) displayed a significantly impaired ability to mediate the degradation of A3G. In particular, a single amino acid change (I107T) in one of the non-functional LTS Vif variants, which has not been previously identified in the Los Alamos databases of vif sequences, was found to be responsible for the lack of anti-A3G activity. Further study demonstrated that HIV-1 carrying an I107T Vif mutation displayed significantly reduced fitness in A3G(+) T cells and PBMCs. Moreover, co-infecting A3G(+) T cells with both the wild-type and I107T Vif viruses resulted in decreased viral replication. Overall, the results of this study indicate that the HIV-1 Vif residue I107 is important for its anti-APOBEC3G activity and viral replication, which may have implications for viral fitness in vivo.

  11. The structure of XIAP BIR2: understanding the selectivity of the BIR domains

    Energy Technology Data Exchange (ETDEWEB)

    Lukacs, Christine, E-mail: cmlukacs230@gmail.com; Belunis, Charles; Crowther, Robert; Danho, Waleed; Gao, Lin; Goggin, Barry; Janson, Cheryl A.; Li, Shirley; Remiszewski, Stacy; Schutt, Andrew [Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Thakur, Manish K.; Singh, Saroj K.; Swaminathan, Srinivasan; Pandey, Rajat; Tyagi, Rajiv; Gosu, Ramachandraiah; Kamath, Ajith V. [Jubilant Biosys Ltd, Bangalore (India); Kuglstatter, Andreas, E-mail: cmlukacs230@gmail.com [Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States)

    2013-09-01

    The high-resolution crystal structures of apo and peptide-bound XIAP BIR2 are presented and compared with BIR3 structures to understand their selectivity. This crystal system can be used to determine the structures of BIR2–inhibitor complexes. XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain–caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3–caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2–caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized; peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2–tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.

  12. Microsatellite (SSR amplification by PCR usually led to polymorphic bands: Evidence which shows replication slippage occurs in extend or nascent DNA strands

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    Abasalt Hossienzadeh-Colagar

    2016-09-01

    Full Text Available Microsatellites or simple sequence repeats (SSRs are very effective molecular markers in population genetics, genome mapping, taxonomic study and other large-scale studies. Variation in number of tandem repeats within microsatellite refers to simple sequence length polymorphism (SSLP; but there are a few studies that are showed SSRs replication slippage may be occurred during in vitro amplification which are produced ‘stutter products’ differing in length from the main products. The purpose of this study is introducing a reliable method to realize SSRs replication slippage. At first, three unique primers designed to amplify SSRs loci in the great gerbil (Rhombomys opimus by PCR. Crush and soak method used to isolate interesting DNA bands from polyacrylamide gel. PCR products analyzed using by sequencing methods. Our study has been shown that Taq DNA polymerase slipped during microsatellite in vitro amplification which led to insertion or deletion of repeats in sense or antisense DNA strands. It is produced amplified fragments with various lengths in gel electrophoresis showed as ‘stutter bands’. Thus, in population studies by SSRs markers recommend that replication slippage effects and stutter bands have been considered.

  13. Characterization of large deletions occurring during a single round of retrovirus vector replication: novel deletion mechanism involving errors in strand transfer.

    Science.gov (United States)

    Pulsinelli, G A; Temin, H M

    1991-09-01

    Retroviruses mutate at a high rate during replication. We used a spleen necrosis virus-based vector system and helper cell line to characterize mutations occurring during a single round of retrovirus replication. The vector used, JD216HyNeo, codes for two drug resistance genes, hygromycin resistance (hygro) and neomycin resistance (neo). The downstream neo gene is expressed only when a mutation alleviates a block to splicing which is located in the upstream hygro gene. The mutations allowing splicing were large deletions, ranging in size from about 500 to about 2,000 bp. Most of the mutant proviruses lacked the encapsidation sequence, as shown by our inability to rescue the mutant proviruses with wild-type reticuloendotheliosis virus strain A and confirmed by Southern blotting and direct DNA sequence analysis. We therefore concluded that most of the deletions arose during reverse transcription in the target cell, rather than during transcription in the host cell. The sequence data also indicated that the deletions occurred by at least three different mechanisms: (i) misalignment of the growing point; (ii) incorrect synthesis and termination in the primer-binding sequence during synthesis of the plus-strand strong-stop DNA; and (iii) incorrect synthesis and termination before the primer-binding sequence during synthesis of the plus-strand strong-stop DNA. The second mechanism also led to the incorporation of cellular sequences into the proviral genome, pointing to a potential novel mechanism by which retroviruses can acquire cellular genes.

  14. Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases.

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    Aroa Relaño-Ginès

    Full Text Available Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.

  15. Break-Induced Replication and Genome Stability

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    Anna Malkova

    2012-10-01

    Full Text Available Genetic instabilities, including mutations and chromosomal rearrangements, lead to cancer and other diseases in humans and play an important role in evolution. A frequent cause of genetic instabilities is double-strand DNA breaks (DSBs, which may arise from a wide range of exogeneous and endogeneous cellular factors. Although the repair of DSBs is required, some repair pathways are dangerous because they may destabilize the genome. One such pathway, break-induced replication (BIR, is the mechanism for repairing DSBs that possesses only one repairable end. This situation commonly arises as a result of eroded telomeres or collapsed replication forks. Although BIR plays a positive role in repairing DSBs, it can alternatively be a dangerous source of several types of genetic instabilities, including loss of heterozygosity, telomere maintenance in the absence of telomerase, and non-reciprocal translocations. Also, mutation rates in BIR are about 1000 times higher as compared to normal DNA replication. In addition, micro-homology-mediated BIR (MMBIR, which is a mechanism related to BIR, can generate copy-number variations (CNVs as well as various complex chromosomal rearrangements. Overall, activation of BIR may contribute to genomic destabilization resulting in substantial biological consequences including those affecting human health.

  16. The Amount of Hepatocyte Turnover That Occurred during Resolution of Transient Hepadnavirus Infections Was Lower When Virus Replication Was Inhibited with Entecavir▿ †

    Science.gov (United States)

    Mason, William S.; Xu, Chunxiao; Low, Huey Chi; Saputelli, Jeffry; Aldrich, Carol E.; Scougall, Catherine; Grosse, Arend; Colonno, Richard; Litwin, Sam; Jilbert, Allison R.

    2009-01-01

    Transient hepadnavirus infections can involve spread of virus to the entire hepatocyte population. In this situation hepatocytes present following recovery are derived from infected hepatocytes. During virus clearance antiviral cytokines are thought to block virus replication and formation of new covalently closed circular DNA (cccDNA), the viral transcriptional template. It remains unclear if existing cccDNA is eliminated noncytolytically or if hepatocyte death and proliferation, to compensate for killing of some of the infected hepatocytes, are needed to remove cccDNA from surviving infected hepatocytes. Interpreting the relationship between hepatocyte death and cccDNA elimination requires knowing both the amount of hepatocyte turnover and whether cccDNA synthesis is effectively blocked during the period of immune destruction of infected hepatocytes. We have addressed these questions by asking if treatment of woodchucks with the nucleoside analog inhibitor of viral DNA synthesis entecavir (ETV) reduced hepatocyte turnover during clearance of transient woodchuck hepatitis virus (WHV) infections. To estimate hepatocyte turnover, complexity analysis was carried out on virus-cell DNA junctions created by integration of WHV and present following recovery in the livers of WHV-infected control or ETV-treated woodchucks. We estimated that, on average, 2.2 to 4.8 times less hepatocyte turnover occurred during immune clearance in the ETV-treated woodchucks. Computer modeling of the complexity data suggests that mechanisms in addition to hepatocyte death were responsible for elimination of cccDNA during recovery from transient infections. PMID:19073743

  17. Replication of biotinylated human immunodeficiency viruses.

    Science.gov (United States)

    Belshan, Michael; Matthews, John M; Madson, Christian J

    2011-01-01

    Previous work demonstrated recently the adaptation of the Escherichia coli biotin ligase BirA - biotin acceptor sequence (BAS) labeling system to produce human immunodeficiency virus type 1 viruses with biotinylated integrase (NLXIN(B)) and matrix (NLXMA(B)) proteins (Belshan et al., 2009). This report describes the construction of an HIV permissive cell line stably expressing BirA (SupT1.BirA). Consistent with the results in the previous report, NLXMA(B) replicated similar to wild-type levels and expressed biotinylated Gag and MA proteins in the SupT1.BirA cells, whereas the replication of NLXIN(B) was reduced severely. Three additional HIV type 2 (HIV-2) viruses were constructed with the BAS inserted into the vpx and vpr accessory genes. Two BAS insertions were made into the C-terminal half of the Vpx, including one internal insertion, and one at the N-terminus of Vpr. All three viruses were replication competent in the SupT1.BirA cells and their target proteins biotinylated efficiently and incorporated into virions. These results demonstrate the potential utility of the biotinylation system to label and capture HIV protein complexes in the context of replicating virus.

  18. BIRS - Bioterrorism Information Retrieval System.

    Science.gov (United States)

    Tewari, Ashish Kumar; Rashi; Wadhwa, Gulshan; Sharma, Sanjeev Kumar; Jain, Chakresh Kumar

    2013-01-01

    Bioterrorism is the intended use of pathogenic strains of microbes to widen terror in a population. There is a definite need to promote research for development of vaccines, therapeutics and diagnostic methods as a part of preparedness to any bioterror attack in the future. BIRS is an open-access database of collective information on the organisms related to bioterrorism. The architecture of database utilizes the current open-source technology viz PHP ver 5.3.19, MySQL and IIS server under windows platform for database designing. Database stores information on literature, generic- information and unique pathways of about 10 microorganisms involved in bioterrorism. This may serve as a collective repository to accelerate the drug discovery and vaccines designing process against such bioterrorist agents (microbes). The available data has been validated from various online resources and literature mining in order to provide the user with a comprehensive information system. The database is freely available at http://www.bioterrorism.biowaves.org.

  19. Differential regulation of hepatitis B virus core protein expression and genome replication by a small upstream open reading frame and naturally occurring mutations in the precore region.

    Science.gov (United States)

    Zong, Li; Qin, Yanli; Jia, Haodi; Ye, Lei; Wang, Yongxiang; Zhang, Jiming; Wands, Jack R; Tong, Shuping; Li, Jisu

    2017-05-01

    Hepatitis B virus (HBV) transcribes two subsets of 3.5-kb RNAs: precore RNA for hepatitis B e antigen (HBeAg) expression, and pregenomic RNA for core and P protein translation as well as genome replication. HBeAg expression could be prevented by mutations in the precore region, while an upstream open reading frame (uORF) has been proposed as a negative regulator of core protein translation. We employed replication competent HBV DNA constructs and transient transfection experiments in Huh7 cells to verify the uORF effect and to explore the alternative function of precore RNA. Optimized Kozak sequence for the uORF or extra ATG codons as present in some HBV genotypes reduced core protein expression. G1896A nonsense mutation promoted more efficient core protein expression than mutated precore ATG, while a +1 frameshift mutation was ineffective. In conclusion, various HBeAg-negative precore mutations and mutations affecting uORF differentially regulate core protein expression and genome replication. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A naturally occurring prfA truncation in a Listeria monocytogenes field strain contributes to reduced replication and cell-to-cell spread.

    Science.gov (United States)

    Rupp, Sebastian; Aguilar-Bultet, Lisandra; Jagannathan, Vidhya; Guldimann, Claudia; Drögemüller, Cord; Pfarrer, Christiane; Vidondo, Beatriz; Seuberlich, Torsten; Frey, Joachim; Oevermann, Anna

    2015-08-31

    Listeria (L.) monocytogenes is an environmental bacterium that may become an intracellular pathogen upon ingestion to cause gastroenteritis, septicaemia, abortions, and/or fatal infections of the central nervous system. We here describe a L. monocytogenes field strain (JF5171) isolated from a bovine placenta in the context of abortion, which exhibited attenuation in bovine brain-slice cultures. The whole genome of strain JF5171 was sequenced, and the invasion, replication, and intercellular spread of JF5171 were further analyzed by quantification of colony forming units and immunofluorescence studies. Phospholipase and hemolysis activity of JF5171 were also quantified along with transcription levels of actA, hly and prfA. The data obtained were compared to those of the widely used L. monocytogenes reference strain, EGD-e. JF5171 exhibited reduced replication and lower levels of phospholipase and hemolysis activity. Invasion and cell-to-cell spread was strongly decreased compared to EGD-e, and actin polymerization was absent. A frame shift deletion was identified in the JF5171 coding region of the major regulator for virulence, prfA. This resulted in a truncated C-terminus sequence (WEN* vs. WGKLN*). In addition, a point mutation resulted in a lysine to arginine substitution at amino acid position 197. Complementation with prfA from EGD-e and with (EGD-e) prfA-K197N increased the replication and spread efficiency of JF5171. In contrast, complementation with the truncated version of prfA had no effect. Taken together, these results suggest that the truncated C-terminus of prfA considerably contributes to the strongly attenuated phenotype observed in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Struktur Nalar Arab-Islam menurut ‘Âbid Al-Jâbirî

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    M. Faishol

    2016-03-01

    Full Text Available The project of ‘Âbid Al-Jâbirî’s thoughts has become epistemological critic to traditional frame of Islam-Arab knowledge through analyzing socio-political background on the logic of Arab formulation. According to Al-Jâbirî, the logic of Arabic thought could be devised into three methods: bayâni, ‘irfâni and burhâni. Therefore, the structure of Islam-Arab culture has occurred based on: (1 authoritative texts—because the logic of Arab is exceedingly based on religious texts, (2 authoritative salaf, that is, focused on ‘ulama’s considerations, and (3 authoritative permissivism along with anti-causality (sult}ah at-tajwîz al-lâsababiyyah. Hence, Arabic culture becomes unproductive, poor of concept and theory. As a solution, Al-Jâbirî invites to contextualize the spirit of critic such as rational-empiricism of Ibn H{azm and al-Shât}ibî on fiqh, Ibn Rushd on philosophy, Ibn Khaldûn on sociology, etc. This article will probe specifically about ‘Âbid Al-Jâbirî’s reform thought. Al-Jâbirî’s thinking distinctiveness lies in the epistemological critique conducted on the science that develops in the Arab-Islamic civilization. The epistemological critique becomes a realm of science that not much attention, especially by Muslim thinkers. Al-Jâbirî’s epistemological critique offers to the Muslim world an attempt to reconstruct the building of reason-epistemic knowledge to keep pace and change its Islamic world towards the progress of civilization.

  2. Gorlin Goltz sendromu: Bir olgu sunumu

    OpenAIRE

    Kestane, Recep; Yurttutan, Mehmet; Şentürk, Mehmet; Koçer, Atilla; Keskin, Ahmet

    2015-01-01

    Gorlin Goltz sendromu esas olarak kutanöz bazal hücreli karsinom, çoklu keratokistik odontojenik tümörler ve iskeletsel anomaliler ile karakterize otozomal dominant bir rahatsızlıktır. Gorlin ve Goltz tarafından tanımlanan bu klasik triada ek olarak diğer nörolojik, oftalmolojik, endokrin ve genital bulgular da sendromun özellikleri arasında yer almaktadır. Bu raporda 12 yaşındaki Gorlin Goltz sendromlu erkek hastanın tedavisi ve 1,5 yıllık takibi sunulmuştur. Bu olgu deride herhangi bir lezy...

  3. BIR 2014 - Bibliometric-enhanced Information Retrieval

    DEFF Research Database (Denmark)

    This first “Bibliometric-enhanced Information Retrieval” (BIR 2014) workshop1 aims to engage with the IR community about possible links to bibliometrics and scholarly communication. Bibliometric techniques are not yet widely used to enhance retrieval processes in digital libraries, although...... for the incorporation of bibliometric-enhanced services into retrieval at the digital library interface. Our interests include information retrieval, information seeking, science modelling, network analysis, and digital libraries. The goal is to apply insights from bibliometrics, scientometrics, and informetrics...

  4. Direct infection and replication of naturally occurring hepatitis C virus genotypes 1, 2, 3 and 4 in normal human hepatocyte cultures.

    Directory of Open Access Journals (Sweden)

    Martina Buck

    Full Text Available BACKGROUND: Hepatitis C virus (HCV infection afflicts about 170 million individuals worldwide. However, the HCV life cycle is only partially understood because it has not been possible to infect normal human hepatocytes in culture. The current Huh-7 systems use cloned, synthetic HCV RNA expressed in hepatocellular carcinoma cells to produce virions, but these cells cannot be infected with naturally occurring HCV obtained from infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a human hepatocyte culture permissible to the direct infection with naturally occurring HCV genotypes 1, 2, 3 and 4 in the blood of HCV-infected patients. The culture system mimics the biology and kinetics of HCV infection in humans, and produces infectious virions that can infect naïve human hepatocytes. CONCLUSIONS/SIGNIFICANCE: This culture system should complement the existing systems, and may facilitate the understanding of the HCV life cycle, its effects in the natural host cell, the hepatocyte, as well as the development of novel therapeutics and vaccines.

  5. Boeing infrared sensor (BIRS) calibration facility

    Science.gov (United States)

    Hazen, John D.; Scorsone, L. V.

    1990-01-01

    The Boeing Infrared Sensor (BIRS) Calibration Facility represents a major capital investment in optical and infrared technology. The facility was designed and built for the calibration and testing of the new generation large aperture long wave infrared (LWIR) sensors, seekers, and related technologies. Capability exists to perform both radiometric and goniometric calibrations of large infrared sensors under simulated environmental operating conditions. The system is presently configured for endoatmospheric calibrations with a uniform background field which can be set to simulate the expected mission background levels. During calibration, the sensor under test is also exposed to expected mission temperatures and pressures within the test chamber. Capability exists to convert the facility for exoatmospheric testing. The configuration of the system is described along with hardware elements and changes made to date are addressed.

  6. BIR 2014 - Bibliometric-enhanced Information Retrieval

    DEFF Research Database (Denmark)

    This first “Bibliometric-enhanced Information Retrieval” (BIR 2014) workshop1 aims to engage with the IR community about possible links to bibliometrics and scholarly communication. Bibliometric techniques are not yet widely used to enhance retrieval processes in digital libraries, although...... analysis of co-authorship network, can improve retrieval services for specific communities, as well as for large, cross-domain collections. This workshop aims to raise awareness of the missing link between information retrieval (IR) and bibliometrics / scientometrics and to create a common ground...... for the incorporation of bibliometric-enhanced services into retrieval at the digital library interface. Our interests include information retrieval, information seeking, science modelling, network analysis, and digital libraries. The goal is to apply insights from bibliometrics, scientometrics, and informetrics...

  7. TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB.

    Science.gov (United States)

    Garrison, J B; Samuel, T; Reed, J C

    2009-04-02

    Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), but its role in NF-kappaB activation is still unclear. Here, we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

  8. Comparative study of factors controlling the groundwater occurrence in Bir Kiseiba and Bir El Shab areas, south western desert, Egypt using hydrogeological and geophysical techniques

    Science.gov (United States)

    Abu Risha, U. A.; Al Temamy, A. M. M.

    2016-05-01

    This research presents a clear example of the significant role of basement relief on the formation of aquifers and the impact of geologic structures on groundwater occurrence. A basement relief map was constructed using the depth to basement data acquired from 20 vertical electrical soundings (VESes), 3 land magnetic profiles, and 27 drilled wells tapping the basement rocks in addition to the elevations of the basement outcrops in the area of study. The map shows three basins underlying the area. The geoelectric survey shows that these basins were formed as a result of series of step faults. The largest basin underlies El-Shab area. The medium basin underlies the area of Bir Kiseiba whereas the smallest one underlies Bir Abu El-Hussein area. The Nubian Sandstone aquifer occurs only in El-Shab basin whereas the other basins are filled completely with the confining layer of Kiseiba Formation. The depth to basement in El-Shab basin ranges from 11 m. (ves-20) to 197 m. (ves-1) m.b.g.s. The depth to basement in Kiseiba basin ranges from 20 m. (Bir Kurayim magnetic profile) to 122 m. (ves-13) m.b.g.s. The depth to basement in Abu El-Husein basin ranges from 0 (basement outcrops) to 64 m. (Abu El-Husein magnetic profile) m.b.g.s. The aquifer thickness ranges from 0 m (where the aquitard rests directly on the basement) to 153 m. (El Shab well No. 79). The aquifer is uncoformably overlain by Kiseiba Formation which represents the aquitard layer at Bir El-Shab. The thickness of the aquitard ranges from 0 (in areas covered by the Nubian Sandstone) to 120 m (ves-13). Each of the aquifer and aquitard consist of three layers. Two of the aquitard layers are water-bearing. However, the estimated transmissivity of the aquitard is very low (11.9 m2/d). The groundwater moves vertically into the overlying aquitard at Bir El-Shab and subsequently flows in concentric pattern into the surrounding areas. Faulting controls groundwater occurrence and quality. Some springs lie on the

  9. Lateral agenezisi olan bir hastanın multidisipliner bir yaklaşımla rehabilitasyonu

    Directory of Open Access Journals (Sweden)

    Nihal Hamamcı

    2012-07-01

    Full Text Available

    Lateral incisor agenesis is an important cause for the esthetic smile disharmony due to strategic location. These clinical cases besides multidisciplinary are always treated under the strong influence of either the orthodontic or the prosthodontic discipline. The first approach consists of orthodontic mesial replacement of the missing lateral with the existing canine and giving it an incisor shape, whereas the last approach constitutes a conventional fixed-partial-denture treatment or implant supported prostheses for the missing incisors. This clinical report represents the multidisciplinary rehabilitation of a 21-year-old male with bilateral congenitally missing upper lateral incisors. After orthodontic therapy and providing the necessary space for the laterals, bilateral implant placement and prosthetic treatment was carried out. Incorporation of zirconium reinforced abutments and all ceramic crowns to the therapy had provided attractive and confident smile for the patient.

    Keywords: Lateral incisor agenesis, orthodontic therapy, single tooth implant therapy, esthetics.

     

    ÖZET

    Lateral diş agenezisi gülümsemedeki stratejik pozisyondan dolayı büyük bir estetik sorun yaratmaktadır. Bu olgularda estetik rehabilitasyon, multidisipliner olmakla birlikte, genelde ya ortodontik ya da protetik tedavi yaklaşımlarının etkisi altında yapılmaktadır. Birinci yaklaşım kanin dişin lateral diş boşluğuna ortodontik tedaviyle getirilip lateral diş formunda restore edilmesinden ibarettir. İkincisi ise lateral diş boşluğunun ortodontik tedaviyle sağlanmasından sonra tek diş implant restorasyonu veya geleneksel köprü protezi ile restore edilmesi şeklindedir. Bu olgu raporunda, çift taraflı üst lateral diş agenezisi olan 21 yaşındaki erkek hastanın multidisipliner yaklaşımla tedavisi anlatılmaktadır. Ortodontik tedavi ile lateral dişler için oluşturulan boşluklara tek di

  10. Reversible Switching of Cooperating Replicators

    Science.gov (United States)

    Urtel, Georg C.; Rind, Thomas; Braun, Dieter

    2017-02-01

    How can molecules with short lifetimes preserve their information over millions of years? For evolution to occur, information-carrying molecules have to replicate before they degrade. Our experiments reveal a robust, reversible cooperation mechanism in oligonucleotide replication. Two inherently slow replicating hairpin molecules can transfer their information to fast crossbreed replicators that outgrow the hairpins. The reverse is also possible. When one replication initiation site is missing, single hairpins reemerge from the crossbreed. With this mechanism, interacting replicators can switch between the hairpin and crossbreed mode, revealing a flexible adaptation to different boundary conditions.

  11. Non‐Canonical Replication Initiation: You’re Fired!

    Directory of Open Access Journals (Sweden)

    Bazilė Ravoitytė

    2017-01-01

    Full Text Available The division of prokaryotic and eukaryotic cells produces two cells that inherit a perfect copy of the genetic material originally derived from the mother cell. The initiation of canonical DNA replication must be coordinated to the cell cycle to ensure the accuracy of genome duplication. Controlled replication initiation depends on a complex interplay of cis‐acting DNA sequences, the so‐called origins of replication (ori, with trans‐acting factors involved in the onset of DNA synthesis. The interplay of cis‐acting elements and trans‐acting factors ensures that cells initiate replication at sequence‐specific sites only once, and in a timely order, to avoid chromosomal endoreplication. However, chromosome breakage and excessive RNA:DNA hybrid formation can cause breakinduced (BIR or transcription‐initiated replication (TIR, respectively. These non‐canonical replication events are expected to affect eukaryotic genome function and maintenance, and could be important for genome evolution and disease development. In this review, we describe the difference between canonical and non‐canonical DNA replication, and focus on mechanistic differences and common features between BIR and TIR. Finally, we discuss open issues on the factors and molecular mechanisms involved in TIR.

  12. Cascades of genetic instability resulting from compromised break-induced replication.

    Directory of Open Access Journals (Sweden)

    Soumini Vasan

    2014-02-01

    Full Text Available Break-induced replication (BIR is a mechanism to repair double-strand breaks (DSBs that possess only a single end that can find homology in the genome. This situation can result from the collapse of replication forks or telomere erosion. BIR frequently produces various genetic instabilities including mutations, loss of heterozygosity, deletions, duplications, and template switching that can result in copy-number variations (CNVs. An important type of genomic rearrangement specifically linked to BIR is half-crossovers (HCs, which result from fusions between parts of recombining chromosomes. Because HC formation produces a fused molecule as well as a broken chromosome fragment, these events could be highly destabilizing. Here we demonstrate that HC formation results from the interruption of BIR caused by a damaged template, defective replisome or premature onset of mitosis. Additionally, we document that checkpoint failure promotes channeling of BIR into half-crossover-initiated instability cascades (HCC that resemble cycles of non-reciprocal translocations (NRTs previously described in human tumors. We postulate that HCs represent a potent source of genetic destabilization with significant consequences that mimic those observed in human diseases, including cancer.

  13. Database Replication

    CERN Document Server

    Kemme, Bettina

    2010-01-01

    Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and

  14. Determination of the sequence specificity of XIAP BIR domains by screening a combinatorial peptide library.

    Science.gov (United States)

    Sweeney, Michael C; Wang, Xianxi; Park, Junguk; Liu, Yusen; Pei, Dehua

    2006-12-12

    Inhibitor of apoptosis (IAP) proteins regulate programmed cell death by inhibiting members of the caspase family of proteases. The X-chromosome-linked IAP (XIAP) contains three baculovirus IAP repeat (BIR) domains, which bind directly to the N-termini of target proteins including those of caspases-3, -7, and -9. In the present study, we defined the consensus sequences of the motifs that interact with the three BIR domains in an unbiased manner. A combinatorial peptide library containing four random residues at the N-terminus was constructed and screened using BIR domains as probes. We found that the BIR3 domain binds a highly specific motif containing an alanine or valine at the N-terminus (P1 position), an arginine or proline at the P3 position, and a hydrophobic residue (Phe, Ile, and Tyr) at the P4 position. The BIR2-binding motif is less stringent. Although it still requires an N-terminal alanine, it tolerates a wide variety of amino acids at P2-P4 positions. The BIR1 failed to bind to any peptides in the library. SPR analysis of individually synthesized peptides confirmed the library screening results. Database searches with the BIR2- and BIR3-binding consensus sequences revealed a large number of potential target proteins. The combinatorial library method should be readily applicable to other BIR domains or other types of protein modular domains.

  15. Hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hepadnaviruses, including human hepatitis B virus (HBV), replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription: it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA,ε, as template, and depends on cellular chaperones;moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids.This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV (DHBV),now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately,not be complemented by three-dimensional structural information on the involved components. However, at least for the s RNA element such information is emerging,raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal,will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.

  16. Prokaryotic BirA ligase biotinylates K4, K9, K18 and K23 in eukaryotic histone H3

    Science.gov (United States)

    BirA ligase, a prokaryotic ortholog of human holocarboxylase synthetase (HCS), is known to biotinylate proteins. Here, we tested the hypothesis that BirA ligase may also catalyze biotinylation of eukaryotic histones. If so, this would render recombinant BirA ligase a useful surrogate for HCS in stud...

  17. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division...

  18. Osmanlı Devleti’nde Teknik Bir Yenilik: Skafander Makinesi A Technical Innovation In The Ottoman State: Scaphandre Machine

    Directory of Open Access Journals (Sweden)

    Cihan ÖZGÜN

    2013-09-01

    Full Text Available Sponge was an important natural source in the Ottoman seas.Sponge divers were gathering sponges different ways and a new methodof sponge hunting began to be applied after the mid-nineteenth century.This method was sponge hunting with the help of scaphandre whichwas called generally “machine” by Ottoman offical records and spongedivers. Scaphandre was consisted of heavy metal helmets thatconnected to a air pump with hose on shipboard, boots and a garmentthat surrounds the whole body. Scaphandre was a costume or devicewhich was designed to remain a sponge hunter undersea longer time.These devices allowed sponge hunters to work at least 1 hour undersea.Thanks to the scaphandre, sponge divers began to hunt more spongesand to gain more profits compared to sponge hunters who don’t use thisdevice. The use of scaphandre in the sponge hunting, as a technicalinnovation in the Ottoman state, led to start a painfull process amongthe sponge hunters. The process of implementation of this method,negative reactions based on social and economic interests occuredamong sponge divers. These reactions firstly began as a little fight butthen they turned into a serious rebellions. In addition, accidents anddiseases were occuring depend on the use of this machine. There wereespecially motor accidents, joint pain, chest pain, speech disorders,dyspnea, visual disturbance, skin complaints among these diseases andaccidents. Some of these accidents resulted in death. Because of thesediseases, accidents and accumulated reactions, Ottoman Statesometimes banned the use of scaphandre. This study examines theproblem of sponge hunting with the use of scaphandre which istechnical innovation in the Ottoman territorial waters. For this study,data and information were collected Ottoman archive documents,commercial reports concerning this period, official statistics and otherpublications. Sünger, Osmanlı denizlerinde önemli bir doğal kaynaktı. Sünger avcıları s

  19. Break-Induced Replication Is a Source of Mutation Clusters Underlying Kataegis

    Directory of Open Access Journals (Sweden)

    Cynthia J. Sakofsky

    2014-06-01

    Full Text Available Clusters of simultaneous multiple mutations can be a source of rapid change during carcinogenesis and evolution. Such mutation clusters have been recently shown to originate from DNA damage within long single-stranded DNA (ssDNA formed at resected double-strand breaks and dysfunctional replication forks. Here, we identify double-strand break (DSB-induced replication (BIR as another powerful source of mutation clusters that formed in nearly half of wild-type yeast cells undergoing BIR in the presence of alkylating damage. Clustered mutations were primarily formed along the track of DNA synthesis and were frequently associated with additional breakage and rearrangements. Moreover, the base specificity, strand coordination, and strand bias of the mutation spectrum were consistent with mutations arising from damage in persistent ssDNA stretches within unconventional replication intermediates. Altogether, these features closely resemble kataegic events in cancers, suggesting that replication intermediates during BIR may be the most prominent source of mutation clusters across species.

  20. Prokaryotic BirA ligase biotinylates K4, K9, K18 and K23 in histone H3.

    Science.gov (United States)

    Kobza, Keyna; Sarath, Gautam; Zempleni, Janos

    2008-04-30

    BirA ligase is a prokaryotic ortholog of holocarboxylase synthetase (HCS) that can biotinylate proteins. This study tested the hypothesis that BirA ligase catalyzes the biotinylation of eukaryotic histones. If so, this would mean that recombinant BirA ligase is a useful surrogate for HCS in studies of histone biotinylation. The biological activity of recombinant BirA ligase was confirmed by enzymatic biotinylation of p67. In particular, it was found that BirA ligase biotinylated both calf thymus histone H1 and human bulk histone extracts. Incubation of recombinant BirA ligase with H3-based synthetic peptides showed that lysines 4, 9, 18, and 23 in histone H3 are the targets for the biotinylation by BirA ligase. Modification of the peptides (e.g., serine phosphorylation) affected the subsequent biotinylation by BirA ligase, suggesting crosstalk between modifications. In conclusion, this study suggests that prokaryotic BirA ligase is a promiscuous enzyme and biotinylates eukaryotic histones. Moreover the biotinylation of histones by BirA ligase is consistent with the proposed role of human HCS in chromatin.

  1. DAO Spectroscopic classification of SN 2016bir in SDSS J131405.16+335510.1

    Science.gov (United States)

    Balam, D. D.; Graham, M. L.

    2016-04-01

    A noisy spectrum was obtained of SN 2016bir (ATEL #8857) on Apr. 10.36 UT using the 1.82-m Plaskett telescope (National Research Council of Canada) covering the range 405-710 nm (resolution 0.32 nm). Cross-correlation with a template library using SNID (Blondin & Tonry 2007, ApJ, 666, 1024) shows 2016bir to most resemble the spectrum of a type-Ib supernova approximately 1 week pre-maximum light.

  2. bir1 deletion causes malfunction of the spindle assembly checkpoint and apoptosis in yeast

    Directory of Open Access Journals (Sweden)

    Qun eRen

    2012-08-01

    Full Text Available Cell division in yeast is a highly regulated and well studied event. Various checkpoints are placed throughout the cell cycle to ensure faithful segregation of sister chromatids. Unexpected events, such as DNA damage or oxidative stress, cause the activation of checkpoint(s and cell cycle arrest. Malfunction of the checkpoints may induce cell death. We previously showed that under oxidative stress, the budding yeast cohesin Mcd1, a homolog of human Rad21, was cleaved by the caspase-like protease Esp1. The cleaved Mcd1 C-terminal fragment was then translocated to mitochondria, causing apoptotic cell death. In the present study, we demonstrated that Bir1 plays an important role in spindle assembly checkpoint and cell death. Similar to H2O2 treatment, deletion of BIR1 using a BIR1-degron strain caused degradation of the securin Pds1, which binds and inactivates Esp1 until metaphase-anaphase transition in a normal cell cycle. BIR1 deletion caused an increase level of ROS and mis-location of Bub1, a major protein for spindle assembly checkpoint. In wild type, Bub1 was located at the kinetochores, but was primarily in the cytoplasm in bir1 deletion strain. When BIR1 was deleted, addition of nocodazole was unable to retain the Bub1 localization on kietochores, further suggesting that Bir1 is required to activate and maintain the spindle assembly checkpoint. Our study suggests that the BIR1 function in cell cycle regulation works in concert with its anti-apoptosis function.

  3. Hedonik tüketim: Kavramsal bir inceleme

    Directory of Open Access Journals (Sweden)

    Ebru Özlem GÜVEN

    2009-01-01

    Full Text Available Tüketimin insanlar için vazgeçilmez bir eylem olduğu günümüz küresel dünyasında pek çok araştırma, farklı ya da benzer koşullar altında tüketimi etkileyen faktörlerin nedenleri ile bunların etkilerini ve tüketim eylemini gerçekleştiren tüketicilerin özellikleri bakımından benzerlikleri ve farklılıklarını irdelemektedir. Bu noktada farklı nedenlerle tüketim yapan tüketicilerin - tüketim biçimi dikkate alınarak - farklı kavramsal başlıklar altında toplandığı görülmektedir. Bu tüketim şekillerinden biri olan ve alışveriş eylemini hazza ve mutluluğa giden yol olarak gösteren hedonik tüketim özellikle de alternatif ürün ve marka sayısının arttığı günümüz pazar koşullarında tüketicinin satın alma eylemine ve satın alacağı markaya atfettiği hazza ve mutluluğa yönelik düşlerinin ortaya çıkarılması bakımından incelemeye değer bir kavramdır. Bu çalışmada, kavramsal düzeyde hedonik tüketim eylemi irdelenmeye çalışılmıştır.

  4. Archaeal DNA replication.

    Science.gov (United States)

    Kelman, Lori M; Kelman, Zvi

    2014-01-01

    DNA replication is essential for all life forms. Although the process is fundamentally conserved in the three domains of life, bioinformatic, biochemical, structural, and genetic studies have demonstrated that the process and the proteins involved in archaeal DNA replication are more similar to those in eukaryal DNA replication than in bacterial DNA replication, but have some archaeal-specific features. The archaeal replication system, however, is not monolithic, and there are some differences in the replication process between different species. In this review, the current knowledge of the mechanisms governing DNA replication in Archaea is summarized. The general features of the replication process as well as some of the differences are discussed.

  5. Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling

    DEFF Research Database (Denmark)

    Damgaard, Rune Busk; Fiil, Berthe Katrine; Speckmann, Carsten;

    2013-01-01

    X-linked Inhibitor of Apoptosis (XIAP) is an essential ubiquitin ligase for pro-inflammatory signalling downstream of the nucleotide-binding oligomerization domain containing (NOD)-1 and -2 pattern recognition receptors. Mutations in XIAP cause X-linked lymphoproliferative syndrome type-2 (XLP2......), an immunodeficiency associated with a potentially fatal deregulation of the immune system, whose aetiology is not well understood. Here, we identify the XIAP baculovirus IAP repeat (BIR)2 domain as a hotspot for missense mutations in XLP2. We demonstrate that XLP2-BIR2 mutations severely impair NOD1/2-dependent...... immune signalling in primary cells from XLP2 patients and in reconstituted XIAP-deficient cell lines. XLP2-BIR2 mutations abolish the XIAP-RIPK2 interaction resulting in impaired ubiquitylation of RIPK2 and recruitment of linear ubiquitin chain assembly complex (LUBAC) to the NOD2-complex. We show...

  6. An immobilized biotin ligase: surface display of Escherichia coli BirA on Saccharomyces cerevisiae.

    Science.gov (United States)

    Parthasarathy, Ranganath; Bajaj, Jitin; Boder, Eric T

    2005-01-01

    The Escherichia coli biotin ligase enzyme BirA has been extensively used in recent years to generate site-specifically biotinylated proteins via a biotin acceptor peptide tag. In the present study, BirA was displayed for the first time on the yeast Saccharomyces cerevisiae using the Aga1p-Aga2p platform and assayed using a peptide-tagged protein as the substrate. The enzyme is fully functional and resembles the soluble form in many of its properties, but the yeast-displayed enzyme demonstrates stability and reusability on the time scale of weeks. Thus, the yeast-displayed BirA system represents a facile and highly economical alternative for producing site-specifically biotinylated proteins.

  7. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis.

    Science.gov (United States)

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-05-24

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus.

  8. Successful conversion of the Bacillus subtilis BirA Group II biotin protein ligase into a Group I ligase

    National Research Council Canada - National Science Library

    Henke, Sarah K; Cronan, John E

    2014-01-01

    ...: bioWAFDBI, yuiG and yhfUTS. Moreover, unlike the paradigm Group II BPL, E. coli BirA, the N-terminal DNA binding domain can be deleted from Bacillus subtilis BirA without adverse effects on its ligase function...

  9. birääkijad löövad oma lubaduste hinda kokku / Argo Ideon

    Index Scriptorium Estoniae

    Ideon, Argo, 1966-

    2011-01-01

    Isamaa ja Res Publica Liidu ning Reformierakonna võimuläbirääkimised on lõppfaasis, edasistel läbirääkimistel võib võtmerolli tõusta rahandusministeeriumi koostatud tabel, kus on täpsustatud lepingupunktide hind

  10. 重组BirA酶的原核表达及其活性鉴定%Expression of Recombinant BirA in Prokaryotic System and Identification of Its Activity

    Institute of Scientific and Technical Information of China (English)

    赵爽佳; 鲍如梦; 唐海科; 杨洪鸣; 唐金宝

    2015-01-01

    构建含有rTEV酶切位点的原核表达载体pUC18-His-BirA,利用E coli DH5α表达重组BirA酶,并通过酶切获得不含His标签肽的BirA酶.PCR方式扩增BirA基因片段重组至质粒pUC18,构建原核表达载体pUC18-His-BirA并转化E coli DH5α;采用冻融法释放菌体蛋白,SDS-PAGE分析目的蛋白的存在形式;冻融上清经金属离子亲和色谱纯化获得目的蛋白His-BirA酶,利用rTEV酶切除His标签肽,并采用HABA方法进行BirA酶活鉴定分析.经双酶切验证、基因测序结果表明重组载体构建正确,SDS-PAGE结果显示表达产物可溶部分比例约占50%;利用rTEV酶将标签切除,经HABA测定该酶相对酶活性可达4 365 U/μg.该研究通过构建pUC18-His-BirA质粒表达载体,实现了重组BirA酶较高比例的可溶性表达.表达产物经rTEV酶酶切后具有较高的酶活性,为实现BirA酶的经济、高效制备奠定了一定的实验基础.

  11. Nucleotide Metabolism and DNA Replication.

    Science.gov (United States)

    Warner, Digby F; Evans, Joanna C; Mizrahi, Valerie

    2014-10-01

    The development and application of a highly versatile suite of tools for mycobacterial genetics, coupled with widespread use of "omics" approaches to elucidate the structure, function, and regulation of mycobacterial proteins, has led to spectacular advances in our understanding of the metabolism and physiology of mycobacteria. In this article, we provide an update on nucleotide metabolism and DNA replication in mycobacteria, highlighting key findings from the past 10 to 15 years. In the first section, we focus on nucleotide metabolism, ranging from the biosynthesis, salvage, and interconversion of purine and pyrimidine ribonucleotides to the formation of deoxyribonucleotides. The second part of the article is devoted to DNA replication, with a focus on replication initiation and elongation, as well as DNA unwinding. We provide an overview of replication fidelity and mutation rates in mycobacteria and summarize evidence suggesting that DNA replication occurs during states of low metabolic activity, and conclude by suggesting directions for future research to address key outstanding questions. Although this article focuses primarily on observations from Mycobacterium tuberculosis, it is interspersed, where appropriate, with insights from, and comparisons with, other mycobacterial species as well as better characterized bacterial models such as Escherichia coli. Finally, a common theme underlying almost all studies of mycobacterial metabolism is the potential to identify and validate functions or pathways that can be exploited for tuberculosis drug discovery. In this context, we have specifically highlighted those processes in mycobacterial DNA replication that might satisfy this critical requirement.

  12. Dynamics of Escherichia coli chromosome segregation during multifork replication.

    Science.gov (United States)

    Nielsen, Henrik J; Youngren, Brenda; Hansen, Flemming G; Austin, Stuart

    2007-12-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks.

  13. birääkijate viis lemmikviga / Max H. Bazerman, Don A Moore

    Index Scriptorium Estoniae

    Bazerman, Max H.

    2008-01-01

    Harvardi Ärikooli professorid annavad nõu, mida teha siis, kui jäädakse läbirääkimistel liigselt pidama esimese pakkumise külge, ollakse jäärapäine, minnakse liiale enesekindlusega või keskendutakse liiga kitsale eesmärgile

  14. Frontotemporal demansa ikincil olarak ortaya çıkan bir mani olgusu

    National Research Council Canada - National Science Library

    TURAN, Engin D; ÖZDEL, Kadir; KIZIL, Erguvan Tuğba Özel

    2007-01-01

    ... bildirilmiştir. Bu yazıda da frontotemporal demansa ikincil ortaya çıkan bir mani olgusu tartışılmıştır. Late-onset bipolar disorders are generally reported to be associated with general medical conditions...

  15. birääkijate viis lemmikviga / Max H. Bazerman, Don A Moore

    Index Scriptorium Estoniae

    Bazerman, Max H.

    2008-01-01

    Harvardi Ärikooli professorid annavad nõu, mida teha siis, kui jäädakse läbirääkimistel liigselt pidama esimese pakkumise külge, ollakse jäärapäine, minnakse liiale enesekindlusega või keskendutakse liiga kitsale eesmärgile

  16. Põhja-Korea lahkus tuumaläbirääkimistelt / Jüri Piirisild

    Index Scriptorium Estoniae

    Piirisild, Jüri

    2005-01-01

    Põhja-Korea teatas tuumaprogrammi alaste läbirääkimiste tähtajatust katkestamisest. Analüütikute arvates peaks USA pehmendama oma jäika hoiakut Põhja-Korea suhtes ning püüdma senisest aktiivsemalt leida kriisile lahendust

  17. Kas sugu on läbirääkimistel tähtis

    Index Scriptorium Estoniae

    2006-01-01

    Ülevaade Harvard Business Schooli uudiskirja Working Knowledge 2006. aasta veebruari numbris ilmunud Dina W. Pradel'i, Hannah Riley Bowles'i ja Kathleen L. McGinn'i artiklist inimese soo mõjust läbirääkimistele

  18. Kas sugu on läbirääkimistel tähtis

    Index Scriptorium Estoniae

    2006-01-01

    Ülevaade Harvard Business Schooli uudiskirja Working Knowledge 2006. aasta veebruari numbris ilmunud Dina W. Pradel'i, Hannah Riley Bowles'i ja Kathleen L. McGinn'i artiklist inimese soo mõjust läbirääkimistele

  19. Üç Faz Transformatörlerde Harmonik Analizler İçin Geliştirilen Bir Uygulama Programı

    OpenAIRE

    ZİLE, M.

    2014-01-01

    Bu çal mada, güç sistemlerinde do rusal olmayan yük ak mlar n n neden oldu u harmonik etkilerini tahmin eden bir uygulama program geli tirilmi tir. Yaz l m program için analitik mant k, basit bir güç sistem ebekesi için geli tirilmi tir. Bu sistem bir transformatör, iki paralele kondansatör, iki iletim hatt , bir güç kayna Windows temelli bir uygulamad r. Bu uygulama program harmonik analizler yapmak için, Microsoft Visual C++ programlama dili kullan larak geli tirilmi tir. Benzetim sonuçlar ...

  20. Güneş Enerjisi Kaynaklı Bir Stirling Motorunun Matlab-Simulink ile Modellenmesi

    Directory of Open Access Journals (Sweden)

    Ş. Melih AKYOL

    2012-06-01

    Full Text Available Sürdürülebilir bir kalkınma için yerli ve yenilenebilir enerji kaynaklarının kullanılması gereklidir.Yenilenebilir Enerji Genel Müdürlüğü (YEGM’nin ölçümlerine göre, ülkemiz günde yeryüzüne düşen ortalama 3600 Wh/m2 ‘lik güneş ışınımı ile önemli bir güneş enerjisi kullanım potansiyeline sahiptir. Bu çalışmada ısı kaynağı olarak güneş enerjisini kullanan beta tipi krank hareket mekanizmalı bir Stirling motoru teorik olarak Matlab-Simulink ortamında modellenmiştir. Hazırlanan model, ülkemizdeki farklı bölgeler için, yılın herhangi bir gününde, yatay veya açılı yüzeylere düşen güneş ışınımı değerlerini tahminleyen bir alt model ile desteklenmiştir. Geliştirilen model ile, Stirling motorunun farklı boyutlandırmaları için güç, çalışma frekansı, verim gibi performans özellikleri hesaplanabilmekte, iş gazının da sıcaklık basınç gibi termodinamik özelliklerinin çevrim boyunca değişimi izlenebilmektedir.

  1. Chromosome replication and segregation in bacteria.

    Science.gov (United States)

    Reyes-Lamothe, Rodrigo; Nicolas, Emilien; Sherratt, David J

    2012-01-01

    In dividing cells, chromosome duplication once per generation must be coordinated with faithful segregation of newly replicated chromosomes and with cell growth and division. Many of the mechanistic details of bacterial replication elongation are well established. However, an understanding of the complexities of how replication initiation is controlled and coordinated with other cellular processes is emerging only slowly. In contrast to eukaryotes, in which replication and segregation are separate in time, the segregation of most newly replicated bacterial genetic loci occurs sequentially soon after replication. We compare the strategies used by chromosomes and plasmids to ensure their accurate duplication and segregation and discuss how these processes are coordinated spatially and temporally with growth and cell division. We also describe what is known about the three conserved families of ATP-binding proteins that contribute to chromosome segregation and discuss their inter-relationships in a range of disparate bacteria.

  2. Replication Restart in Bacteria.

    Science.gov (United States)

    Michel, Bénédicte; Sandler, Steven J

    2017-07-01

    In bacteria, replication forks assembled at a replication origin travel to the terminus, often a few megabases away. They may encounter obstacles that trigger replisome disassembly, rendering replication restart from abandoned forks crucial for cell viability. During the past 25 years, the genes that encode replication restart proteins have been identified and genetically characterized. In parallel, the enzymes were purified and analyzed in vitro, where they can catalyze replication initiation in a sequence-independent manner from fork-like DNA structures. This work also revealed a close link between replication and homologous recombination, as replication restart from recombination intermediates is an essential step of DNA double-strand break repair in bacteria and, conversely, arrested replication forks can be acted upon by recombination proteins and converted into various recombination substrates. In this review, we summarize this intense period of research that led to the characterization of the ubiquitous replication restart protein PriA and its partners, to the definition of several replication restart pathways in vivo, and to the description of tight links between replication and homologous recombination, responsible for the importance of replication restart in the maintenance of genome stability. Copyright © 2017 American Society for Microbiology.

  3. Completion of DNA replication in Escherichia coli.

    Science.gov (United States)

    Wendel, Brian M; Courcelle, Charmain T; Courcelle, Justin

    2014-11-18

    The mechanism by which cells recognize and complete replicated regions at their precise doubling point must be remarkably efficient, occurring thousands of times per cell division along the chromosomes of humans. However, this process remains poorly understood. Here we show that, in Escherichia coli, the completion of replication involves an enzymatic system that effectively counts pairs and limits cellular replication to its doubling point by allowing converging replication forks to transiently continue through the doubling point before the excess, over-replicated regions are incised, resected, and joined. Completion requires RecBCD and involves several proteins associated with repairing double-strand breaks including, ExoI, SbcDC, and RecG. However, unlike double-strand break repair, completion occurs independently of homologous recombination and RecA. In some bacterial viruses, the completion mechanism is specifically targeted for inactivation to allow over-replication to occur during lytic replication. The results suggest that a primary cause of genomic instabilities in many double-strand-break-repair mutants arises from an impaired ability to complete replication, independent from DNA damage.

  4. Percieved functions of naturally occurring autobiographical memories

    DEFF Research Database (Denmark)

    Treebak, L. S.; Henriksen, J. R.; Lundhus, S.

    2005-01-01

    The main empirical reference on functions of autobiographical memories is still Hyman & Faries (1992) who used the cue-word-method and retrospective judgements. We used diaries to sample naturally occurring autobiographical memories and participants? perceived use of these. Results partly replicate...

  5. Semiconservative replication in the quasispecies model

    Science.gov (United States)

    Tannenbaum, Emmanuel; Deeds, Eric J.; Shakhnovich, Eugene I.

    2004-06-01

    This paper extends Eigen’s quasispecies equations to account for the semiconservative nature of DNA replication. We solve the equations in the limit of infinite sequence length for the simplest case of a static, sharply peaked fitness landscape. We show that the error catastrophe occurs when μ , the product of sequence length and per base pair mismatch probability, exceeds 2 ln [2/ ( 1+1/k ) ] , where k>1 is the first-order growth rate constant of the viable “master” sequence (with all other sequences having a first-order growth rate constant of 1 ). This is in contrast to the result of ln k for conservative replication. In particular, as k→∞ , the error catastrophe is never reached for conservative replication, while for semiconservative replication the critical μ approaches 2 ln 2 . Semiconservative replication is therefore considerably less robust than conservative replication to the effect of replication errors. We also show that the mean equilibrium fitness of a semiconservatively replicating system is given by k ( 2 e-μ/2 -1 ) below the error catastrophe, in contrast to the standard result of k e-μ for conservative replication (derived by Kimura and Maruyama in 1966). From this result it is readily shown that semiconservative replication is necessary to account for the observation that, at sufficiently high mutagen concentrations, faster replicating cells will die more quickly than more slowly replicating cells. Thus, in contrast to Eigen’s original model, the semiconservative quasispecies equations are able to provide a mathematical basis for explaining the efficacy of mutagens as chemotherapeutic agents.

  6. Endometrium clear cell karsinomlu bir olguda achromobacter xylosoxidans'ın sebep olduğu ürosepsis

    OpenAIRE

    2013-01-01

    Amaç: Achromobacter xylosoxidans, diğer adıyla Alcaligenes xylosoxidans gram negatif, aerob, oksidaz pozitif, nonfermentatif, hareketli, çomak şeklinde bir bakteridir. Doğada, toprak ve suda bulunabilen bir mikroorganizma olup, immün sistemi baskılanmış kişilerde fırsatçı enfeksiyonlara neden olmaktadır.

  7. Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

    OpenAIRE

    Smith, Owen K.; Aladjem, Mirit I.

    2014-01-01

    The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes ...

  8. Tekrarlayan akciğer infeksiyonunun nadir bir nedeni: Kartagener sendromu

    OpenAIRE

    ÇELİKSOY, Mehmet; Güner, Şükrü; ÇALIŞKAN, Burcu; Sancak, Recep; Söğüt, Ayhan

    2013-01-01

    Kartagener sendromu otozomal resesif geçişli sinüzit, bronşektazi, situs inversus ile karakterize bir hastalıktır. Primer silier diskinezili olguların % 50’sini Kartagener sendromu oluşturur. Primer silier diskinezinin temel özellikleri sıklıkla hayatın ilk ayında başlayan üst ve alt solunum sistemi bulgularıdır, ancak tanı gecikir, çünkü bu özellikler diğer pediatrik hastalıklarla karıştırılır. Bu vaka raporunda, Kartagener sendromlu bir olgunun klinik ve radyolojik özelliklerini tartı...

  9. DNA replication and cancer

    DEFF Research Database (Denmark)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-01-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways...... causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy....

  10. Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression

    Directory of Open Access Journals (Sweden)

    Yee Mon Thu

    2016-05-01

    Full Text Available Loss of minichromosome maintenance protein 10 (Mcm10 causes replication stress. We uncovered that S. cerevisiae mcm10-1 mutants rely on the E3 SUMO ligase Mms21 and the SUMO-targeted ubiquitin ligase complex Slx5/8 for survival. Using quantitative mass spectrometry, we identified changes in the SUMO proteome of mcm10-1 mutants and revealed candidates regulated by Slx5/8. Such candidates included subunits of the chromosome passenger complex (CPC, Bir1 and Sli15, known to facilitate spindle assembly checkpoint (SAC activation. We show here that Slx5 counteracts SAC activation in mcm10-1 mutants under conditions of moderate replication stress. This coincides with the proteasomal degradation of sumoylated Bir1. Importantly, Slx5-dependent mitotic relief was triggered not only by Mcm10 deficiency but also by treatment with low doses of the alkylating drug methyl methanesulfonate. Based on these findings, we propose a model in which Slx5/8 allows for passage through mitosis when replication stress is tolerable.

  11. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  12. Mechanism of chromosomal DNA replication initiation and replication fork stabilization in eukaryotes.

    Science.gov (United States)

    Wu, LiHong; Liu, Yang; Kong, DaoChun

    2014-05-01

    Chromosomal DNA replication is one of the central biological events occurring inside cells. Due to its large size, the replication of genomic DNA in eukaryotes initiates at hundreds to tens of thousands of sites called DNA origins so that the replication could be completed in a limited time. Further, eukaryotic DNA replication is sophisticatedly regulated, and this regulation guarantees that each origin fires once per S phase and each segment of DNA gets duplication also once per cell cycle. The first step of replication initiation is the assembly of pre-replication complex (pre-RC). Since 1973, four proteins, Cdc6/Cdc18, MCM, ORC and Cdt1, have been extensively studied and proved to be pre-RC components. Recently, a novel pre-RC component called Sap1/Girdin was identified. Sap1/Girdin is required for loading Cdc18/Cdc6 to origins for pre-RC assembly in the fission yeast and human cells, respectively. At the transition of G1 to S phase, pre-RC is activated by the two kinases, cyclindependent kinase (CDK) and Dbf4-dependent kinase (DDK), and subsequently, RPA, primase-polα, PCNA, topoisomerase, Cdc45, polδ, and polɛ are recruited to DNA origins for creating two bi-directional replication forks and initiating DNA replication. As replication forks move along chromatin DNA, they frequently stall due to the presence of a great number of replication barriers on chromatin DNA, such as secondary DNA structures, protein/DNA complexes, DNA lesions, gene transcription. Stalled forks must require checkpoint regulation for their stabilization. Otherwise, stalled forks will collapse, which results in incomplete DNA replication and genomic instability. This short review gives a concise introduction regarding the current understanding of replication initiation and replication fork stabilization.

  13. The Replication Recipe: What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

    2014-01-01

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  14. Modeling DNA Replication.

    Science.gov (United States)

    Bennett, Joan

    1998-01-01

    Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)

  15. Eukaryotic DNA Replication Fork.

    Science.gov (United States)

    Burgers, Peter M J; Kunkel, Thomas A

    2017-06-20

    This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.

  16. Abiotic self-replication.

    Science.gov (United States)

    Meyer, Adam J; Ellefson, Jared W; Ellington, Andrew D

    2012-12-18

    The key to the origins of life is the replication of information. Linear polymers such as nucleic acids that both carry information and can be replicated are currently what we consider to be the basis of living systems. However, these two properties are not necessarily coupled. The ability to mutate in a discrete or quantized way, without frequent reversion, may be an additional requirement for Darwinian evolution, in which case the notion that Darwinian evolution defines life may be less of a tautology than previously thought. In this Account, we examine a variety of in vitro systems of increasing complexity, from simple chemical replicators up to complex systems based on in vitro transcription and translation. Comparing and contrasting these systems provides an interesting window onto the molecular origins of life. For nucleic acids, the story likely begins with simple chemical replication, perhaps of the form A + B → T, in which T serves as a template for the joining of A and B. Molecular variants capable of faster replication would come to dominate a population, and the development of cycles in which templates could foster one another's replication would have led to increasingly complex replicators and from thence to the initial genomes. The initial genomes may have been propagated by RNA replicases, ribozymes capable of joining oligonucleotides and eventually polymerizing mononucleotide substrates. As ribozymes were added to the genome to fill gaps in the chemistry necessary for replication, the backbone of a putative RNA world would have emerged. It is likely that such replicators would have been plagued by molecular parasites, which would have been passively replicated by the RNA world machinery without contributing to it. These molecular parasites would have been a major driver for the development of compartmentalization/cellularization, as more robust compartments could have outcompeted parasite-ridden compartments. The eventual outsourcing of metabolic

  17. Adenovirus DNA Replication

    OpenAIRE

    Hoeben, Rob C.; Uil, Taco G.

    2013-01-01

    Adenoviruses have attracted much attention as probes to study biological processes such as DNA replication, transcription, splicing, and cellular transformation. More recently these viruses have been used as gene-transfer vectors and oncolytic agents. On the other hand, adenoviruses are notorious pathogens in people with compromised immune functions. This article will briefly summarize the basic replication strategy of adenoviruses and the key proteins involved and will deal with the new deve...

  18. Görme Agnozisi İle Seyreden Bir Oksipital İnfrakt Olgusu

    OpenAIRE

    TUNALI, G.

    2010-01-01

    SUMMARY A CASE WITH VISUAL AGNOSIA DUE TO OCCIPITAL INFARCT In this paper, a case who had visual agnosia, alexia and complex visual halusinations was presented. CT scan showed left occipi¬tal infarct which also involved posterior temporal lobe. The propable mechanism of visual agnosia was discussed in wiev of the literature. ÖZET Bu yazıda görme agnozisi, aleksi ve kompleks görme halüsinasyonları olan bir vaka sunuldu. Bu vakada BT sol tarafta posterior temporal loba da yayılan...

  19. Minichromosome replication in vitro: inhibition of re-replication by replicatively assembled nucleosomes.

    Science.gov (United States)

    Krude, T; Knippers, R

    1994-08-19

    Single-stranded circular DNA, containing the SV40 origin sequence, was used as a template for complementary DNA strand synthesis in cytosolic extracts from HeLa cells. In the presence of the replication-dependent chromatin assembly factor CAF-1, defined numbers of nucleosomes were assembled during complementary DNA strand synthesis. These minichromosomes were then induced to semiconservatively replicate by the addition of the SV40 initiator protein T antigen (re-replication). The results indicate that re-replication of minichromosomes appears to be inhibited by two independent mechanisms. One acts at the initiation of minichromosome re-replication, and the other affects replicative chain elongation. To directly demonstrate the inhibitory effect of replicatively assembled nucleosomes, two types of minichromosomes were prepared: (i) post-replicative minichromosomes were assembled in a reaction coupled to replication as above; (ii) pre-replicative minichromosomes were assembled independently of replication on double-stranded DNA. Both types of minichromosomes were used as templates for DNA replication under identical conditions. Replicative fork movement was found to be impeded only on post-replicative minichromosome templates. In contrast, pre-replicative minichromosomes allowed one unconstrained replication cycle, but re-replication was inhibited due to a block in fork movement. Thus, replicatively assembled chromatin may have a profound influence on the re-replication of DNA.

  20. Investigating variation in replicability: A "Many Labs" replication project

    NARCIS (Netherlands)

    Klein, R.A.; Ratliff, K.A.; Vianello, M.; Adams, R.B.; Bahnik, S.; Bernstein, M.J.; Bocian, K.; Brandt, M.J.; Brooks, B.; Brumbaugh, C.C.; Cemalcilar, Z.; Chandler, J.; Cheong, W.; Davis, W.E.; Devos, T.; Eisner, M.; Frankowska, N.; Furrow, D.; Galliani, E.M.; Hasselman, F.W.; Hicks, J.A.; Hovermale, J.F.; Hunt, S.J.; Huntsinger, J.R.; IJzerman, H.; John, M.S.; Joy-Gaba, J.A.; Kappes, H.B.; Krueger, L.E.; Kurtz, J.; Levitan, C.A.; Mallett, R.K.; Morris, W.L.; Nelson, A.J.; Nier, J.A.; Packard, G.; Pilati, R.; Rutchick, A.M.; Schmidt, K.; Skorinko, J.L.M.; Smith, R.; Steiner, T.G.; Storbeck, J.; Van Swol, L.M.; Thompson, D.; Veer, A.E. van 't; Vaughn, L.A.; Vranka, M.; Wichman, A.L.; Woodzicka, J.A.; Nosek, B.A.

    2014-01-01

    Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently.

  1. Butterfly Species Diversity of Bir-Billing Area of Dhauladhar Range of Western Himalayas in Northern India

    Directory of Open Access Journals (Sweden)

    Sangeeta Chandel

    2013-10-01

    Full Text Available The present study of butterfly species diversity was carried out in the Bir-Biling area of Dhauladhar Range of the Western Himalayas in Northern India. The study was done since April 2012 to March 2013, throughout the year during the routine field visits to Bir-Billing. A total of 50 butterfly species were recorded from the study areas which belonge to five families i.e. Nymphalidae, Pieridae, Papilionidae, Lycaenidae and Hesperiidae and 39 genera. The Nymphalidae family was the most dominant family in the study area having 32 species and followed by Lycaenidae family with 7 species.

  2. Psychology, replication & beyond.

    Science.gov (United States)

    Laws, Keith R

    2016-06-01

    Modern psychology is apparently in crisis and the prevailing view is that this partly reflects an inability to replicate past findings. If a crisis does exists, then it is some kind of 'chronic' crisis, as psychologists have been censuring themselves over replicability for decades. While the debate in psychology is not new, the lack of progress across the decades is disappointing. Recently though, we have seen a veritable surfeit of debate alongside multiple orchestrated and well-publicised replication initiatives. The spotlight is being shone on certain areas and although not everyone agrees on how we should interpret the outcomes, the debate is happening and impassioned. The issue of reproducibility occupies a central place in our whig history of psychology.

  3. Homology Requirements and Competition between Gene Conversion and Break-Induced Replication during Double-Strand Break Repair.

    Science.gov (United States)

    Mehta, Anuja; Beach, Annette; Haber, James E

    2017-02-02

    Saccharomyces cerevisiae mating-type switching is initiated by a double-strand break (DSB) at MATa, leaving one cut end perfectly homologous to the HMLα donor, while the second end must be processed to remove a non-homologous tail before completing repair by gene conversion (GC). When homology at the matched end is ≤150 bp, efficient repair depends on the recombination enhancer, which tethers HMLα near the DSB. Thus, homology shorter than an apparent minimum efficient processing segment can be rescued by tethering the donor near the break. When homology at the second end is ≤150 bp, second-end capture becomes inefficient and repair shifts from GC to break-induced replication (BIR). But when pol32 or pif1 mutants block BIR, GC increases 3-fold, indicating that the steps blocked by these mutations are reversible. With short second-end homology, absence of the RecQ helicase Sgs1 promotes gene conversion, whereas deletion of the FANCM-related Mph1 helicase promotes BIR. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Türkiye'de Yükselen Bir Turizm Çeşidi: Helal Turizm

    Directory of Open Access Journals (Sweden)

    Nazlı Kardeş

    2017-06-01

    Full Text Available Turizm, günümüzde gittikçe önemi artan sektörlerin başında gelmektedir. Dünya’da turizm her geçen gün büyümekte, alternatif turizm çeşitleri artmakta ve her yıl daha çok insan küresel düzeyde turizm hareketinin bir parçası haline gelmektedir. Teknolojide, iletişimde, refah seviyesin de, eğitim düzeyinde görülen ilerleme Müslüman kesimin yaşamdan beklentilerini artırmış ve Müslüman kesimi dinin gereklerine uyarak tatil yapmaya yönlendirmiştir. Turizm sektöründeki yoğun rekabet ortamı turistlerin taleplerinin çeşitlenmesine yol açmıştır. Bu gelişmelere bağlı olarak bir turistik ürün çeşidi olarak ortaya çıkan “Helal Turizm”, gün geçtikçe önemi artan bir kavram olarak ortaya çıkmaktadır. Helal turizm, konaklama, seyahat, ulaşım, rekreasyon vb. turizm faaliyetlerinden doğan ihtiyaçların İslami kural ve inanışlara uygun şekilde karşılanması ile ilgili faaliyetlerdir. Bu araştırmanın amacı Türkiye’nin helal turizm açısından mevcut durumunu değerlendirmek, gün geçtikte rekabetin arttığı helal turizm alanında Türkiye’nin potansiyelini kullanarak bu turizm çeşidinin nasıl geliştirebileceğine yönelik düşünceleri ortaya koymak ve gelecek çalışmalara yol göstermektir. Bu amaç doğrultusunda konuyla ilgili geniş bir literatür taraması yapılarak helal turizmin kavramsal çerçevesi ortaya konmuş ve derinlemesine incelenen literatür çalışmaları, istatistik verileri ile Türkiye’nin mevcut kültürü ve Müslüman bir ülke olmasına rağmen diğer ülkelerden geride olduğu ve mevcut potansiyelini iyi kullanamadığı sonucuna varılmıştır. Bu sonuca yönelik öneriler getirilmiştir.

  5. DNA replication origins in archaea

    OpenAIRE

    Zhenfang eWu; Jingfang eLiu; Haibo eYang; Hua eXiang

    2014-01-01

    DNA replication initiation, which starts at specific chromosomal site (known as replication origins), is the key regulatory stage of chromosome replication. Archaea, the third domain of life, use a single or multiple origin(s) to initiate replication of their circular chromosomes. The basic structure of replication origins is conserved among archaea, typically including an AT-rich unwinding region flanked by several conserved repeats (origin recognition box, ORB) that are located adjacent to ...

  6. Replication studies in longevity

    DEFF Research Database (Denmark)

    Varcasia, O; Garasto, S; Rizza, T

    2001-01-01

    In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...

  7. Replication-Fork Dynamics

    NARCIS (Netherlands)

    Duderstadt, Karl E.; Reyes-Lamothe, Rodrigo; van Oijen, Antoine M.; Sherratt, David J.

    2014-01-01

    The proliferation of all organisms depends on the coordination of enzymatic events within large multiprotein replisomes that duplicate chromosomes. Whereas the structure and function of many core replisome components have been clarified, the timing and order of molecular events during replication re

  8. Coronavirus Attachment and Replication

    Science.gov (United States)

    1988-03-28

    synthesis during RNA replication of vesicular stomatitis virus. J. Virol. 49:303-309. Pedersen, N.C. 1976a. Feline infectious peritonitis: Something old...receptors on intestinal brush border membranes from normal host species were developed for canine (CCV), feline (FIPV), porcine (TGEV), human (HCV...gastroenteritis receptor on pig BBMs ...... ................. ... 114 Feline infectious peritonitis virus receptor on cat BBMs ... .............. 117 Human

  9. Bir Yüzü Sanat, Bir Yüzü Bilime Dönük Adam: Mehmed Çavuşoğlu

    OpenAIRE

    Yılmaz, Durali

    2006-01-01

    bunların ağzından hiç şiir duymadım. Ezberlerinde bir mısra bile yoktur çün— kü,’ diye dert yanar. Prof. Dr. Bali, Çavuşoğlu’nun sınıf arkadaşıdır. Tıpkı Çavuşoğlu gibi, onun da hafızasında yüzlerce şiir vardır. Bunlara, Çavuş-— oğlu’ nunkiler de dahildir. Şimdi İstanbul Kültür ÜniYersiteSinde birlikte görev yapmaktayız. Muhan Hocamız, Çavuşoğlu’nun yukarıdaki şiinni okudııktan sonra genellikle ekler: “Bunu kendisine okuduğumda, yüzüme sevecenlikle baktı, benim bile unuttüğuın bu şiiri ...

  10. Bussijuhtide ja Go Busi läbirääkimised jätkuvad / Jano Purga

    Index Scriptorium Estoniae

    Purga, Jano

    2007-01-01

    Maakonnaliinide turuvalitseja Go Bus katkestab lepingud Hiiumaal, Valgamaal ja Saaremaal, kuid jätkab läbirääkimisi bussijuhtide ametiühinguga palgatõusu üle, samas teeb ametiühing ettevalmistusi streigiks, mis algab 11. detsembril

  11. Dünya Denizcilik Eğitim Faaliyetleriyle İlgili Genel Bir Kıyaslama

    Directory of Open Access Journals (Sweden)

    Feramuz AŞKIN

    2015-12-01

    Full Text Available Deniz taşımacılığındaki artan profesyonelleşme gereksinimleri bu alanda hizmet veren personel ve mürettebatın aynı düzeyde eğitim alması ile cevap bulacaktır. Bu da eğitim veren kurum ve üniversitelerin belirli bir standartta eğitim vermesi ile mümkün olacaktır. Burada üzerinde durulması gereken konu eğitim veren kurumların eğitim düzeylerinin alt ve üst noktası arasındaki farkın mümkün mertebede birbirine yakın olması ile belirli bir kalite düzeyinde tutulabilecek olmasıdır. Bunun için eğitim veren kurumların uyması gereken başta STCW Manila kararları gibi uluslararası standartlar olmak üzere, iç mevzuatlar, çeşitli idarelerin önerileri ve kararları, EMSA gibi denetleyici birimlerin üzerinde durmuş olduğu çeşitli standartlar bir dayanak noktası oluşturacaktır. Bu çalışmada yazarlar, farklı düzeylerde eğitim veren örnek eğitim sistemlerinin karşılaştırılması yolu ile bu standartların uygulanması hususunu göz önüne sermeyi hedeflemektedir. Böylece bu bildirinin yazım amacı olan ve standartlarla genel kaideleri belirlenmiş daha kaliteli ve profesyonel eğitim sistemine geçişe katkıda bulunulabilecektir.

  12. ULUSLARIN REKABET ÜSTÜNLÜĞÜ VE ELMAS MODELI ÜZERINE BIR DEĞERLENDIRME

    Directory of Open Access Journals (Sweden)

    Murat KOC

    2014-07-01

    Full Text Available Günümüzde, rekabet kavramı daha çok firma düzeyinde bir kavram olmakla beraber, artık ulusal düzeyde de ele alınmaya başlanmıştır. Rekabet şartlarının değişken bir yapı içerisinde olması ve yaşanan küreselleşme, bir ulusun rekabet üstünlüğünün analiz edilebilmesi açısından yeni yöntemlerin uygulanması gerekliliğini ortaya koymuştur. Bu kapsamda Michael E. Porter, kapsamlı bir araştırma niteliği taşımakta olan, Elmas Modeli (Diamond Model’ni ortaya koymuştur. “Bazı ulusların neden diğerlerine göre belirli sektörlerde daha rekabetçi olduğu” sorusuna yanıt vermeye çalışılan model, belirli bir sektörde ulusal rekabet gücünü belirleyen bazı unsurların birbirleriyle ilişkili olarak incelenmesini öngörmektedir. Bu çalışmanın amacı, ulusların rekabet üstünlüğü sağlamasında Porter’ın literatüre kazandırdığı “Elmas Modeli” yaklaşımının değerlendirilmesi ve modele yönelik eleştirilerin ortaya konulmasıdır.

  13. DNA Replication via Entanglement Swapping

    CERN Document Server

    Pusuluk, Onur

    2010-01-01

    Quantum effects are mainly used for the determination of molecular shapes in molecular biology, but quantum information theory may be a more useful tool to understand the physics of life. Molecular biology assumes that function is explained by structure, the complementary geometries of molecules and weak intermolecular hydrogen bonds. However, both this assumption and its converse are possible if organic molecules and quantum circuits/protocols are considered as hardware and software of living systems that are co-optimized during evolution. In this paper, we try to model DNA replication as a multiparticle entanglement swapping with a reliable qubit representation of nucleotides. In the model, molecular recognition of a nucleotide triggers an intrabase entanglement corresponding to a superposition state of different tautomer forms. Then, base pairing occurs by swapping intrabase entanglements with interbase entanglements.

  14. Liderlikte post-modern bir paradigma: dönüşümcü liderlik

    Directory of Open Access Journals (Sweden)

    Levent Eraslan

    2006-12-01

    Full Text Available Heraklitos’un “Her şey akıştadır ve hiçbir şey duruşta değildir.” deyişi  ile insanlığın değişimi anlama, algılama ve ona uyum sağlama sürecinin başladığı kabul edilir. Değişim denen bu karmaşık  olgu, günümüzde bütün sosyal sistemlerin yaşama ilişkin kültürlerini ve yönetim biçimlerini hızlı bilgi artışı, hızlı gelişme ve hızlı iletişim ile birlikte derinden etkilemektedir. Bu değişim sürecinin  yükümlülüğü oluşturmak ve bunu başarmak için “liderlik” olgusu önemli bir rol oynamaktadır. Dönüşümü sağlamada geleneksel liderlik anlayışının yeterli olmadığının bilinmesi de, değişimin etkisinin yoğun olarak hissedildiği günümüzde, değişim temelli bir liderlik anlayışının yapılandırılması gerekliliğini ortaya çıkarmıştır. Bu  liderlik anlayışının da "Dönüşümcü Liderlik" olduğu ileri sürülmektedir. Aralıksız devam eden değişim sürecinde, dönüşümcü liderliğin tüm sektörlerde önemi gittikçe artmaktadır. Dönüşümcü liderler, vizyon yaratarak ve bu vizyonu paylaşarak izleyenleri ile sürekli iletişim kuran, güvenilir, saygı duyulan sosyal mimarlardır. Yeni zorlukların yaşanacağı  yeni çağda; "dönüşümcü liderlik"  bu zorlukların aşılmasında en iyi çözüm yolu olarak kabul edilmektedir. Tarihsel sürece baktığımızda ise Dönüşümcü liderliğe verilecek en büyük örneğin Türkiye Cumhuriyetinin Kurucusu M.Kemal Atatürk olduğunu görmekteyiz. Büyük Lider Atatürk dönüşümcü liderliğin  bütün karakteristik özelliklerini taşımaktadır. Yıkılmış bir imparatorluktan, her şeyi ile yeni bir devlet kurarak, yönetsel,sosyal,ekonomik ve kültürel yaşamda köklü bir dönüşüm süreci gerçekleştirmiştir. Atatürk’te Dönüşümcü liderliğin başat özelliklerinden;  Ortak Vizyon Oluşturma ve Paylaşma, Zihinsel Uyarım ve Yaratıcı olma, Karizmatik Etkiye Sahip

  15. Radyonun Demokratikleştirilmesinde Yeni Bir Olanak: İnternet Radyoculuğu

    Directory of Open Access Journals (Sweden)

    Ersoy Soydan

    2016-10-01

    Full Text Available Radyonun yazılı basından sonra geniş kitlelere seslenen en eski kitle iletişim aracı olduğu kabul edilmektedir. Radyo, 1920-1960 yılları arasında da en yaygın kitle iletişim aracı olmuştur. Radyo yayınlarının başlamasıyla birlikte işlevi de sorgulanmaya başlamıştır. Özellikle radyo yayınlarının hükümetin denetiminde olduğu Avrupa ülkelerinde yayın kuruluşları maddi açıdan hükümetlere bağımlı olmuş, bu durum doğal olarak hükümetlerin radyo yayınlarına karışması sonucunu doğurmuştur. Uzun yıllar boyunca Avrupa'da radyoculuk alanında devlet tekeli olduğu için toplumun büyük bir kesimi radyoda kendisine yeterince yer bulamamıştır. Hükümetlerin denetimindeki radyo yayıncılığına karşı muhalefet ve işlevinin değiştirilmesi talebi ise çok geçmeden dillendirilmeye başlamıştır. Örneğin Alman yazar Bertolt Brecht daha 1932 yılında radyonun işlevinin değiştirilerek demokratikleştirilmesi gerektiğini, yani radyoyu bir iletim aygıtı olmaktan çıkarıp, iletişim aygıtına dönüştürmek gerektiğini söylemiştir.1950’li yıllardan sonra televizyonun yaygınlaşmasıyla birlikte radyonun insan yaşamındaki yeri kaçınılmaz olarak gerilemiştir. Bunun sonucu olarak ta tüm dünyada “radyo öldü mü?” tartışması yaşanmıştır. Ancak korsan yayınlarla başlayıp devlet tekellerinin yıkılmasıyla sonuçlanan alternatif radyo akımı daha önce radyodan sesini duyuramayan toplulukların seslerini duyurabilmesini ve radyonun demokratikleşerek yeniden gündeme gelmesini sağlamıştır. Radyonun demokratikleştirilmesi tartışması internetin yaygınlaşmasıyla birlikte bir kez daha gündeme gelmiştir. İnternet teknolojisi radyodan sesini duyurmak isteyen herkesin son derece basit ve ucuz bir şekilde dünyanın dört bir tarafına sesini duyurmasını sağlayarak, radyonun daha önce olmadığı kadar demokratikleşmesinin yolunu açmıştır.

  16. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  17. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  18. Initiation of adenovirus DNA replication.

    OpenAIRE

    Reiter, T; Fütterer, J; Weingärtner, B; Winnacker, E L

    1980-01-01

    In an attempt to study the mechanism of initiation of adenovirus DNA replication, an assay was developed to investigate the pattern of DNA synthesis in early replicative intermediates of adenovirus DNA. By using wild-type virus-infected cells, it was possible to place the origin of adenovirus type 2 DNA replication within the terminal 350 to 500 base pairs from either of the two molecular termini. In addition, a variety of parameters characteristic of adenovirus DNA replication were compared ...

  19. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization. During cell division the entire genome must be accurately replicated and the chromatin landscape reproduced on new DNA. Chromatin and nuclear structure influence where and when DNA replication...... initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  20. Replication Research and Special Education

    Science.gov (United States)

    Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

    2016-01-01

    Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

  1. Replication Research and Special Education

    Science.gov (United States)

    Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

    2016-01-01

    Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

  2. Replication data collection highlights value in diversity of replication attempts

    Science.gov (United States)

    DeSoto, K. Andrew; Schweinsberg, Martin

    2017-01-01

    Researchers agree that replicability and reproducibility are key aspects of science. A collection of Data Descriptors published in Scientific Data presents data obtained in the process of attempting to replicate previously published research. These new replication data describe published and unpublished projects. The different papers in this collection highlight the many ways that scientific replications can be conducted, and they reveal the benefits and challenges of crucial replication research. The organizers of this collection encourage scientists to reuse the data contained in the collection for their own work, and also believe that these replication examples can serve as educational resources for students, early-career researchers, and experienced scientists alike who are interested in learning more about the process of replication. PMID:28291224

  3. Anatomy of Mammalian Replication Domains

    Science.gov (United States)

    Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2017-01-01

    Genetic information is faithfully copied by DNA replication through many rounds of cell division. In mammals, DNA is replicated in Mb-sized chromosomal units called “replication domains.” While genome-wide maps in multiple cell types and disease states have uncovered both dynamic and static properties of replication domains, we are still in the process of understanding the mechanisms that give rise to these properties. A better understanding of the molecular basis of replication domain regulation will bring new insights into chromosome structure and function. PMID:28350365

  4. Modeling inhomogeneous DNA replication kinetics.

    Directory of Open Access Journals (Sweden)

    Michel G Gauthier

    Full Text Available In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.

  5. Kosovo albaanlaste imelootus hääbub läbirääkimiste kiuste / Triin Oppi

    Index Scriptorium Estoniae

    Oppi, Triin

    2007-01-01

    Serbia ja Kosovo provintsi esindajate läbirääkimistest Viinis ning ÜRO esindaja Martti Ahtisaari ettepanekust Kosovo suhtes, kus välditakse sõna "iseseisvus". Euroopa Liit üritab Kosovot juhtida iseseisvuse teele, pakkudes Serbiale võimalust mitte anda välja Haagi sõjatribunalile Ratko Mladicit. Vt. samas: Kosovo äärmuslased õhkisid kolm ÜRO sõidukit. Kaart

  6. Replicated Spectrographs in Astronomy

    CERN Document Server

    Hill, Gary J

    2014-01-01

    As telescope apertures increase, the challenge of scaling spectrographic astronomical instruments becomes acute. The next generation of extremely large telescopes (ELTs) strain the availability of glass blanks for optics and engineering to provide sufficient mechanical stability. While breaking the relationship between telescope diameter and instrument pupil size by adaptive optics is a clear path for small fields of view, survey instruments exploiting multiplex advantages will be pressed to find cost-effective solutions. In this review we argue that exploiting the full potential of ELTs will require the barrier of the cost and engineering difficulty of monolithic instruments to be broken by the use of large-scale replication of spectrographs. The first steps in this direction have already been taken with the soon to be commissioned MUSE and VIRUS instruments for the Very Large Telescope and the Hobby-Eberly Telescope, respectively. MUSE employs 24 spectrograph channels, while VIRUS has 150 channels. We compa...

  7. Multifork chromosome replication in slow-growing bacteria

    Science.gov (United States)

    Trojanowski, Damian; Hołówka, Joanna; Ginda, Katarzyna; Jakimowicz, Dagmara; Zakrzewska-Czerwińska, Jolanta

    2017-01-01

    The growth rates of bacteria must be coordinated with major cell cycle events, including chromosome replication. When the doubling time (Td) is shorter than the duration of chromosome replication (C period), a new round of replication begins before the previous round terminates. Thus, newborn cells inherit partially duplicated chromosomes. This phenomenon, which is termed multifork replication, occurs among fast-growing bacteria such as Escherichia coli and Bacillus subtilis. In contrast, it was historically believed that slow-growing bacteria (including mycobacteria) do not reinitiate chromosome replication until the previous round has been completed. Here, we use single-cell time-lapse analyses to reveal that mycobacterial cell populations exhibit heterogeneity in their DNA replication dynamics. In addition to cells with non-overlapping replication rounds, we observed cells in which the next replication round was initiated before completion of the previous replication round. We speculate that this heterogeneity may reflect a relaxation of cell cycle checkpoints, possibly increasing the ability of slow-growing mycobacteria to adapt to environmental conditions. PMID:28262767

  8. SUMO and KSHV Replication

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Pei-Ching [Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan (China); Kung, Hsing-Jien, E-mail: hkung@nhri.org.tw [Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan (China); Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616 (United States); UC Davis Cancer Center, University of California, Davis, CA 95616 (United States); Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (China)

    2014-09-29

    Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.

  9. Coordination between chromosome replication, segregation, and cell division in Caulobacter crescentus

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

    Progression through the Caulobacter crescentus cell cycle is coupled to a cellular differentiation program. The swarmer cell is replicationally quiescent, and DNA replication initiates at the swarmer-to-stalked cell transition. There is a very short delay between initiation of DNA replication......, and the completely replicated terminus regions stay associated with each other after chromosome replication is completed, disassociating very late in the cell cycle shortly before the final cell division event. Invagination of the cytoplasmic membrane occurs earlier than separation of the replicated terminus regions...

  10. An Evaluation on Library Cooperation in Turkey Türkiye'de Kütüphanelerarası İşbirliği Üzerine Bir Değerlendirme

    Directory of Open Access Journals (Sweden)

    Mehmet Emin Küçük

    2004-06-01

    Full Text Available No library in the world has the sufficient budget, space, and professionals to acquire all existing information sources, and to organise and serve the acquired materials. For this reason, libraries cooperate in collection development, cata loguing, providing access to the others' collections and document delivery. Aiming at evaluating the co-operation efforts during the Republican era from the perspective of the historical, organisational and practicable fields of implementation, this paper examines the library co-operation in Turkey. To determine the present situation, the Turkish National Library, General Directorate of Libraries and Publications, National Academic Network and Information Centr, and some special and school libraries in Ankara, Ministry of National Education, university libraries, consortia, and professional associations are examined, and the data gathered from literature and interviews are evaluated. In conclusion, it has been observed that in recent years, co-operation effort has gained momentum, two consortia have emerged to provide access to the electronic information sources, document delivery projects between university libraries have been started, but efforts in some practicable fields of co-operation, such as preparing union catalogues, sharing bibliographic data, and developing authority files have been unsuccessful. It has also been observed that there is lack of co-operation except among university libraries, and that institutions have failed in establishing a "common wisdom" and consequently in developing the skills of planning and organisation. Inadequacy of resources, legislation, and infrastructure, and most importantly the lack of dedication resulted in discontinuity of the ongoing projects and the production of the new ones. Dünyadaki hiç bir kütüphane varolan tüm bilgi kaynaklarını sağlama, düzenleme ve hizmete sunmada yeterli bütçe, bina ve profesyonele sahip değildir. Bu nedenle k

  11. Efficient usage of Adabas replication

    CERN Document Server

    Storr, Dieter W

    2011-01-01

    In today's IT organization replication becomes more and more an essential technology. This makes Software AG's Event Replicator for Adabas an important part of your data processing. Setting the right parameters and establishing the best network communication, as well as selecting efficient target components, is essential for successfully implementing replication. This book provides comprehensive information and unique best-practice experience in the field of Event Replicator for Adabas. It also includes sample codes and configurations making your start very easy. It describes all components ne

  12. Solving the Telomere Replication Problem

    Science.gov (United States)

    Maestroni, Laetitia; Matmati, Samah; Coulon, Stéphane

    2017-01-01

    Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at the ends of the chromosomes. This is known as the telomere replication problem. In this article, different and new aspects of telomere replication, that can threaten the integrity of telomeres, will be reviewed. In particular, we will focus on the functions of shelterin and the replisome for the preservation of telomere integrity. PMID:28146113

  13. Etkili Bir Halkla İlişkiler Aracı Olarak Sosyal Medya

    OpenAIRE

    aslan, mahmut mert

    2017-01-01

    Etkili Bir Halkla İlişkiler Aracı Olarak Sosyal MedyaÖZETDünyanın İnternet teknolojisi iletanışması, 90’lı yıllara rastlamaktadır. Sonradan mobil iletişim ile İnternetteknolojisinin bütünleşmesi, iletişimde mesafeleri ortadan kaldırmıştır. Çokgeçmeden bu yeniliklerin iş dünyasında ürünlerin tanıtım ve pazarlamasında biraraç olarak kullanılabileceği fikri ortaya atılmış olsa da, o dönemde bununilgililer tarafından dikkate alındığını söylemek pek mümkün değildir. Bununnedeni, olasılıkla, o döne...

  14. Türkiye’de Leasıng Sözleşmesi ve Bir Uygulama

    OpenAIRE

    Taşabatlı, Gökhan

    2004-01-01

    Leasing ilk kez, 1930’lu yıllarda Amerika Birleşik Devletleri’nde ekonomik bunalım sonrası yaşanan finansman güçlüklerini gidermek amacıyla ortaya çıkmış ve II.Dünya Savaşı sonrası diğer Avrupa ülkelerine hızla yayılmaya başlamıştır. Leasing’in Kıta Avrupası ülkelerine yayılması 1960’lı yıllara rastlamaktadır. 1970 sonrası petrol şoku ile beraber birçok firma finansman darboğazı ile karşı karşıya kalmıştır. Bu gelişmeler işletmeleri mülkiyet yerine kullanım olanağı veren leasing müessesesine ...

  15. İşletmelerin Rekabet Stratejilerinin Eşbiçimliliği ve Bir Uygulama

    OpenAIRE

    2003-01-01

    Bu çalışma, Türkiye’de faaliyet gösteren işletmelerin stratejilerini neye göre ve nasıl oluşturduklarını ortaya koyarak, kurumsal baskıların örgütsel yapıları, stratejileri ve uygulamaları nasıl etkilediği ve işleri yürütme biçimleri bakımından birbirine benzer örgütleri nasıl ortaya çıkardığını belirlemeye yöneliktir. Örgütlerin varlık nedenlerini ya da işleyiş biçimlerini geçmişte ele alan pek çok çalışmaya karşılık, teknik ve sosyal bir olgu olarak örgütlerin incelenmesinde ortaya çıka...

  16. Assessing long-term water demand of constantine province in Kébir-Rhumel Mediterranean catchment

    Science.gov (United States)

    Kiniouar, H.; Hani, A.; Younsi, A.

    2017-02-01

    By mid-century, in the southern Mediterranean countries, levies probably reach the limit level of renewable water resources. Algeria is one of the poorest countries in renewable water resources, with an annual storage capacity of 14.6 million m3 in the Mediterranean coastal watersheds, representing 7% of the land area and accounts for 90 % of total surface runoff of the country. In this paper, we assess water demand to meet the needs of water users in Constantine province. The latter is located in the Kébir-Rhumel Mediterranean basin under semi-arid climate with relatively high growth rate of population, agricultural and industrial activities. Using Water Evaluation And Planning system (WEAP), we built a model for managing water demand of Constantine province. A business as usual and five scenarii of «water demand " were calculated by WEAP model to simulate the uncertainties over the period of 20 years (2008-2027) : (1) Population growth, (2) increase in irrigated crop lands, (3) decrease in basic drinking water consumption, (4) decrease in basic irrigation water consumption and (5) increase in basic industrial water consumption. The results showed that scenario 3 is the best alternative scenario and the most efficient by reducing drinking water demand for about 12 Mm3 in 20 years, and thus preserve reaching the limits of water resources potentialities.

  17. Myasis occuring in a neonate

    Science.gov (United States)

    Obasa, Temitope O.; Sowunmi, Funmilola Olusola

    2012-01-01

    Myasis is the infestation of skin by larvae or maggots of a variety of flies. It is a condition that occurs more commonly in adults who are living and/or have visited tropical countries. It rarely occurs in neonates, and even when seen, only few larvae are extracted. This case report describes myasis occurring in an 11-day-old female who had 47 larvae in her skin. PMID:23355934

  18. Myasis occuring in a neonate

    Directory of Open Access Journals (Sweden)

    Temitope O. Obasa

    2012-12-01

    Full Text Available Myasis is the infestation of skin by larvae or maggots of a variety of flies. It is a condition that occurs more commonly in adults who are living and/or have visited tropical countries. It rarely occurs in neonates, and even when seen, only few larvae are extracted. This case report describes myasis occurring in an 11-day-old female who had 47 larvae in her skin.

  19. Mitochondrial biology. Replication-transcription switch in human mitochondria.

    Science.gov (United States)

    Agaronyan, Karen; Morozov, Yaroslav I; Anikin, Michael; Temiakov, Dmitry

    2015-01-30

    Coordinated replication and expression of the mitochondrial genome is critical for metabolically active cells during various stages of development. However, it is not known whether replication and transcription can occur simultaneously without interfering with each other and whether mitochondrial DNA copy number can be regulated by the transcription machinery. We found that interaction of human transcription elongation factor TEFM with mitochondrial RNA polymerase and nascent transcript prevents the generation of replication primers and increases transcription processivity and thereby serves as a molecular switch between replication and transcription, which appear to be mutually exclusive processes in mitochondria. TEFM may allow mitochondria to increase transcription rates and, as a consequence, respiration and adenosine triphosphate production without the need to replicate mitochondrial DNA, as has been observed during spermatogenesis and the early stages of embryogenesis.

  20. Otistik Çocuklar İçin Davranışsal Eğitim Programı (OÇİDEP Ev Uygulamasının Bir Çocukla İncelenmesi

    Directory of Open Access Journals (Sweden)

    Yeşim Güleç-Aslan

    2009-01-01

    Full Text Available Yoğun davranışsal eğitim, otizm tanılı çocuklar üzerindeki etkileri bilimsel araştırma bulgularıyla desteklenmiş bir uygulamadır. Otistik Çocuklar için Davranışsal Eğitim Programı (OÇİDEP Türkiye’de bu tür eğitim sunmak üzere geliştirilen öncü programlar arasında yer almaktadır. Bu araştırmada OÇİDEP ev uygulamasının bir çocukla yürütülme süreci incelenmiştir. Araştırma, program uygulama sürecinin incelenmesi amacıyla yürütülen, nicel veri toplama ve analiz tekniklerini de içeren bir nitel araştırmadır. Araştırmanın katılımcısı dokuz yaşında, otizm tanılı bir erkek çocuktur. Bulgular; (a OÇİDEP ev uygulamasının planlama aşamasında belirlenen genel ilkelerde değişiklikler ya da uyarlamalar yapılarak yürütülebildiğini, (b uygulama boyunca çeşitli davranış ve öğretim sorunları yaşandığını ve bu sorunlara yönelik uygun önlemler alınarak yürütmenin sürdürüldüğünü, (c uygulama süresince OÇİDEP ekip üyelerinin bilgi ve becerilerinde artışlar olduğunu, (d OÇİDEP ev uygulaması katılımcısında program içinde ve dışında çeşitli gelişmeler görüldüğünü, (e ekip üyelerinin ve ailenin OÇİDEP’in çocukların gelişimine önemli katkılarda bulunan, ancak, belirli unsurlara dikkat edilerek uygulanması gereken bir program olduğu yönünde görüşleri olduğunu göstermiştir. Intensive Behavioral Intervention (IBI is an evidence-based practice for children with autism. Intensive Behavioral Home Intervention Program called OCIDEP is one of the first IBI-type programs in Turkey. The purpose of the present study was to investigate the implementation process of the OCIDEP home program with one nine-years- old boy with autism. During the study both qualitative and quantitative data collection and analysis methods were systematically utilized on a regular basis. Findings of the study were as follows: (a some of the guidelines did not

  1. Charter School Replication. Policy Guide

    Science.gov (United States)

    Rhim, Lauren Morando

    2009-01-01

    "Replication" is the practice of a single charter school board or management organization opening several more schools that are each based on the same school model. The most rapid strategy to increase the number of new high-quality charter schools available to children is to encourage the replication of existing quality schools. This policy guide…

  2. The Cell Cycle Timing of Human Papillomavirus DNA Replication.

    Science.gov (United States)

    Reinson, Tormi; Henno, Liisi; Toots, Mart; Ustav, Mart; Ustav, Mart

    2015-01-01

    Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV) vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research.

  3. LHCb experience with LFC replication

    CERN Document Server

    Bonifazi, F; Perez, E D; D'Apice, A; dell'Agnello, L; Düllmann, D; Girone, M; Re, G L; Martelli, B; Peco, G; Ricci, P P; Sapunenko, V; Vagnoni, V; Vitlacil, D

    2008-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

  4. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    Directory of Open Access Journals (Sweden)

    Hendro Nindito

    2014-01-01

    Full Text Available The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MySQL running on Linux as the destination. The method applied in this research is prototyping in which the processes of development and testing can be done interactively and repeatedly. The key result of this research is that the replication technology applied, which is called Oracle GoldenGate, can successfully manage to do its task in replicating data in real-time and heterogeneous platforms.

  5. LHCb experience with LFC replication

    CERN Document Server

    Carbone, Angelo; Dafonte Perez, Eva; D'Apice, Antimo; dell'Agnello, Luca; Duellmann, Dirk; Girone, Maria; Lo Re, Giuseppe; Martelli, Barbara; Peco, Gianluca; Ricci, Pier Paolo; Sapunenko, Vladimir; Vagnoni, Vincenzo; Vitlacil, Dejan

    2007-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informations (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

  6. In vitro replication of cyanobacterial plasmids from Synechocystis PCC 6803.

    Science.gov (United States)

    Yang, X; Daniell, H; McFadden, B

    1994-09-01

    Little knowledge of DNA replication in cyanobacteria is available. In this study, we report the development and characterization of an in vitro system for studies of replication of the endogenous plasmids from the unicellular cyanobacterium Synechocystis 6803. This system (fraction III) was isolated at high salt concentrations and partially purified on a heparin-agarose column. DNA polymerases in Synechocystis 6803 appeared to be associated with membranes and could be released by the addition of ammonium sulfate to 20% saturation. DNA synthesis in fraction III was dependent on the addition of cyanobacterial plasmids isolated from the same strain. The in vitro replication products consist mostly of the supercoiled form of the plasmids. Unlike replication of many Escherichia coli plasmids, replication of cyanobacterial plasmids did not require added ATP, was not inhibited by omission of the ribonucleotides, and was insensitive to the RNA polymerase inhibitor rifampicin and the gyrase inhibitor novobiocin, but was inhibited by ethidium bromide. These data suggest that RNA may not be involved in the initiation of replication of cyanobacterial plasmids from Synechocystis 6803. In addition, intermediates of replication have been detected by two-dimensional gel electrophoresis. Density labeling experiments also indicate that cyanobacterial plasmid synthesis in vitro occurs by a semiconservative replication.

  7. Replication protein of tobacco mosaic virus cotranslationally binds the 5′ untranslated region of genomic RNA to enable viral replication

    Science.gov (United States)

    Kawamura-Nagaya, Kazue; Ishibashi, Kazuhiro; Huang, Ying-Ping; Miyashita, Shuhei; Ishikawa, Masayuki

    2014-01-01

    Genomic RNA of positive-strand RNA viruses replicate via complementary (i.e., negative-strand) RNA in membrane-bound replication complexes. Before replication complex formation, virus-encoded replication proteins specifically recognize genomic RNA molecules and recruit them to sites of replication. Moreover, in many of these viruses, selection of replication templates by the replication proteins occurs preferentially in cis. This property is advantageous to the viruses in several aspects of viral replication and evolution, but the underlying molecular mechanisms have not been characterized. Here, we used an in vitro translation system to show that a 126-kDa replication protein of tobacco mosaic virus (TMV), a positive-strand RNA virus, binds a 5′-terminal ∼70-nucleotide region of TMV RNA cotranslationally, but not posttranslationally. TMV mutants that carried nucleotide changes in the 5′-terminal region and showed a defect in the binding were unable to synthesize negative-strand RNA, indicating that this binding is essential for template selection. A C-terminally truncated 126-kDa protein, but not the full-length 126-kDa protein, was able to posttranslationally bind TMV RNA in vitro, suggesting that binding of the 126-kDa protein to the 70-nucleotide region occurs during translation and before synthesis of the C-terminal inhibitory domain. We also show that binding of the 126-kDa protein prevents further translation of the bound TMV RNA. These data provide a mechanistic explanation of how the 126-kDa protein selects replication templates in cis and how fatal collision between translating ribosomes and negative-strand RNA-synthesizing polymerases on the genomic RNA is avoided. PMID:24711385

  8. Limiting DNA replication to once and only once

    OpenAIRE

    2000-01-01

    In Escherichia coli cells, the origin of chromosomal replication is temporarily inactivated after initiation has occurred. Origin sequestration is the first line of defence against over-initiation, providing a time window during which the initiation potential can be reduced by: (i) titration of DnaA proteins to newly replicated chromosomal elements; (ii) regulation of the activity of the DnaA initiator protein; and (iii) sequestration of the dnaA gene promoter. This review represents the firs...

  9. The hunt for origins of DNA replication in multicellular eukaryotes

    DEFF Research Database (Denmark)

    Urban, J. M.; Foulk, M. S.; Casella, Cinzia;

    2015-01-01

    Origins of DNA replication (ORIs) occur at defined regions in the genome. Although DNA sequence defines the position of ORIs in budding yeast, the factors for ORI specification remain elusive in metazoa. Several methods have been used recently to map ORIs in metazoan genomes with the hope...... that features for ORI specification might emerge. These methods are reviewed here with analysis of their advantages and shortcomings. The various factors that may influence ORI selection for initiation of DNA replication are discussed....

  10. Single molecule analysis of replicated DNA reveals the usage of multiple KSHV genome regions for latent replication.

    Directory of Open Access Journals (Sweden)

    Subhash C Verma

    2011-11-01

    Full Text Available Kaposi's sarcoma associated herpesvirus (KSHV, an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA. Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD. Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA

  11. NACSA Charter School Replication Guide: The Spectrum of Replication Options. Authorizing Matters. Replication Brief 1

    Science.gov (United States)

    O'Neill, Paul

    2010-01-01

    One of the most important and high-profile issues in public education reform today is the replication of successful public charter school programs. With more than 5,000 failing public schools in the United States, there is a tremendous need for strong alternatives for parents and students. Replicating successful charter school models is an…

  12. 8051 Mikrodenetleyicili Bir Sumo Robot Tasarımı ve Uygulaması

    Directory of Open Access Journals (Sweden)

    Mehmet ALBAYRAK

    2009-04-01

    Full Text Available Bu çalısmada, 8051 mikrodenetleyici kontrollü bir sumo robotun mekanik tasarımı, kontrol kartı ve yazılımı gerçeklestirilmistir. Robot, yarısma ve egitim amaçlı tasarlandıgı için hücum amaçlı strateji içeren yazılım gelistirilerek yüklenmistir. 8051 mikrodenetleyici içindeki kontrol yazılımı PC 'nin seri portuna baglı mikrodenetleyici programlama kartına takılıp, kolaylıkla güncellenebildigi için yazılım stratejisi her yarısma için degistirilebilir niteliktedir. Microdenetleyici yazılımı μVision Keil derleyicisinde C kodu kullanılarak hazırlanmıstır. Mekanik tasarım asamasında robot dıs yüzeyinin darbelere dayanıklı malzemeden seçilmesine ve tekerleklerin sürtünmesinin fazla (kaymaz olmasına özen gösterilmistir. Robotun gücünü belirlenen agırlık sınırları içinde en fazla hale getirebilmek için 4 ayrı disli DC motor ve 4 amperlik akü kullanılmıstır. Rakip algılama mesafe sensörü ve kontrast sensörü (beyaz algılama seçiminde cevap verme süresi çok az olan sensörler tercih edilmistir.

  13. Random Forests Yöntemi ve Sağlık Alanında Bir Uygulama

    Directory of Open Access Journals (Sweden)

    Muhammet AKMAN

    2011-01-01

    Full Text Available Amaç: Veri madenciliği, genel olarak tanımlayıcı ve tahmin edici olmak üzere iki ana başlıkta incelenmektedir. Özellikle tıp alanında veri madenciliği daha çok tahmin edici yönüyle kullanılmaktadır. Bu çalışmada, ağaç tabanlı veri madenciliği yöntemlerinden birisi olan Random Forests (RF yönteminin incelenmesi ve sağlık alanından elde edilen bir veri seti üzerine uygulaması yapılarak sonuçlarının tartışılması amaçlanmıştır. Gereç ve Yöntemler: RF yönteminde, karar ormanını oluşturan karar ağaçları orijinal veri setinden bootstrap yöntemiyle seçilen farklı örneklerden oluşturulmaktadır. Her karar ağacında veri setindeki tüm değişkenlerden rastgele seçilen az sayıda değişken kullanılmaktadır. Her ağaç bir sınıf için oy vermektedir ve orman sınıflayıcısı bütün ağaçların verdiği oyları toplayarak bir sınıf için son tahminini yapmaktadır. Yöntemin uygulanması amacıyla Diş hekimliği alanından elde edilen bir veri seti kullanılmıştır. Bulgular: Toplam 43 tane demografik, dental ve serolojik özelliklere ait veriler kullanılarak RF yöntemi ile %95.4 oranında başarılı bir sınıflandırma yapılmıştır. Bu karar ormanının hata oranı ise %3.33 olarak bulunmuştur. Aynı veri seti için Bagging ve CART yöntemi ile de sınıflama yapılmış ve Bagging yöntemi ile hata oranı %5.4, CART yöntemi ile %8.75 olarak bulunmuştur. Sonuç: RF yöntemi ile veri setindeki değişken sayısı ve örnek sayısı ne kadar çok olursa olsun genellikle hata oranı düşük sınıflamalar yapılmaktadır. Hata oranının düşüklüğü ise bir topluluk yöntemi olmasından kaynaklanmaktadır. Özelikle çok sayıda değişkenin olduğu DNA veri seti gibi binlerce gen arasından önemli olanları tespit etmek için kullanılabilir.

  14. Yeni Medya Gazeteciliğinde Etik Bir Paradigma Belirlemenin Kapsamı ve Sınırları

    Directory of Open Access Journals (Sweden)

    İlker ERDOĞAN

    2013-09-01

    Full Text Available Yeni medya gazeteciliği, çok büyük iletişim potansiyeliyle, modern bir haber toplama ve yayımlama biçimidir ya da pek çok farklı katılımcının bağlanabildiği çevrimiçi (online bir forumdur. Ayrıca, bu biçim ya da forum, dijital ya da çevrimiçi (online gazetecilik olarak adlandırılan, medya profesyonellerine sınırsız kaynaklar ve teknolojik olanaklar sunan internet üzerinde ve internet aracılığıyla gerçekleştirilen internete özgü bir gazetecilik türüne gönderme yapmaktadır. Yeni medya, teknolojik gelişmelerin ve değişimlerin paralelinde gelişim sürecini sürdürmekte, hızlı olduğu kadar da belirli kurallara bağlı kalmadan geliştiği için yeni sorunları beraberinde getirmekte ve bu nedenle, yeni medya gazeteciliğinin etik düzenlemelere acil olarak kavuşturulması gerekmektedir. Yeni medya gazeteciliğindeki etik sorunları ya da ikilemleri, genel olarak, editöryal bağımsızlık, editöryal kontrol eksikliği, enformasyonun yeniden dağıtılması-telif hakları, haber-reklam-ticari enformasyon ilişkisi, çevrimiçi (online içeriğin yayımlanma hızı, ticari baskı, köprülerin (hyperlink kullanımı, doğruluk ve güvenilirlik, kaynaklar, mahremiyet, düzenleme, haber toplama yöntemleri, kaynak şeffaflığı, bloggerlar, yurttaş gazeteciler, profesyonel olmayan gazeteciler, dijital manipülasyon ile nefret söylemi ve saldırgan içerik olmak üzere on sekiz ayrı kategoride sınıflandırmak mümkündür. Bu çalışmada, yeni medya gazeteciliğinde etik bir model önerisinin oluşturulması açısından etik sorunlar iletişim etiği bağlamında değerlendirilerek kuramsal çerçevenin belirlenmesine çalışılmakta ve modern iletişimin vazgeçilmez bir alanı olan yeni medya gazeteciliğinde etik bir paradigma belirlemenin kapsamı ve sınırları tartışılmaktadır.

  15. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

    to local environments and under the impact of new learning. To illuminate these issues, we draw on a longitudinal in-depth study of Swedish home furnishing giant IKEA, involving more than 70 interviews. We find that IKEA has developed organizational mechanisms that support an ongoing learning process aimed......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator....

  16. The Psychology of Replication and Replication in Psychology.

    Science.gov (United States)

    Francis, Gregory

    2012-11-01

    Like other scientists, psychologists believe experimental replication to be the final arbiter for determining the validity of an empirical finding. Reports in psychology journals often attempt to prove the validity of a hypothesis or theory with multiple experiments that replicate a finding. Unfortunately, these efforts are sometimes misguided because in a field like experimental psychology, ever more successful replication does not necessarily ensure the validity of an empirical finding. When psychological experiments are analyzed with statistics, the rules of probability dictate that random samples should sometimes be selected that do not reject the null hypothesis, even if an effect is real. As a result, it is possible for a set of experiments to have too many successful replications. When there are too many successful replications for a given set of experiments, a skeptical scientist should be suspicious that null or negative findings have been suppressed, the experiments were run improperly, or the experiments were analyzed improperly. This article describes the implications of this observation and demonstrates how to test for too much successful replication by using a set of experiments from a recent research paper.

  17. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

    Preserving genome integrity is essential for cell survival. To this end, mechanisms that supervise DNA replication and respond to replication perturbations have evolved. One such mechanism is the replication checkpoint, which responds to DNA replication stress and acts to ensure replication pausing...

  18. Adenovirus replication and transcription sites are spatially separated in the nucleus of infected cells.

    Science.gov (United States)

    Pombo, A; Ferreira, J; Bridge, E; Carmo-Fonseca, M

    1994-11-01

    We have visualized the intranuclear topography of adenovirus replication and transcription in infected HeLa cells. The results show that viral DNA replication occurs in multiple foci that are highly organized in the nucleoplasm. Pulse-chase experiments indicate that newly synthesized viral double-stranded DNA molecules are displaced from the replication foci and spread throughout the nucleoplasm, while the single-stranded DNA replication intermediates accumulate in adjacent sites. Double-labelling experiments and confocal microscopy show that replication occurs in foci localized at the periphery of the sites where single-stranded DNA accumulates. The simultaneous visualization of viral replication and transcription reveals that the sites of transcription are predominantly separated from the sites of replication. Transcription is detected adjacent to the replication foci and extends around the sites of single-stranded DNA accumulation. These data indicate that newly synthesized double-stranded DNA molecules are displaced from the replication foci and spread in the surrounding nucleoplasm, where they are used as templates for transcription. Splicing snRNPs are shown to co-localize with the sites of transcription and to be excluded from the sites of replication. This provides evidence that splicing of viral RNAs occurs co-transcriptionally and that the sites of viral DNA replication are spatially distinct from the sites of RNA transcription and processing.

  19. Metode Pembacaan Turâts Arab-Islam: Perspekti Muhammad ‘Abid al-Jâbirî

    Directory of Open Access Journals (Sweden)

    Abdul Mukti Ro’uf

    2010-06-01

    Full Text Available The way how turâts (a term only found in contemporary Arabic-Islam or tradition is viewed has been a critical problem. This is because queries about it imply rise and or fall of a civilization. This thesis has at least been proved by facts of history that since the midst 19th century the world of Arabic-Islam thoughts have been moving backward compared to that in the Western-modern thoughts. This research will analyze Muhammad ‘Âbid al-Jâbirî’s thoughts that represented contemporary thinkers. Al-Jâbirî was a muslim intellectual born in Feiji Southeast-Marocco in 1936. His initial acquaintance with philosophical thoughts related to three prominent figures of Karl Marx (1818-1890, Gaston Bachelard (1884-1962, and Louis Althusser (1918-1990. He was grown up in a setting of Maghribi thoughts (Marocco-Andalusia, which was influenced by traditions of French philosophy of Marxian. However, he doubted Marxian approaches in Islamic history context.Abstrak: Cara bagaimana turâts—sebuah terma yang hanya ditemukan dalam tradisi Arab-Islam kontemporer—dipahami telah menjadi suatu problem yang amat mendesak. Hal itu karena pengabaian atasnya akan berimplikasi pada kebangkitan atau kejatuhan suatu peradaban. Tesis itu setidaknya telah dibuktikan oleh kenyataan sejarah bahwa semenjak pertengahan abad XIX pemikiran Arab-Islam mengalami kemunduran dibandingkan dengan pemikiran-pemikiran Barat moderen. Kajian ini akan menganalisis pemikiran Muhammad ‘Âbid al-Jâbirî’s yang merepresentasikan para pemikir kontemporer. Al-Jâbirî adalah seorang intelektual muslim yang terlahir di Feiji, Maroko Tenggara, pada tahun 1936.  Perkenalan awalnya dengan pemikiran filosofis berkaitan dengan tiga figur penting, yaitu Karl Marx (1818-1890, Gaston Bachelard (1884-1962, and Louis Althusser (1918-1990. Dia tumbuh besar dalam latar pemikiran-pemikiran Maghribi (Marocco-Andalusia, yang dipengaruhi oleh tradisi filsafat Perancis yang Marxian. Namun demikian

  20. Örgütsel İmaj Yönetim Sisteminin İncelenmesi ve Bir Uygulama

    OpenAIRE

    Küçükaslan, Aslı

    2014-01-01

    Bu çalışma işletmelerin paydaşları tarafından nasıl algılandıklarını ölçmeye çalışmaktadır. Çalışanların, müşterilerin ve işletme sisteminin diğer unsurlarının algılamalarını etkileyen birçok faktör vardır.

  1. Angiodysplasia Occurring in Jejunal Diverticulosis

    OpenAIRE

    Edward A Jones; Hugh Chaun; Phillip Switzer; David J Clow; Ronald J Hancock

    1990-01-01

    The first case of angiodysplasia occurring in acquired jejunal diverticulosis is reported. The patient presented with occult gastrointestinal bleeding and chronic anemia, and was created successfully by resection of a 25 cm long segment of jejunum. Possible pathogenetic mechanisms for both angiodysplasia and jejunal diverticulosis are discussed.

  2. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... with their chronological age and present health status, help define their current rate of aging and contribute to establish personalized therapy plans to reduce, counteract or even avoid the appearance of aging biomarkers....

  3. Plasmid Rolling-Circle Replication.

    Science.gov (United States)

    Ruiz-Masó, J A; MachóN, C; Bordanaba-Ruiseco, L; Espinosa, M; Coll, M; Del Solar, G

    2015-02-01

    Plasmids are DNA entities that undergo controlled replication independent of the chromosomal DNA, a crucial step that guarantees the prevalence of the plasmid in its host. DNA replication has to cope with the incapacity of the DNA polymerases to start de novo DNA synthesis, and different replication mechanisms offer diverse solutions to this problem. Rolling-circle replication (RCR) is a mechanism adopted by certain plasmids, among other genetic elements, that represents one of the simplest initiation strategies, that is, the nicking by a replication initiator protein on one parental strand to generate the primer for leading-strand initiation and a single priming site for lagging-strand synthesis. All RCR plasmid genomes consist of a number of basic elements: leading strand initiation and control, lagging strand origin, phenotypic determinants, and mobilization, generally in that order of frequency. RCR has been mainly characterized in Gram-positive bacterial plasmids, although it has also been described in Gram-negative bacterial or archaeal plasmids. Here we aim to provide an overview of the RCR plasmids' lifestyle, with emphasis on their characteristic traits, promiscuity, stability, utility as vectors, etc. While RCR is one of the best-characterized plasmid replication mechanisms, there are still many questions left unanswered, which will be pointed out along the way in this review.

  4. Naturally Occurring Radioactive Materials (NORM)

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training).

  5. FOTOVOLTAiK SiSTEMLERiN DENETLENMESi iÇiN YENi BiR KONTROL KARTI VE BiLGiSAYAR YAZILIMI

    Directory of Open Access Journals (Sweden)

    Mustafa Berkant SELEK

    2008-02-01

    Full Text Available Bu çalısmada, İzmir ili Bornova ilçesindeki Ege Üniversitesi Günes Enerjisi Enstitüsü bünyesinde kurulan bir yenilenebilir enerji sisteminin elektrik akısını kontrol eden bir mikroislemci kartı tasarlanmıs ve bilgisayar yazılımı gelistirilmistir. Bu amaçla, anahtarlama görevi yapan güç elektronigi devre elemanlarının bulundugu ayrı bir elektronik kartın kontrol islemini üstlenen PIC18F452 mikrodenetleyicisi kullanan bir elektronik devre gerçeklestirilmistir. Piyasadaki standart kontrol kartları tek seviyeli eviricilerin anahtarlanmasına olanak saglamaktadır. Gelistirilen kontrol kartı ise çok seviyeli eviricilerle çalısmak üzere tasarlanmıstır. Bunun yanı sıra, günes enerjisi panellerinin verimleri oldukça düsük oldugundan, günes panellerinin maksimum güç noktasında (MPP çalıstırmak çok önemlidir. Bu yüzden, tasarlanan kontrol kartı üzerinde MPP algoritması da bulunmaktadır. Ayrıca, tasarlanan kontrol kartının üzerinde RS232 seri haberlesme arabirimi mevcuttur. Böylece, kontrol kartı üzerinde gerçeklestirilen tüm fonksiyonların kullanıcının istegine göre bir bilgisayar yazılımı aracılıgı ile seçilebilmesine ve istenirse kullanıcıya rapor olarak verilebilmesine olanak tanınmıstır. Son olarak, gelistirilen kontrol kartının, gelistirdigimiz yazılım ile haberlesebilmesi için bir komut seti olusturulmustur. Böylece, kendi kontrol kartını gelistirmek isteyen veya daha görsel bir yazılım gelistirmek isteyen diger arastırmacılar için ortak bir taban olusturulması hedeflenmistir.

  6. FBH1 Catalyzes Regression of Stalled Replication Forks

    Directory of Open Access Journals (Sweden)

    Kasper Fugger

    2015-03-01

    Full Text Available DNA replication fork perturbation is a major challenge to the maintenance of genome integrity. It has been suggested that processing of stalled forks might involve fork regression, in which the fork reverses and the two nascent DNA strands anneal. Here, we show that FBH1 catalyzes regression of a model replication fork in vitro and promotes fork regression in vivo in response to replication perturbation. Cells respond to fork stalling by activating checkpoint responses requiring signaling through stress-activated protein kinases. Importantly, we show that FBH1, through its helicase activity, is required for early phosphorylation of ATM substrates such as CHK2 and CtIP as well as hyperphosphorylation of RPA. These phosphorylations occur prior to apparent DNA double-strand break formation. Furthermore, FBH1-dependent signaling promotes checkpoint control and preserves genome integrity. We propose a model whereby FBH1 promotes early checkpoint signaling by remodeling of stalled DNA replication forks.

  7. The bimodal lifestyle of intracellular Salmonella in epithelial cells: replication in the cytosol obscures defects in vacuolar replication.

    Directory of Open Access Journals (Sweden)

    Preeti Malik-Kale

    Full Text Available Salmonella enterica serovar Typhimurium invades and proliferates within epithelial cells. Intracellular bacteria replicate within a membrane bound vacuole known as the Salmonella containing vacuole. However, this bacterium can also replicate efficiently in the cytosol of epithelial cells and net intracellular growth is a product of both vacuolar and cytosolic replication. Here we have used semi-quantitative single-cell analyses to investigate the contribution of each of these replicative niches to intracellular proliferation in cultured epithelial cells. We show that cytosolic replication can account for the majority of net replication even though it occurs in less than 20% of infected cells. Consequently, assays for net growth in a population of infected cells, for example by recovery of colony forming units, are not good indicators of vacuolar proliferation. We also show that the Salmonella Type III Secretion System 2, which is required for SCV biogenesis, is not required for cytosolic replication. Altogether this study illustrates the value of single cell analyses when studying intracellular pathogens.

  8. Nef’î Hakkında Bir Bibliyografya Denemesi An Essay Of Bibliography About Nef’i

    Directory of Open Access Journals (Sweden)

    Halil Sercan KOŞİK

    2013-03-01

    Full Text Available Nef’î who lived in the first half of 17th century was born in Hasankale one of districts of Erzurum. The poet whose real name was Ömer had a life full of struggles but he managed to produce some important works through his life. Nef’î, one of the leading poets of divan poetry was celebrated much at his age and after his death. Such a reputation is originated from the sharpness of his pen, his talent as well as his wit. Nef’î whose usage of praise and satire is extreme is known forhis mastership in using rhythm and rhyme in his poems. While attaching importance to meaning and utterance he tried to use a new language and accomplished that to a great degree. His knowledge of Persian Language and Literature played a considerable role.A lot has been written so far about Nef’î and a great many research exists about his works too. However it is obvious that there will be many works about Nef’î, a productive poet. In this study a classification of Nef’î’s works and scientific studies about him and his works will be presented. Our research focuses to illustrate which part of his works is the center of modern researches and which parts are not. In addition, it is expected that our research will provided useful information to researchers studying Nef’î as a guide for sources regarding him. On yedinci yüzyılın ilk yarısında yaşamış olan Nef’î, Erzurum’un Hasankale ilçesinde doğmuştur. Asıl adı Ömer olan şair, oldukça mücadele dolu bir hayat geçirmiş ve bu hayata aynı zamanda önemli denilebilecek eserler de sığdırabilmeyi başarmıştır. Divan şiirinin önde gelen şairlerden biri olan Nef’î, adından hem yaşadığı dönemde hem de sonrasında çokça söz ettirmiştir. Nef’î’nin böyle bir şöhrete kavuşması onun edebi yeteneği ve kıvrak zekası yanında kaleminin keskin olmasından kaynaklanmaktadır. Övdüğünü çok iyi öven, yerdiğini de çok kötü bir şekilde yeren Nef

  9. Godot Üzerine Bir Karşılaştırma A Comparison On Godot Summary

    Directory of Open Access Journals (Sweden)

    Halil ADIYAMAN

    2013-09-01

    Full Text Available The top works in world literature are composed by the way of imitation or endorsement (zeyl Samuel Beckett’s absurd theatre “waiting for Godot” is called as incongruous theatres in Turkish Literature. ”Waiting for Godot” which was written by Cahit Atay resembles in many ways when compared about fiction, place, time and characters. In Turkish Literature Ferhan Şensoy also writes about this topic, but Cahit Atay doesn’t change the things about basic fiction. But when looking at the basic difference, Beckett’s work is based on the waiting for Godot, while Atay doesn’t care about the fact of waiting forGodot. For Atay it doesn’t matter you can wait or not, but for BeckettGodot is an important thing to be waited. Godot who is waited to comein any time frightens people. It isn’t clear that who is Godot, what kindof things Godot bring or take away and what kind of character is Godot.For Atay, Godot is figured as a character which carries humanisticfeatures. Even if you can draw the portrait of Godot, Atay’s Godot isalso an abstract character.In the Works which include different facts about places, thecommon place is based on the property of a foreign person. For specialmeaning in two Works which include different cultures and civilizationsplace differs. Atay talks about different thing like concrete?Environment and the matters of our time. About characters, he changesthe names of them but he doesn’t change the mood and the attitudes ofthem. Dünya edebiyatındaki zirve eserler, taklit veya zeyl yoluyla yeniden oluşturulmaktadır. Samuel Beckett’in Godot’yu Beklerken isimli absürt oyunu Türk edebiyatında uyumsuz tiyatro oyunları olarak kaleme alınır. Cahit Atay’ın kaleme aldığı Godot’yu Beklerken kurgu, mekân, zaman ve şahıs kadrosu açısından değerlendirildiğinde birçok unsur bakımından benzerlikler gösterir. Türk edebiyatında Ferhan Şensoy’un da eser verdiği bu alanda, Cahit Atay temel

  10. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.

  11. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  12. Shell Separation for Mirror Replication

    Science.gov (United States)

    1999-01-01

    NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. Optics replication uses reusable forms, called mandrels, to make telescope mirrors ready for final finishing. MSFC optical physicist Bill Jones monitors a device used to chill a mandrel, causing it to shrink and separate from the telescope mirror without deforming the mirror's precisely curved surface.

  13. Bir İlkokul 4. Sınıf Öğrencisinin Okuma Bozukluğu ve Anlama Güçlüğü: Bir Durum Çalışması

    Directory of Open Access Journals (Sweden)

    Nergiz KARDAŞ İŞLER

    2016-03-01

    Full Text Available Bu araştırmanın amacı, okuma güçlüğü çeken bir ilkokul dördüncü sınıf öğrencisinin okuma alanındaki sorunlarının ortaya konulması ve bu sorunların giderilmesine yönelik uygulamalar gerçekleştirilmesidir. Bu amaç doğrultusunda öğrencinin okuma alanındaki sorunlarını çözmeye yönelik “Paragrafın önceden dinlenmesi stratejisi” ve “Eşli okuma stratejisi” kullanılmıştır. Nitel araştırma yaklaşımının kullanıldığı bu araştırma, 2013–2014 eğitim öğretim yılının toplam 13 saatlik sürecini kapsamaktadır. Araştırma, bütüncül tek durum desenli bir durum araştırmasında nitel bir araştırmadır. Gözlemler ve doküman incelemesi veri toplama araçları olarak kullanılmaktadır. Uygulama öncesinde, öğrencinin tekrar ederek, heceleyerek, heceleri ve sözcükleri atlayarak okuduğu, okurken eklemeler yaptığı, yanlış okuduğu ve noktalama işaretlerine dikkat etmeden okuduğu tespit edilmiştir. Elde edilen bu veriler doğrultusunda Türkçe ders ve hikâye kitaplarından öğrencinin düzeyine uygun metinler seçilmiştir. Tüm bu çalışmalar ses kaydına alınmıştır. Bu çalışmalar sonucunda okuma ve okuduğunu anlama sorunlarında kullanılan stratejilerle öğrencinin problemleri azalmıştır.

  14. Personality and Academic Motivation: Replication, Extension, and Replication

    Science.gov (United States)

    Jones, Martin H.; McMichael, Stephanie N.

    2015-01-01

    Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…

  15. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

    facilitate replication recovery after MMS-induced replication stress. Our data reveal that control of Mrc1 turnover through the interplay between posttranslational modifications and INQ localization adds another layer of regulation to the replication checkpoint. We also add replication recovery to the list...... is mediated by Mrc1, which ensures Mec1 presence at the stalled replication fork thus facilitating Rad53 phosphorylation. When replication can be resumed safely, the replication checkpoint is deactivated and replication forks restart. One mechanism for checkpoint deactivation is the ubiquitin......-targeted proteasomal degradation of Mrc1. In this study, we describe a novel nuclear structure, the intranuclear quality control compartment (INQ), which regulates protein turnover and is important for recovery after replication stress. We find that upon methyl methanesulfonate (MMS)-induced replication stress, INQ...

  16. Partiklid jah, jaa ning jajaa naaberpaari järelliikmena müügiläbirääkimistes / Riina Kasterpalu

    Index Scriptorium Estoniae

    Kasterpalu, Riina

    2005-01-01

    Vastavate partiklite funktsionaalsetest ülesannetest, kasutamisest ja tähendustest müügivestlustes telefoni teel peetud müügiläbirääkimisi analüüsides. Järgneb: Keel ja Kirjandus, 2005, nr. 12

  17. Partiklid jah, jaa ning jajaa naaberpaari järelliikmena müügiläbirääkimistes / Riina Kasterpalu

    Index Scriptorium Estoniae

    Kasterpalu, Riina

    2005-01-01

    Vastavate partiklite funktsionaalsetest ülesannetest, kasutamisest ja tähendustest müügivestlustes telefoni teel peetud müügiläbirääkimisi analüüsides. Järgneb: Keel ja Kirjandus, 2005, nr. 12

  18. Riiklik lepitaja tahab vahepeal läbirääkimistele joone alla tõmmata / Henn Pärn ; interv. Peep Talimaa

    Index Scriptorium Estoniae

    Pärn, Henn, 1941-

    2007-01-01

    Riiklik lepitaja Henn Pärn vastab küsimustele tervishoiutöötajate alampalgaläbirääkimiste kohta. Vt. ka Eesti Arstide Liidu ja Eesti Keskastme Tervishoiutöötajate Kutseliidu avalikku pöördumist riikliku lepitaja poole, lk. 4

  19. RTA Occupancy of the Origin of Lytic Replication during Murine Gammaherpesvirus 68 Reactivation from B Cell Latency

    Directory of Open Access Journals (Sweden)

    Alexis L. Santana

    2017-02-01

    Full Text Available RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS/toll-like receptor (TLR4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB signaling during murine gammaherpesvirus 68 (MHV68 infection: a latent B cell line (HE-RIT inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio that enabled in vivo biotinylation of RTA in BirA transgenic mice. LPS acted as a second stimulus to drive virus reactivation from latency in the context of induced expression of RTA-Flag. ORF6, the gene encoding the single-stranded DNA binding protein, was one of many viral genes that were directly responsive to RTA induction; expression was further increased upon treatment with LPS. However, NF-κB sites in the promoter of ORF6 did not influence RTA transactivation in response to LPS in HE-RIT cells. We found no evidence for RTA occupancy of the minimal RTA-responsive region of the ORF6 promoter, yet RTA was found to complex with a portion of the right origin of lytic replication (oriLyt-R that contains predicted RTA recognition elements. RTA occupancy of select regions of the MHV-68 genome was also evaluated in our novel in vivo RTA biotinylation system. Streptavidin isolation of RTA-Bio confirmed complex formation with oriLyt-R in LPS-treated primary splenocytes from BirA mice infected with MHV68 RTA-Bio. We demonstrate the utility of reactivation-inducible B cells coupled with in vivo RTA biotinylation for mechanistic investigations of the interplay of host signaling with RTA.

  20. RTA Occupancy of the Origin of Lytic Replication during Murine Gammaherpesvirus 68 Reactivation from B Cell Latency

    Science.gov (United States)

    Santana, Alexis L.; Oldenburg, Darby G.; Kirillov, Varvara; Malik, Laraib; Dong, Qiwen; Sinayev, Roman; Marcu, Kenneth B.; White, Douglas W.; Krug, Laurie T.

    2017-01-01

    RTA, the viral Replication and Transcription Activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. Lipopolysaccharide (LPS)/toll-like receptor (TLR)4 engagement enhances rhadinovirus reactivation. We developed two new systems to examine the interaction of RTA with host NF-kappaB (NF-κB) signaling during murine gammaherpesvirus 68 (MHV68) infection: a latent B cell line (HE-RIT) inducible for RTA-Flag expression and virus reactivation; and a recombinant virus (MHV68-RTA-Bio) that enabled in vivo biotinylation of RTA in BirA transgenic mice. LPS acted as a second stimulus to drive virus reactivation from latency in the context of induced expression of RTA-Flag. ORF6, the gene encoding the single-stranded DNA binding protein, was one of many viral genes that were directly responsive to RTA induction; expression was further increased upon treatment with LPS. However, NF-κB sites in the promoter of ORF6 did not influence RTA transactivation in response to LPS in HE-RIT cells. We found no evidence for RTA occupancy of the minimal RTA-responsive region of the ORF6 promoter, yet RTA was found to complex with a portion of the right origin of lytic replication (oriLyt-R) that contains predicted RTA recognition elements. RTA occupancy of select regions of the MHV-68 genome was also evaluated in our novel in vivo RTA biotinylation system. Streptavidin isolation of RTA-Bio confirmed complex formation with oriLyt-R in LPS-treated primary splenocytes from BirA mice infected with MHV68 RTA-Bio. We demonstrate the utility of reactivation-inducible B cells coupled with in vivo RTA biotinylation for mechanistic investigations of the interplay of host signaling with RTA. PMID:28212352

  1. Yağ dokusu İçeren Nadir Bir Stafne Kemik Kavitesi Olgusu

    Directory of Open Access Journals (Sweden)

    Erman Şenel

    2012-07-01

    nerilmektedir. Manyetik rezonans görüntüleme (MR, bu kavitelerin içeriği hakkında cerrahlara ayrıntılı bilgi vermektedir. Bu makalede, yağlı içeriğe sahip nadir bir Stafne Kemik Kavitesi olgusu sunulmaktadır. Ayırıcı tanısı, DBT ve MR ile gerçekleştirilmiştir.

  2. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  3. Hyperthermia stimulates HIV-1 replication.

    Science.gov (United States)

    Roesch, Ferdinand; Meziane, Oussama; Kula, Anna; Nisole, Sébastien; Porrot, Françoise; Anderson, Ian; Mammano, Fabrizio; Fassati, Ariberto; Marcello, Alessandro; Benkirane, Monsef; Schwartz, Olivier

    2012-01-01

    HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  4. Cellular Responses to Replication Problems

    NARCIS (Netherlands)

    M. Budzowska (Magdalena)

    2008-01-01

    textabstractDuring every S-phase cells need to duplicate their genomes so that both daughter cells inherit complete copies of genetic information. It is a tremendous task, given the large sizes of mammalian genomes and the required precision of DNA replication. A major threat to the accuracy and eff

  5. Covert Reinforcement: A Partial Replication.

    Science.gov (United States)

    Ripstra, Constance C.; And Others

    A partial replication of an investigation of the effect of covert reinforcement on a perceptual estimation task is described. The study was extended to include an extinction phase. There were five treatment groups: covert reinforcement, neutral scene reinforcement, noncontingent covert reinforcement, and two control groups. Each subject estimated…

  6. Depletion of acidic phospholipids influences chromosomal replication in Escherichia coli.

    Science.gov (United States)

    Fingland, Nicholas; Flåtten, Ingvild; Downey, Christopher D; Fossum-Raunehaug, Solveig; Skarstad, Kirsten; Crooke, Elliott

    2012-12-01

    In Escherichia coli, coordinated activation and deactivation of DnaA allows for proper timing of the initiation of chromosomal synthesis at the origin of replication (oriC) and assures initiation occurs once per cell cycle. In vitro, acidic phospholipids reactivate DnaA, and in vivo depletion of acidic phospholipids, results in growth arrest. Growth can be restored by the expression of a mutant form of DnaA, DnaA(L366K), or by oriC-independent DNA synthesis, suggesting acidic phospholipids are required for DnaA- and oriC-dependent replication. We observe here that when acidic phospholipids were depleted, replication was inhibited with a concomitant reduction of chromosomal content and cell mass prior to growth arrest. This global shutdown of biosynthetic activity was independent of the stringent response. Restoration of acidic phospholipid synthesis resulted in a resumption of DNA replication prior to restored growth, indicating a possible cell-cycle-specific growth arrest had occurred with the earlier loss of acidic phospholipids. Flow cytometry, thymidine uptake, and quantitative polymerase chain reaction data suggest that a deficiency in acidic phospholipids prolonged the time required to replicate the chromosome. We also observed that regardless of the cellular content of acidic phospholipids, expression of mutant DnaA(L366K) altered the DNA content-to-cell mass ratio.

  7. Phenotype switching is a natural consequence of Staphylococcus aureus replication.

    Science.gov (United States)

    Edwards, Andrew M

    2012-10-01

    The pathogen Staphylococcus aureus undergoes phenotype switching in vivo from its normal colony phenotype (NCP) to a slow-growing, antibiotic-resistant small-colony-variant (SCV) phenotype that is associated with persistence in host cells and tissues. However, it is not clear whether phenotype switching is the result of a constitutive process that is selected for under certain conditions or is triggered by particular environmental stimuli. Examination of cultures of diverse S. aureus strains in the absence of selective pressure consistently revealed a small gentamicin-resistant SCV subpopulation that emerged during exponential-phase NCP growth and increased in number until NCP stationary phase. Treatment of replicating bacteria with the antibiotic gentamicin, which inhibited NCP but not SCV replication, resulted in an initial decrease in SCV numbers, demonstrating that SCVs arise as a consequence of NCP replication. However, SCV population expansion in the presence of gentamicin was reestablished by selection of phenotype-stable SCVs and subsequent SCV replication. In the absence of selective pressure, however, phenotype switching was bidirectional and occurred at a high frequency during NCP replication, resulting in SCV turnover. In summary, these data demonstrate that S. aureus phenotype switching occurs via a constitutive mechanism that generates a dynamic, antibiotic-resistant subpopulation of bacteria that can revert to the parental phenotype. The emergence of SCVs can therefore be considered a normal part of the S. aureus life cycle and provides an insurance policy against exposure to antibiotics that would otherwise eliminate the entire population.

  8. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss

    2013-05-01

    Full Text Available Criniviruses comprise one of the genera within the family Closteroviridae. Members in this family are restricted to the phloem and rely on whitefly vectors of the genera Bemisia and/or Trialeurodes for plant-to-plant transmission. All criniviruses have bipartite, positive-sense ssRNA genomes, although there is an unconfirmed report of one having a tripartite genome. Lettuce infectious yellows virus (LIYV is the type species of the genus, the best studied so far of the criniviruses and the first for which a reverse genetics system was available. LIYV RNA 1 encodes for proteins predicted to be involved in replication, and alone is competent for replication in protoplasts. Replication results in accumulation of cytoplasmic vesiculated membranous structures which are characteristic of most studied members of the Closteroviridae. These membranous structures, often referred to as BYV-type vesicles, are likely sites of RNA replication. LIYV RNA 2 is replicated in trans when co-infecting cells with RNA 1, but is temporally delayed relative to RNA1. Efficient RNA 2 replication also is dependent on the RNA 1-encoded RNA binding protein, P34. No LIYV RNA 2-encoded proteins have been shown to affect RNA replication, but at least four, CP, CPm, Hsp70h, and p59 are virion structural components and CPm is a determinant of whitefly transmissibility. Roles of other LIYV RNA 2-encoded proteins are largely as yet unknown, but P26 is a non-virion protein that accumulates in cells as characteristic plasmalemma deposits which in plants are localized within phloem parenchyma and companion cells over plasmodesmata connections to sieve elements. The two remaining crinivirus-conserved RNA 2-encoded proteins are P5 and P9. P5 is 39 amino acid protein and is encoded at the 5’ end of RNA 2 as ORF1 and is part of the hallmark closterovirus gene array. The orthologous gene in BYV has been shown to play a role in cell-to-cell movement and indicated to be localized to the

  9. When Yawning Occurs in Elephants

    Science.gov (United States)

    Rossman, Zoë T.; Hart, Benjamin L.; Greco, Brian J.; Young, Debbie; Padfield, Clare; Weidner, Lisa; Gates, Jennifer; Hart, Lynette A.

    2017-01-01

    Yawning is a widely recognized behavior in mammalian species. One would expect that elephants yawn, although to our knowledge, no one has reported observations of yawning in any species of elephant. After confirming a behavioral pattern matching the criteria of yawning in two Asian elephants (Elephas maximus) in a zoological setting, this study was pursued with nine captive African elephants (Loxodonta africana) at a private reserve in the Western Cape, South Africa, the Knysna Elephant Park. Observations were made in June–September and in December. In the daytime, handlers managed seven of the elephants for guided interactions with visitors. At night, all elephants were maintained in a large enclosure with six having limited outdoor access. With infrared illumination, the elephants were continuously recorded by video cameras. During the nights, the elephants typically had 1–3 recumbent sleeping/resting bouts, each lasting 1–2 h. Yawning was a regular occurrence upon arousal from a recumbency, especially in the final recumbency of the night. Yawning was significantly more frequent in some elephants. Yawning was rare during the daytime and during periods of standing around in the enclosure at night. In six occurrences of likely contagious yawning, one elephant yawned upon seeing another elephant yawning upon arousal from a final recumbency; we recorded the sex and age category of the participants. The generality of yawning in both African and Asian elephants in other environments was documented in video recordings from 39 zoological facilities. In summary, the study provides evidence that yawning does occur in both African and Asian elephants, and in African elephants, yawning was particularly associated with arousal from nighttime recumbencies. PMID:28293560

  10. Preventing DNA over-replication: a Cdk perspective

    Directory of Open Access Journals (Sweden)

    Porter Andrew CG

    2008-01-01

    Full Text Available Abstract The cell cycle is tightly controlled to ensure that replication origins fire only once per cycle and that consecutive S-phases are separated by mitosis. When controls fail, DNA over-replication ensues: individual origins fire more than once per S-phase (re-replication or consecutive S-phases occur without intervening mitoses (endoreduplication. In yeast the cell cycle is controlled by a single cyclin dependent kinase (Cdk that prevents origin licensing at times when it promotes origin firing, and that is inactivated, via proteolysis of its partner cyclin, as cells undergo mitosis. A quantitative model describes three levels of Cdk activity: low activity allows licensing, intermediate activity allows firing but prevents licensing, and high activity promotes mitosis. In higher eukaryotes the situation is complicated by the existence of additional proteins (geminin, Cul4-Ddb1Cdt2, and Emi1 that control licensing. A current challenge is to understand how these various control mechanisms are co-ordinated and why the degree of redundancy between them is so variable. Here the experimental induction of DNA over-replication is reviewed in the context of the quantitative model of Cdk action. Endoreduplication is viewed as a consequence of procedures that cause Cdk activity to fall below the threshold required to prevent licensing, and re-replication as the result of procedures that increase that threshold value. This may help to explain why over-replication does not necessarily require reduced Cdk activity and how different mechanisms conspire to prevent over-replication. Further work is nevertheless required to determine exactly how losing just one licensing control mechanism often causes over-replication, and why this varies between cell systems.

  11. Çok Katlı Yapılarda Uniform Olmayan Burulma Nedeniyle Oluşan Tesirlerin Belirlenmesi için Bir Yöntem

    Directory of Open Access Journals (Sweden)

    Tuncay Aydoğuş

    2015-07-01

    Full Text Available Bu çalışmada, yüksek yapılarda yatay yükler etkisinde oluşan, Vlasov uniform olmayan burulması nedeniyle taşıyıcı yapı elemanlarda oluşan tesirlerin belirlenmesi için bir yöntem önerilmiştir. Bu yöntemde, mevcut yöntemlerde yapıya yüksekliği boyunca uniform yayılı bir yatay yük etkimesi kabulü yerine, daha gerçekçi olan kat seviyelerinde farklı büyüklüklere sahip yatay yüklerin etkimesi kabulü yapılmıştır. Önerilen yöntemde, herhangi bir enkesitin kesit özelliklerinin hesaplandığı ve birim çapılma diyagramının çizildiği bir algoritma hazırlanmış ve bu algoritma MATHCAD programında yazılmış ve böylece zaman alıcı diferansiyel denklem çözümüne gerek kalmadan kısa sürede sonuçların elde edilmesi sağlanmıştır. Yöntem Taranath, Smith ve Coull'un çalışmaları ile karşılaştırılmış, hassaslığını tespit için konsol bir kiriş ele alınarak ANSYS ve CONSTEEL analiz programları ile karşılaştırma yapılmıştır.

  12. Orta Ölçekli Bir İşletmenin Enerji İzleme Sisteminin Tasarlanması

    Directory of Open Access Journals (Sweden)

    Erdal Irmak

    2012-02-01

    Full Text Available Bu uygulamada, orta ölçekli bir işletmenin gerçek zamanlı ve geçmişe yönelik enerji takibinin bilgisayar ara yüzünden izlenmesi gerçekleştirilmiştir. Enerjinin ölçülmesi için akım ve gerilim bilgilerini Programlanabilir Lojik Kontrolörün ( PLC algılayacağı seviyeye getiren bir kart tasarlanmıştır. Bu karttan alınan akım ve gerilim bilgileri, PLC'nin analog kanalları ile okunmaktadır. Sistemin güç katsayısının algılanması için, bir sıfır geçiş detektörü tasarlanmıştır. Sıfır geçiş detektöründen elde edilen sinyaller arasındaki zaman farkı FM 350-1 sayıcı modül kullanılarak ölçülmüştür. Alınan bilgiler, PLC tarafından RS485/RS232 dönüştürme protokolü kullanarak, bilgisayarın seri iletişim kanalı aracılığı ile veritabanına aktarılmaktadır. Elde edilen veriler, C# programlama dili kullanılarak tasarlanan bir arayüz ile anlık takip edilebilmektedir. Elde edilen veriler sürekli olarak kaydedilerek geçmişe yönelik enerji analizleri yapma olanağı sağlanmıştır. Böylece, istenildiğinde belirlenen zaman aralığında kullanılan aktif, reaktif ve görünür güçler gözlemlenebilmektedir. Geçmişe yönelik enerji izleme sistemi kullanılarak işletmelerin fazla enerji harcadığı zamanlar tespit edilebilmektedir. Böylece, yoğun çalışma saatleri enerjinin ucuz olduğu zamanlara kaydırılarak kullanılan enerjinin işletmeye olan maliyetinin azaltılması gibi olanaklar sağlanmaktadır.

  13. Bir tekstil sanayi sevkiyat bölümünde R’WOT analizi uygulaması

    OpenAIRE

    Gürbüz, Feyza; ÖZTÜRK, Emrah

    2013-01-01

    Kurumsal yapının bir takım kriterlere tabi tutularak incelenmesi teknikleri, modern iş yönetiminin elinden düşmeyen araçlardır. Bu sayede o kurumun şu anki durumu, doğru işleyip işlemediği kolaylıkla belirlenmiş olur. Bu tekniklerden biri olan "SWOT Analizi", firmanızın kurumsal işlerliği, rekabet gücü, sektördeki konumu, piyasadaki dış tehditlerin varlığı vs. gibi iç ve dış değerlendirmelerin yapılabildiği en etkili değerlendirme yöntemlerinden biridir. Ancak swot analizi sonuçları...

  14. Pratique de l’extranéité dans l’écriture d’Abdelkébir Khatibi

    Directory of Open Access Journals (Sweden)

    Hassan Moustir

    2013-11-01

    Full Text Available Promoted to the rank of operational concept in writing, the notion of "foreign professional" means in both fictional and critical work of Abdelkébir Khatibi (1938-2009 this cosmopolitan otherness that reduces identity disparities and cultural differences. Late Khatibi’s fictions, including Un été à Stockholm (1990 and Féerie d’un mutant (2005 represent an ontological extraneous out with all cultural and identity anchors and discourse representations. Op-erating in a global space, and private of a fixed identity and separated cultural roots, the characters of these two fictions embody the thought of foreignness and border crossing practice, at the linguistic and the cultural levels. This fact grows to reflect on what would be writing and deterritorialized identity.

  15. Electromagnetic, magnetic, and gravimetric surveys at the Bi'r Jarbuah gold prospect, Kingdom of Saudi Arabia

    Science.gov (United States)

    Miller, C.H.; Showail, A.A.; Bazzari, M.A.; Khoja, J.A.; Hajour, M.O.

    1990-01-01

    Bi'r Jarbuah is a potential gold-bearing site located east of the Ishmas gold district in the southeastern part of the Arabian Shield. Surface rocks are mostly diorite and granodiorite plutons and the metavolcanic and metasedimentary rocks they have intruded. Extensive thin alluvial deposits cover approximately 40 percent of the area studied. Diorite, granodiorite, aplite porphyry, granite, granite pegmatite, and mafic dikes intrude the plutons and the metavolcanic and metasedimentary rocks. Veins of quartz, carbonate materials, and associated carbonate-altered rocks containing limonite and hematite cut all rock types. The veins were extensively mined by ancient people, and recent trenching has revealed small amounts of free gold associated with these veins and adjacent altered country rocks.

  16. Sıçan testisinde subakut deltametrin maruziyetinin etkileri: Histopatolojik bir çalışma

    OpenAIRE

    Kılıç, Kubilay Doğan; Çavuşoğlu, Türker; Yiğittürk, Gürkan; Erbaş, Oytun; Çetin, Emel Öykü; Uyanıkgil, Yiğit

    2016-01-01

    Amaç: Bu çalışmada bir hayvan modelinde deltametrinin toksisitenin testis histolojisi üzerindeki etkileri değerlendirildi.Gereç ve yöntemler: Ağırlıkları 200-220 gram olan toplam 36 yetişkin erkek Sprague-Dawley albino cinsi sıçan dört gruba ayrıldı. Grup 1 sıçanlara deltametrin 15 mg/kg/gün, grup 2 sıçanlara deltametrin 30 mg/kg/gün, grup 3 sıçanlara deltametrin 60 mg/kg/gün ve grup 4 sıçanlara (kontrol grubu) %0.9 sodyum klorür 1 mL/kg/gün 30 gün boyunca oral gavaj yolu ile verildi.B...

  17. Replication-Uncoupled Histone Deposition during Adenovirus DNA Replication

    OpenAIRE

    Komatsu, Tetsuro; Nagata, Kyosuke

    2012-01-01

    In infected cells, the chromatin structure of the adenovirus genome DNA plays critical roles in its genome functions. Previously, we reported that in early phases of infection, incoming viral DNA is associated with both viral core protein VII and cellular histones. Here we show that in late phases of infection, newly synthesized viral DNA is also associated with histones. We also found that the knockdown of CAF-1, a histone chaperone that functions in the replication-coupled deposition of his...

  18. Regulation of DNA replication and chromosomal polyploidy by the MLL-WDR5-RBBP5 methyltransferases

    Science.gov (United States)

    Lu, Fei; Wu, Xiaojun; Yin, Feng; Chia-Fang Lee, Christina; Yu, Min; Mihaylov, Ivailo S.; Yu, Jiekai; Sun, Hong

    2016-01-01

    ABSTRACT DNA replication licensing occurs on chromatin, but how the chromatin template is regulated for replication remains mostly unclear. Here, we have analyzed the requirement of histone methyltransferases for a specific type of replication: the DNA re-replication induced by the downregulation of either Geminin, an inhibitor of replication licensing protein CDT1, or the CRL4CDT2 ubiquitin E3 ligase. We found that siRNA-mediated reduction of essential components of the MLL-WDR5-RBBP5 methyltransferase complexes including WDR5 or RBBP5, which transfer methyl groups to histone H3 at K4 (H3K4), suppressed DNA re-replication and chromosomal polyploidy. Reduction of WDR5/RBBP5 also prevented the activation of H2AX checkpoint caused by re-replication, but not by ultraviolet or X-ray irradiation; and the components of MLL complexes co-localized with the origin recognition complex (ORC) and MCM2-7 replicative helicase complexes at replication origins to control the levels of methylated H3K4. Downregulation of WDR5 or RBBP5 reduced the methylated H3K4 and suppressed the recruitment of MCM2-7 complexes onto replication origins. Our studies indicate that the MLL complexes and H3K4 methylation are required for DNA replication but not for DNA damage repair. PMID:27744293

  19. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

    structured master surface (3a, 3b, 3c, 3d) having a lateral master pattern and a vertical master profile. The microscale structured master surface (3a, 3b, 3c, 3d) has been provided by localized pulsed laser treatment to generate microscale phase explosions. A method for producing a part with microscale......The invention relates to a replication tool (1, 1a, 1b) for producing a part (4) with a microscale textured replica surface (5a, 5b, 5c, 5d). The replication tool (1, 1a, 1b) comprises a tool surface (2a, 2b) defining a general shape of the item. The tool surface (2a, 2b) comprises a microscale...... energy directors on flange portions thereof uses the replication tool (1, 1a, 1b) to form an item (4) with a general shape as defined by the tool surface (2a, 2b). The formed item (4) comprises a microscale textured replica surface (5a, 5b, 5c, 5d) with a lateral arrangement of polydisperse microscale...

  20. Sezai Karakoç'un Bir Sorusu Üzerine On A Question Of Sezai Karakoç

    Directory of Open Access Journals (Sweden)

    Fırat CANER

    2013-07-01

    Full Text Available The voice in Sezai Karakoç’s Hızırla Kırk Saat says that he learned how to break the idols made of rocks from Abraham, but he doesn’t know how to destroy the idols made of words. This voice constitutes a typical 20th century philosopher concerned with pornography. Those philosophers who live in the age of images, and whose minds areblurred by the excessive bombardment of images, generally act as ifthey were iconaclasts in the age of Byzantium. Philosophers and literarywriters of our age are hopeless because of the pornographic patternswhich determine our lives. This hopelessness is driven by volontarismwhen they speak about the future, and/but by determinism when theyspeak about the past. But we should take the historical necessities intoaccount when what’s at stake is a consideration of the future. Thencewe can foresee that pornography will lose its effect on our lives becauseof the historical necessities. As a result of the coexistence of thousandsof images, no image can sufficiently satisfy or provoke the eye. That’swhy iconaclasts are not different from romantic revolutionists whohopefully dream that they can change the world in a moment.Consequently we can say that satisfying the eye is a stage within theprocess of images’ losing their effect on out minds. Sezai Karakoç’un Hızırla Kırk Saat adlı eserindeki ses, mermer putları nasıl devireceğini Hz. İbrahim’den öğrendiğini, buna karşılık, nesnesi olmayan putları, örneğin sözlerle, yani zihinlerde inşa edilen putları nasıl devireceğini bilmediğini, bunu kimsenin öğretmediğini söyler. Sözlerle inşa edilen putların nasıl kırılacağını bilmediğini söyleyen ses, pornografi hakkında yazan tipik bir 20. yüzyıl düşünürü sesidir. İmaj çağının imaj bombardımanı altında zihni bulanan bu düşünürler, genel olarak, Bizans tarihindeki put kırıcıların tavrını benimsemişlerdir. Günümüz felsefe ve edebiyatının günlük ya

  1. Torus mandibularis varlığında kısmi dişsiz bir hastanın protetik rehabilitasyonu: olgu sunumu

    Directory of Open Access Journals (Sweden)

    Arife Dogan

    2011-10-01

    Full Text Available

    The torus mandibularis is the one of the most common intraoral exostoses. It is often bilateral, occurs at the canin to premolar region on the lingual aspect of the mandible. It has been reported that the factors such as genetic and environmental factors, masticator hiperfunction, nutrition, race and ethnic groups might play role in occurence of them. Such type of bony protuberances may present many challenges when fabricating a removable partial or complete

    dentures. In this case report, after a general knowledge about mandibular tori, the prosthetic rehabilitation of a partially edentulous patient had bilaterally mandibular tori has been presented.

    ÖZET

    Torus mandibularis ağız içinde en sık görülen eksostoz türlerinden biridir. Genellikle, mandibulanın lingual yüzeyinde, kanin ve premolar bölgesinde yerleşim göstermesiyle karakterizedir. Etyolojisinde kalıtım, çevresel faktörler, artmış çiğneme fonksiyonu, beslenme, ırk ve etnik grup farklılıklarının etkili olduğu düşünülmektedir. Bu tür kemik büyümeleri hareketli parsiyel veya tam protez yapımında güçlüklere neden olabilir. Bu olgu sunumunda kısmi dişsiz ve çift taraflı mandibular torusa sahip bir hastanın protetik tedavisi bildirilmiş ve toruslar hakkında genel bilgi verilmiştir.

    Anahtar sözcükler: Torus mandibularis, kısmi dişsiz hasta

  2. Replicator dynamics in value chains

    DEFF Research Database (Denmark)

    Cantner, Uwe; Savin, Ivan; Vannuccini, Simone

    2016-01-01

    The pure model of replicator dynamics though providing important insights in the evolution of markets has not found much of empirical support. This paper extends the model to the case of firms vertically integrated in value chains. We show that i) by taking value chains into account, the replicator...... dynamics may revert its effect. In these regressive developments of market selection, firms with low fitness expand because of being integrated with highly fit partners, and the other way around; ii) allowing partner's switching within a value chain illustrates that periods of instability in the early...... stage of industry life-cycle may be the result of an 'optimization' of partners within a value chain providing a novel and simple explanation to the evidence discussed by Mazzucato (1998); iii) there are distinct differences in the contribution to market selection between the layers of a value chain...

  3. Therapeutic targeting of replicative immortality

    OpenAIRE

    Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo

    2015-01-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persis...

  4. Alphavirus polymerase and RNA replication.

    Science.gov (United States)

    Pietilä, Maija K; Hellström, Kirsi; Ahola, Tero

    2017-01-16

    Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands. Different parts of nsP4 recognize the promoters for minus and plus strands but the binding also requires the other nsPs. The alphavirus polymerase has been purified and is capable of de novo RNA synthesis only in the presence of the other nsPs. The purified nsP4 also has terminal adenylyltransferase activity, which may generate the poly(A) tail at the 3' end of the genome. Membrane association of the nsPs is vital for replication, and alphaviruses induce membrane invaginations called spherules, which form a microenvironment for RNA synthesis by concentrating replication components and protecting double-stranded RNA intermediates. The RCs isolated as crude membrane preparations are active in RNA synthesis in vitro, but high-resolution structure of the RC has not been achieved, and thus the arrangement of viral and possible host components remains unknown. For some alphaviruses, Ras-GTPase-activating protein (Src-homology 3 (SH3) domain)-binding proteins (G3BPs) and amphiphysins have been shown to be essential for RNA replication and are present in the RCs. Host factors offer an additional target for antivirals, as only few alphavirus polymerase inhibitors have been described.

  5. The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

    DEFF Research Database (Denmark)

    Larsen, Nicolai B; Sass, Ehud; Suski, Catherine

    2014-01-01

    Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus......, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither...

  6. Dynamic replication of Web contents

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The phenomenal growth of the World Wide Web has brought huge increase in the traffic to the popular web sites.Long delays and denial of service experienced by the end-users,especially during the peak hours,continues to be the common problem while accessing popular sites.Replicating some of the objects at multiple sites in a distributed web-server environment is one of the possible solutions to improve the response time/Iatency. The decision of what and where to replicate requires solving a constraint optimization problem,which is NP-complete in general.In this paper, we consider the problem of placing copies of objects in a distributed web server system to minimize the cost of serving read and write requests when the web servers have Iimited storage capacity.We formulate the problem as a 0-1 optimization problem and present a polynomial time greedy algorithm with backtracking to dynamically replicate objects at the appropriate sites to minimize a cost function.To reduce the solution search space,we present necessary condi tions for a site to have a replica of an object jn order to minimize the cost function We present simulation resuIts for a variety of problems to illustrate the accuracy and efficiency of the proposed algorithms and compare them with those of some well-known algorithms.The simulation resuIts demonstrate the superiority of the proposed algorithms.

  7. Sanayi-î Nefise Mektebinden Üniversiteye Bir Mekânın Tasarım ve Değişimi

    Directory of Open Access Journals (Sweden)

    Nezih R. Aysel

    2012-05-01

    Full Text Available Kuruluşundan, 1927 yılında Fındıklı’da Sultan Abdülmecid’in kızları Cemile ve Münire Sultan için yapılmış olan Çifte Saraydan Osmanlı’nın son meclisi olarak da kullanılan Cemile Sultan Sarayına taşınana değin çok farklı binalarda eğitim yapan Sanayi-i Nefise Mektebi Alisi, bu tarihinde ilk kez yerleşik bir düzene geçiyordu. Bu rahatlama 1948 yılına dek sürecek, bir yangın ile Akademi’nin kurmaya çalıştığı düzen bir süreliğine bozulacaktır. 1953 yılında yenilenen Akademi binası, saray yapısının planlama ilkelerini modern mimari ilkeleri ile birleştirmiştir.Bu yazıya konu olan Konferans Salonu, binanın saray döneminde üst sofası’dır. 1954 yenilemesinde de aynı yerde benzer bir anlayışla sergi ve toplantı amaçlı bir salon planlanır. Akademi’nin yükselme devri olarak anılabilecek olan 1960’lı yıllarda salon projelendirilerek çok amaçlı kullanıma yönelik esnek bir çözüm getirilir. Daha sonraları ise mekan ihtiyaçları, derslik sorunları ve bahçeye yapılan yeni toplantı salonunun da etkisiyle Konferans Salonu giderek küçülmeye ve kurum içindeki önemini yitirmeye başlar.Bu yazı, Konferans Salonunun 1927 yılından günümüze kadar uzanan mekansal değişimini, Akademi ortamı ile aktarmaya çalışmaktadır.

  8. Endüstriyel İşletmelerde Franchising Model Önerisi: Hazır Beton Sektöründe Bir Uygulama

    Directory of Open Access Journals (Sweden)

    İpek Kazançoğlu

    2016-12-01

    Full Text Available Endüstriyel pazarda faaliyet gösteren firmaların daha hızlı büyüyerek, yeni pazarlara açılmasında franchising sistemi bir yeni bir satış, dağıtım kanalı olarak değerlendirilmektedir. Bu araştırmada amaç,  hazır beton sektöründe faaliyet gösteren bir firmanın franchising sistemini bir iş modeli olarak benimseme kararında dikkat etmesi gereken unsurları ve karşılaşılan zorlukları incelemektedir. Örnek olay çalışması olarak ele alınan çalışmada,  BATIBETON A.Ş. firmasının yedi yöneticiyle BATIBETON markasının franchising uygulamalarına ilişkin görüşlerini öğrenmek amacıyla derinlemesine görüşmeler yapılmıştır. Bu görüşmeler sonucunda, franchising sisteminin hazır beton sektöründe bir model önerisi olarak uygulanıp/uygulanmayacağı değerlendirilmiştir. Yapılan görüşmelerden elde edilen bulguların diğer endüstriyel işletmeler içinde geliştirilebilecek bir franchising iş modeli kararında etkili olabilecek faktörlerin anlaşılması yönünden uygulamaya katkı sağlayacağı düşünülmektedir.

  9. Evaluating replicability of laboratory experiments in economics.

    Science.gov (United States)

    Camerer, Colin F; Dreber, Anna; Forsell, Eskil; Ho, Teck-Hua; Huber, Jürgen; Johannesson, Magnus; Kirchler, Michael; Almenberg, Johan; Altmejd, Adam; Chan, Taizan; Heikensten, Emma; Holzmeister, Felix; Imai, Taisuke; Isaksson, Siri; Nave, Gideon; Pfeiffer, Thomas; Razen, Michael; Wu, Hang

    2016-03-25

    The replicability of some scientific findings has recently been called into question. To contribute data about replicability in economics, we replicated 18 studies published in the American Economic Review and the Quarterly Journal of Economics between 2011 and 2014. All of these replications followed predefined analysis plans that were made publicly available beforehand, and they all have a statistical power of at least 90% to detect the original effect size at the 5% significance level. We found a significant effect in the same direction as in the original study for 11 replications (61%); on average, the replicated effect size is 66% of the original. The replicability rate varies between 67% and 78% for four additional replicability indicators, including a prediction market measure of peer beliefs.

  10. Achromobacter Xylosoxidans’a Bağlı Akut Prostatit: Bir Olgu Sunumu,

    OpenAIRE

    2014-01-01

    Achromobacter xylosoxidans is a rare cause of the urinary system infections and occurs usually in patients under immunosuppressive treatment. We present a case with acute prostatitis which result from urodynamic investigation, with positive urine culture caused by Achromobacter xylosoxidans

  11. Adenovirus sequences required for replication in vivo.

    OpenAIRE

    Wang, K.; Pearson, G D

    1985-01-01

    We have studied the in vivo replication properties of plasmids carrying deletion mutations within cloned adenovirus terminal sequences. Deletion mapping located the adenovirus DNA replication origin entirely within the first 67 bp of the adenovirus inverted terminal repeat. This region could be further subdivided into two functional domains: a minimal replication origin and an adjacent auxillary region which boosted the efficiency of replication by more than 100-fold. The minimal origin occup...

  12. Transcription-replication collision increases recombination efficiency between plasmids.

    Science.gov (United States)

    Jialiang, Li; Feng, Chen; Zhen, Xu; Jibing, Chen; Xiang, Lv; Lingling, Zhang; Depei, Liu

    2013-11-01

    It has been proposed that the stalling of the replication forks can induce homologous recombination in several organisms, and that arrested replication forks may offer nuclease targets, thereby providing a substrate for proteins involved in double-strand repair. In this article, we constructed a plasmid with the potential for transcription-replication collision (TRC), in which DNA replication and RNA transcription occur on the same DNA template simultaneously. Theoretically, transcription will impede DNA replication and increase homologous recombination. To validate this hypothesis, another plasmid was constructed that contained a homologous sequence with the exception of some mutated sites. Co-transfection of these two plasmids into 293T cells resulted in increased recombination frequency. The ratio of these two plasmids also affected the recombination frequency. Moreover, we found high expression levels of RAD51, which indicated that the increase in the recombination rate was probably via the homologous recombination pathway. These results indicate that mutant genes in plasmids can be repaired by TRC-induced recombination.

  13. Replication Origin Specification Gets a Push.

    Science.gov (United States)

    Plosky, Brian S

    2015-12-03

    During the gap between G1 and S phases when replication origins are licensed and fired, it is possible that DNA translocases could disrupt pre-replicative complexes (pre-RCs). In this issue of Molecular Cell, Gros et al. (2015) find that pre-RCs can be pushed along DNA and retain the ability to support replication.

  14. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

    DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...

  15. Managing Single-Stranded DNA during Replication Stress in Fission Yeast

    Directory of Open Access Journals (Sweden)

    Sarah A. Sabatinos

    2015-09-01

    Full Text Available Replication fork stalling generates a variety of responses, most of which cause an increase in single-stranded DNA. ssDNA is a primary signal of replication distress that activates cellular checkpoints. It is also a potential source of genome instability and a substrate for mutation and recombination. Therefore, managing ssDNA levels is crucial to chromosome integrity. Limited ssDNA accumulation occurs in wild-type cells under stress. In contrast, cells lacking the replication checkpoint cannot arrest forks properly and accumulate large amounts of ssDNA. This likely occurs when the replication fork polymerase and helicase units are uncoupled. Some cells with mutations in the replication helicase (mcm-ts mimic checkpoint-deficient cells, and accumulate extensive areas of ssDNA to trigger the G2-checkpoint. Another category of helicase mutant (mcm4-degron causes fork stalling in early S-phase due to immediate loss of helicase function. Intriguingly, cells realize that ssDNA is present, but fail to detect that they accumulate ssDNA, and continue to divide. Thus, the cellular response to replication stalling depends on checkpoint activity and the time that replication stress occurs in S-phase. In this review we describe the signs, signals, and symptoms of replication arrest from an ssDNA perspective. We explore the possible mechanisms for these effects. We also advise the need for caution when detecting and interpreting data related to the accumulation of ssDNA.

  16. Choosing a suitable method for the identification of replication origins in microbial genomes

    Directory of Open Access Journals (Sweden)

    Chengcheng eSong

    2015-09-01

    Full Text Available As the replication of genomic DNA is arguably the most important task performed by a cell and given that it is controlled at the initiation stage, the events that occur at the replication origin play a central role in the cell cycle. Making sense of DNA replication origins is important for improving our capacity to study cellular processes and functions in the regulation of gene expression, genome integrity in much finer detail. Thus, clearly comprehending the positions and sequences of replication origins which are fundamental to chromosome organization and duplication is the first priority of all. In view of such important roles of replication origins, tremendous work has been aimed at identifying and testing the specificity of replication origins. A number of computational tools based on various skew types have been developed to predict replication origins. Using various in silico approaches such as Ori-Finder 2, and databases such as DoriC and oriDB, researchers have predicted the locations of replication origins sites for thousands bacterial chromosomes and archaeal genomes. Based on the predicted results, we should choose an effective method for identifying and confirming the interactions at origins of replication. Here we describe the main existing experimental methods that aimed to determine the replication origin regions and list some of the many the practical applications of these methods.

  17. Türk Bankacılık Sistemi İçin Çok Kriterli Karar Alma Analizine Dayalı Bir Erken Uyarı Modelinin Tahmini

    National Research Council Canada - National Science Library

    KILIÇ, Süleyman Bilgin

    2006-01-01

    ... (ÇKKA) dayanan bir erken uyarı modelinin tahmin edilmesi amaçlanmıştır. Çalışmada, öncelikle mali başarısızlığın yaşanmasından bir yıl öncesi için, başarısız olan ve faaliyetini...

  18. Sosyal Öyküler: Otistik Çocuklara Yönelik Bir Sağaltım

    Directory of Open Access Journals (Sweden)

    Selda Özdemir

    2007-07-01

    Full Text Available Sosyal öyküler bir özel eğitim öğretmeni olan Carol Gray (1994 tarafından otizmden etkilenmiş çocukların sosyal durumları daha iyi anlamaları için geliştirilmiş kısa ve bireyselleştirilmiş öykülerdir. Bu öyküler farklı sosyal durumlar ile ilgili sosyal bilgi ve ipuçlarını çocuğun doğru olarak anlamasına yardımcı olur ve sosyal durumun kim, ne, nerede, ve kiminle gibi özel sorularına yönelik olarak bilgi aktarır. Sosyal öyküler rutin durumlarda ortaya çıkan değişiklikleri açıklamak, akademik becerileri öğretmek, uyum becerileri edindirmek, sosyal durumları ürkütücü olmayan bir yolla açıklamak, ve saldırgan ya da takıntılı davranış gibi problem davranışların üstesinden gelmek gibi farklı amaçlar için kullanılabilirler. Bu makalenin amacı otistik çocuklarla özellikle eğitim ortamlarında yaygınlıkla kullanılan sosyal öyküleri tanıtmak ve sosyal öykülerin bir sağaltım tekniği olarak yazım ve uygulama kuralları hakkında bilgi vermektir. Sosyal hikaleyelerin etkililiğinin değerlendirilmesi sürecinin nasıl uygulanacağı da ayrıca bu makalede incelenmiştir. Social Stories are short and individualized stories developed by Carol Gray (1994, a special education teacher, intended for children with autism to understand social situations. Social Stories attempt to help ensure a child’s accurate understanding of social information and social cues for a given setting and gives instruction regarding the who, what, when, where, and why of a social situation. Social stories can be used for a variety of purposes including explaining changes in routines, teaching academic skills, training adaptive skills, describing social situations in a way that is non-intimidating, and dealing with difficult behaviors, including aggression or obsessive behavior. The purpose of this study was to present social stories used commonly by educators and provide information on how to write and

  19. Süreç Yönetimi Olgunluk Modelleri ve Bir Organizasyonun ve Süreç Yönetimi Olgunluğunun Değerlendirilmesi

    OpenAIRE

    Özveri, Onur; Kabak, Muhammed

    2016-01-01

    Süreç yönetimi olgunluk modelleri işletmelerin süreç yönetimi olgunluk seviyelerini belirleyen ve bir üst olgunluk aşamasına ulaşmak adına atılması gereken adımlarla ilgili işletme yöneticilerine rehberlik eden modellerdir. Süreç yönetimi olgunluk modelleri açısından işletmenin bulunduğu seviyeye göre bir üst olgunluk seviyesi, süreç yönetimine ilişkin daha başarılı uygulama ve sonuçları ifade etmektedir. Literatürde süreç olgunluğunun değerlendirilmesi amacıyla geliştirilmiş çok ...

  20. Factors influencing the replication of somatic coliphages in the water environment.

    Science.gov (United States)

    Muniesa, Maite; Jofre, Juan

    2004-07-01

    The potential replication of somatic coliphages in the environment has been considered a drawback for their use as viral indicators, although the extent to which this affects their numbers in environmental samples has not been assessed. In this study, the replication of somatic coliphages in various conditions was assayed using suspensions containing naturally occurring somatic coliphages and Escherichia coli WG5, which is a host strain recommended for detecting somatic coliphages. The effects on phage replication of exposing strain WG5 and phages to a range of physiological conditions and the effects of the presence of suspended particles or other bacteria were also assayed. Phage replication was further tested using a strain of Klebsiella terrigena and naturally occurring E. coli cells as hosts. Our results indicate that threshold densities of both host bacterium and phages should occur simultaneously to ensure appreciable phage replication. Host cells originating from a culture in the exponential growth phase and incubation at 37 degrees C were the best conditions for phage replication in E. coli WG5. In these conditions the threshold densities required to ensure phage replication were about 10(4) host cells/ml and 10(3) phages/ml, or 10(3) host cells/ml and 10(4) phages/ml, or intermediate values of both. The threshold densities needed for phage replication were higher when the cells proceeded from a culture in the stationary growth phase or when suspended particles or other bacteria were present. Furthermore E. coli WG5 was more efficient in supporting phage replication than either K. terrigenae or E. coli cells naturally occurring in sewage. Our results indicate that the phage and bacterium densities and the bacterial physiological conditions needed for phage replication are rarely expected to be found in the natural water environments.

  1. Replication of micro and nano surface geometries

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Hocken, R.J.; Tosello, Guido

    2011-01-01

    : manufacture of net-shape micro/nano surfaces, tooling (i.e. master making), and surface quality control (metrology, inspection). Replication processes and methods as well as the metrology of surfaces to determine the degree of replication are presented and classified. Examples from various application areas...... are given including replication for surface texture measurements, surface roughness standards, manufacture of micro and nano structured functional surfaces, replicated surfaces for optical applications (e.g. optical gratings), and process chains based on combinations of repeated surface replication steps....

  2. Replication of prions in differentiated muscle cells.

    Science.gov (United States)

    Herbst, Allen; Aiken, Judd M; McKenzie, Debbie

    2014-01-01

    We have demonstrated that prions accumulate to high levels in non-proliferative C2C12 myotubes. C2C12 cells replicate as myoblasts but can be differentiated into myotubes. Earlier studies indicated that C2C12 myoblasts are not competent for prion replication. (1) We confirmed that observation and demonstrated, for the first time, that while replicative myoblasts do not accumulate PrP(Sc), differentiated post-mitotic myotube cultures replicate prions robustly. Here we extend our observations and describe the implication and utility of this system for replicating prions.

  3. SIP Tabanlı Telefon Servislerinin IPTV Sistemine Bütünleştirilebilmesi İçin Yeni Bir Protokol Önerisi

    Directory of Open Access Journals (Sweden)

    Hasan Yükselten

    2011-06-01

    Full Text Available Bu çalışmada, oturum başlatma protokolü (SIP tabanlı çağrı sunucusuyla sağlanan telefon servislerinin IPTV sistemiyle bütünleşmesini sağlayacak yeni bir mimari yapı önerilmiş ve bu amaca yönelik yeni bir protokol (Bağımsız Bildirim Protokolü tasarlanarak geliştirilen mimari yapının avantajları incelenmiştir. Önerilen mimari yapı ve bunu destekleyen protokoller, bildirim mimarisinde arabirim katmanına (middleware olan gereksinimi ortadan kaldırmaktadır. Böylece, bildirim mimari yapısı bir katman azaltılmakta, arabirim katmanına olan bağımlılık sona ermekte, her türlü arabirim katmanı ile bildirim mimarisi kurulabilmektedir. Geliştirilen mimari yapı ve protokolün testleri sonucunda, bildirim bant genişliğinin, mevcut bildirim mimari yapılarındakinin %10’una kadar düştüğü ve önerilen mimari yapının başarılı bir şekilde çalıştığı görülmüştür.

  4. Ortodonti ve periodontoloji işbirliği. Modern biyolojik ortodontide periodontal konular

    Directory of Open Access Journals (Sweden)

    Tancan Uysal

    2011-01-01

    ;">    Ortodontistlerin ve periodontologların yaptıkları klinik tedavilerde periodontoloji ile ortodonti arasındaki ilişkinin biyolojik temellerinin farkında olması gerekmektedir. İki uzmanlık dalı arasındaki uyum, tedavi sonuçlarının olumlu olmasını sağlamaktadır. Bölümler arasında gerçekleştirilen işbirliği ile ortodontik tedavi periodontal sağlığı geliştirdiği gibi periodontal tedavi de ortodontik tedavi sonuçlarını daha da başarılı hale getirebilmektedir. Teknoloji, uzmanlık dalları arasında etkileşimi sağlarken, tedavinin temelini biyoloji oluşturmaktadır. Yeni yüzyılın ortodontisti; bilgili, deneyimli ve sorumluluk sahibi periodontolog ile beraber çalışmalıdır. Ortodontik tedavi görecek hastalar, periodontal riskler, dişeti büyümeleri ve olası alveolar kemik kaybından haberdar edilmelidir. Bu derlemede, aselüler dermal matriks, mine matriks proteinleri, periodontal plastik cerrahi ve yeni bir ortognatik cerrahi alternatifi olan “periodontal olarak hızlandırılmış osteojenik ortodonti” gibi güncel tedaviler ile geleneksel tedaviler tartışılacaktır. Ayrıca aşağıdaki sorulara cevaplar bulunmaya çalışılacaktır; “Ortodontik tedavi periodontal hastalığa sebep olur mu?”, “Periodontal olarak enfekte olan hastalar ortodontik diş hareketleri ile tedavi edilebilir mi?”, “Hastalara ne zaman ve hangi cerrahi yaklaşımlar yapılmaktadır?”, “Hangi tedavi seçenekleri en iyi sonuçları verir ve periodontal dokulara daha az zarar verir?”, “Ne sıklıkla ortodonti hastaları periodontolog tarafından takip edilmelidir?”. Ayrıca periodontal açıdan ortodontik tedavinin endikasyonları, kontrendikasyonları, sınırlamaları, avantaj ve dezavantajları tartışılacaktır.

    DNA replication stress: causes, resolution and disease.

    Science.gov (United States)

    Mazouzi, Abdelghani; Velimezi, Georgia; Loizou, Joanna I

    2014-11-15

    DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Replication Stress: A Lifetime of Epigenetic Change

    Directory of Open Access Journals (Sweden)

    Simran Khurana

    2015-09-01

    Full Text Available DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs and has been linked to both genome instability and irreversible cell cycle arrest (senescence. Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function.

  6. Hayvan Islahında Güncel Bir Yaklaşım: CRISPR/Cas9 Genom Modifikasyon Sistemi

    Directory of Open Access Journals (Sweden)

    Fatih Bilgi

    2016-12-01

    Full Text Available Genom modifikasyonları, verimin arttırılmasında ve hastalıklara karşı direncin kazandırılması konusunda önemli avantajlar sağlama potansiyeli içermektedir. Bireyin zaten sahip olduğu bir genin susturulmasını ya da ifade edilmesini sağlayan gen düzenlenmesi yöntemleri (gene editing çevreyi en az etkileyerek genetik yapının geliştirilmesi konusunda önemli olanaklar sağlamaktadır. Son zamanlarda yeni genetik düzenleme yöntemleri geliştirilmiştir. Bunlar ZFN (Zinc Finger Nuclease’ler, TALEN (Transcription Activator-like Effector Nuclease’ler ve CRISPR/Cas nükleaz sistemleridir. CRISPR/Cas sistemi yabancı genetik materyalleri yok etmek için RNA güdümlü nükleazları kullanan bir mikrobiyal immün sistem olup, bu sistemin günümüzde hayvanlarda basit ve etkili bir gen düzenleme mekanizması olarak kullanılabilme potansiyeli değerlendirilmektedir. Bu derlemede CRISPR/Cas9 sistemi ve hayvan ıslahında kullanılabilirliği özetlenmiştir.

  7. Internet kullanicilarinin demografik özellikleri ile önde gelen web arama motorlari tercihleri arasindaki ilişki üzerine bir araştirma

    Directory of Open Access Journals (Sweden)

    Evren AYRANCI

    2010-10-01

    Full Text Available Günümüzde milyarlarca insan interneti farklı amaçlar için kullanmaktadır. Web arama motorları internet kullanıcıları arasında, ihtiyaç duyulan bilgiyi bulmak için çok popülerdir. Bu makale, internet kullanıcılarının bazı demografik özellikleri ile önde gelen web arama motorları tercihleri arasında bir ilişkinin olup olmadığını anlamak için yapılan bir araştırmayı içermektedir. Elde edilen sonuçlara göre demografik özelliklerin çoğu önde gelen web arama motorları tercihleri ile bir takım bağlantılara sahiptir.

  8. Internet kullanicilarinin demografik özellikleri ile önde gelen web arama motorlari tercihleri arasindaki ilişki üzerine bir araştirma

    OpenAIRE

    Evren AYRANCI

    2010-01-01

    Günümüzde milyarlarca insan interneti farklı amaçlar için kullanmaktadır. Web arama motorları internet kullanıcıları arasında, ihtiyaç duyulan bilgiyi bulmak için çok popülerdir. Bu makale, internet kullanıcılarının bazı demografik özellikleri ile önde gelen web arama motorları tercihleri arasında bir ilişkinin olup olmadığını anlamak için yapılan bir araştırmayı içermektedir. Elde edilen sonuçlara göre demografik özelliklerin çoğu önde gelen web arama motorları tercihleri ile bir takım bağla...

  9. Veri Zarflama Analizi Tabanlı Yeni Bir Hibrid İki Gruplu Sınıflandırma Modeli

    Directory of Open Access Journals (Sweden)

    H. Hasan ÖRKCÜ

    2015-12-01

    Full Text Available Bu çalışmada iki gruplu sınıflandırma problemlerinin çözümünde kullanılabilecek yeni bir sınıflandırma modeli geliştirilmiştir. Bu model Veri Zarflama Analizi BCC modeline dayanan Pendharkar ve Troutt (2014 modeli ile Sueyoshi (2004 tarafından önerilen iki aşamalı sınıflandırma modelinin bir karmasıdır. Çalışmanın amacı, BCC modelindeki parçalı doğrusal etkinlik sınırı ve iki aşamalı detaylı inceleme fikri sayesinde iki gruplu sınıflandırma problemlerini ele almaktır. Önerilen yeni yaklaşım Pendharkar ve Troutt (2014’den alınan bir örnek üzerinde ayrıntılı olarak incelenmiş ve ayrıca yapılan simülasyon çalışmasından önerilen yöntemin sınıflandırma performansının diğer iki yöntemden daha iyi olduğu gözlenmiştir.

  10. Türkiye’de göç yönetişimi: Kurumsal yapı ve işbirliği

    OpenAIRE

    2015-01-01

    Göç özünde yer değişikliğini içeren bir hareketliliktir. Bu hareketliliğin sebebi bazen doğal bir afet, bazen savaşlar, bazen ekonomik gerekçeler, bazen zulüm korkusu olabilir. Göç zamanla sınır aşan bir sorun haline gelmiş ve artan uluslararası göç hareketleri göç yönetiminin yeniden şekillenmesini ve küresel göç yönetişimin ortaya çıkmasını sağlamıştır. Uluslararası göç hareketlerinde en fazla etkilenen ülkelerden Türkiye de göç yönetişimine uyum sağlayacak yasal ve kurums...

  11. Replication-Coupled Recruitment of Viral and Cellular Factors to Herpes Simplex Virus Type 1 Replication Forks for the Maintenance and Expression of Viral Genomes

    Science.gov (United States)

    Dembowski, Jill A.

    2017-01-01

    Herpes simplex virus type 1 (HSV-1) infects over half the human population. Much of the infectious cycle occurs in the nucleus of cells where the virus has evolved mechanisms to manipulate host processes for the production of virus. The genome of HSV-1 is coordinately expressed, maintained, and replicated such that progeny virions are produced within 4–6 hours post infection. In this study, we selectively purify HSV-1 replication forks and associated proteins from virus-infected cells and identify select viral and cellular replication, repair, and transcription factors that associate with viral replication forks. Pulse chase analyses and imaging studies reveal temporal and spatial dynamics between viral replication forks and associated proteins and demonstrate that several DNA repair complexes and key transcription factors are recruited to or near replication forks. Consistent with these observations we show that the initiation of viral DNA replication is sufficient to license late gene transcription. These data provide insight into mechanisms that couple HSV-1 DNA replication with transcription and repair for the coordinated expression and maintenance of the viral genome. PMID:28095497

  12. Accelerated gene evolution through replication-transcription conflicts.

    Science.gov (United States)

    Paul, Sandip; Million-Weaver, Samuel; Chattopadhyay, Sujay; Sokurenko, Evgeni; Merrikh, Houra

    2013-03-28

    Several mechanisms that increase the rate of mutagenesis across the entire genome have been identified; however, how the rate of evolution might be promoted in individual genes is unclear. Most genes in bacteria are encoded on the leading strand of replication. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand. Here we identify the ubiquitous (core) genes in Bacillus subtilis and determine that 17% of them are on the lagging strand. We find a higher rate of point mutations in the core genes on the lagging strand compared with those on the leading strand, with this difference being primarily in the amino-acid-changing (nonsynonymous) mutations. We determine that, overall, the genes under strong negative selection against amino-acid-changing mutations tend to be on the leading strand, co-oriented with replication. In contrast, on the basis of the rate of convergent mutations, genes under positive selection for amino-acid-changing mutations are more commonly found on the lagging strand, indicating faster adaptive evolution in many genes in the head-on orientation. Increased gene length and gene expression amounts are positively correlated with the rate of accumulation of nonsynonymous mutations in the head-on genes, suggesting that the conflict between replication and transcription could be a driving force behind these mutations. Indeed, using reversion assays, we show that the difference in the rate of mutagenesis of genes in the two orientations is transcription dependent. Altogether, our findings indicate that head-on replication-transcription conflicts are more mutagenic than co-directional conflicts and that these encounters can significantly increase adaptive structural variation in the coded proteins. We propose that bacteria, and potentially other organisms, promote faster evolution of specific genes through orientation

  13. Errors and alternatives in prebiotic replication and catalysis.

    Science.gov (United States)

    Ninio, Jacques

    2007-04-01

    The work on nonenzymatic nucleic acid replication performed by Leslie Orgel and co-workers over the last four decades, now extended by work on artificial selection of RNA aptamers and ribozymes, is generating some pessimism concerning the 'naked gene' theories of the origin of life. It is suggested here that the low probability of finding RNA aptamers and ribozymes within pools of random sequences is not as disquieting as the poor gain in efficiency obtained with increases in information content. As acknowledged by Orgel and many other authors, primitive RNA replication and catalysis must have occurred within already complex and dynamic environments. I, thus, propose to pay attention to a number of possibilities that bridge the gap between 'naked gene' theories, on one side, and metabolic theories in which complex systems self-propagate by growth and fragmentation, on the other side. For instance, one can de-emphasize nucleotide-by-nucleotide replication leading to long informational polymers, and view instead long random polymers as storage devices, from which shorter oligomers are excised. Catalytic tasks would be mainly performed by complexes associating two or more oligomers belonging to the same or to different chemical families. It is proposed that the problems of stability, binding affinity, reactivity, and specificity could be easier to handle by heterogeneous complexes of short oligomers than by long, single-stranded polymers. Finally, I point out that replication errors in a primitive replication context should include incorporations of alternative nucleotides with interesting, chemically reactive groups. In this way, an RNA sequence could be at the same time an inert sequence when copied without error, and a ribozyme, when a chemically reactive nucleotide is inadvertently introduced during replication.

  14. APOBEC3A damages the cellular genome during DNA replication.

    Science.gov (United States)

    Green, Abby M; Landry, Sébastien; Budagyan, Konstantin; Avgousti, Daphne C; Shalhout, Sophia; Bhagwat, Ashok S; Weitzman, Matthew D

    2016-01-01

    The human APOBEC3 family of DNA-cytosine deaminases comprises 7 members (A3A-A3H) that act on single-stranded DNA (ssDNA). The APOBEC3 proteins function within the innate immune system by mutating DNA of viral genomes and retroelements to restrict infection and retrotransposition. Recent evidence suggests that APOBEC3 enzymes can also cause damage to the cellular genome. Mutational patterns consistent with APOBEC3 activity have been identified by bioinformatic analysis of tumor genome sequences. These mutational signatures include clusters of base substitutions that are proposed to occur due to APOBEC3 deamination. It has been suggested that transiently exposed ssDNA segments provide substrate for APOBEC3 deamination leading to mutation signatures within the genome. However, the mechanisms that produce single-stranded substrates for APOBEC3 deamination in mammalian cells have not been demonstrated. We investigated ssDNA at replication forks as a substrate for APOBEC3 deamination. We found that APOBEC3A (A3A) expression leads to DNA damage in replicating cells but this is reduced in quiescent cells. Upon A3A expression, cycling cells activate the DNA replication checkpoint and undergo cell cycle arrest. Additionally, we find that replication stress leaves cells vulnerable to A3A-induced DNA damage. We propose a model to explain A3A-induced damage to the cellular genome in which cytosine deamination at replication forks and other ssDNA substrates results in mutations and DNA breaks. This model highlights the risk of mutagenesis by A3A expression in replicating progenitor cells, and supports the emerging hypothesis that APOBEC3 enzymes contribute to genome instability in human tumors.

  15. Macaristan Türkolojisi Üzerine Bir Biyo-Biyografi Denemesi An Attempt At A Bioagrapy of Hungarian Turkology

    Directory of Open Access Journals (Sweden)

    Mehmet GÜMÜŞKILIÇ

    2012-12-01

    Full Text Available Hungary is the place where Turcology studies started in modern terms. For many years Hungarian scientists have been engaged in Turkish studies- as a part of their research of their own roots -. Theyhad great contribution to Turkish language, history, literature,geography, ethnography and music. It may also be supposed thatTurkish Hungarian relations were better than now. However, todayTurkish Hungarian relations have been enjoying a revival again.Considering the closeness of Hungarians and Turks, it is obvious thatthe two nations share some responsibilities in improving their relations.In this article, after organizing the names of all the HungarianTurcologs who have conducted studies on Turks after the foundation ofmodern Turcology in alphabetical order, their articles on Turcologyfromoldest to newest will be presented as well as their career lives.Also the lists of some of the studies on some of the Turcologs will begiven. The Hungarian scientists and their studies mentioned in thisarticle do not encompass all of them. If we include other articles, books,presentations, credits, reviews and the studies of other scientists thatwe haven’t been able to mention here, the number will swell and gobeyond the limits of this article. In the future, we hope that furtherdetailed studies will be conducted on Hungarian Turcology. Through anattempt at biyo biography, we have tried to touch briefly on theimportance Hungarians give to Turks.Undoubtedly in the future, Turkish Hungarian relations andfriendship will further improve with the help of further detailed studies.This article will serve its purpose if we have a tiny contribution. Modern anlamda Türkoloji çalışmalarının başladığı yer Macaristan’dır. Macar bilim adamları yıllar boyu -bir bakıma kendi köklerini de arama çabaları sebebiyle- Türklük bilimiyle uğraştılar. Türk diline, tarihine, kültürüne, edebiyatına, coğrafyasına, etnoğrafyasına, musikîsine b

  16. Yenidoğanda Nadir Bir Enterokolit Nedeni: İnek Sütü Entoleransı

    OpenAIRE

    Kutlu, Tufan; Erkan, Tülay; Çokuğraş, Fügen; Göksel, Süha; T.Tümay, Güngör

    1995-01-01

    Otuzsekiz günlük bir kız çocuğu inek sütü içeren hazır mama ile beslenmeye başlandıktan sonra ortaya çıkan kusma kanlı ishal ve karın şişliği nedeniyle getirildi İnce barsak biyopsisinde total villus atrofisi bulunması betalaktoglobulin antikorları pozitifliği ve inek sütü içeren mamanın diyetten çıkarılması ile semptomların kaybolması üzerine enterokolit tablosunun inek sütü entoleransına bağlı olduğu düşünüldü Bu olgu bize yenidoğanlarda kusma ve kanlı ishal varlığında ayırıcı tanıda inek s...

  17. (Yeni) Bir Sözlükbilim Teorisine İhtiyacımız Var mı?

    DEFF Research Database (Denmark)

    Tarp, Sven

    2014-01-01

    sorusu gündeme gelmiştir. Bu soruyu cevaplamak için öncelikle bu makale, bir sözlükbilim teorisinin var olup olmadığını mümkün olduğu ölçüde tartışmaktadır. Çeşitli yaklaşımlar sözlükbilimsel daire çerçevesinde özellikle teori kavramının yaygın olarak tartışmalı olduğunu göstermektedir. Bu bağlamda......, kısaca, sadece doğal olaylarla ilgili olan, sanat ve zanaatın etki alanına atıfta bulunan bilime göre Anglo-Sakson akademik gelenek tartışılmakta ve bu geleneğin yaygın olarak dünyanın diğer bölgelerindeki gelenekler tarafından karşı olduğunu göstermektedir. Bu temel üzerine makale, sözlükbilimsel...

  18. Correlation of fine needle aspiration cytology with histopathology findings in cases of thyroid lesions in Bir Hospital

    Directory of Open Access Journals (Sweden)

    PB Thapa

    2014-01-01

    Full Text Available Aims: To correlate the findings of fine needle aspiration cytology (FNAC with the histopathology( HPE of the excised nodule or specimen and to assess the accuracy and efficacy of FNAC in the diagnosis of the thyroid nodules. Materials and methods: This is a prospective study conducted at the Department of Ear Nose Throat (ENT & Head & NecK Surgery( HNS, National Academy of Medical Sciences, Bir Hospital, Kathmandu from 2nd January 2009 to 29th December 2011. One hundred patients with thyroid nodule were included in the study. Results: Out of 100 patients 77 were females and 23 males. The age ranged from 11-60 years. Statistical analysis of results for Benign Thyroid lesion showed 98.6% sensitivity, 75 % specificity. Likewise, results for Malignant thyroid lesions showed 75 % sensitivity, 98.6 % specificity . Conclusion: FNAC has high accuracy in the diagnostic evaluation of thyroid lesions. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-1, 23-29 DOI: http://dx.doi.org/10.3126/jcmsn.v9i1.9670

  19. Self-replication of DNA rings

    Science.gov (United States)

    Kim, Junghoon; Lee, Junwye; Hamada, Shogo; Murata, Satoshi; Ha Park, Sung

    2015-06-01

    Biology provides numerous examples of self-replicating machines, but artificially engineering such complex systems remains a formidable challenge. In particular, although simple artificial self-replicating systems including wooden blocks, magnetic systems, modular robots and synthetic molecular systems have been devised, such kinematic self-replicators are rare compared with examples of theoretical cellular self-replication. One of the principal reasons for this is the amount of complexity that arises when you try to incorporate self-replication into a physical medium. In this regard, DNA is a prime candidate material for constructing self-replicating systems due to its ability to self-assemble through molecular recognition. Here, we show that DNA T-motifs, which self-assemble into ring structures, can be designed to self-replicate through toehold-mediated strand displacement reactions. The inherent design of these rings allows the population dynamics of the systems to be controlled. We also analyse the replication scheme within a universal framework of self-replication and derive a quantitative metric of the self-replicability of the rings.

  1. Regulation of the switch from early to late bacteriophage lambda DNA replication.

    Science.gov (United States)

    Baranska, S; Gabig, M; Wegrzyn, A; Konopa, G; Herman-Antosiewicz, A; Hernandez, P; Schvartzman, J B; Helinski, D R; Wegrzyn, G

    2001-03-01

    There are two modes of bacteriophage lambda DNA replication following infection of its host, Escherichia coli. Early after infection, replication occurs according to the theta (theta or circle-to-circle) mode, and is later switched to the sigma (sigma or rolling-circle) mode. It is not known how this switch, occurring at a specific time in the infection cycle, is regulated. Here it is demonstrated that in wild-type cells the replication starting from orilambda proceeds both bidirectionally and unidirectionally, whereas in bacteria devoid of a functional DnaA protein, replication from orilambda is predominantly unidirectional. The regulation of directionality of replication from orilambda is mediated by positive control of lambda p(R) promoter activity by DnaA, since the mode of replication of an artificial lambda replicon bearing the p(tet) promoter instead of p(R) was found to be independent of DnaA function. These findings and results of density-shift experiments suggest that in dnaA mutants infected with lambda, phage DNA replication proceeds predominantly according to the unidirectional theta mechanism and is switched early after infection to the sigma mode. It is proposed that in wild-type E. coli cells infected with lambda, phage DNA replication proceeds according to a bidirectional theta mechanism early after infection due to efficient transcriptional activation of orilambda, stimulated by the host DnaA protein. After a few rounds of this type of replication, the resulting increased copy number of lambda genomic DNA may cause a depletion of free DnaA protein because of its interaction with the multiple DnaA-binding sites in lambda DNA. It is proposed that this may lead to inefficient transcriptional activation of orilambda resulting in unidirectional theta replication followed by sigma type replication.

  2. Host ESCRT proteins are required for bromovirus RNA replication compartment assembly and function.

    Directory of Open Access Journals (Sweden)

    Arturo Diaz

    2015-03-01

    Full Text Available Positive-strand RNA viruses genome replication invariably is associated with vesicles or other rearranged cellular membranes. Brome mosaic virus (BMV RNA replication occurs on perinuclear endoplasmic reticulum (ER membranes in ~70 nm vesicular invaginations (spherules. BMV RNA replication vesicles show multiple parallels with membrane-enveloped, budding retrovirus virions, whose envelopment and release depend on the host ESCRT (endosomal sorting complexes required for transport membrane-remodeling machinery. We now find that deleting components of the ESCRT pathway results in at least two distinct BMV phenotypes. One group of genes regulate RNA replication and the frequency of viral replication complex formation, but had no effect on spherule size, while a second group of genes regulate RNA replication in a way or ways independent of spherule formation. In particular, deleting SNF7 inhibits BMV RNA replication > 25-fold and abolishes detectable BMV spherule formation, even though the BMV RNA replication proteins accumulate and localize normally on perinuclear ER membranes. Moreover, BMV ESCRT recruitment and spherule assembly depend on different sets of protein-protein interactions from those used by multivesicular body vesicles, HIV-1 virion budding, or tomato bushy stunt virus (TBSV spherule formation. These and other data demonstrate that BMV requires cellular ESCRT components for proper formation and function of its vesicular RNA replication compartments. The results highlight growing but diverse interactions of ESCRT factors with many viruses and viral processes, and potential value of the ESCRT pathway as a target for broad-spectrum antiviral resistance.

  3. Host ESCRT proteins are required for bromovirus RNA replication compartment assembly and function.

    Science.gov (United States)

    Diaz, Arturo; Zhang, Jiantao; Ollwerther, Abigail; Wang, Xiaofeng; Ahlquist, Paul

    2015-03-01

    Positive-strand RNA viruses genome replication invariably is associated with vesicles or other rearranged cellular membranes. Brome mosaic virus (BMV) RNA replication occurs on perinuclear endoplasmic reticulum (ER) membranes in ~70 nm vesicular invaginations (spherules). BMV RNA replication vesicles show multiple parallels with membrane-enveloped, budding retrovirus virions, whose envelopment and release depend on the host ESCRT (endosomal sorting complexes required for transport) membrane-remodeling machinery. We now find that deleting components of the ESCRT pathway results in at least two distinct BMV phenotypes. One group of genes regulate RNA replication and the frequency of viral replication complex formation, but had no effect on spherule size, while a second group of genes regulate RNA replication in a way or ways independent of spherule formation. In particular, deleting SNF7 inhibits BMV RNA replication > 25-fold and abolishes detectable BMV spherule formation, even though the BMV RNA replication proteins accumulate and localize normally on perinuclear ER membranes. Moreover, BMV ESCRT recruitment and spherule assembly depend on different sets of protein-protein interactions from those used by multivesicular body vesicles, HIV-1 virion budding, or tomato bushy stunt virus (TBSV) spherule formation. These and other data demonstrate that BMV requires cellular ESCRT components for proper formation and function of its vesicular RNA replication compartments. The results highlight growing but diverse interactions of ESCRT factors with many viruses and viral processes, and potential value of the ESCRT pathway as a target for broad-spectrum antiviral resistance.

  4. Parasites Sustain and Enhance RNA-Like Replicators through Spatial Self-Organisation.

    Directory of Open Access Journals (Sweden)

    Enrico Sandro Colizzi

    2016-04-01

    Full Text Available In a prebiotic RNA world, parasitic behaviour may be favoured because template dependent replication happens in trans, thus being altruistic. Spatially extended systems are known to reduce harmful effects of parasites. Here we present a spatial system to show that evolution of replication is (indirectly enhanced by strong parasites, and we characterise the phase transition that leads to this mode of evolution. Building on the insights of this analysis, we identify two scenarios, namely periodic disruptions and longer replication time-span, in which speciation occurs and an evolved parasite-like lineage enables the evolutionary increase of replication rates in replicators. Finally, we show that parasites co-evolving with replicators are selected to become weaker, i.e. worse templates for replication when the duration of replication is increased. We conclude that parasites may not be considered a problem for evolution in a prebiotic system, but a degree of freedom that can be exploited by evolution to enhance the evolvability of replicators, by means of emergent levels of selection.

  5. Parasites Sustain and Enhance RNA-Like Replicators through Spatial Self-Organisation.

    Science.gov (United States)

    Colizzi, Enrico Sandro; Hogeweg, Paulien

    2016-04-01

    In a prebiotic RNA world, parasitic behaviour may be favoured because template dependent replication happens in trans, thus being altruistic. Spatially extended systems are known to reduce harmful effects of parasites. Here we present a spatial system to show that evolution of replication is (indirectly) enhanced by strong parasites, and we characterise the phase transition that leads to this mode of evolution. Building on the insights of this analysis, we identify two scenarios, namely periodic disruptions and longer replication time-span, in which speciation occurs and an evolved parasite-like lineage enables the evolutionary increase of replication rates in replicators. Finally, we show that parasites co-evolving with replicators are selected to become weaker, i.e. worse templates for replication when the duration of replication is increased. We conclude that parasites may not be considered a problem for evolution in a prebiotic system, but a degree of freedom that can be exploited by evolution to enhance the evolvability of replicators, by means of emergent levels of selection.

  6. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  7. İletişim Çalışmalarında Yeni Bir Mecra: Finansal İletişim

    Directory of Open Access Journals (Sweden)

    Gökhan Gökgöz

    2013-09-01

    Full Text Available 1970’li yıllar toplumsal ve politik tarih açısından önemli bir uğrağı temsil eder. Bu yılların başında yaşanan kriz, ekonominin işleyiş süreçlerini, devletin yapısını ve toplumsal alanın tasavvur edilme biçimini büyük ölçüde değiştirmiştir. Bu dönemde, finansal sermaye, kapitalizm içerisinde bir hegemonik lider olarak ön plana çıkmış; devlet, bir yandan üretimin çekirdeğinden uzak bir yerde konumlandırılırken diğer yandan paranın dolaşım kanallarının rehabilitasyonu işine odaklanmış; insana ilişkin değerler, kültürel mefhumlar ve toplumsal pratikler ise birer değişken olarak ekonomi-politikanın merkezine taşınmıştır. Kültür ile ekonomi arasındaki geleneksel ilişki bozulmuş; bir ekonomi-politikanın başarısı, toplumsal aktörlere temas etme kabiliyeti ile paralel hale gelmiştir. Finansallaşma sürecinde bu temas, iletişim politikaları vasıtasıyla sağlanır; ekonomi-politika ve bundan sorumlu merkezi kurumlarla toplumsal alan arasındaki bağ, iletişim stratejileri üzerinden kurulur; ekonomik alan ile kültürel alan arasındaki boşluk, iletişim kanalları içerisinden taşınan enformasyon marifetiyle doldurulur; insana ilişkin öngörülemezlikler, iletişim süreçleri vasıtasıyla öngörülebilir kılınır. Bu çalışmada, iletişim çalışmaları içerisinde yeni bir mecra olarak çağrılan “finansal iletişim”in farklı temas noktalarına işaret edilecek ve her bir uğrağın finansal iletişim alanına bağlandığı nokta, modeller üzerinden gösterilecektir. 

  8. Identification of imprinted genes using a novel screening method based on asynchronous DNA replication

    Energy Technology Data Exchange (ETDEWEB)

    Kawame, H.; Hansen, R.S.; Gartler, S.M. [Univ. of Washington, Seattle, WA (United States)

    1994-09-01

    Genomic imprinting refers to the process of epigenetic change that occurs during germ cell development that results in either maternal- or paternal-specific gene expression. Identification of imprinted genes is of primary importance to the understanding of imprinting mechanisms and the role of specific imprinted genes in human disease. Recently, it has been established that chromosomal regions known to contain imprinted genes replicate asynchronously. We propose a novel screening method to identify imprinted genes based on replication asynchrony as a marker for imprinted domains. Dividing human cells were pulse-labeled with BrdU and separated into different fractions of S-phase by flow cytometry. A library of late-replicating inter-Alu sequences should be enriched in gene-associated sequences that replicate early on one chromosome and late on the other homologue. Clones were analyzed for replication timing by hybridization to inter-Alu replication profiles. Candidates for replication asynchrony exhibited broad or biphasic replication timing, and these were analyzed for chromosomal location by hybridizations to inter-Alu products from a hybrid mapping panel. Initial screening of 123 clones resulted in 3 asynchronously-replicating clones that localized to single chromosomes. Chromosome 17 and chromosome 19 candidates might be located in regions thought to be imprinted by synteny with mouse chromosomes. A chromosome 15 clone was further characterized because of its possible localization to the Prader-Willi/Angelman locus. This sequence was localized outside the region deleted in Prader-Willi patients, and was found to be expressed in human cell lines. Replication asynchrony for this sequence appears to be polymorphic because cells derived from some individuals indicated synchronous replication. This appears to be the first example of a polymorphism in replication asynchrony.

  9. Regulation of Unperturbed DNA Replication by Ubiquitylation

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    Sara Priego Moreno

    2015-06-01

    Full Text Available Posttranslational modification of proteins by means of attachment of a small globular protein ubiquitin (i.e., ubiquitylation represents one of the most abundant and versatile mechanisms of protein regulation employed by eukaryotic cells. Ubiquitylation influences almost every cellular process and its key role in coordination of the DNA damage response is well established. In this review we focus, however, on the ways ubiquitylation controls the process of unperturbed DNA replication. We summarise the accumulated knowledge showing the leading role of ubiquitin driven protein degradation in setting up conditions favourable for replication origin licensing and S-phase entry. Importantly, we also present the emerging major role of ubiquitylation in coordination of the active DNA replication process: preventing re-replication, regulating the progression of DNA replication forks, chromatin re-establishment and disassembly of the replisome at the termination of replication forks.

  10. Links between DNA Replication, Stem Cells and Cancer

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    Alex Vassilev

    2017-01-01

    Full Text Available Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in early embryos give rise to all of the cell lineages in the embryo and adult, but when they mislocate to ectopic sites, they produce tumors. Remarkably, pluripotent stem cells, like many cancer cells, depend on the Geminin protein to prevent excess DNA replication from triggering DNA damage-dependent apoptosis. This link between the control of DNA replication during early development and germ cell neoplasia reveals Geminin as a potential chemotherapeutic target in the eradication of cancer progenitor cells.

  11. Links between DNA Replication, Stem Cells and Cancer.

    Science.gov (United States)

    Vassilev, Alex; DePamphilis, Melvin L

    2017-01-25

    Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in early embryos give rise to all of the cell lineages in the embryo and adult, but when they mislocate to ectopic sites, they produce tumors. Remarkably, pluripotent stem cells, like many cancer cells, depend on the Geminin protein to prevent excess DNA replication from triggering DNA damage-dependent apoptosis. This link between the control of DNA replication during early development and germ cell neoplasia reveals Geminin as a potential chemotherapeutic target in the eradication of cancer progenitor cells.

  12. 18β-glycyrrhetinic acid inhibits rotavirus replication in culture

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    Hardy Michele E

    2012-05-01

    Full Text Available Abstract Background Glycyrrhizin (GA and primary metabolite 18β-glycyrrhetinic acid (GRA are pharmacologically active components of the medicinal licorice root, and both have been shown to have antiviral and immunomodulatory properties. Although these properties are well established, the mechanisms of action are not completely understood. In this study, GA and GRA were tested for the ability to inhibit rotavirus replication in cell culture, toward a long term goal of discovering natural compounds that may complement existing vaccines. Methods Epithelial cells were treated with GA or GRA various times pre- or post-infection and virus yields were measured by immunofluorescent focus assay. Levels of viral proteins VP2, VP6, and NSP2 in GRA treated cells were measured by immunoblot to determine if there was an effect of GRA treatment on the accumulation of viral protein. Results GRA treatment reduced rotavirus yields by 99% when added to infected cultures post-- virus adsorption, whereas virus yields in GA treated cultures were similar to mock treated controls. Time of addition experiments indicated that GRA-mediated replication inhibition likely occurs at a step or steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were substantially reduced when GRA was added to cultures up to two hours post-entry. Conclusions GRA, but not GA, has significant antiviral activity against rotavirus replication in vitro, and studies to determine whether GRA attenuates rotavirus replication in vivo are underway.

  13. Psoriatik Artritli Bir Hastada Ižnfliksimab Tedavisi Sirasinda Gelisen Guillain-Barre Sendromu: Olgu Sunumu

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    Osman Tufekci

    2014-12-01

    Full Text Available Tumor necrosis factor (TNF-α plays an important role in many aspects of immune system development, immune-response regulation, and T-cell–mediated tissue injury. The evidence that TNF-α, released by auto reactive T cells and macrophages, may contribute to the pathogenesis of immune-mediated demyelinating neuropathies is reviewed. Demyelinating neuropathies are rare adverse events of anti–TNF-α therapy. Improvement usually occurs after drug interruption and/or in association with conventional treatments for demyelinating neuropathies. We aimed to report a patient with demyelinating neuropathy occurring after TNF blocker (infliximab treatment. The development of Guillain-Barre syndrome in this report may have been secondary to anti-TNF-α treatment.  The influence of anti-TNF-α treatment continuation on the long-term course of neuropathy is variable, suggesting that anti-TNF-α treatment withdrawal is not always necessary for neuropathy control. But such as the report, anti-TNF-α treatment may be stopped.

  14. Regulation of chromosomal replication in Caulobacter crescentus.

    Science.gov (United States)

    Collier, Justine

    2012-03-01

    The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Comparison of three replication strategies in complex multicellular organisms: Asexual replication, sexual replication with identical gametes, and sexual replication with distinct sperm and egg gametes

    Science.gov (United States)

    Tannenbaum, Emmanuel

    2008-01-01

    This paper studies the mutation-selection balance in three simplified replication models. The first model considers a population of organisms replicating via the production of asexual spores. The second model considers a sexually replicating population that produces identical gametes. The third model considers a sexually replicating population that produces distinct sperm and egg gametes. All models assume diploid organisms whose genomes consist of two chromosomes, each of which is taken to be functional if equal to some master sequence, and defective otherwise. In the asexual population, the asexual diploid spores develop directly into adult organisms. In the sexual populations, the haploid gametes enter a haploid pool, where they may fuse with other haploids. The resulting immature diploid organisms then proceed to develop into mature organisms. Based on an analysis of all three models, we find that, as organism size increases, a sexually replicating population can only outcompete an asexually replicating population if the adult organisms produce distinct sperm and egg gametes. A sexual replication strategy that is based on the production of large numbers of sperm cells to fertilize a small number of eggs is found to be necessary in order to maintain a sufficiently low cost for sex for the strategy to be selected for over a purely asexual strategy. We discuss the usefulness of this model in understanding the evolution and maintenance of sexual replication as the preferred replication strategy in complex, multicellular organisms.

  16. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    Science.gov (United States)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  17. The International Framework of Information Policies Enformasyon Politikalarına Küresel Bir Bakış

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    Nick Moore

    2000-03-01

    Full Text Available The emergence of information societies is one of the defining characteristics of the last decade of the twentieth century. Countries all over the world are repositioning themselves to take advantage of the opportunities offered by the information age. They share common objectives although there are significant differences in the motivations underlying the re-positioning and in the mechanisms chosen to implement information society developments. Formal frameworks of policy are being established to steer the development of information societies. There can be few other examples of technological change stimulating formal policy creation in order to bring about social change. This paper surveys the approaches to information policy in various countries all over the world and forecasts future progress with views as to how to ensure that the information society will work for the good of every one. 20. yüzyılın son on yılının belirleyici karakteristiklerinden biri enformasyon toplumlarının ortaya çıkması olmuştur. Dünyanın dört bir yanında ülkeler, enformasyon çağının yarattığı olanaklardan yararlanabilmek için konumlarını gözden geçirmektedirler. Bu ülkelerin hedefleri aynı olmakla birlikte, yönelimlerinin ardındaki motivasyonlar her zaman aynı değildir ve enformasyon toplumu gelişmelerini uygulamaya sokmak için seçtikleri mekanizmalar önemli farklılıklar göstermektedir. Enformasyon toplumuna geçişi harekete geçirmek için resmi politikalar saptanmaktadır. Bunun dışında, teknolojik değişimin, bağlantılı bir toplumsal değişimi sağlamak için resmi politikalar belirlenmesini zorladığı çok ender görülmüştür. Bu bildiride dünyanın çeşitli ülkelerinde enformasyon politikalarına yaklaşımların neler olduğu gözden geçirilmekte, geleceğe yönelik görüşler sunulmakta ve enformasyon toplumunun herkesin yararına gelişmesi için neler yapılması gerektiği konusu işlenmektedir.

  18. Zihin Kuramı ve Dil Arasındaki İlişki: Bir Derleme

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    Bahar Keçeli Kaysılı

    2014-08-01

    Full Text Available Diğerlerinin duygularını, düşüncelerini ve isteklerini anlama yani zihin kuramı başarılı bir iletişim için gereklidir. Bu derleme çalışmasında normal gelişen çocuklarda zihin kuramı ve dil ilişkisi ele alınmıştır. Zihin kuramı kazanımını açıklayan teorilerden biri sözdizimi ve zihinsel durum ifade eden eylemlerin, yanlış inancın temsiline olanak sağladığını belirterek bu ilişkiyi incelemektedir. Bu varsayım dil ile zihin kuramı arasındaki ilişkinin doğasını tanımladığı için önemli görülmektedir. Alanyazından derlenen bu çalışmanın çocukların iletişim ve dil gelişimlerini desteklemede, öğretmenlere yol göstereceği düşünülmektedir. Understanding of others’ feelings, thoughts and wishes or a ‘theory of mind’ is essential for competent communication. This study described how language and theory of mind development are related in typically developing children. One of the hypothesis that explains the acquisition of theory of mind, proposed that syntax and mental states verbs provides children to understand representational thoughts like false belief. Because this hypothesis aimed to identify more specifically the nature of this role it is thought to be important. This review of selected literature will help teachers enhance children’s communication and language development.

  19. /ı/ Türkçede Bir Anasesbirim midir? Is The Letter of /ı/ Archiphoneme In Turkish?

    Directory of Open Access Journals (Sweden)

    Fatih ÖZEK

    2013-03-01

    Full Text Available We can mention two letters of /ı/ in world languages. One ofthem is /ı/ (ы vowel called "yeri" in Russian language and the other is/ı/ vowel that is designated with [ï] in alphabet of internationaltranscription and that almost belongs to the Turkish language. The /ı/vowel of the Turkish language is a velarized, narrow, flat velum vowel interms of its characteristic features. It has normal duration. /a/, /i/ and/u/ vowels are generally deemed as cardinal vowels of the Turkishlanguage. According to this common view, eight vowels in the Turkishlanguage derived from these vowels. However, A.N. Baskakov thinksthat /ı/ is an archiphoneme and [i,u,ü] vowels are variants of the /ı/phoneme. This different view has had an influence on issuance of thispaper. It is possible to define the archiphoneme as main voicecontaining characteristics of more than one voice or first known voicesof a language. The archiphonemes are strong voices. They usually retaintheir existences. However, such characteristics are not seen in /ı/phoneme. Following determinations can be considered as evidenceshereof:1. qlıç (~ qılıç [cliç, cliz/kiliç] writings in Codex Cumanicus,2. Front palatalization of the /ı/ vowel in the first syllable (Uigur biş- ~ bış-‘mature, age out ’; Khorezm biş-; Kipchak biş- ~ piş-; Chagatai piş-; ETT piş-; Bashkir,Tatar, Turkmen, Azerbaijani biş-; Kazakh pis-; Uzbek, New Uigur, Gagauz, Trk. piş- Dünya dillerinde iki tane /ı/’dan bahsedilebilir. Bunlardan bir tanesi Rusça “yeri” adı verilen /ı/ (ы ünlüsü, diğeri ise uluslar arası transkripsiyon alfabesinde [ï] işaretiyle gösterilen ve neredeyse tamamen Türkçeye ait olan /ı/ ünlüsüdür. Türkçeye has /ı/ ünlüsü nitelik özellikleri bakımından kalın, dar, düz bir art damak ünlüsüdür. Nicelik bakımından ise normal sürelidir. /a/, /i/ ve /u/ ünlüleri genel olarak Türkçenin temel ünlüleri olarak kabul edilir. Bu yaygın görüşe g

  20. Temettü Ödemelerinin Belirleyicileri ve Firma Değeri: Kavramsal Bir Model ve Tahminlemesi

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    Şaban Çelik

    2016-12-01

    Full Text Available Bu çalışmanın amacı temettü politikalarının belirleyicileri ile firma değeri arasındaki ilişkiyi kavramsal bir model çerçevesinde açıklayıp tahminlemesini yapmaktır. Bu kapsamda üç temel hipotez grubu oluşturulup test edilmiştir. Birinci hipotez grubu risk faktörü ile temettü politikaları; ikinci hipotez grubu kurumsal yönetim faktörü ile temettü politikaları ve üçüncü hipotez grubu da temettü polikaları ile firma değeri ilişkisi şeklinde oluşturulmuştur. Birinci ve ikinci hipotez gruplarının test sonuçlarına göre, risk ve kurumsal yönetimin temettü politikaları arasındaki ilişkinin, analiz edilen veri seti ve zaman aralığı kısıtları çerçevesinde red edilmediği görülmüştür. Buna karşın üçüncü hipotez grubu olan temettü politikası ve firma değeri ilişkisi kısmi olarak red edilememiştir.

  1. Ekonomik gerikalmışlık ve ekonomik dengesizlik kavramları üzerine bir deneme

    Directory of Open Access Journals (Sweden)

    Ahmet Ali KARACA

    2010-01-01

    Full Text Available Bu makalede öncelikle azgelişmişlik kavramı üzerinde durulmuş bu konuda en önde gelen yerli ve yabancı kaynaklar belirlenmiştir. Ardından da bu kaynaklarda yer alan çalışmalar incelenmiş ve özellikle daha güncel tarihli çalışmalarda ele alınan ana ve alt konular üzerinde durulmuştur. Ayrıca azgelişmişlik düzeyini ölçen kriterler ayrıntılı olarak incelenmiştir. Özellikle; Dünya ekonomisine entegrasyon kriterleri, endüstrileşme kriterleri, sosyo-ekonomik kriterler, jeo-politik kriterler başlıklarında detaylı bilgiler verilmiştir. Literatürde ekonomik gerikalmışlık kriterlerini inceleyen çok çeşitli makaleler vardır. Bu makaleler genelde geri kalmışlık yaklaşımlarını genel değerlendirme perspektifinden aktarmaktadırlar. Bu makalede ise ekonomik geri kalmışlık kavramı ekonomik kalkınma iktisadı açısından incelenmiş ve ekonomik dengesizlikler ve kriterleri detaylı bir şekilde verilmiştir.

  2. Tezkire Niteliğinde Bir Şiir Mecmuası A Macmua Of Poem Feature Of Periodical (Tazkirah

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    Uğur ÖZTÜRK

    2013-03-01

    Full Text Available Connotating compiled, collected, gathered, "majmuas" among betwixt "poem majmuas" are of major sources as for being enjoyed to compose history of Ottoman literature. In general terms, it is appropriate to classify the majmuas in recordinds of selected poems inreference to a certain alphabetical order or poem majmuas. Biographicdetails of a majmua which is retained in Atatürk Kitaplığı, MuallimCevdet Section No: K.479 and distinctive for the era written in has beenworken on. From the scripts in the introduction, partially in the middleand at the end of the majmua, as understood, disconnexion exists.Identity of writer and inking time are precarious. It has been inferedfrom the scripts in the majmua that it has been written in the last 15years of era of Suleyman The Great.Author of the majmua placed famous writers before his day andboth fameless and famous during his day. In general, he presentedshort biographic information before poems, even sometimes madeassessments about poets in this informations. What makes a majmuahere is of biographic information in and poets never mentioned intezkires. Poems chosen for majmua show parallelism with ones in 16.centuriy and have generally characteristics of "berceste" Poets likeHayali Bey, Baki, Ahmed Paşa, Necati Bey, Atayi, Muhibbi, Nazmi arepredominant in these majmuas. The others like Savmi, Hazani Bey,Halisi Bey have no records in majmuas. Bir araya getirilmiş, toplamış manasını taşıyan mecmualar içerisinde şiir mecmuları Osmanlı edebiyatı tarihine kaynaklık etmesi açısından birincil kaynaklar arasında yer almaktadır. Şiir mecmualarına genel olarak bakıldığında bu mecmuaları belli bir harf düzenine göre yazılmış seçme şiirlerden oluşan şiir defterleri veya nazire mecmuası diye adlandırmak yerindedir. Atatürk Kitaplığı Muallim Cevdet Bölümü K.479 numarada yer alan ve yazıldığı dönemin açısından önemli olan bir şiir mecmuasının biyografik bilgileri

  3. Malezya’da Din-Devlet İlişkisine Kısa Bir Bakış

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    Mehmet Özay

    2013-03-01

    Full Text Available AbstractStarting from the second half of the 1960s onwards, socio-religious youth movements, which are regarded as the initial element of civil expressions on university campuses, were constructively influential on the perception of the political elites’ understanding of Islam and political evolution of the Islamisation policies in the process in Malaysia. There are opinions that this effect encompassed the efforts of Islamisation particularly in the 1980s. In this process, the task of the state apparatus, as a political power, which managed the religious domain mostly considered belonging to the civil sector, deserves to be scrutinized in relation with at least some influential factors in the near and distant past of the Muslim Malay community. And, it cannot be overseen that the functions of the traditional Malay rulers, say, Sultans, were transferred, to some or larger extent, to the Federal government after the independence. With regard to this, in this article, the present writer will focus on some aspects of the policies of Dr. Mahathir Mohamad, who has molded majorily the history of modern Malaysia, regarding his Islamisation policy aligned with the state-religion relationship.ÖzetMalezya’da 1960’lı yılların ikinci yarısından itibaren üniversite kampüslerinde başlayan ve sivilleşmenin bir unsuru olarak telâkki edilen dini-toplumsal hareketlerin İslam’ın ülke siyasi elitince algılanmasında ve pratikte İslamlaştırma adıyla anılabilecek politikalara evrilmesinde önemli etkisi olmuştur. Bu etkinin, özellikle 1980’li yıllarda devlet eliyle İslamlaştırma çabalarına yol açtığı konusunda görüşler bulunmaktadır. Bu süreçte, yani devletin siyasi bir güç olarak sivil alana dahil olan dini çekip çevirme işini üstlenmesinde, özellikle Müslüman Malay toplumunun yakın ve uzak geçmişindeki kimi faktörler dikkate alınmayı hak etmektedir. Bu bağlamda, geleneksel Malay devletlerinde Sultanlar

  4. Surface micro topography replication in injection moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf

    of the mechanisms controlling topography replication. Surface micro topography replication in injection moulding depends on the main elements of  Process conditions  Plastic material  Mould topography In this work, the process conditions is the main factor considered, but the impact of plastic material...

  5. Replication and Robustness in Developmental Research

    Science.gov (United States)

    Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.

    2014-01-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  6. Replication and Robustness in Developmental Research

    Science.gov (United States)

    Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.

    2014-01-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  7. Using Replication Projects in Teaching Research Methods

    Science.gov (United States)

    Standing, Lionel G.; Grenier, Manuel; Lane, Erica A.; Roberts, Meigan S.; Sykes, Sarah J.

    2014-01-01

    It is suggested that replication projects may be valuable in teaching research methods, and also address the current need in psychology for more independent verification of published studies. Their use in an undergraduate methods course is described, involving student teams who performed direct replications of four well-known experiments, yielding…

  8. How frog embryos replicate their DNA reliably

    Science.gov (United States)

    Bechhoefer, John; Marshall, Brandon

    2007-03-01

    Frog embryos contain three billion base pairs of DNA. In early embryos (cycles 2-12), DNA replication is extremely rapid, about 20 min., and the entire cell cycle lasts only 25 min., meaning that mitosis (cell division) takes place in about 5 min. In this stripped-down cell cycle, there are no efficient checkpoints to prevent the cell from dividing before its DNA has finished replication - a disastrous scenario. Even worse, the many origins of replication are laid down stochastically and are also initiated stochastically throughout the replication process. Despite the very tight time constraints and despite the randomness introduced by origin stochasticity, replication is extremely reliable, with cell division failing no more than once in 10,000 tries. We discuss a recent model of DNA replication that is drawn from condensed-matter theories of 1d nucleation and growth. Using our model, we discuss different strategies of replication: should one initiate all origins as early as possible, or is it better to hold back and initiate some later on? Using concepts from extreme-value statistics, we derive the distribution of replication times given a particular scenario for the initiation of origins. We show that the experimentally observed initiation strategy for frog embryos meets the reliability constraint and is close to the one that requires the fewest resources of a cell.

  9. Cronbach’ın Alfası, Tek Boyutluluğun veya Benzeşikliğin (Homojenliğin) Bir Ölçüsü Değildir

    OpenAIRE

    BADEMCİ, Vahit

    2014-01-01

    Güvenirlik, testler veya ölçme araçlarının değil, ölçümlerin bir özelliğidir. Cronbach’ın alfası katsayısı yöntemi, bir test ya da ölçme aracından elde edilen ölçümlerin güvenirliğini kestirme yöntemlerinden biridir. Başka bir ifadeyle, Cronbach’ın alfası, [madde] ölçümler[i] arasındaki iç tutarlılık üzerine temellenmiş bir ölçüm güvenirliğinin kestirilmesidir. Bunun yanı sıra, Cronbach’ın alfası katsayısı, ölçme aracının benzeşikliğinin (homojenliğinin) bir göstergesi olarak alınmamalı veya ...

  10. Separation of DNA replication from the assembly of break-competent meiotic chromosomes.

    Directory of Open Access Journals (Sweden)

    Hannah G Blitzblau

    Full Text Available The meiotic cell division reduces the chromosome number from diploid to haploid to form gametes for sexual reproduction. Although much progress has been made in understanding meiotic recombination and the two meiotic divisions, the processes leading up to recombination, including the prolonged pre-meiotic S phase (meiS and the assembly of meiotic chromosome axes, remain poorly defined. We have used genome-wide approaches in Saccharomyces cerevisiae to measure the kinetics of pre-meiotic DNA replication and to investigate the interdependencies between replication and axis formation. We found that replication initiation was delayed for a large number of origins in meiS compared to mitosis and that meiotic cells were far more sensitive to replication inhibition, most likely due to the starvation conditions required for meiotic induction. Moreover, replication initiation was delayed even in the absence of chromosome axes, indicating replication timing is independent of the process of axis assembly. Finally, we found that cells were able to install axis components and initiate recombination on unreplicated DNA. Thus, although pre-meiotic DNA replication and meiotic chromosome axis formation occur concurrently, they are not strictly coupled. The functional separation of these processes reveals a modular method of building meiotic chromosomes and predicts that any crosstalk between these modules must occur through superimposed regulatory mechanisms.

  11. Rescue from replication stress during mitosis.

    Science.gov (United States)

    Fragkos, Michalis; Naim, Valeria

    2017-04-03

    Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

  12. Recruitment of wild-type and recombinant adeno-associated virus into adenovirus replication centers.

    Science.gov (United States)

    Weitzman, M D; Fisher, K J; Wilson, J M

    1996-03-01

    Replication of a human parvovirus, adeno-associated virus (AAV), is facilitated by coinfection with adeno-virus to provide essential helper functions. We have used the techniques of in situ hybridization and immunocytochemistry to characterize the localization of AAV replication within infected cells, Previous studies have shown that adenovirus establishes foci called replication centers within the nucleus, where adenoviral replication and transcription occur. Our studies indicate that AAV is colocalized with the adenovirus replication centers, where it may utilize adenovirus and cellular proteins for its own replication. Expression of the AAV Rep protein inhibits the normal maturation of the adenovirus centers. Similar experiments were performed with recombinant AAV (rAAV) to establish a relationship between intranuclear localization and rAAV transduction. rAAV efficiently entered the cell, and its genome was faintly detectable in a perinuclear distribution and was mobilized to replication centers when the cell was infected with adenovirus. The recruitment of the replication-defective genome into the intranuclear adenovirus domains resulted in enhanced transduction. These studies illustrate the importance of intracellular compartmentalization for such complex interactions as the relationship between AAV and adenovirus.

  13. The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

    Science.gov (United States)

    O'Driscoll, Mark

    2017-01-01

    Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. DNA replication restart and cellular dynamics of Hef helicase/nuclease protein in Haloferax volcanii.

    Science.gov (United States)

    Lestini, Roxane; Delpech, Floriane; Myllykallio, Hannu

    2015-11-01

    Understanding how frequently spontaneous replication arrests occur and how archaea deal with these arrests are very interesting and challenging research topics. Here we will described how genetic and imaging studies have revealed the central role of the archaeal helicase/nuclease Hef belonging to the XPF/MUS81/FANCM family of endonucleases in repair of arrested replication forks. Special focus will be on description of a recently developed combination of genetic and imaging tools to study the dynamic localization of a functional Hef::GFP (Green Fluorescent Protein) fusion protein in the living cells of halophilic archaea Haloferax volcanii. As Archaea provide an excellent and unique model for understanding how DNA replication is regulated to allow replication of a circular DNA molecule either from single or multiple replication origins, we will also summarize recent studies that have revealed peculiar features regarding DNA replication, particularly in halophilic archaea. We strongly believe that fundamental knowledge of our on-going studies will shed light on the evolutionary history of the DNA replication machinery and will help to establish general rules concerning replication restart and the key role of recombination proteins not only in bacteria, yeast and higher eukaryotes but also in archaea.

  15. Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis.

    Science.gov (United States)

    Hua, Hui; Namdar, Mandana; Ganier, Olivier; Gregan, Juraj; Méchali, Marcel; Kearsey, Stephen E

    2013-03-01

    Meiosis involves two successive rounds of chromosome segregation without an intervening S phase. Exit from meiosis I is distinct from mitotic exit, in that replication origins are not licensed by Mcm2-7 chromatin binding, but spindle disassembly occurs during a transient interphase-like state before meiosis II. The absence of licensing is assumed to explain the block to DNA replication, but this has not been formally tested. Here we attempt to subvert this block by expressing the licensing control factors Cdc18 and Cdt1 during the interval between meiotic nuclear divisions. Surprisingly, this leads only to a partial round of DNA replication, even when these factors are overexpressed and effect clear Mcm2-7 chromatin binding. Combining Cdc18 and Cdt1 expression with modulation of cyclin-dependent kinase activity, activation of Dbf4-dependent kinase, or deletion of the Spd1 inhibitor of ribonucleotide reductase has little additional effect on the extent of DNA replication. Single-molecule analysis indicates this partial round of replication results from inefficient progression of replication forks, and thus both initiation and elongation replication steps may be inhibited in late meiosis. In addition, DNA replication or damage during the meiosis I-II interval fails to arrest meiotic progress, suggesting absence of checkpoint regulation of meiosis II entry.

  16. A Signature of Genomic Instability Resulting from Deficient Replication Licensing

    Science.gov (United States)

    Qin, Maochun; Wang, Jianmin; Kunnev, Dimiter; Freeland, Amy

    2017-01-01

    Insufficient licensing of DNA replication origins has been shown to result in genome instability, stem cell deficiency, and cancers. However, it is unclear whether the DNA damage resulting from deficient replication licensing occurs generally or if specific sites are preferentially affected. To map locations of ongoing DNA damage in vivo, the DNAs present in red blood cell micronuclei were sequenced. Many micronuclei are the product of DNA breaks that leave acentromeric remnants that failed to segregate during mitosis and should reflect the locations of breaks. To validate the approach we show that micronuclear sequences identify known common fragile sites under conditions that induce breaks at these locations (hydroxyurea). In MCM2 deficient mice a different set of preferred breakage sites is identified that includes the tumor suppressor gene Tcf3, which is known to contribute to T-lymphocytic leukemias that arise in these mice, and the 45S rRNA gene repeats. PMID:28045896

  17. Metabolic aspects of LPP cyanophage replication in the cyanobacterium Plectonema boryanum.

    Science.gov (United States)

    Ginzberg, D; Padan, E; Shilo, M

    1976-03-12

    Cyanophage LPP1G is reproduced at the same yield in heterotrophic conditions (dark, glucose) as in photoautotrophic conditions; aerobiosis is required for dark cyanophage replication. Exogenous glucose is not required for the cyanophage replication in the dark in heterotrophically grown cells. In photoautotrophically grown cells, the maximum burst size in dark and glucose is delayed for a period corresponding to glucose uptake induction. Cyanophage LPP2SPI replication occurs in conditions where only Photosystem I operates. Of photosynthesis parameters tested, only CO2 photoassimilation is affected during cyanophage LPP1G infection under photoautotrophic conditions.

  18. Mutual Interference between Genomic RNA Replication and Subgenomic mRNA Transcription in Brome Mosaic Virus

    OpenAIRE

    Grdzelishvili, Valery Z.; Garcia-Ruiz, Hernan; Watanabe, Tokiko; Ahlquist, Paul

    2005-01-01

    Replication by many positive-strand RNA viruses includes genomic RNA amplification and subgenomic mRNA (sgRNA) transcription. For brome mosaic virus (BMV), both processes occur in virus-induced, membrane-associated compartments, require BMV replication factors 1a and 2a, and use negative-strand RNA3 as a template for genomic RNA3 and sgRNA syntheses. To begin elucidating their relations, we examined the interaction of RNA3 replication and sgRNA transcription in Saccharomyces cerevisiae expres...

  19. Dynamics of small autocatalytic reaction network; 2, replication, mutation and catalysis

    CERN Document Server

    Stadler, P F; Först, C J; Schuster, P; Stadler, Peter F; Schnabl, Wolfgang; Forst, Christian V; Schuster, Peter; Biotechnology, Molecuar

    1994-01-01

    Mutation is introduced into autocatalytic reaction networks. Examples of low dimensional dynamical systems --- n = 2, 3 and 4 --- are discussed and complete qualitative analysis is presented. Error thresholds known from simple replication-mutation kinetics with frequency independent replication rates occur here as well. Instead of cooperative transitions or higher order phase transistions the thresholds appear here as supercritical or subcritical bifurcations being analogous to first order phase transitions.

  20. A New Replication Norm for Psychology

    Directory of Open Access Journals (Sweden)

    Etienne P LeBel

    2015-10-01

    Full Text Available In recent years, there has been a growing concern regarding the replicability of findings in psychology, including a mounting number of prominent findings that have failed to replicate via high-powered independent replication attempts. In the face of this replicability “crisis of confidence”, several initiatives have been implemented to increase the reliability of empirical findings. In the current article, I propose a new replication norm that aims to further boost the dependability of findings in psychology. Paralleling the extant social norm that researchers should peer review about three times as many articles that they themselves publish per year, the new replication norm states that researchers should aim to independently replicate important findings in their own research areas in proportion to the number of original studies they themselves publish per year (e.g., a 4:1 original-to-replication studies ratio. I argue this simple approach could significantly advance our science by increasing the reliability and cumulative nature of our empirical knowledge base, accelerating our theoretical understanding of psychological phenomena, instilling a focus on quality rather than quantity, and by facilitating our transformation toward a research culture where executing and reporting independent direct replications is viewed as an ordinary part of the research process. To help promote the new norm, I delineate (1 how each of the major constituencies of the research process (i.e., funders, journals, professional societies, departments, and individual researchers can incentivize replications and promote the new norm and (2 any obstacles each constituency faces in supporting the new norm.

  1. Sıcak Presleme Yöntemi Kullanılarak Kompozit Malzemelerin Üretilebilirliği Üzerine Bir Değerlendirme

    Directory of Open Access Journals (Sweden)

    Engin Nas, ,

    2013-12-01

    Full Text Available Araştırmacılar, endüstriyel malzemelerin dayanım özelliklerini, gün geçtikçe artan endüstriyel beklentileri karşılamak amacıyla, sürekli geliştirme çalışmalarına devam etmektedirler. Bu çalışmaların birçoğu; kompozit malzemelerin (KM geliştirilmesi üzerinedir. Bu malzemeler, günümüzde geleneksel malzemelerden ayrı düşünülemez bir malzeme grubunu oluşturmaktadır. Kompozit; metal, seramik, plastik ve refrakter gibi geleneksel malzeme gruplarına, çoğunlukla fiber, kılcal kristal, pulcuk, parçacık vd., formlarda takviye elemanı ilavesiyle elde edilen karma yapılı bir malzemedir. Kompozit malzemelerin genel üretim yöntemleri, ana fazın hal durumuna bağlı olarak sıvı, katı ve katı~sıvı hal olmak üzere üç ana grupta toplanır. Günümüzde, katı hal üretim tekniklerinden toz metalürjisi (TM kompozitlerin üretiminde yaygın kullanım alanına sahiptir. Bu çalışmada, toz metalürji üretim tekniğinde kullanılan sıcak presleme (SP yönteminin, kompozit malzemelerin üretilebilirliği üzerindeki etkileri değerlendirilmiştir.

  2. Data from Investigating Variation in Replicability: A “Many Labs” Replication Project

    Directory of Open Access Journals (Sweden)

    Richard A. Klein

    2014-04-01

    Full Text Available This dataset is from the Many Labs Replication Project in which 13 effects were replicated across 36 samples and over 6,000 participants. Data from the replications are included, along with demographic variables about the participants and contextual information about the environment in which the replication was conducted. Data were collected in-lab and online through a standardized procedure administered via an online link. The dataset is stored on the Open Science Framework website. These data could be used to further investigate the results of the included 13 effects or to study replication and generalizability more broadly.

  3. Örgütsel Çekicilik : Bir Ölçek Uyarlama Çalışması

    Directory of Open Access Journals (Sweden)

    Seda DURAL

    2014-12-01

    Full Text Available Bu çalışmanın amacı, Highhouse vd. (2003 tarafından geliştirilen Örgütsel Çekicilik Ölçeğini (ÖÇÖ Türkçe’ye kazandırmak ve geçerlik ve güvenirlik analizlerini yapmaktır. Ölçek, öncelikle araştırmacılar ve bir dil uzmanı tarafından Türkçe’ye çevrilmiş, ardından ifadeler iki dilli 15 uzmanın görüşüne başvurularak dil ve anlam uygunluğu bakımından değerlendirilmiştir. Öneriler doğrultusunda son şeklini alan Türkçe form iki aşamada uygulanmıştır. İlk aşamada, test-tekrar test güvenirliğini sınamak amacıyla ölçek iki hafta ara ile 50 öğrenciye uygulanmıştır. Test tekrar-test güvenirlik katsayısı birincil değerlendirme için 0,85, ikincil değerlendirme için 0,89 olarak bulunmuştur. Uygulamanın ikinci aşamasında anket 257 öğrenciye uygulanarak ölçeğin iç tutarlılık katsayısı 0,89 olarak bulunmuştur. Yapılan analizler sonucunda ÖÇÖ’nün özgün ölçekte olduğu gibi üç faktörlü bir yapı gösterdiği belirlenmiştir. Hiçbir madde atılmadan 15 madde ile üç boyutu ölçen geçerli ve güvenilir bir ölçek elde edilmiştir.

  4. Mahalli Fıkra Tipine Bir Örnek: Erzurumlu Naim Hoca One Type of Anecdote of Local Example: Hoca Erzurumlu Naim

    Directory of Open Access Journals (Sweden)

    Yusuf KOTAN

    2012-09-01

    Full Text Available One of the important types of folk literature satire, in a large geographical area consisting of many thousands of years, products of oral tradition of folk literaturen. These products, although oral edebiyatımız as a kind of took its place in the literature long ago, particularly after the Tanzimat era has gained vitality. This vitality,though no doubt in some quarters that the jokes have suffered tab, inalmost every nation acquires an important social and cultural life.Feeling and thinking, of a nation, intelligence, humor, and mostimportantly the power of judgment to reflect the common opinion is ofgreat importance in terms of paragraphs. One of the important elementsin the formation of these clauses in the clause types. These types, asdescribed in the paragraph is the hero, as well as to express thecommon characteristics of living is important for society. These typeswith almost every region of Anatolia, and they faced a yararlanmaktayızthis narrative. Who live in this very important region in terms ofreflecting the properties of typecasting, giving expressions to represent aparticular feature of the local stage.Erzurum folklore, is a rich resource for Turkish folklore. Althoughthis has been a rich source folklorumuzun on the part of many researchstudies conducted on jokes is almost negligible. Based on theseapproaches, we also provide a contribution to the folklore of Erzurum inboth types of clause in Erzurum, an important place in the memory ofour people who had said Naim Hodja jokes we introduce this valuableanecdotes of people will try to share with you. Halk edebiyatımızın önemli türlerinden biri olan fıkralar, çok geniş bir coğrafi alan içinde oluşan binlerce yıldan beri sözlü gelenekte yaşayan halk edebiyatı ürünleridir. Bu ürünler, sözlü edebiyatımız içerisinde yerini çok öncelerden almış olsa da bir tür olarak edebiyatımızda bilhassa Tanzimat döneminden sonra canlılık kazanmıştır. Bu canl

  5. ‘Play Time’ Filmi ve Modern Mimarlık Kuramlarına İlişkin Eleştirel Bir Deneme

    Directory of Open Access Journals (Sweden)

    Mehmet Şener

    2016-01-01

    Full Text Available ÖzJacques Tati sineması, gerek dünya sinema tarihinde, gerek de mimarlık (tarihi sinema ilişkisi bağlamında çok önemli bir yere sahiptir. Tati’nin 1967 yılında çektiği ‘Play Time’ filmi de, mimari ve kentsel unsurlar üzerine şekillenir ve dönemine bu çerçevelerden ışık tutan bir filmdir. Bu makalede, Tati’nin ‘Play Time’ filmi üzerinden yapılacak mekânsal analizler doğrultusunda modern mimarlık ve şehircilik kuramları üzerine eleştirel bir bakış getirilmesi amaçlanmaktadır. Bu çerçevede, ilk bölümde Jacques Tati filmlerinin sinema dünyası ve tarihindeki yeri ile ‘Play Time’ filminin sinematografik yapısı incelenecektir. Bundan sonraki kısımlarda filme dair mekansal analiz ve bulgular üzerine değerlendirmeler yapılacak olup; öncelikle modern mimarinin başat unsurlarından olan “prizmatik” kamusal yapılar ve “kutu mekanlar”, sonrasında da filmde yer alan sergi mekânı, mobilya tasarımı bağlamında yabancılaşma metaforu üzerinden ele alınacaktır. Bunu müteakip, filmdeki sembolik mimari ifade araçlarından biri olan “cam”, modern yaşamda ifade ettiği anlam çerçevesinde; konut yaşantısının resmedildiği sahneler de, modern yaşamın konut ve yapı mahremiyetine etkileri üzerinden analiz edilecektir. Son kısımda da, restoran sahnelerinin incelenmesi üzerinden modern tasarım anlayışına dair eleştirel bir inceleme yapılacak ve sonuç kısmıyla makale tamamlanacaktır.     

  6. Eğitimde Özelleştirme Tartışmaları: Kavramsal Bir Analiz Disscussions on Privatization in Education: A conceptual Analysis

    Directory of Open Access Journals (Sweden)

    Ramazan YİRCİ

    2013-09-01

    politika alanında önemli düşünce değişimlerin meydana geldiği bir dönem olmuştur. Bu değişimler toplumun hayatında önemli bir yere sahip olan eğitim sisteminde de değişik uygulamaların uygulanıp uygulanamayacağı sorusunu gündeme getirmiştir. Bu çalışma ile ekonomi alanında pek çok ülkede yaygın bir şekilde kullanılan özelleştirme kavramını ele almak, eğitimde özelleştirme ve finansman ilişkisini incelemek, eğitimde özelleştirmenin dünyadaki örneklerine göz atmak amaçlanmıştır. Eğitim insana yatırım yapan ve çıktısı yine insan olan önemli bir hizmet koludur. Devletin iyi eğitimli bireyler yetiştirmesi toplumun kalkınmasını sağlayacaktır. Bireylerin iyi yetiştirilmesi işi eğitim sistemi içinde faaliyet gösteren okulların etkili performanslarına bağlıdır. Bu çalışmada eğitimde özelleştirme uygulamalarının değişik ülkelerde gerçekleşme biçimine, eğitimin finansmanında devletin ve özel sektörün konumuna, eğitimde özelleştirmeyi destekleyenlerin ve karşı çıkanların görüşlerine yer verilmiştir. Eğitim gibi önemli bir konuda özel sektörün etkinliğini artırması devletin yükünü hafifletebilir. Burada dikkat edilecek husus özel kesimin daha fazla eğitim alanında faaliyet göstermesini sağlarken, eğitim kalitesinden ödün vermeden, toplumdaki sosyal adalet duygusunu incitmeden adımlar atabilmektir. Dünyadaki en iyi yüz üniversite sıralamasında özelleştirme uygulamalarının büyük ölçüde uygulandığı Amerika, İngiltere, Japonya gibi ülkelerden pek çok üniversitenin bulunması dikkat çekici bir durumdur. Aynı listeye Türkiye’den hiçbir üniversitenin girememiş olması da eğitim sisteminin yapısında yeniden yapılanmanın ne kadar büyük bir ihtiyaç olduğunu göstermektedir. Bu bağlamda özelleştirme eğitimde ülkemiz okullarının yaşadığı nitelik sorununa alternatif bir çözüm yolu geliştirmeye yardımcı olabilir.

  7. The Problem of Anonymity in Archives: A Literature Review=Arşivlerde Anonimlik Sorunu: Bir Literatür Değerlendirmesi

    Directory of Open Access Journals (Sweden)

    Emily Ross

    2013-12-01

    Full Text Available Archivists processing documents rely on factors such as authorship and provenance to contextualize their materials and render them searchable. But in my past experience as an archives user, I repeatedly came across instances of anonymity: letters and diaries by unnamed authors or to unknown recipients, photographs of unknown subjects. In some cases this anonymity is a loss of information that was once there, but in other case it enabled the material to come into existence in the first place: such as in the case of satirical political poetry, for which a writer might face legal censure. In this literature review, the issue of anonymity in the archives is explored, both in a pragmatic sense (recommended strategies for managing it, and a philosophical sense (according anonymous documents the same status as documents with known authors./Arşivcilikte belgelerin işlenmesi, materyallerin kavramsallaştırılması ve aranabilir hale gelmesinde önemli olan yazarlık ve kaynak (menşe gibi faktörlere dayanmaktadır. Ancak bir arşiv kullanıcısı olarak deneyimlerimizde defalarca isimsiz yazarlar tarafından bilinmeyen kişilere atfedilmiş mektuplar ve günlükler, bilinmeyen konuların fotoğrafları gibi anonim eserlerle karşılaşmaktayız. Bir zamanlar bu anonimlik bazen bir bilgi kaybı olarak görülürken bazen de belgenin yazarının yasal kınamaya maruz kalabildiği hicivli siyasi bir şiir örneğinde olduğu gibi eserin ilk etapta ortaya çıkmasını sağlamaktaydı. Bu literatür taramasında arşivlerde anonimlik sorunu hem pragmatik anlamda (konunun yönetimi için önerilen stratejiler hem de felsefi anlamda (anonim belgelere uygun olarak bilinen yazarlı belgelerle aynı statüde ele alınmaktadır.

  8. Replication forks reverse at high frequency upon replication stress in Physarum polycephalum.

    Science.gov (United States)

    Maric, Chrystelle; Bénard, Marianne

    2014-12-01

    The addition of hydroxyurea after the onset of S phase allows replication to start and permits the successive detecting of replication-dependent joint DNA molecules and chicken foot structures in the synchronous nuclei of Physarum polycephalum. We find evidence for a very high frequency of reversed replication forks upon replication stress. The formation of these reversed forks is dependent on the presence of joint DNA molecules, the impediment of the replication fork progression by hydroxyurea, and likely on the propensity of some replication origins to reinitiate replication to counteract the action of this compound. As hydroxyurea treatment enables us to successively detect the appearance of joint DNA molecules and then of reversed replication forks, we propose that chicken foot structures are formed both from the regression of hydroxyurea-frozen joint DNA molecules and from hydroxyurea-stalled replication forks. These experiments underscore the transient nature of replication fork regression, which becomes detectable due to the hydroxyurea-induced slowing down of replication fork progression.

  9. A quantitative model of DNA replication in Xenopus embryos: reliable replication despite stochasticity

    Science.gov (United States)

    Cheng-Hsin Yang, Scott; Bechhoefer, John

    2008-03-01

    DNA synthesis in Xenopus frog embryos initiates stochastically in time at many sites (origins) along the chromosome. Stochastic initiation implies fluctuations in the replication time and may lead to cell death if replication takes longer than the cell cycle time (˜ 25 min.). Surprisingly, although the typical replication time is about 20 min., in vivo experiments show that replication fails to complete only about 1 in 250 times. How is replication timing accurately controlled despite the stochasticity? Biologists have proposed two mechanisms: the first uses a regular spatial distribution of origins, while the second uses randomly located origins but increases their probability of initiation as the cell cycle proceeds. Here, we show that both mechanisms yield similar end-time distributions, implying that regular origin spacing is not needed for control of replication time. Moreover, we show that the experimentally inferred time-dependent initiation rate satisfies the observed low failure probability and nearly optimizes the use of replicative proteins.

  10. Geniş Bir Skalp Defektinin Onarımında Doku Genişleticilerin İntraoperatif Mükerrer Kullanımı Olgu Sunumu

    OpenAIRE

    Demir, Canser Y.; Gürlek, Ali; Çoban, Y.Kenan; Alaybeyoğlu, Nezih; Aydoğan, Hakan; Ersöz, Ayşe

    2003-01-01

    Doku genişletme uygulamaları günümüzde skalp rekonstrüksiyonunda sık tercih edilen bir yöntemdir. Bu teknik 1950 li yılların sonlarında Argenta ve Manders tarafından skalp defektlerinin onarımı için kullanılmıştır. Geniş saçlı deri defektlerinin, normal saçla kapanmasına olanak sağladığı ve vücudun başka bir yerinde donör alan morbiditesi oluşturmadığı için son derecede önemli ve efektif bir tedavi yöntemidir. Bu makalede, patoz yaralanmasına bağlı çok geniş skalp defektinin d...

  11. Targeting DNA Replication Stress for Cancer Therapy

    Science.gov (United States)

    Zhang, Jun; Dai, Qun; Park, Dongkyoo; Deng, Xingming

    2016-01-01

    The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR) mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress. PMID:27548226

  12. Oncogene v-jun modulates DNA replication.

    Science.gov (United States)

    Wasylyk, C; Schneikert, J; Wasylyk, B

    1990-07-01

    Cell transformation leads to alterations in both transcription and DNA replication. Activation of transcription by the expression of a number of transforming oncogenes is mediated by the transcription factor AP1 (Herrlich & Ponta, 1989; Imler & Wasylyk, 1989). AP1 is a composite transcription factor, consisting of members of the jun and fos gene-families. c-jun and c-fos are progenitors of oncogenes, suggestion that an important transcriptional event in cell transformation is altered activity of AP1, which may arise either indirectly by oncogene expression or directly by structural modification of AP1. We report here that the v-jun oncogene and its progenitor c-jun, as fusion proteins with the lex-A-repressor DNA binding domain, can activate DNA replication from the Polyoma virus (Py) origin of replication, linked to the lex-A operator. The transcription-activation region of v-jun is required for activation of replication. When excess v-jun is expressed in the cell, replication is inhibited or 'squelched'. These results suggest that one consequence of deregulated jun activity could be altered DNA replication and that there are similarities in the way v-jun activates replication and transcription.

  13. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  14. A whole genome RNAi screen identifies replication stress response genes.

    Science.gov (United States)

    Kavanaugh, Gina; Ye, Fei; Mohni, Kareem N; Luzwick, Jessica W; Glick, Gloria; Cortez, David

    2015-11-01

    Proper DNA replication is critical to maintain genome stability. When the DNA replication machinery encounters obstacles to replication, replication forks stall and the replication stress response is activated. This response includes activation of cell cycle checkpoints, stabilization of the replication fork, and DNA damage repair and tolerance mechanisms. Defects in the replication stress response can result in alterations to the DNA sequence causing changes in protein function and expression, ultimately leading to disease states such as cancer. To identify additional genes that control the replication stress response, we performed a three-parameter, high content, whole genome siRNA screen measuring DNA replication before and after a challenge with replication stress as well as a marker of checkpoint kinase signalling. We identified over 200 replication stress response genes and subsequently analyzed how they influence cellular viability in response to replication stress. These data will serve as a useful resource for understanding the replication stress response.

  15. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Direct replication of creatural scarfskins to form biomimetic surfaces with relatively vivid morphology is a new attempt of the bio-replicated forming technology at animal body. Taking shark skins as the replication templates, and the micro-embossing and micro-molding as the material forming methods, the micro-replicating technology of the outward morphology on shark skins was demonstrated. The preliminary analysis on replication precision indicates that the bio-replicated forming technology can replicate the outward morphology of the shark scales with good precision, which validates the application of the bio-replicated forming technology in the direct morphology replication of the firm creatural scarfskins.

  16. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  17. Replicated Data Management for Mobile Computing

    CERN Document Server

    Douglas, Terry

    2008-01-01

    Managing data in a mobile computing environment invariably involves caching or replication. In many cases, a mobile device has access only to data that is stored locally, and much of that data arrives via replication from other devices, PCs, and services. Given portable devices with limited resources, weak or intermittent connectivity, and security vulnerabilities, data replication serves to increase availability, reduce communication costs, foster sharing, and enhance survivability of critical information. Mobile systems have employed a variety of distributed architectures from client-server

  18. Excess Cdt1 inhibits nascent strand elongation by repressing the progression of replication forks in Xenopus egg extracts.

    Science.gov (United States)

    Nakazaki, Yuta; Tsuyama, Takashi; Seki, Masayuki; Takahashi, Mikiko; Enomoto, Takemi; Tada, Shusuke

    2016-02-01

    Cdt1 is a protein essential for initiation of DNA replication; it recruits MCM helicase, a core component of the replicative DNA helicase, onto replication origins. In our previous study, we showed that addition of excess Cdt1 inhibits nascent strand elongation during DNA replication in Xenopus egg extracts. In the present study, we investigated the mechanism behind the inhibitory effect of Cdt1. We found that addition of recombinant Cdt1 inhibited nascent DNA synthesis in a reinitiation-independent manner. To identify the mechanism by which Cdt1 inhibits nascent strand elongation, the effect of Cdt1 on loading of Mcm4 and Rpa70 onto chromatin was examined. The results showed that Cdt1 suppressed the excessive Rpa70 binding caused by extensive, aphidicolin-induced DNA unwinding; this unwinding occurs between stalled DNA polymerases and advancing replication forks. These findings suggested that excess Cdt1 suppressed the progression of replication forks.

  19. A transcription and translation-coupled DNA replication system using rolling-circle replication.

    Science.gov (United States)

    Sakatani, Yoshihiro; Ichihashi, Norikazu; Kazuta, Yasuaki; Yomo, Tetsuya

    2015-05-27

    All living organisms have a genome replication system in which genomic DNA is replicated by a DNA polymerase translated from mRNA transcribed from the genome. The artificial reconstitution of this genome replication system is a great challenge in in vitro synthetic biology. In this study, we attempted to construct a transcription- and translation-coupled DNA replication (TTcDR) system using circular genomic DNA encoding phi29 DNA polymerase and a reconstituted transcription and translation system. In this system, phi29 DNA polymerase was translated from the genome and replicated the genome in a rolling-circle manner. When using a traditional translation system composition, almost no DNA replication was observed, because the tRNA and nucleoside triphosphates included in the translation system significantly inhibited DNA replication. To minimize these inhibitory effects, we optimized the composition of the TTcDR system and improved replication by approximately 100-fold. Using our system, genomic DNA was replicated up to 10 times in 12 hours at 30 °C. This system provides a step toward the in vitro construction of an artificial genome replication system, which is a prerequisite for the construction of an artificial cell.

  20. Using autonomous replication to physically and genetically define human origins of replication

    Energy Technology Data Exchange (ETDEWEB)

    Krysan, P.J.

    1993-01-01

    The author previously developed a system for studying autonomous replication in human cells involving the use of sequences from the Epstein-Barr virus (EBV) genome to provide extrachromosomal plasmids with a nuclear retention function. Using this system, it was demonstrated that large fragments of human genomic DNA could be isolated which replicate autonomously in human cells. In this study the DNA sequences which function as origins of replication in human cells are defined physically and genetically. These experiments demonstrated that replication initiates at multiple locations distributed throughout the plasmid. Another line of experiments addressed the DNA sequence requirements for autonomous replication in human cells. These experiments demonstrated that human DNA fragments have a higher replication activity than bacterial fragments do. It was also found, however, that the bacterial DNA sequence could support efficient replication if enough copies of it were present on the plasmid. These findings suggested that autonomous replication in human cells does not depend on extensive, specific DNA sequences. The autonomous replication system which the author has employed for these experiments utilizes a cis-acting sequence from the EBV origin and the trans-acting EBNA-1 protein to provide plasmids with a nuclear retention function. It was therefore relevant to verify that the autonomous replication of human DNA fragments did not depend on the replication activity associated with the EBV sequences utilized for nuclear retention. To accomplish this goal, the author demonstrated that plasmids carrying the EBV sequences and large fragments of human DNA could support long-term autonomous replication in hamster cells, which are not permissive for EBV replication.

  1. Replicating chromatin: a tale of histones

    DEFF Research Database (Denmark)

    Groth, Anja

    2009-01-01

    Chromatin serves structural and functional roles crucial for genome stability and correct gene expression. This organization must be reproduced on daughter strands during replication to maintain proper overlay of epigenetic fabric onto genetic sequence. Nucleosomes constitute the structural...

  2. Control of chromosome replication in caulobacter crescentus.

    Science.gov (United States)

    Marczynski, Gregory T; Shapiro, Lucy

    2002-01-01

    Caulobacter crescentus permits detailed analysis of chromosome replication control during a developmental cell cycle. Its chromosome replication origin (Cori) may be prototypical of the large and diverse class of alpha-proteobacteria. Cori has features that both affiliate and distinguish it from the Escherichia coli chromosome replication origin. For example, requirements for DnaA protein and RNA transcription affiliate both origins. However, Cori is distinguished by several features, and especially by five binding sites for the CtrA response regulator protein. To selectively repress and limit chromosome replication, CtrA receives both protein degradation and protein phosphorylation signals. The signal mediators, proteases, response regulators, and kinases, as well as Cori DNA and the replisome, all show distinct patterns of temporal and spatial organization during cell cycle progression. Future studies should integrate our knowledge of biochemical activities at Cori with our emerging understanding of cytological dynamics in C. crescentus and other bacteria.

  3. LHCb Data Replication During SC3

    CERN Multimedia

    Smith, A

    2006-01-01

    LHCb's participation in LCG's Service Challenge 3 involves testing the bulk data transfer infrastructure developed to allow high bandwidth distribution of data across the grid in accordance with the computing model. To enable reliable bulk replication of data, LHCb's DIRAC system has been integrated with gLite's File Transfer Service middleware component to make use of dedicated network links between LHCb computing centres. DIRAC's Data Management tools previously allowed the replication, registration and deletion of files on the grid. For SC3 supplementary functionality has been added to allow bulk replication of data (using FTS) and efficient mass registration to the LFC replica catalog.Provisional performance results have shown that the system developed can meet the expected data replication rate required by the computing model in 2007. This paper details the experience and results of integration and utilisation of DIRAC with the SC3 transfer machinery.

  4. Initiation of Replication in Escherichia coli

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob

    The circular chromosome of Escherichia coli is replicated by two replisomes assembled at the unique origin and moving in the opposite direction until they meet in the less well defined terminus. The key protein in initiation of replication, DnaA, facilitates the unwinding of double-stranded DNA...... to single-stranded DNA in oriC. Although DnaA is able to bind both ADP and ATP, DnaA is only active in initiation when bound to ATP. Although initiation of replication, and the regulation of this, is thoroughly investigated it is still not fully understood. The overall aim of the thesis was to investigate...... the regulation of initiation, the effect on the cell when regulation fails, and if regulation was interlinked to chromosomal organization. This thesis uncovers that there exists a subtle balance between chromosome replication and reactive oxygen species (ROS) inflicted DNA damage. Thus, failure in regulation...

  5. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf; Hansen, Hans Nørgaard; Kjær, Erik Michael

    2005-01-01

    carried out with rough EDM (electrical discharge machining) mould surfaces, a PS grade, and by applying established three-dimensional topography parameters. Significant quantitative relationships between process parameters and topography parameters were established. It further appeared that replication...

  6. Allergies and Asthma: They Often Occur Together

    Science.gov (United States)

    ... you miserable. A lot, as it turns out. Allergies and asthma often occur together. The same substances that trigger your hay fever symptoms, such as pollen, dust mites and pet dander, may also cause asthma signs ...

  7. Multiple Primary Cancers: Simultaneously Occurring Prostate ...

    African Journals Online (AJOL)

    2016-05-20

    May 20, 2016 ... occurring prostate cancer and other primary tumors-our experience and literature ... carcinoma, primary liver cell carcinoma, and thyroid follicular carcinoma in both ..... malignancies in women with papillary thyroid cancer.

  8. ST elevation occurring during stress testing

    Directory of Open Access Journals (Sweden)

    Diana Malouf

    2016-04-01

    Full Text Available A case is presented of significant reversible ST elevation occurring during treadmill testing, and the coronary anatomy and subsequent course are described, indicating that ischemia is a potential cause of this electrocardiographic finding.

  9. Dengue virus replicates and accumulates in Aedes aegypti salivary glands.

    Science.gov (United States)

    Raquin, Vincent; Lambrechts, Louis

    2017-07-01

    Dengue virus (DENV) is an RNA virus transmitted among humans by mosquito vectors, mainly Aedes aegypti. DENV transmission requires viral dissemination from the mosquito midgut to the salivary glands. During this process the virus undergoes several population bottlenecks, which are stochastic reductions in population size that restrict intra-host viral genetic diversity and limit the efficiency of natural selection. Despite the implications for virus transmission and evolution, DENV replication in salivary glands has not been directly demonstrated. Here, we used a strand-specific quantitative RT-PCR assay to demonstrate that negative-strand DENV RNA is produced in Ae. aegypti salivary glands, providing conclusive evidence that viral replication occurs in this tissue. Furthermore, we showed that the concentration of DENV genomic RNA in salivary glands increases significantly over time, indicating that active replication likely replenishes DENV genetic diversity prior to transmission. These findings improve our understanding of the biological determinants of DENV fitness and evolution. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effect of CD4 gene expression on adenovirus replication.

    Science.gov (United States)

    Hotta, J; Shi, L; Ginsberg, H S

    1994-11-01

    The gene encoding the CD4 receptor was introduced into KB cells to establish the KBT4 cell line, a cell line susceptible to infection with human immunodeficiency virus type 1. Adenovirus replication was found to be significantly less in these cells than in the parental KB cells. Similar decreased adenovirus type 5 (Ad5) replication occurred in HeLaT4 cells compared with the original HeLa cells. The presence of CD4 did not alter the cell surface population of KB cell adenovirus receptors, since viral adsorption was similar in the two cell lines. Moreover, addition of soluble CD4 did not reduce viral replication in either KB or KBT4 infected cells. Uncoating of viral DNA was also unchanged in KBT4 cells compared with the parental KB cells. In contrast, migration to or entrance of viral DNA into nuclei and synthesis of early viral RNAs was delayed and reduced in KBT4 cells. These effects were more pronounced for Ad7 than for Ad5. The yields of infectious viruses were the same in both cell lines, however, after transfection of naked viral DNAs to initiate infection. These results imply that the expression of the CD4 gene in KBT4 cells interfered with passage of uncoated virus across endosomal vesicles and/or transfer of uncoated core viral DNA into the nucleus.

  11. Hepatitis B virus: pathogenesis, viral intermediates, and viral replication.

    Science.gov (United States)

    Lee, Jia-Yee; Locarnini, Stephen

    2004-05-01

    Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of genotype-phenotype relationships should help in the development of improved antiviral strategies and management approaches. Although the probability of developing viral resistance is directly proportional to the intensity of selection pressure and the diversity of quasispecies, potent inhibition of HBV replication should be able to prevent development of drug resistance because mutagenesis is replication dependent. If viral replication can be suppressed for a sufficient length of time, viral load should decline to a point where the continued production of quasispecies with the potential to resist new drug treatments no longer occurs. Clinical application of this concept will require optimization of combination therapies analogous to highly active antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will require elimination of the intranuclear pool of viral minichromosomes, which will probably only be achieved by normal cell turnover, reactivation of host immunity, or elucidation of the antiviral mechanisms operating during cytokine clearance in acute hepatitis B (see Fig. 1).

  12. Species radiation by DNA replication that systematically exchanges nucleotides?

    Science.gov (United States)

    Seligmann, Hervé

    2014-12-21

    RNA and DNA syntheses share many properties. Therefore, the existence of 'swinger' RNAs, presumed 'orphan' transcripts matching genomic sequences only if transcription systematically exchanged nucleotides, suggests replication producing swinger DNA. Transcripts occur in many short-lived copies, the few cellular DNA molecules are long-lived. Hence pressures for functional swinger DNAs are greater than for swinger RNAs. Protein coding properties of swinger sequences differ from original sequences, suggesting rarity of corresponding swinger DNA. For genes producing structural RNAs, such as tRNAs and rRNAs, three exchanges (AT, CG and AT+CG) conserve self-hybridization properties. All nuclear eukaryote swinger DNA sequences detected in GenBank are for rRNA genes assuming AT+CG exchanges. In brachyuran crabs, 25 species had AT+CG swinger 18S rDNA, all matching the reverse-exchanged version of regular 18S rDNA of a related species. In this taxon, swinger replication of 18S rDNA apparently associated with, or even resulted in species radiation. AT+CG transformation doesn't invert sequence direction, differing from inverted repeats. Swinger repeats (detectable only assuming swinger transformations, AT+CG swinger repeats most frequent) within regular human rRNAs, independently confirm swinger polymerizations for most swinger types. Swinger replication might be an unsuspected molecular mechanism for ultrafast speciation.

  13. Dynamics of Nucleosome Positioning Maturation following Genomic Replication

    Directory of Open Access Journals (Sweden)

    Pauline Vasseur

    2016-09-01

    Full Text Available Chromatin is thought to carry epigenetic information from one generation to the next, although it is unclear how such information survives the disruptions of nucleosomal architecture occurring during genomic replication. Here, we measure a key aspect of chromatin structure dynamics during replication—how rapidly nucleosome positions are established on the newly replicated daughter genomes. By isolating newly synthesized DNA marked with 5-ethynyl-2′-deoxyuridine (EdU, we characterize nucleosome positions on both daughter genomes of S. cerevisiae during chromatin maturation. We find that nucleosomes rapidly adopt their mid-log positions at highly transcribed genes, which is consistent with a role for transcription in positioning nucleosomes in vivo. Additionally, experiments in hir1Δ mutants reveal a role for HIR in nucleosome spacing. We also characterized nucleosome positions on the leading and lagging strands, uncovering differences in chromatin maturation dynamics at hundreds of genes. Our data define the maturation dynamics of newly replicated chromatin and support a role for transcription in sculpting the chromatin template.

  14. MÜSLÜMAN TÜRK KÜLTÜRÜNDE İNANÇ GELİŞİMİ (Bir Model Denemesi)

    OpenAIRE

    Yapıcı, Asım

    2016-01-01

    Bu makaleMüslüman-Türk toplumunda inanç gelişiminin nasıl gerçekleştiğini araştırmakistemektedir. Çünkü insanı sadece Batılı paradigma, kuram ve modellerleanlamaya çalışmak Doğulu bilinci ve Doğu insanının öznelliğini yok saymaanlamına gelmektedir. Bu durum, gerek Müslüman gerekse Hıristiyan bir çevrededoğup büyüyen bir kişinin inanç gelişiminin aynı ya da benzer süreçlerdengeçerek şekillendiği iddiasına dayanmaktadır. Kuşkusuz Doğulu ve Batılıbireylerin dini gelişim süreçlerinde bazı hususla...

  15. Bir Tutundurma Aracı Olarak Sosyal Medyanın Marka Bağlılığına Etkileri

    OpenAIRE

    Yüksel KÖKSAL

    2012-01-01

    Tutundurma kanallarının artması işletmeler açısından rekabeti daha geniş alanlara yaymaktadır. İşletmecilikte geleneksel yaklaşımlarla devam ederek, yükselen trendleri yakalayamama ve o alanda geri kalma rekabet koşulları açısından önemli bir kayıptır. Günümüzün yeni trendlerinden olan sosyal medyanın, pazarlamadaki rolü ve önemi işletmeler için bir merak konusudur. Bu çalışmada sosyal medyanın marka bağlılığı üzerindeki etkileri araştırılmıştır. Araştırma; ülkemizin saygın markaların...

  16. Disiplinler Arası Bir Disiplin Olarak Türkçe Eğitimi Turkish Education as an Interdisciplinary Discipline

    Directory of Open Access Journals (Sweden)

    Namık Kemal ŞAHBAZ

    2012-09-01

    , grammarteaching, first reading and writing teaching, children’s literature,training Turkish teachers and historical development of Turkisheducation. Disiplinler arasılık, günümüz sosyal bilimleri için bir gerekliliktir. Çoğu kez, herhangi bir soruna bir tek disiplinin çerçevesinden bakmak yetersiz olabilir. Disiplinler arası araştırmalar, bilgiye farklı bakış açıları sunar. Bu çalışmada görece yeni bir bilimsel disiplin olan Türkçe eğitiminin disiplinler arası niteliği gerek kuramsal gerek de uygulama boyutuyla betimlenmeye çalışılmıştır. Bu amaçla öncelikle Türkçe eğitiminin araştırma alanları (Okuma eğitimi, konuşma eğitimi, yazma eğitimi, dinleme eğitimi, dil bilgisi öğretimi, ilk okuma ve yazma öğretimi, çocuk edebiyatı, Türkçe öğretmeni yetiştirme, Türkçe eğitimi tarihi açıklanmış, daha sonra Türkçe eğitiminin disiplinler arası araştırmalara neden gereksinim duyduğu tartışılmıştır. Çalışmada, araştırılması amaçlanan olgu ve olgular hakkında bilgi içeren yazılı materyallerin analizini kapsayan doküman inceleme yöntemi kullanılmıştır. Türkçe eğitimi ile eğitim bilimleri, dilbilim, yazınbilim, sosyoloji, psikoloji, tarih ve tıp disiplinleri arasındaki disiplinler arası ilişkiler irdelenmiştir. Bilimsel bir disiplin olarak ele alınmasa da kişisel gelişim konularıyla (ikna, etkili iletişim, yapay zekâ, duygusal zekâ, NLP Türkçe eğitimi arasındaki etkileşim, bu çalışmada açıklanmaya çalışılmıştır. Bu çalışma, Türkçe eğitimi alanında yapılacak yeni araştırmalara farklı bir boyut ve bir bakış açısı kazandıracak olması nedeniyle önemlidir. Araştırmanın sonuçları itibariyle hâlihazırda Türkçe eğitimine yönelik disiplinler arası çalışmalar yapılmaktadır. Ancak okuma eğitimi, konuşma eğitimi, yazma eğitimi, dinleme eğitimi, dil bilgisi öğretimi, ilkokuma ve yazma öğretimi, çocuk edebiyatı, Türkçe

  17. Replicating vesicles as models of primitive cell growth and division.

    Science.gov (United States)

    Hanczyc, Martin M; Szostak, Jack W

    2004-12-01

    Primitive cells, lacking the complex bio-machinery present in modern cells, would have had to rely on the self-organizing properties of their components and on interactions with their environment to achieve basic cellular functions such as growth and division. Many bilayer-membrane vesicles, depending on their composition and environment, can exhibit complex morphological changes such as growth, fusion, fission, budding, internal vesicle assembly and vesicle-surface interactions. The rich dynamic properties of these vesicles provide interesting models of how primitive cellular replication might have occurred in response to purely physical and chemical forces.

  18. Trichotillomania and Co-occurring Anxiety

    Science.gov (United States)

    Grant, Jon E.; Redden, Sarah A.; Leppink, Eric W.; Chamberlain, Samuel R.

    2017-01-01

    Background Trichotillomania appears to be a fairly common disorder, with high rates of co-occurring anxiety disorders. Many individuals with trichotillomania also report that pulling worsens during periods of increased anxiety. Even with these clinical links to anxiety, little research has explored whether trichotillomania with co-occurring anxiety is a meaningful subtype. Methods 165 adults with trichotillomania were examined on a variety of clinical measures including symptom severity, functioning, and comorbidity. Participants also underwent cognitive testing assessing motor inhibition and cognitive flexibility. Clinical features and cognitive functioning were compared between those with current co-occurring anxiety disorders (i.e. social anxiety, generalized anxiety disorder, panic disorder, and anxiety disorder NOS) (n=38) and those with no anxiety disorder (n=127). Results Participants with trichotillomania and co-occurring anxiety reported significantly worse hair pulling symptoms, were more likely to have co-occurring depression, and were more likely to have a first-degree relative with obsessive compulsive disorder. Those with anxiety disorders also exhibited significantly worse motor inhibitory performance on a task of motor inhibition (stop-signal task). Conclusions This study suggests that anxiety disorders affect the clinical presentation of hair pulling behavior. Further research is needed to validate our findings and to consider whether treatments should be specially tailored differently for adults with trichotillomania who have co-occurring anxiety disorders, or more pronounced cognitive impairment. PMID:27668531

  19. Commercial Building Partnerships Replication and Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Antonopoulos, Chrissi A.; Dillon, Heather E.; Baechler, Michael C.

    2013-09-16

    This study presents findings from survey and interview data investigating replication efforts of Commercial Building Partnership (CBP) partners that worked directly with the Pacific Northwest National Laboratory (PNNL). PNNL partnered directly with 12 organizations on new and retrofit construction projects, which represented approximately 28 percent of the entire U.S. Department of Energy (DOE) CBP program. Through a feedback survey mechanism, along with personal interviews, PNNL gathered quantitative and qualitative data relating to replication efforts by each organization. These data were analyzed to provide insight into two primary research areas: 1) CBP partners’ replication efforts of technologies and approaches used in the CBP project to the rest of the organization’s building portfolio (including replication verification), and, 2) the market potential for technology diffusion into the total U.S. commercial building stock, as a direct result of the CBP program. The first area of this research focused specifically on replication efforts underway or planned by each CBP program participant. Factors that impact replication include motivation, organizational structure and objectives firms have for implementation of energy efficient technologies. Comparing these factors between different CBP partners revealed patterns in motivation for constructing energy efficient buildings, along with better insight into market trends for green building practices. The second area of this research develops a diffusion of innovations model to analyze potential broad market impacts of the CBP program on the commercial building industry in the United States.

  20. Mycobacterium tuberculosis replicates within necrotic human macrophages

    Science.gov (United States)

    Lerner, Thomas R.; Repnik, Urska; Herbst, Susanne; Collinson, Lucy M.; Griffiths, Gareth

    2017-01-01

    Mycobacterium tuberculosis modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication is less characterized. In this study, we investigate the impact of plasma membrane (PM) integrity on bacterial replication in different functional populations of human primary macrophages. We discovered that IFN-γ enhanced bacterial replication in macrophage colony-stimulating factor–differentiated macrophages more than in granulocyte–macrophage colony-stimulating factor–differentiated macrophages. We show that permissiveness in the different populations of macrophages to bacterial growth is the result of a differential ability to preserve PM integrity. By combining live-cell imaging, correlative light electron microscopy, and single-cell analysis, we found that after infection, a population of macrophages became necrotic, providing a niche for M. tuberculosis replication before escaping into the extracellular milieu. Thus, in addition to bacterial dissemination, necrotic cells provide first a niche for bacterial replication. Our results are relevant to understanding the environment of M. tuberculosis replication in the host. PMID:28242744

  1. Kitle İletişiminde Çağdaş Söylen Üretimi: Kuramsal Bir Değerlendirme

    Directory of Open Access Journals (Sweden)

    Birol Demircan

    2015-08-01

    Full Text Available Söylenler, iktidarın uygulamalarının rasyonelleştirilmesi ve meşrulaştırılması ile toplumsal bir iletişim gerçekleşmesine hala kaynaklık etmektedir. Bu amaçla çalışmada, kitle iletişimi ile dolayımlanan söylenler aracılığıyla yaratılan karizmatik otoriter öznelerin oluşturulma süreci üzerinde durulmuştur. Kitle iletişimin sahte doğallığı ile toplumun gerçekliğini çarpıttığı iddiası bu çalışmanın incelemek istediği temel sorundur. Bu doğrultuda, kitle iletişim ve mitoloji arasında kavramsal ilişki kurarak mitolojinin meşrulaştırma işlevinin izlerini kitle iletişim süreçlerinde aranmıştır. Kitle iletişim araçları ile dolayımlanan iletişim biçimleri ile söylenlerin oluşturulduğunu ve bu söylenlerin iktidar ilişkileri içerisinde bir meşrulaştırma işlevini yerine getirdiği savunulmuştur. Bu savunu doğrultusunda, kullanılan propaganda teknikleri ile özellikle politik liderlerin kahramanlaştırılmasında etkin bir söylen kullanımının varlığı amaçlı örneklem yöntemi ile seçilen örnekler üzerinden tartışılmıştır. Böylelikle, medya ve söylen üretimi arasındaki bağ kurulmak istenmiştir.  Özellikle, kahramanlık mitinin haber dilinde ideolojik belirlenimle üretilmesi sürecinde örtük bir çabanın varlığı tespit edilmiştir. Sonuç olarak, kitle iletişimi ile dolayımlanan söylenler aracılığıyla yaratılan karizmatik otoritenin dönemsel iktidar ilişkileri içersinde en çok rıza gösterilen sistemik bir efsane insan haline geldiği açıklanmıştır.

  2. A new method of social marketing: Community based social marketingYeni bir sosyal pazarlama yöntemi: “Toplumsal tabanlı sosyal pazarlama”

    Directory of Open Access Journals (Sweden)

    Sabahattin Çelik

    2016-07-01

    Full Text Available Especially in developed and developing countries, social marketing practises is used which is an innovative approach for the problems that require social change. Community based social marketing as a new method of social merketing, can be defined as making analysis and planning, implementing and the assessment of the programmes which are all designed to affect the behaviors of the target group to be made voluntarily in order to increase the welfare of the community of the individuals and the community that they exist in. “Community based social marketing” approach aims to create a positive behavior by starting up the behavioral change tools and eliminating the barriers in front of the target groups in order to have a positive attitude for a sustainable future. Community based social marketing tools and techniques provide provides a very important event that organize the behavior change, regardless of collecting knowledge in the area of conventional commercial marketing. The main purpose of the article within the framework of this information is to explain what ‘community based social marketing’ is and show how effective it is on the positive behavior change of the communities. For this purpose, a detailed literature review has been conducted and relevant concepts and examples have been examined.   Özet Özellikle gelişmiş ve gelişmekte olan ülkelerde sosyal değişim gerektiren problemler için yenilikçi bir yaklaşım olan sosyal pazarlama uygulamaları kullanılmaktadır. Yeni bir sosyal pazarlama yöntemi olan “Toplumsal Tabanlı Sosyal Pazarlama” ise bireylerin ve içinde bulundukları toplumun refahını arttırmak için, hedef kitlenin gönüllü olarak yapacakları davranışları etkilemek üzere tasarlanan programların analizi, planlanması, uygulanması ve değerlendirilmesi için pazarlama teknolojilerine başvurulması olarak tanımlanabilir. “Toplumsal Tabanlı Sosyal Pazarlama” (TTSP yaklaşımı, s

  3. Organization of Replication of Ribosomal DNA in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Linskens, Maarten H.K.; Huberman, Joel A.

    1988-01-01

    Using recently developed replicon mapping techniques, we have analyzed the replication of the ribosomal DNA in Saccharomyces cerevisiae. The results show that (i) the functional origin of replication colocalizes with an autonomously replicating sequence element previously mapped to the

  4. HIV-1 Vpr increases HCV replication through VprBP in cell culture.

    Science.gov (United States)

    Yan, Yanling; Huang, Fang; Yuan, Ting; Sun, Binlian; Yang, Rongge

    2016-09-02

    Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs at a high frequency, in which HIV shows a promotion of HCV-derived liver diseases. However, the mechanism of how this occurs is not well understood. Our previous work has demonstrated that the HIV-1 accessory protein Vpr enhances HCV RNA replication in cell culture. Because Vpr performs most of its functions through host protein VprBP (DCAF1), the role of VprBP in the regulation of HCV by Vpr was investigated in this study. We found that the Vpr mutant Q65R, which is deficient in VprBP binding, could not enhance HCV replication. Furthermore, Vpr-mediated enhancement of HCV replication was severely diminished in VprBP knockdown cells. In addition, an inhibitor of Cullin RING E3 ligases, MLN4924, impaired the function of Vpr during HCV replication. Together, these results suggest that Vpr promotes HCV replication in a VprBP-dependent manner, and that the activity of Cullin RING E3 ligases is essential to this process. In conclusion, our findings demonstrate that HIV-1 Vpr makes the cellular environment more suitable for HCV replication, which might relate with the host ubiquitination system.

  5. Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation.

    Science.gov (United States)

    Devlin, Rebecca; Marques, Catarina A; Paape, Daniel; Prorocic, Marko; Zurita-Leal, Andrea C; Campbell, Samantha J; Lapsley, Craig; Dickens, Nicholas; McCulloch, Richard

    2016-05-26

    Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating - a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility.

  6. A novel nucleoid-associated protein coordinates chromosome replication and chromosome partition.

    Science.gov (United States)

    Taylor, James A; Panis, Gaël; Viollier, Patrick H; Marczynski, Gregory T

    2017-09-06

    We searched for regulators of chromosome replication in the cell cycle model Caulobacter crescentus and found a novel DNA-binding protein (GapR) that selectively aids the initiation of chromosome replication and the initial steps of chromosome partitioning. The protein binds the chromosome origin of replication (Cori) and has higher-affinity binding to mutated Cori-DNA that increases Cori-plasmid replication in vivo. gapR gene expression is essential for normal rapid growth and sufficient GapR levels are required for the correct timing of chromosome replication. Whole genome ChIP-seq identified dynamic DNA-binding distributions for GapR, with the strongest associations at the partitioning (parABS) locus near Cori. Using molecular-genetic and fluorescence microscopy experiments, we showed that GapR also promotes the first steps of chromosome partitioning, the initial separation of the duplicated parS loci following replication from Cori. This separation occurs before the parABS-dependent partitioning phase. Therefore, this early separation, whose mechanisms is not known, coincides with the poorly defined mechanism(s) that establishes chromosome asymmetry: C. crescentus chromosomes are partitioned to distinct cell-poles which develop into replicating and non-replicating cell-types. We propose that GapR coordinates chromosome replication with asymmetry-establishing chromosome separation, noting that both roles are consistent with the phylogenetic restriction of GapR to asymmetrically dividing bacteria. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Replicating DNA by cell factories: roles of central carbon metabolism and transcription in the control of DNA replication in microbes, and implications for understanding this process in human cells.

    Science.gov (United States)

    Barańska, Sylwia; Glinkowska, Monika; Herman-Antosiewicz, Anna; Maciąg-Dorszyńska, Monika; Nowicki, Dariusz; Szalewska-Pałasz, Agnieszka; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2013-05-29

    Precise regulation of DNA replication is necessary to ensure the inheritance of genetic features by daughter cells after each cell division. Therefore, determining how the regulatory processes operate to control DNA replication is crucial to our understanding and application to biotechnological processes. Contrary to early concepts of DNA replication, it appears that this process is operated by large, stationary nucleoprotein complexes, called replication factories, rather than by single enzymes trafficking along template molecules. Recent discoveries indicated that in bacterial cells two processes, central carbon metabolism (CCM) and transcription, significantly and specifically influence the control of DNA replication of various replicons. The impact of these discoveries on our understanding of the regulation of DNA synthesis is discussed in this review. It appears that CCM may influence DNA replication by either action of specific metabolites or moonlighting activities of some enzymes involved in this metabolic pathway. The role of transcription in the control of DNA replication may arise from either topological changes in nucleic acids which accompany RNA synthesis or direct interactions between replication and transcription machineries. Due to intriguing similarities between some prokaryotic and eukaryotic regulatory systems, possible implications of studies on regulation of microbial DNA replication on understanding such a process occurring in human cells are discussed.

  8. Seyyid Vehbi'nin Divanında Yer Almayan Bir Kasidesi The Kaside That Doesn’t Take Place In Divan Of Seyyid Vehbi

    Directory of Open Access Journals (Sweden)

    Haluk GÖKALP

    2013-03-01

    Full Text Available Perodicals include kinds of poems. In addition they comprise artistic and cultural accumulation when they were written. Pastiche collections give knowledge abaut pastiche tradition and interactions between poets. Poem notebooks which can collect diffrent subjects contribute to history of literatüre. So, pastiche collections or other collections are one of the main source of classical poetry. Contributions of periodicals to classical school of poetry investigating, may be collected with three groups. Firsh of all, periodicals reflect the plcasure of poem when they were written and poems which were approued can be determined. Second one, they contribute to recognition of poets who weren’t mentioned in history of literature. Third one, investigetors can benefit from periodicals for poems which weren’t mentioned in poet’s divan which include their poems. By this way, investigators can collect all poems of poet. İn this study, we evalvated the contributions of periodicals to classical poetry investigators. And than we are going to publish Seyyid Vehbi’s kaside in “Sıhhatname ve Sur-ı Hıtana Müteallik Kasaid” which was found from Topkapı Palace Library. With this study, Seyyid Vehbi’s poem which weren’t mentioned in other 31 copy is going to be presented to investigator’s advantage. Şiir mecmuaları çeşitli şiirleri derlemekle birlikte yazıldığı devrin sanat ve kültür birikimini de bir araya getirirler. Nazire mecmuaları nazire geleneğini ve şairler arası etkileşimi örnekleriyle gözler önüne sererken, farklı konular etrafında toplanan ya da -tamamen okuyucunun zevkine göre gelişigüzel toplanan- şiir defterleri edebiyat tarihini bir bütünlük içinde görmemize olumlu katkılar sağlar. Bu nedenle nazire mecmuaları ya da diğer şiir mecmuaları, divan şiiri araştırmalarının başlıca kaynaklarındandır. Genel olarak baktığımızda mecmuaların divan edebiyatı araştırmalarına katk

  9. Türkçede Edatlar Üzerine Bir Bibliyografya Denemesi A Bibliografphy Study about Particles İn Turkish

    Directory of Open Access Journals (Sweden)

    Birol İPEK

    2012-12-01

    Full Text Available Many bibliographies on various topics was conducted in Turkey Turkish. This study was conducted on Turkey Turkish prepositions include bibliographies. Particles are the words making a sense when used together with other words with no meaning on their own. Particles are one of the eight types of words being used in Turkish. Particleswithin Turkish words rank as auxiliary word class. Because they areauxiliary words, they have a wide usage area. Several studies have beencarried out in respect to the roots, functions and usage area ofparticles. However, no bibliography study on particles has been done sofar. We have created a particles bibliography by gathering, to someextend we can reach, the studies carried out on particles. Whenchoosing bibliography studies have included working more directly tothe subject of particles.Bibliography attempt study contains articles published inperiodicals, statements of congress, convention and symposium, masterand doctoral studies, and books related to particles. This studycontains publications discussing the subject of particles from oldTurkish to the present day. With regard to integrity of the subject, itwas also given place to study discussing particles in ContemporaryTurkish Dialects and Turkey’s Turkish Dialects. We aimed at suchstudy to provide more convenient access to particles bibliography forscientists and researchers who want to do research on particles.Studies ordered by the authors last name. Articles and papers names inquotation marks "...", are given in the track of the names are written initalics. In this study, Bibliography, particles scanned resources andconstraints sections. The study included a total of 114 given in thebibliography. Türkiye Türkçesinde çeşitli konularda birçok bibliyografya çalışması yapılmıştır. Bu çalışma, Türkiye Türkçesinde edatlarla ilgili yapılmış bibliyografyaları içermektedir. Edatlar tek başlarına anlamları olmayan diğer kelimelerle

  10. Optical tweezers reveal how proteins alter replication

    Science.gov (United States)

    Chaurasiya, Kathy

    Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

  11. Võidukas läbirääkija Vladimir Panov : Keskerakonna koalitsioonis püsides tagan veehinna stabiilsuse 2010 aastani / Vladimir Panov ; interv. Allan Alaküla

    Index Scriptorium Estoniae

    Panov, Vladimir, 1941-

    2002-01-01

    Ilmunud ka: Stolitsa 30.august lk.3. AS Tallinna Vesi ja Tallinna linn leppisid kokku uues tariifi muutmise struktuuris järgmisteks aastateks. Tallinna abilinnapea Vladimir Panov vastab küsimustele, mis puudutavad läbirääkimisi Tallinna Vee ja Tallinna linna vahel

  12. Self-replication with magnetic dipolar colloids.

    Science.gov (United States)

    Dempster, Joshua M; Zhang, Rui; Olvera de la Cruz, Monica

    2015-10-01

    Colloidal self-replication represents an exciting research frontier in soft matter physics. Currently, all reported self-replication schemes involve coating colloidal particles with stimuli-responsive molecules to allow switchable interactions. In this paper, we introduce a scheme using ferromagnetic dipolar colloids and preprogrammed external magnetic fields to create an autonomous self-replication system. Interparticle dipole-dipole forces and periodically varying weak-strong magnetic fields cooperate to drive colloid monomers from the solute onto templates, bind them into replicas, and dissolve template complexes. We present three general design principles for autonomous linear replicators, derived from a focused study of a minimalist sphere-dimer magnetic system in which single binding sites allow formation of dimeric templates. We show via statistical models and computer simulations that our system exhibits nonlinear growth of templates and produces nearly exponential growth (low error rate) upon adding an optimized competing electrostatic potential. We devise experimental strategies for constructing the required magnetic colloids based on documented laboratory techniques. We also present qualitative ideas about building more complex self-replicating structures utilizing magnetic colloids.

  13. A Self-Replicating Ligase Ribozyme

    Science.gov (United States)

    Paul, Natasha; Joyce, Gerald F.

    2002-01-01

    A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of Itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 per min, whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 x 10(exp -11) M per min. Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication.

  14. Spacetime replication of continuous variable quantum information

    Science.gov (United States)

    Hayden, Patrick; Nezami, Sepehr; Salton, Grant; Sanders, Barry C.

    2016-08-01

    The theory of relativity requires that no information travel faster than light, whereas the unitarity of quantum mechanics ensures that quantum information cannot be cloned. These conditions provide the basic constraints that appear in information replication tasks, which formalize aspects of the behavior of information in relativistic quantum mechanics. In this article, we provide continuous variable (CV) strategies for spacetime quantum information replication that are directly amenable to optical or mechanical implementation. We use a new class of homologically constructed CV quantum error correcting codes to provide efficient solutions for the general case of information replication. As compared to schemes encoding qubits, our CV solution requires half as many shares per encoded system. We also provide an optimized five-mode strategy for replicating quantum information in a particular configuration of four spacetime regions designed not to be reducible to previously performed experiments. For this optimized strategy, we provide detailed encoding and decoding procedures using standard optical apparatus and calculate the recovery fidelity when finite squeezing is used. As such we provide a scheme for experimentally realizing quantum information replication using quantum optics.

  15. COPI is required for enterovirus 71 replication.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 (EV71, a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11, is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies.

  16. Extremal dynamics in random replicator ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Kärenlampi, Petri P., E-mail: petri.karenlampi@uef.fi

    2015-10-02

    The seminal numerical experiment by Bak and Sneppen (BS) is repeated, along with computations with replicator models, including a greater amount of features. Both types of models do self-organize, and do obey power-law scaling for the size distribution of activity cycles. However species extinction within the replicator models interferes with the BS self-organized critical (SOC) activity. Speciation–extinction dynamics ruins any stationary state which might contain a steady size distribution of activity cycles. The BS-type activity appears as a dissimilar phenomenon in comparison to speciation–extinction dynamics in the replicator system. No criticality is found from the speciation–extinction dynamics. Neither are speciations and extinctions in real biological macroevolution known to contain any diverging distributions, or self-organization towards any critical state. Consequently, biological macroevolution probably is not a self-organized critical phenomenon. - Highlights: • Extremal Dynamics organizes random replicator ecosystems to two phases in fitness space. • Replicator systems show power-law scaling of activity. • Species extinction interferes with Bak–Sneppen type mutation activity. • Speciation–extinction dynamics does not show any critical phase transition. • Biological macroevolution probably is not a self-organized critical phenomenon.

  17. İki Spor Kulübünün Hisse Senedi Getirileri Üzerine Bir İnceleme

    Directory of Open Access Journals (Sweden)

    Deniz PARLAK

    2014-12-01

    Full Text Available Futbol, günümüz dünyasında bir eğlence unsuru olmaktan çıkarak endüstri kolu haline gelmiştir. Bu sporun Türkiye’deki en önemli temsilcileri olan Fenerbahçe ve Galatasaray’ın arasındaki rekabet hem takım düzeyinde sahada hem de şirket düzeyinde borsada yaşanmaktadır. Çalışmanın amacı bu iki futbol takımının yaptıkları karşılaşmalarda aldıkları sonuçların borsada işlem gören hisselerine ait fiyatlara etkisini incelemektir. Takımların kendi sonuçlarının yanı sıra rakibinin aldığı sonuçların da şirketin hisse senedi getirisine etki edip etmediği araştırılmıştır. Kullanılan üç günlük olay etüdü analizi ile maç sonuçlarına ait beklentilerin maçtan bir gün önce, maç sonuçlarının ise maçtan bir gün sonra kümülatif anormal getiri yarattığını göstermiştir. Kümülatif anormal getirinin rakibin elde ettiği sonuçlara göre farklılık göstermediği saptanmıştır.

  18. Çocuklar İçin Felsefe Eğitimi Üzerine Nitel Bir Araştırma

    Directory of Open Access Journals (Sweden)

    Nihan Akkocaoğlu Çayır

    2016-04-01

    Full Text Available Çocuklar için felsefe çocukların, bir metin, öykü ya da örnek olaydan yola çıkarak bilgi, doğru, gerçek, güzel, adalet gibi felsefi kavramları bir yetişkin rehberliğinde tartışmalarıdır. Bu araştırma çocuklar için felsefe eğitiminin, ilkokul üçüncü sınıf öğrencilerini bilişsel, duyuşsal ve sosyal alanlarda nasıl etkilediğini tespit etmek amacıyla on dört hafta toplam yirmi sekiz saat sürecinde nitel araştırma yöntemi kullanılarak yürütülmüştür. Çocuklarla felsefe yapmak üzere hazırlanan ders planları iki ayrı sınıfta, kırk sekiz öğrenciye, iki öğretmen tarafından uygulanmıştır. Süreç sonunda öğrencilerde bilişsel alanda, felsefe, felsefe soruları ve filozofların özelliklerini anlama, kavramlar arası ilişki kurma, kavramları günlük hayatla ilişkilendirme, düşünme hatalarını kavrama, düşünmeye yönelme, farklı açılardan düşünme gibi değişimler gözlemlenmiştir. Duyuşsal alanda ise filozoflardan, felsefeden hoşlanma ve kavramlara yönelik farkındalıklar söz konusu olmuştur. Sosyal alanda ise öğrencilerin sorun çözme ve birbirlerini tanımaları noktasında değişimler yaşanmıştır. Çocuklar için felsefe, okul öncesinden liseye kadar farklı yaş düzeylerindeki pek çok dersin programlarıyla bütünleştirilebilir ya da ayrı bir ders olarak okutulabilir.

  19. In vivo dynamics of EBNA1-oriP interaction during latent and lytic replication of Epstein-Barr virus.

    Science.gov (United States)

    Daikoku, Tohru; Kudoh, Ayumi; Fujita, Masatoshi; Sugaya, Yutaka; Isomura, Hiroki; Tsurumi, Tatsuya

    2004-12-24

    The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is required for maintenance of the viral genome DNA during the latent phase of EBV replication but continues to be synthesized after the induction of viral productive replication. An EBV genome-wide chromatin immunoprecipitation assay revealed that EBNA1 constantly binds to oriP of the EBV genome during not only latent but also lytic infection. Although the total levels of EBNA1 proved constant throughout the latter, the levels of the oriP-bound form were increased as lytic infection proceeded. EBV productive DNA replication occurs at discrete sites in nuclei, called replication compartments, where viral replication proteins are clustered. Confocal laser microscopic analyses revealed that whereas EBNA1 was distributed broadly in nuclei as fine punctate dots during the latent phase of infection, the protein became redistributed to the viral replication compartments and localized as distinct spots within and/or nearby the compartments after the induction of lytic replication. Taking these findings into consideration, oriP regions of the EBV genome might be organized by EBNA1 into replication domains that may set up scaffolding for lytic replication and transcription.

  20. Content replication and placement in mobile networks

    CERN Document Server

    La, Chi-Anh; Casetti, Claudio; Chiasserini, Carla-Fabiana; Fiore, Marco

    2011-01-01

    Performance and reliability of content access in mobile networks is conditioned by the number and location of content replicas deployed at the network nodes. Location theory has been the traditional, centralized approach to study content replication: computing the number and placement of replicas in a static network can be cast as a facility location problem. The endeavor of this work is to design a practical solution to the above joint optimization problem that is suitable for mobile wireless environments. We thus seek a replication algorithm that is lightweight, distributed, and reactive to network dynamics. We devise a solution that lets nodes (i) share the burden of storing and providing content, so as to achieve load balancing, and (ii) autonomously decide whether to replicate or drop the information, so as to adapt the content availability to dynamic demands and time-varying network topologies. We evaluate our mechanism through simulation, by exploring a wide range of settings, including different node ...

  1. Evolution of Database Replication Technologies for WLCG

    CERN Document Server

    Baranowski, Zbigniew; Blaszczyk, Marcin; Dimitrov, Gancho; Canali, Luca

    2015-01-01

    In this article we summarize several years of experience on database replication technologies used at WLCG and we provide a short review of the available Oracle technologies and their key characteristics. One of the notable changes and improvement in this area in recent past has been the introduction of Oracle GoldenGate as a replacement of Oracle Streams. We report in this article on the preparation and later upgrades for remote replication done in collaboration with ATLAS and Tier 1 database administrators, including the experience from running Oracle GoldenGate in production. Moreover, we report on another key technology in this area: Oracle Active Data Guard which has been adopted in several of the mission critical use cases for database replication between online and offline databases for the LHC experiments.

  2. Replicating Cardiovascular Condition-Birth Month Associations

    Science.gov (United States)

    Li, Li; Boland, Mary Regina; Miotto, Riccardo; Tatonetti, Nicholas P.; Dudley, Joel T.

    2016-01-01

    Independent replication is vital for study findings drawn from Electronic Health Records (EHR). This replication study evaluates the relationship between seasonal effects at birth and lifetime cardiovascular condition risk. We performed a Season-wide Association Study on 1,169,599 patients from Mount Sinai Hospital (MSH) to compute phenome-wide associations between birth month and CVD. We then evaluated if seasonal patterns found at MSH matched those reported at Columbia University Medical Center. Coronary arteriosclerosis, essential hypertension, angina, and pre-infarction syndrome passed phenome-wide significance and their seasonal patterns matched those previously reported. Atrial fibrillation, cardiomyopathy, and chronic myocardial ischemia had consistent patterns but were not phenome-wide significant. We confirm that CVD risk peaks for those born in the late winter/early spring among the evaluated patient populations. The replication findings bolster evidence for a seasonal birth month effect in CVD. Further study is required to identify the environmental and developmental mechanisms. PMID:27624541

  3. Synchronization of DNA array replication kinetics

    Science.gov (United States)

    Manturov, Alexey O.; Grigoryev, Anton V.

    2016-04-01

    In the present work we discuss the features of the DNA replication kinetics at the case of multiplicity of simultaneously elongated DNA fragments. The interaction between replicated DNA fragments is carried out by free protons that appears at the every nucleotide attachment at the free end of elongated DNA fragment. So there is feedback between free protons concentration and DNA-polymerase activity that appears as elongation rate dependence. We develop the numerical model based on a cellular automaton, which can simulate the elongation stage (growth of DNA strands) for DNA elongation process with conditions pointed above and we study the possibility of the DNA polymerases movement synchronization. The results obtained numerically can be useful for DNA polymerase movement detection and visualization of the elongation process in the case of massive DNA replication, eg, under PCR condition or for DNA "sequencing by synthesis" sequencing devices evaluation.

  4. GFLV replication in electroporated grapevine protoplasts.

    Science.gov (United States)

    Valat; Toutain; Courtois; Gaire; Decout; Pinck; Mauro; Burrus

    2000-06-29

    Grapevine fanleaf virus (GFLV), responsible for the economically important court-noué disease, is exclusively transmitted to its natural host in the vineyards through Xiphinema nematodes. We have developed direct inoculation of GFLV into grapevine through protoplast electroporation. Protoplasts were isolated from mesophyll of in vitro-grown plants and from embryogenic cell suspensions. Permeation conditions were determined by monitoring calcein uptake. Low salt poration medium was selected. Electrical conditions leading to strong transient gene expression were also tested for GFLV inoculation (isolate F13). GFLV replication was detected with either virus particles (2 µg) or viral RNA (10 ng) in both protoplast populations, as shown by anti-P38 Western blotting. Direct inoculation and replication were also observed with Arabis mosaic virus (ArMV), a closely related nepovirus, as well as with another GFLV isolate. These results will be valuable in grapevine biotechnology, for GFLV replication studies, transgenic plant screening for GFLV resistance, and biorisk evaluation.

  5. Ethical issues occurring within nursing education.

    Science.gov (United States)

    Fowler, Marsha D; Davis, Anne J

    2013-03-01

    The large body of literature labeled "ethics in nursing education" is entirely devoted to curricular matters of ethics education in nursing schools, that is, to what ought to be the ethics content that is taught and what theory or issues ought to be included in all nursing curricula. Where the nursing literature actually focuses on particular ethical issues, it addresses only single topics. Absent from the literature, however, is any systematic analysis and explication of ethical issues or dilemmas that occur within the context of nursing education. The objective of this article is to identify the spectrum of ethical issues in nursing education to the end of prompting a systematic and thorough study of such issues, and to lay the groundwork for research by identifying and provisionally typologizing the ethical issues that occur within the context of academic nursing.

  6. Molten Metal Explosions are Still Occurring

    Science.gov (United States)

    2009-02-01

    pans which can give rise to Force 2 incidents if unheated or contain foreign matter. Handling hot dross represents a particular hazard. Force 3...explosions have occurred from hot dross transfer, cooling and dumping into storage areas. In one recent incident, an employee reportedly dumped a load of...thermiting dross into a water puddle and was fatally burned. Casting: Incidents continue to be reported for dc casting arising from bleed-outs

  7. Suppression of Adenovirus Replication by Cardiotonic Steroids.

    Science.gov (United States)

    Grosso, Filomena; Stoilov, Peter; Lingwood, Clifford; Brown, Martha; Cochrane, Alan

    2017-02-01

    The dependence of adenovirus on the host pre-RNA splicing machinery for expression of its complete genome potentially makes it vulnerable to modulators of RNA splicing, such as digoxin and digitoxin. Both drugs reduced the yields of four human adenoviruses (HAdV-A31, -B35, and -C5 and a species D conjunctivitis isolate) by at least 2 to 3 logs by affecting one or more steps needed for genome replication. Immediate early E1A protein levels are unaffected by the drugs, but synthesis of the delayed protein E4orf6 and the major late capsid protein hexon is compromised. Quantitative reverse transcription-PCR (qRT-PCR) analyses revealed that both drugs altered E1A RNA splicing (favoring the production of 13S over 12S RNA) early in infection and partially blocked the transition from 12S and 13S to 9S RNA at late stages of virus replication. Expression of multiple late viral protein mRNAs was lost in the presence of either drug, consistent with the observed block in viral DNA replication. The antiviral effect was dependent on the continued presence of the drug and was rapidly reversible. RIDK34, a derivative of convallotoxin, although having more potent antiviral activity, did not show an improved selectivity index. All three drugs reduced metabolic activity to some degree without evidence of cell death. By blocking adenovirus replication at one or more steps beyond the onset of E1A expression and prior to genome replication, digoxin and digitoxin show potential as antiviral agents for treatment of serious adenovirus infections. Furthermore, understanding the mechanism(s) by which digoxin and digitoxin inhibit adenovirus replication will guide the development of novel antiviral therapies.

  8. Yüzde tabanlı String Eşleme Problemi için yeni bir donanım modülü tasarımı

    Directory of Open Access Journals (Sweden)

    İbrahim Şahin

    2016-12-01

    Full Text Available Bir verinin bir dizgi içerisinde veya bir gen yapısının bir DNA gen dizilimi içerisinde arama işleminin gerçekleştirilmesi için çeşitli algoritmalar kullanılmaktadır. Kullanılan bu algoritmalardan bazıları bize mutlak eşleşme olmadığı durumlarda olumsuz dönüt vermekte, bazıları ise “bunu mu arıyorsunuz” diye alternatifler sunmaktadır. Her iki algoritma da genel amaçlı PC’lerde saniyeler süren işlemler sonucunda bize dönüt verebilmektedir. Bu çalışmada bize hem mutlak eşleşmeyi hem de hedef dizgi içinde yüzdelik eşleşme oranlarının gerçekleştiği konumu veren FPGA çiplerine yönelik yüksek performanslı bir donanım modülü tasarlanmıştır. Geliştirilen modülün veri işleme hızı farklı PC’lerle karşılaştırılmış ve 2300 kata kadar daha hızlı arama gerçekleştirdiği karşılaştırma sonuçlarından elde edilen veriler ile doğrulanmıştır.

  9. Yapay Sinir Ağları ile Çok Aşamalı Fiyat Tahmini: BIST30 Senetleri Üzerine Bir Araştırma

    Directory of Open Access Journals (Sweden)

    Mehmet Özçalıcı

    2016-12-01

    Full Text Available Zaman serileri tahmini literatürde ilgi gören bir konudur. Hisse senedi fiyatları da zaman serisi oluşturmaktadır ve hisse senedi fiyat tahmininin birçok avantajlı tarafı mevcuttur. Literatürde hisse senedi fiyat tahmini üzerine yapılan çalışmalarda genellikle bir gün sonraki fiyatların veya eğilimin tahmin edildiği görülmektedir. Bu çalışmada literatürden farklı olarak 1 gün sonraki, 2 gün sonraki ve 20 gün sonraki hisse senedi kapanış fiyatları tahmin edilmiştir. Veri seti olarak Borsa Istanbul 30 endeksinde listelenen hisse senetlerinin Ocak 2010 ile Kasım 2015 tarihleri arasındaki fiyat ve hacim bilgileri kullanılmış ve girdi olarak teknik göstergeler hesaplanmıştır. Çalışmada tahmin yöntemi olarak yapay sinir ağları kullanılmıştır. Sonuçta hisse senetlerindeki fiyat hareketleri %72.88 e varan oranda 20 gün önceden doğru bir şekilde tahmin edilebilmiştir. Araştırmada elde edilen bulgular, orta dönemli fiyat tahminlerinin de derinlemesine inceleme gerektiren önemli bir potansiyele sahip olduğu sonucunu ortaya çıkarmaktadır.

  10. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

    Wæhrens, Brian Vejrum; Yang, Cheng; Madsen, Erik Skov

    2012-01-01

    . Design/methodology/approach – Two case studies are introduced. Empirical data were collected over a period of two years based on interviews and participating observations. Findings – The findings show that (1) knowledge transfer within the replication of a production line is a stepwise expansive process......Purpose – With the aim to support offshore production line replication, this paper specifically aims to explore the use of templates and principles to transfer expansive productive knowledge embedded in a production line and understand the contingencies that influence the mix of these approaches...... and principles to transfer productive knowledge in a specific context, which, in this paper, is a production line....

  11. Chromatin challenges during DNA replication and repair

    DEFF Research Database (Denmark)

    Groth, Anja; Rocha, Walter; Verreault, Alain

    2007-01-01

    Inheritance and maintenance of the DNA sequence and its organization into chromatin are central for eukaryotic life. To orchestrate DNA-replication and -repair processes in the context of chromatin is a challenge, both in terms of accessibility and maintenance of chromatin organization. To meet...... the challenge of maintenance, cells have evolved efficient nucleosome-assembly pathways and chromatin-maturation mechanisms that reproduce chromatin organization in the wake of DNA replication and repair. The aim of this Review is to describe how these pathways operate and to highlight how the epigenetic...

  12. Involvement of Autophagy in Coronavirus Replication

    Directory of Open Access Journals (Sweden)

    Paul Britton

    2012-11-01

    Full Text Available Coronaviruses are single stranded, positive sense RNA viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. This provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of RNA synthesis. The membranes observed in coronavirus infected cells include double membrane vesicles. By nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. In addition, coronavirus infection has been demonstrated to induce autophagy. Here we review current knowledge of coronavirus induced membrane rearrangements and the involvement of autophagy or autophagy protein microtubule associated protein 1B light chain 3 (LC3 in coronavirus replication.

  13. The Analytic Hierarchy Process (AHP and an Application: The Selection of a Library Director as a Leader Analitik Hiyerarşi Süreci (AHS ve Bir Uygulama: Lider bir Kütüphane Müdürü Seçimi

    Directory of Open Access Journals (Sweden)

    Murat Yılmaz

    2010-06-01

    Full Text Available The librarians have to take various decisions to deal with the problems met in library and information centers. Before having made the decisions, the librarians should firstly define the problem with all details. If the librarians have clear information about the relevant problem, they can easily define and solve it. But the problems met by librarians in library and information centers sometimes may have a complex and an unclear structure. The librarians need a powerful method to deal with such a problem having a complex and an unclear structure. This method may be Analytic Hierarchy Process (AHP. The main purpose of this study is to explain how to use the AHP. Furthermore, in this study it is also explained how to select a library director as a leader. Kütüphane ve bilgi merkezlerinde karşılaşılan problemlerin üstesinden gelmek için kütüphaneciler, çeşitli kararlar almak zorundadır. Karar vermek için kütüphanecilerin öncelikle problemi tanımlaması gerekir. Kütüphanecilerin problemle ilgili net verilere sahip olmaları söz konusu problemin tanımlanmasını ve çözümünü kolaylaştırır. Fakat kütüphanecilerin kütüphane ve bilgi merkezlerinde karşılaştıkları sorunlara ilişkin veriler bazen karmaşık ve belirsiz bir yapıda olabilir. Kütüphanecilerin karmaşık ve belirsiz bir yapıya sahip bu tür problemlerin üstesinden gelmeleri için güçlü bir yöntemden yararlanması gerekir. Bu yöntem, Analitik Hiyerarşi Süreci (AHS olabilir. Bu araştırmanın temel amacı, AHS yönteminden nasıl yararlanılacağını açıklamaktır. Araştırmamızda ayrıca AHS yöntemiyle lider bir kütüphane müdürünün nasıl seçileceği de açıklanmıştır.

  14. Replication, recombination, and repair: going for the gold.

    Science.gov (United States)

    Klein, Hannah L; Kreuzer, Kenneth N

    2002-03-01

    DNA recombination is now appreciated to be integral to DNA replication and cell survival. Recombination allows replication to successfully maneuver through the roadblocks of damaged or collapsed replication forks. The signals and controls that permit cells to transition between replication and recombination modes are now being identified.

  15. Direct visualization of replication dynamics in early zebrafish embryos.

    Science.gov (United States)

    Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Okochi, Nanami; Hattori, Kaede; Ogata, Shin; Takebayashi, Shin-Ichiro; Ogata, Masato; Tamaru, Yutaka; Okumura, Katsuzumi

    2016-05-01

    We analyzed DNA replication in early zebrafish embryos. The replicating DNA of whole embryos was labeled with the thymidine analog 5-ethynyl-2'-deoxyuridine (EdU), and spatial regulation of replication sites was visualized in single embryo-derived cells. The results unveiled uncharacterized replication dynamics during zebrafish early embryogenesis.

  16. Spatial regulation and organization of DNA replication within the nucleus.

    Science.gov (United States)

    Natsume, Toyoaki; Tanaka, Tomoyuki U

    2010-01-01

    Duplication of chromosomal DNA is a temporally and spatially regulated process. The timing of DNA replication initiation at various origins is highly coordinated; some origins fire early and others late during S phase. Moreover, inside the nuclei, the bulk of DNA replication is physically organized in replication factories, consisting of DNA polymerases and other replication proteins. In this review article, we discuss how DNA replication is organized and regulated spatially within the nucleus and how this spatial organization is linked to temporal regulation. We focus on DNA replication in budding yeast and fission yeast and, where applicable, compare yeast DNA replication with that in bacteria and metazoans.

  17. Regulation of eukaryotic DNA replication and nuclear structure

    Institute of Scientific and Technical Information of China (English)

    WUJIARUI

    1999-01-01

    In eukaryote,nuclear structure is a key component for the functions of eukaryotic cells.More and more evidences show that the nuclear structure plays important role in regulating DNA replication.The nuclear structure provides a physical barrier for the replication licensing,participates in the decision where DNA replication initiates,and organizes replication proteins as replication factory for DNA replication.Through these works,new concepts on the regulation of DNA replication have emerged,which will be discussed in this minireview.

  18. Dereceli Puanlama Anahtarı Kullanan Öğrencilerin Başarıları Üzerine Bir İnceleme

    Directory of Open Access Journals (Sweden)

    Ayşegül BAYRAKTAR

    2016-10-01

    Full Text Available Bu çalışmanın genel amacı, performans ödevlerini hazırlarken Derecelendirilmiş Puanlama Anahtarı (DPA kullanan ortaokul öğrencileriyle kullanmayan öğrencilerin başarıları arasında fark olup olmadığını belirlemektir. Çalışma grubu, aynı Türkçe öğretmeninden ders alan ve Türkçe dersindeki akademik başarıları birbirine denk iki 6 sınıf öğrencisinden (n=44 oluşmaktadır. Bu gruplardan birisi rastlantısal atama yoluyla deney grubu (n=22, diğeri ise kontrol grubu (n=22 olarak belirlenmiştir. Araştırmanın verileri öğrencilerin performans ödevlerinden aldıkları puanlardan toplanmıştır. Çalışmanın ilk aşamasında öğrencilerin düzeyine ve 6. Sınıf Türkçe Öğretimi Programı’nın kazanımlarına uygun bir performans ödevi hazırlanmıştır. Daha sonra bu ödevin nasıl yapılacağını açıklayan ve her iki gruptaki öğrencilere de verilen ayrıntılı bir yönerge ile alanyazın taraması, uzmanların görüş ve önerileri doğrultusunda 9 boyutu olan çözümleyici (analitik bir DPA hazırlanmıştır. Ayrıntılı yönerge her iki gruba, DPA ise yalnızca deney grubuna verilmiştir. Öğrencilerin hazırladıkları ödevler bu DPA’nın belirlenen 9 boyutuna göre deneyimli iki Türkçe öğretmeni tarafından değerlendirilmiştir. Shapiro-Wilk testine göre dağılımların normal olduğu belirlenmiş, bu nedenle Pearson korelasyon katsayısı hesaplanmış ve değerlendiriciler arasındaki tutarlılık (0,77. olarak belirlenmiştir. Bu değer .05 düzeyinde anlamlı olup, aynı zamanda iki puanlayıcı uyumu için yeterli düzeydedir. İki grubun performans ödevlerindeki başarı puanları arasında fark olup olmadığına Mann-Whitney U testi ile bakılmış; sonuçta yalnızca Dil ve Anlatım boyutlarında deney grubu öğrencilerinin lehine anlamlı bir fark olduğu görülmüştür.

  19. A Pragmatic Approach to the National Information Policy Issue Ulusal Bilgi Politikası Sorunsalına Pragmatik Bir Yaklaşım

    Directory of Open Access Journals (Sweden)

    Selma Alpay Aslan

    1997-09-01

    Full Text Available The paper argues that development of a national information policy in a country is closely related with other policies, priorities and preferences of governments. Recently developed national information policies have a tendency to concentrate on information industry and information society, where library and information services receive only lip service, if mentioned at all. Global trends play an important role in the way information policy issues are handled. Governments in some countries like Turkey have no wish to produce a comprehensive national policy, and some priority areas such as intellectual property or information infrastructure are handled individually in a piecemeal approach. Under these circumstances, it may be wiser for information professionals to discuss policy issues amongst themselves, develop views and work on individual issues rather than trying to impose that it is a need to develop a national information policy. Bu makalede, bir ülkede ulusal bilgi politikası oluşturulmasının hükümetlerin diğer politikaları, öncelikleri ve tercihleri ile yakından ilgili olduğu savunulmaktadır, tartışılmaktadır. Son yıllarda geliştirilen ulusal bilgi politikaları bilgi endüstrisi ve bilgi toplumu konularında yoğunlaşmaktadır. Kütüphane ve bilgi hizmetlerine bazen hiç değinilmemekte ya da yalnızca bazı yönlerine değinilmektedir. Küresel eğilimler bilgi politikalarına yaklaşımlarda önemli rol oynamaktadır. Türkiye gibi bazı ülkelerde hükümetler kapsamlı bir bilgi politikası oluşturmaya istekli görünmemekte olup, politika geliştirmeye gerek duyulan telif hakları, teknolojik altyapı gibi bazı konuları tek tek ele almışlardır. Bu koşullarda bilgi hizmetleri alanında çalışanlar, kendi aralarında politika konularını tartışarak görüşler oluşturmaları ve bir ulusal bilgi politikası geliştirilmesi gerektiği konusunda yoğunlaşmak yerine, öncelikli olarak politika geli

  20. Wilson İlkeleri’nin Türk Dış Politikasına Yansımaları: Realist ve Pragmatist Bir Perspektif

    Directory of Open Access Journals (Sweden)

    Asena Boztaş

    2014-06-01

    Full Text Available Türk dış politikası ve uluslararası politikanın yapılanarak günümüze evrilmesinde mihenk taşı olarak addedilen Birinci Dünya Savaşı sonrası süreçte özellikle Wilson İlkeleri büyük önem taşımaktadır. On dört maddeden oluşan ve aslında ifade ettikleri ve hedefledikleri farklılıklar gösteren Wilson İlkeleri 1918 yılında ilan edilmiştir. İlanıyla birlikte savaşın mağlup ülkelerinin tamamında olduğu gibi Genç Türkiye’de de büyük heyecan ve umut yaratan İlkeler, çalışma kapsamında farklı bir perspektiften değerlendirilerek günümüz Türk dış politikasına etkileri nezdinde incelenecektir. Wilson İlkeleri’nin kısaca dönemin Amerikan başkanı Thomas Woodrow Wilson tarafından açıklanan, Amerika Birleşik Devletleri (ABD’nin Birinci Dünya Savaşı’na ilişkin on dört maddelik savaş amaçları bildirisi olduğu ifade edilebilir. Self-determinasyon ilkesi temelinde uluslararası bir yapılanmayı önermesi bakımından dönemin Türk aydınları tarafından da kabul görmüş olan İlkeler, aslında gizli amaçları çerçevesinde kendi ülkesine hizmet etmeyi planlayan bir zihniyetin çalışması olarak değerlendirilebilir. Bu bağlamda çalışma kapsamında Birinci Dünya Savaşı sonrası büyük güçler tarafından oldukça önemli olduğu bilinen Genç Türkiye’nin Wilson İlkeleri’nin özellikle beşinci ve on ikinci maddeleriyle değerlendirilerek, günümüzde Wilson İlkeleri benzeri içtihadi normlar kapsamında Türkiye’nin uluslararası ve özellikle Kürt meselesi bağlamında bölgesel politikalarının nasıl şekillendiği analiz edilecektir. Bu değerlendirmede öncelikle tarihsel arka plana yer verilecek ve günümüzde de benzeri nitelikte yaşanan bir sürecin varlığına işaret edilerek, Türk dış politikasının nasıl şekillendiği, bu politikaların olumlu ve olumsuz yönleri ele alınacaktır.

  1. Tedarik zinciri yönetiminde scor modelin dcor ve ccor model ile genişletilmesi ve mobilya sektöründe bir uygulama

    OpenAIRE

    TORUL, Yağmur; Kalender, Fatma Yeşim

    2014-01-01

    Bugüne kadar geliştirilen analitik ve sayısal modeller tedarik zincirini bir bütün olarak ele almakta yetersiz kalmıştır. 1996 yılında Tedarik Zinciri Konseyi tedarik zinciri yönetimi için endüstriler arası standart olarak Tedarik Zinciri İşletim Referans Modelini (SCOR) geliştirmiştir. Bu çalışmada 2005 yılında geliştirilen Costumer Chain Operation Reference Model (CCOR) ve Design Chain Operation Reference Model (DCOR) kullanılarak SCOR modelinin kapsamı nasıl genişletildiği anlatılmıştır. D...

  2. Assembly of Slx4 signaling complexes behind DNA replication forks.

    Science.gov (United States)

    Balint, Attila; Kim, TaeHyung; Gallo, David; Cussiol, Jose Renato; Bastos de Oliveira, Francisco M; Yimit, Askar; Ou, Jiongwen; Nakato, Ryuichiro; Gurevich, Alexey; Shirahige, Katsuhiko; Smolka, Marcus B; Zhang, Zhaolei; Brown, Grant W

    2015-08-13

    Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress.

  3. Equine infectious anemia virus replication is upregulated during differentiation of blood monocytes from acutely infected horses.

    OpenAIRE

    Sellon, D C; Walker, K M; Russell, K E; Perry, S T; Covington, P; Fuller, F J

    1996-01-01

    Equine infectious anemia virus is a lentivirus that replicates in mature tissue macrophages of horses. Ponies were infected with equine infectious anemia virus. During febrile episodes, proviral DNA was detectable, but viral mRNA was not detectable. As cultured blood monocytes from these ponies differentiated into macrophages, viral expression was upregulated. In situ hybridization confirmed that viral transcription occurred in mature macrophages.

  4. ULUSLARARASI PORTFÖY YÖNETIMINDE REJIM GEÇIŞKEN KARAR DESTEK MODELLERI: GELIŞMEKTE OLAN MENKUL KIYMET PIYASALARI ÜZERINE BIR UYGULAMA

    Directory of Open Access Journals (Sweden)

    Kadir TUNA

    2014-04-01

    Full Text Available Bu makale, portföy yatırımlarında bir karar destek sistemi olarak rejim geçişken modellerin ne şekilde kullanılabileceğini gelişmekte olan hisse senedi piyasalarına ait zaman serilerini ve Gauss yazılım programını kullanarak incelemektedir. Yönetim bilişim sistemlerinde, model riskinin minimize edilmesi, karar destek siteminin uygulanacağı problemin net olarak tanımlanması ve bu problemin çözümünde kullanılacak modelin doğru seçilmesi ile mümkündür. Ekonometrik testlerin sonuçları, Ukrayna hariç, gelişmekte olan ekonomilerde hisse senetleri piyasalarında 09/01/2004-13/09/2007 tarihleri arasında, ABD hisse senedi piyasaları ile karşılaştırıldığında kalıcı bir volatilitenin gözlemlendiğini ortaya koymaktadır. Bu kapsamda, Türkiye, Rusya, Ukrayna, Brezilya, Lübnan, ABD (Dow Jones Industrial Average ve MSCI (Morgan Stanley Composite Index hisse senedi piyasalarında rejim geçişkenliği ekonometrik olarak karşılaştırmalı incelenmiştir.

  5. Biyodizel ve Karışımlarının Kullanıldığı bir Dizel Motorda Performans ve Emisyon Analizi

    Directory of Open Access Journals (Sweden)

    Ahmet Necati ÖZSEZEN

    2009-02-01

    Full Text Available Bu çalışmada, atık palmiye yağı kökenli biyodizel ve petrol kökenli dizel yakıtı (PKDY ile karışımlarının, bir dizel motordaki performans ve emisyon karakteristikleri üç boyutlu haritalar üzerinden analiz edilmiştir. Biyodizel ve karışımlarının performans ve emisyon karakterlerini belirlemek amacıyla, motor tam yük ve değişik devir testlerine tabi tutulmuştur. Analiz sonucunda, karışımdaki biyodizel oranı arttıkça PKDY'a göre özgül yakıt tüketiminde artış olduğu, motorun döndürme momentinde ise azalma meydana geldiği tespit edilmiştir. Emisyon analizi sonucunda ise, karışımdaki biyodizel oranı ile ilişkili olarak PKDY'a kıyasla yanmamış hidrokarbon (HC, karbon monoksit (CO ve duman koyuluğu emisyonlarında iyileşmeler olduğu, bununla birlikte karbon dioksit (CO2 ve azot oksit (NOx emisyonlarının motor devrine göre kararlı bir yapı sergilemediği belirlenmiştir.

  6. Inhibitor of apoptosis (IAP)-like protein lacks a baculovirus IAP repeat (BIR) domain and attenuates cell death in plant and animal systems.

    Science.gov (United States)

    Kim, Woe Yeon; Lee, Sun Yong; Jung, Young Jun; Chae, Ho Byoung; Nawkar, Ganesh M; Shin, Mi Rim; Kim, Sun Young; Park, Jin Ho; Kang, Chang Ho; Chi, Yong Hun; Ahn, Il Pyung; Yun, Dae Jin; Lee, Kyun Oh; Kim, Young-Myeong; Kim, Min Gab; Lee, Sang Yeol

    2011-12-09

    A novel Arabidopsis thaliana inhibitor of apoptosis was identified by sequence homology to other known inhibitor of apoptosis (IAP) proteins. Arabidopsis IAP-like protein (AtILP) contained a C-terminal RING finger domain but lacked a baculovirus IAP repeat (BIR) domain, which is essential for anti-apoptotic activity in other IAP family members. The expression of AtILP in HeLa cells conferred resistance against tumor necrosis factor (TNF)-α/ActD-induced apoptosis through the inactivation of caspase activity. In contrast to the C-terminal RING domain of AtILP, which did not inhibit the activity of caspase-3, the N-terminal region, despite displaying no homology to known BIR domains, potently inhibited the activity of caspase-3 in vitro and blocked TNF-α/ActD-induced apoptosis. The anti-apoptotic activity of the AtILP N-terminal domain observed in plants was reproduced in an animal system. Transgenic Arabidopsis lines overexpressing AtILP exhibited anti-apoptotic activity when challenged with the fungal toxin fumonisin B1, an agent that induces apoptosis-like cell death in plants. In AtIPL transgenic plants, suppression of cell death was accompanied by inhibition of caspase activation and DNA fragmentation. Overexpression of AtILP also attenuated effector protein-induced cell death and increased the growth of an avirulent bacterial pathogen. The current results demonstrated the existence of a novel plant IAP-like protein that prevents caspase activation in Arabidopsis and showed that a plant anti-apoptosis gene functions similarly in plant and animal systems.

  7. Naturally occurring radionuclides and Earth sciences

    Directory of Open Access Journals (Sweden)

    G. Ferrara

    1997-06-01

    Full Text Available Naturally occurring radionuclides are used in Earth sciences for two fundamental purposes: age determination of rocks and minerals and studies of variation of the isotopic composition of radiogenic nuclides. The methodologies that are in use today allow us to determine ages spanning from the Earth's age to the late Quaternary. The variations of isotopic composition of radiogenic nuclides can be applied to problems of mantle evolution, magma genesis and characterization with respect to different geodynamic situations and can provide valuable information not obtainable by elemental geochemistry.

  8. Donor's age and replicative senescence favour the in-vitro mineralization potential of human fibroblasts.

    Science.gov (United States)

    Boraldi, Federica; Bartolomeo, Angelica; Di Bari, Caterina; Cocconi, Andrea; Quaglino, Daniela

    2015-12-01

    Aberrant mineralization of soft connective tissues (ectopic calcification) may occur as a frequent age-related complication. Still, it remains unclear the role of mesenchymal cell donor's age and of replicative senescence on ectopic calcification. Therefore, the ability of cells to deposit in-vitro hydroxyapatite crystals and the expression of progressive ankylosis protein homolog (ANKH), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), tissue non specific alkaline phosphatase (TNAP) and osteopontin (OPN) have been evaluated in human dermal fibroblasts derived from neonatal (nHDF) and adult (aHDF) donors (ex-vivo ageing model) or at low and high cumulative population doublings (CPD) up to replicative senescence (in-vitro ageing model). This study demonstrates that: 1) replicative senescence favours hydroxyapatite formation in cultured fibroblasts; 2) donor's age acts as a major modulator of the mineralizing potential of HDF, since nHDF are less prone than aHDF to induce calcification; 3) donor's age and replicative senescence play in concert synergistically increasing the calcification process; 4) the ANKH+ENPP1/TNAP ratio, being crucial for pyrophosphate/inorganic phosphate balance, is greatly influenced by donor's age, as well as by replicative senescence, and regulates mineral deposition; 5) OPN is only modulated by replicative senescence.

  9. Nucleosome occupancy as a novel chromatin parameter for replication origin functions

    Science.gov (United States)

    Rodriguez, Jairo; Lee, Laura; Lynch, Bryony; Tsukiyama, Toshio

    2017-01-01

    Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. PMID:27895110

  10. Variety of DNA Replication Activity Among Cyanobacteria Correlates with Distinct Respiration Activity in the Dark.

    Science.gov (United States)

    Ohbayashi, Ryudo; Yamamoto, Jun-Ya; Watanabe, Satoru; Kanesaki, Yu; Chibazakura, Taku; Miyagishima, Shin-Ya; Yoshikawa, Hirofumi

    2016-11-10

    Cyanobacteria exhibit light-dependent cell growth since most of their cellular energy is obtained by photosynthesis. In Synechococcus elongatus PCC 7942, one of the model cyanobacteria, DNA replication depends on photosynthetic electron transport. However, the critical signal for the regulatory mechanism of DNA replication has not been identified. In addition, conservation of this regulatory mechanism has not been investigated among cyanobacteria. To understand this regulatory signal and its dependence on light, we examined the regulation of DNA replication under both light and dark conditions among three model cyanobacteria, S. elongatus PCC 7942, Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120. Interestingly, DNA replication activity in Synechocystis and Anabaena was retained when cells were transferred to the dark, although it was drastically decreased in S. elongatus. Glycogen metabolism and respiration were higher in Synechocystis and Anabaena than in S. elongatus in the dark. Moreover, DNA replication activity in Synechocystis and Anabaena was reduced to the same level as that in S. elongatus by inhibition of respiratory electron transport after transfer to the dark. These results demonstrate that there is disparity in DNA replication occurring in the dark among cyanobacteria, which is caused by the difference in activity of respiratory electron transport.

  11. Insights into the Determination of the Templating Nucleotide at the Initiation of φ29 DNA Replication.

    Science.gov (United States)

    del Prado, Alicia; Lázaro, José M; Longás, Elisa; Villar, Laurentino; de Vega, Miguel; Salas, Margarita

    2015-11-06

    Bacteriophage φ29 from Bacillus subtilis starts replication of its terminal protein (TP)-DNA by a protein-priming mechanism. To start replication, the DNA polymerase forms a heterodimer with a free TP that recognizes the replication origins, placed at both 5' ends of the linear chromosome, and initiates replication using as primer the OH-group of Ser-232 of the TP. The initiation of φ29 TP-DNA replication mainly occurs opposite the second nucleotide at the 3' end of the template. Earlier analyses of the template position that directs the initiation reaction were performed using single-stranded and double-stranded oligonucleotides containing the replication origin sequence without the parental TP. Here, we show that the parental TP has no influence in the determination of the nucleotide used as template in the initiation reaction. Previous studies showed that the priming domain of the primer TP determines the template position used for initiation. The results obtained here using mutant TPs at the priming loop where Ser-232 is located indicate that the aromatic residue Phe-230 is one of the determinants that allows the positioning of the penultimate nucleotide at the polymerization active site to direct insertion of the initiator dAMP during the initiation reaction. The role of Phe-230 in limiting the internalization of the template strand in the polymerization active site is discussed.

  12. DNA moves sequentially towards the nuclear matrix during DNA replication in vivo

    Directory of Open Access Journals (Sweden)

    Aranda-Anzaldo Armando

    2011-01-01

    Full Text Available Abstract Background In the interphase nucleus of metazoan cells DNA is organized in supercoiled loops anchored to a nuclear matrix (NM. There is varied evidence indicating that DNA replication occurs in replication factories organized upon the NM and that DNA loops may correspond to the actual replicons in vivo. In normal rat liver the hepatocytes are arrested in G0 but they synchronously re-enter the cell cycle after partial-hepatectomy leading to liver regeneration in vivo. We have previously determined in quiescent rat hepatocytes that a 162 kbp genomic region containing members of the albumin gene family is organized into five structural DNA loops. Results In the present work we tracked down the movement relative to the NM of DNA sequences located at different points within such five structural DNA loops during the S phase and after the return to cellular quiescence during liver regeneration. Our results indicate that looped DNA moves sequentially towards the NM during replication and then returns to its original position in newly quiescent cells, once the liver regeneration has been achieved. Conclusions Looped DNA moves in a sequential fashion, as if reeled in, towards the NM during DNA replication in vivo thus supporting the notion that the DNA template is pulled progressively towards the replication factories on the NM so as to be replicated. These results provide further evidence that the structural DNA loops correspond to the actual replicons in vivo.

  13. The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A

    Science.gov (United States)

    Lei, Xiaobo; Xiao, Xia; Zhang, Zhenzhen; Ma, Yijie; Qi, Jianli; Wu, Chao; Xiao, Yan; Zhou, Zhuo; He, Bin; Wang, Jianwei

    2017-01-01

    Enterovirus 71 (EV71) is a human pathogen that causes hand, foot, mouth disease and neurological complications. Although EV71, as well as other enteroviruses, initiates a remodeling of intracellular membrane for genomic replication, the regulatory mechanism remains elusive. By screening human cDNA library, we uncover that the Golgi resident protein acyl-coenzyme A binding domain-containing 3 (ACBD3) serves as a target of the 3A protein of EV71. This interaction occurs in cells expressing 3A or infected with EV71. Genetic inhibition or deletion of ACBD3 drastically impairs viral RNA replication and plaque formation. Such defects are corrected upon restoration of ACBD3. In infected cells, EV71 3A redirects ACBD3, to the replication sites. I44A or H54Y substitution in 3A interrupts the binding to ACBD3. As such, viral replication is impeded. These results reveal a mechanism of EV71 replication that involves host ACBD3 for viral replication. PMID:28303920

  14. Asynchronous replication and autosome-pair non-equivalence in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Devkanya Dutta

    Full Text Available A number of mammalian genes exhibit the unusual properties of random monoallelic expression and random asynchronous replication. Such exceptional genes include genes subject to X inactivation and autosomal genes including odorant receptors, immunoglobulins, interleukins, pheromone receptors, and p120 catenin. In differentiated cells, random asynchronous replication of interspersed autosomal genes is coordinated at the whole chromosome level, indicative of chromosome-pair non-equivalence. Here we have investigated the replication pattern of the random asynchronously replicating genes in undifferentiated human embryonic stem cells, using fluorescence in situ hybridization based assay. We show that allele-specific replication of X-linked genes and random monoallelic autosomal genes occur in human embryonic stem cells. The direction of replication is coordinated at the whole chromosome level and can cross the centromere, indicating the existence of autosome-pair non-equivalence in human embryonic stem cells. These results suggest that epigenetic mechanism(s that randomly distinguish between two parental alleles are emerging in the cells of the inner cell mass, the source of human embryonic stem cells.

  15. THE VILLAGE UTOPIS AS THE PRESENTATION OF THE IDEAL PLACE ON THE MODERN NATION-STATE PROJECT MODERN ULUS DEVLET PROJESİNDE BIR İDEAL MEKÂN TEMSILI OLARAK KÖY ÜTOPYASI

    Directory of Open Access Journals (Sweden)

    Esra DİCLE

    2012-01-01

    Full Text Available Foucault says that space is an area of power warfare, conflict between organizing and disciplinizing authority and the people who live there. He emphasizes that the politics of town planning of power has a direct relationship with the ideology of power. In this respect, power, organizes the space and also disciplines the individual by separating the areas of power to parts, making individuals visible, normalizing the behaviors, Space is a stage on which ideological transfers occur. It is an instrument that forwards the power’s being to subjects and legitimizes and normalizes this power. After the eighteenth century, town planning and the organization of public sphere have an important role in almost all political debates. As Foucault says power is dispersed to all social places and can be seen every part of the city as a stage and sign. Power’s being is transferred to the conscious of individual by means of signs and passwords that are positioned on all around the city. Turkish Republic’s ekonomic, cultural and political projects are based on the village politics of Kemalizm, after the 1930’s. Kemalizm thinks that the ekonomic independence and the modernization of the country should start from the villages. In this period, they determine the problems of the village where the ideology will be produced. Kemalism has two main aims about the village modernization project: To supply the development of the village and to educate peasents. It is possible to encounter with the Kemalist village discourse on the plays which are written to be staged on People’s Houses. These plays represent peasants as the origin of Turkish identity, express the importance of statepeasant unification, education of the villagers and the industrilazion of village. Foucault, mekânın iktidar mücadelesinin de bir alanı olduğunu söyler. Mekân, düzenleyen ve disipline edenle, yaşayan ve kendiliğinden olanın çatışma alanıdır. Bu noktada iktidarların

  16. Spatial regulation and organization of DNA replication within the nucleus

    OpenAIRE

    2009-01-01

    Duplication of chromosomal DNA is a temporally and spatially regulated process. The timing of DNA replication initiation at various origins is highly coordinated; some origins fire early and others late during S phase. Moreover, inside the nuclei, the bulk of DNA replication is physically organized in replication factories, consisting of DNA polymerases and other replication proteins. In this review article, we discuss how DNA replication is organized and regulated spatially within the nucleu...

  17. An archaeological data assessment of Persian ethnicity in LydiaLydia’da Pers etnisitesine ait arkeolojik bir veri değerlendirmesi

    Directory of Open Access Journals (Sweden)

    Hatice Kalkan

    2014-04-01

    ğerlendirilmektedir.Gömü hediyesi olarak iki lekythos, bir bronz Akhaimenid kâsenin saptandığı buluntu grubunun bu bölgede geç dönemde varlığından haberdar olduğumuz Pers etnisitesi açısından anlamı sorgulanmaktadır. 2014 yılında Ödemiş Müze Müdürlüğü tarafından yapılan Beydağ tümülüs kazılarında da parçalar halindeki benzer bir lahitle birlikte ele geçirilmiş  Akhaimenid kâseler bu alanda olası bir Anahita bağlantılı ölü kült geleneğinin araştırılmasını gerektirmiştir. Benzer bir durumun Nif Dağı araştırmalarında da ortaya çıkmış olması ve kontekstlerden gömü beraberinde bu kase tipinin ele geçmesi ön görümüzü güçlendirmektedir. Bölgedeki Hellenistik ve Roma Dönemlerinde var olan Pers etnisitesinin yazıt, sikke ve antik kaynaklardaki kanıtları bilinmektedir. Bunun  yanı sıra materyal kültür açısından  burada konu edilen yeni izlerin gömü geleneklerinde  takip edilebilmesi, Pers etkisinin başka bir yansıması olarak önem taşımaktadır. Anahita inancının Akhaimenid dönemden Roma dönemine kadar sürmüş olan popülerliği, burada sadece “Lydialı İranlılar” değil tüm yerli ve Romalı nüfus üzerinde etki yaratmış görünmektedir. Ancak Pers nüfusunun mevcudiyeti büyük ölçüde Anahita inanç ve kült pratikleri ile ilişkilidir. Bu nedenle Akhaimenid kültürünün en bilinen kültik formu phialelerin ise zaman zaman gömüler beraberinde ele geçiyor olmasının Hellenistik Dönemde özellikle Pers etnisitesinin belirlenmesinde güçlü bir arkeolojik veri olduğu göz önünde tutulmalıdır.

  18. Memet Baydur Tiyatrosu ve Dramatik Bir Pazarlık Oyunu: Kamyon Memet Baydur Theatre A Dramatic Bargain Play: The Lorry

    Directory of Open Access Journals (Sweden)

    Kemal EROL

    2013-07-01

    Full Text Available Memet Baydur (1951-2001 is a playwright who appointed hisplace in Modern Turkish Theatre with 23 of his plays written in thesocial realist approach, in the last 20 years of his life. His plays coverthe 1980’s. Baydur reflected on the events and facts experiencedduring this historical period, writing his plays through a critic’s eye.Baydur’s plays tell us about the class conflict in society through theinner world conflict of social classes and life conditions of people whocame from different classes. These conditions create the main points ofhis plays, not the events themselves. These texts, each of which wereperformed in private and state theatres, question some problematicrealities about humans and society.The Lorry (1990, is his 9thplay after his first play Lemon (1982. Itfocuses on the difficult working conditions of a certain part of societyduring that era. This work evokes sadness in the controversialeconomical relations. It is the raw story of people who are bored withdespair, lacking alternatives, shown through needy immigrant peasantsin tough life conditions. It is the drama of the New World’s peonsyearning to live like a human, who put their lives in danger to maintainhis family and put their strength in bargain. In this aspect, The Lorry, is“a bargain play, a bargain of life” in Baydur’s words. The work aims todemonstrate the social realities while adding some conventional senseof humor, instead of just saying the social realities as they are.In this work, document searching method has been used. Thepurpose of this paper is to introduce Memet Baydur Theatre in generalterms and to analyze The Lorry in terms of subject, fiction, time,characters and theme and to determine its scientific value. Memet Baydur (1951-2001, ömrünün son yirmi yılında sosyal gerçekçi sanat anlayışı çizgisinde yazdığı 23 oyunla çağdaş Türk tiyatrosundaki yerini tayin eden bir yazardır. Onun tiyatro oyunları, dönem olarak 1980

  19. Chemistry: Small molecular replicators go organic

    Science.gov (United States)

    Taylor, Annette F.

    2016-09-01

    The emergence of complex, dynamic molecular behaviour might have had a role in the origin of life. Such behaviour has now been seen in a reaction network involving small, organic, self-replicating molecules of biological relevance. See Letter p.656

  20. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf; Hansen, Hans Nørgaard; Kjær, Erik Michael

    2005-01-01

    The surface micro topography of injection moulded plastic parts can be important for aesthetical and technical reasons. The quality of replication of mould surface topography onto the plastic surface depends among other factors on the process conditions. A study of this relationship has been...

  1. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

    Wæhrens, Brian Vejrum; Yang, Cheng; Madsen, Erik Skov

    2012-01-01

    exploration, the small sample size is an obvious limitation for generalisation. Practical implications – A roadmap for knowledge transfer within the replication of a production line is suggested, which, together with four managerial suggestions, provides strong support and clear directions to managers...

  2. Replication and Inhibitors of Enteroviruses and Parechoviruses

    Directory of Open Access Journals (Sweden)

    Lonneke van der Linden

    2015-08-01

    Full Text Available The Enterovirus (EV and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV. They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.

  3. Representation dimension of m-replicated algebras

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Let A be a finite-dimensional hereditary algebra over an algebraically closed field and A(m) be the m-replicated algebra of A.We prove that the representation dimension of A(m) is at most 3,and that the dominant dimension of A(m) is at least m.

  4. Multiseason occupancy models for correlated replicate surveys

    Science.gov (United States)

    Hines, James; Nichols, James; Collazo, Jaime

    2014-01-01

    Occupancy surveys collecting data from adjacent (sometimes correlated) spatial replicates have become relatively popular for logistical reasons. Hines et al. (2010) presented one approach to modelling such data for single-season occupancy surveys. Here, we present a multiseason analogue of this model (with corresponding software) for inferences about occupancy dynamics. We include a new parameter to deal with the uncertainty associated with the first spatial replicate for both single-season and multiseason models. We use a case study, based on the brown-headed nuthatch, to assess the need for these models when analysing data from the North American Breeding Bird Survey (BBS), and we test various hypotheses about occupancy dynamics for this species in the south-eastern United States. The new model permits inference about local probabilities of extinction, colonization and occupancy for sampling conducted over multiple seasons. The model performs adequately, based on a small simulation study and on results of the case study analysis. The new model incorporating correlated replicates was strongly favoured by model selection for the BBS data for brown-headed nuthatch (Sitta pusilla). Latitude was found to be an important source of variation in local colonization and occupancy probabilities for brown-headed nuthatch, with both probabilities being higher near the centre of the species range, as opposed to more northern and southern areas. We recommend this new occupancy model for detection–nondetection studies that use potentially correlated replicates.

  5. Structure and replication of hepatitis delta virus

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Unidade de Biologia Molecular, Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, ... molecules of both delta antigens (Ryu et al., 1993). This ..... Glenn JS, Watson JA, Havel CM, White JO (1992). ... HDV RNA encoding the large delta antigen cannot replicate. J. Gen.

  6. Are renal ciliopathies (replication) stressed out?

    NARCIS (Netherlands)

    Slaats, Gisela G; Giles, R

    2015-01-01

    Juvenile renal failure is commonly caused by the ciliopathy nephronophthisis (NPHP). Since all NPHP genes regulate cilia function, it has been assumed that NPHP onset is due to cilia loss. However, recent data suggest that DNA damage caused by replication stress, possibly concomitant with or upstrea

  7. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  8. A network of cancer genes with co-occurring and anti-co-occurring mutations.

    Directory of Open Access Journals (Sweden)

    Qinghua Cui

    Full Text Available Certain cancer genes contribute to tumorigenesis in a manner of either co-occurring or mutually exclusive (anti-co-occurring mutations; however, the global picture of when, where and how these functional interactions occur remains unclear. This study presents a systems biology approach for this purpose. After applying this method to cancer gene mutation data generated from large-scale and whole genome sequencing of cancer samples, a network of cancer genes with co-occurring and anti-co-occurring mutations was constructed. Analysis of this network revealed that genes with co-occurring mutations prefer direct signaling transductions and that the interaction relations among cancer genes in the network are related with their functional similarity. It was also revealed that genes with co-occurring mutations tend to have similar mutation frequencies, whereas genes with anti-co-occurring mutations tend to have different mutation frequencies. Moreover, genes with more exons tend to have more co-occurring mutations with other genes, and genes having lower local coherent network structures tend to have higher mutation frequency. The network showed two complementary modules that have distinct functions and have different roles in tumorigenesis. This study presented a framework for the analysis of cancer genome sequencing outputs. The presented data and uncovered patterns are helpful for understanding the contribution of gene mutations to tumorigenesis and valuable in the identification of key biomarkers and drug targets for cancer.

  9. Replisome speed determines the efficiency of the Tus−Ter replication termination barrier

    KAUST Repository

    Elshenawy, Mohamed

    2015-08-31

    In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a \\'replication fork trap\\' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes. ©2015 Macmillan Publishers Limited. All rights reserved.

  10. Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability.

    Science.gov (United States)

    Schalbetter, Stephanie A; Mansoubi, Sahar; Chambers, Anna L; Downs, Jessica A; Baxter, Jonathan

    2015-08-18

    Faithful genome duplication and inheritance require the complete resolution of all intertwines within the parental DNA duplex. This is achieved by topoisomerase action ahead of the replication fork or by fork rotation and subsequent resolution of the DNA precatenation formed. Although fork rotation predominates at replication termination, in vitro studies have suggested that it also occurs frequently during elongation. However, the factors that influence fork rotation and how rotation and precatenation may influence other replication-associated processes are unknown. Here we analyze the causes and consequences of fork rotation in budding yeast. We find that fork rotation and precatenation preferentially occur in contexts that inhibit topoisomerase action ahead of the fork, including stable protein-DNA fragile sites and termination. However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3. In the absence of Tof1/Timeless, excessive fork rotation and precatenation cause extensive DNA damage following DNA replication. With Tof1, damage related to precatenation is focused on the fragile protein-DNA sites where fork rotation is induced. We conclude that although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin.

  11. ReplicationDomain: a visualization tool and comparative database for genome-wide replication timing data

    Directory of Open Access Journals (Sweden)

    Yokochi Tomoki

    2008-12-01

    Full Text Available Abstract Background Eukaryotic DNA replication is regulated at the level of large chromosomal domains (0.5–5 megabases in mammals within which replicons are activated relatively synchronously. These domains replicate in a specific temporal order during S-phase and our genome-wide analyses of replication timing have demonstrated that this temporal order of domain replication is a stable property of specific cell types. Results We have developed ReplicationDomain http://www.replicationdomain.org as a web-based database for analysis of genome-wide replication timing maps (replication profiles from various cell lines and species. This database also provides comparative information of transcriptional expression and is configured to display any genome-wide property (for instance, ChIP-Chip or ChIP-Seq data via an interactive web interface. Our published microarray data sets are publicly available. Users may graphically display these data sets for a selected genomic region and download the data displayed as text files, or alternatively, download complete genome-wide data sets. Furthermore, we have implemented a user registration system that allows registered users to upload their own data sets. Upon uploading, registered users may choose to: (1 view their data sets privately without sharing; (2 share with other registered users; or (3 make their published or "in press" data sets publicly available, which can fulfill journal and funding agencies' requirements for data sharing. Conclusion ReplicationDomain is a novel and powerful tool to facilitate the comparative visualization of replication timing in various cell types as well as other genome-wide chromatin features and is considerably faster and more convenient than existing browsers when viewing multi-megabase segments of chromosomes. Furthermore, the data upload function with the option of private viewing or sharing of data sets between registered users should be a valuable resource for the

  12. Active RNA replication of hepatitis C virus downregulates CD81 expression.

    Science.gov (United States)

    Ke, Po-Yuan; Chen, Steve S-L

    2013-01-01

    So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

  13. Active RNA replication of hepatitis C virus downregulates CD81 expression.

    Directory of Open Access Journals (Sweden)

    Po-Yuan Ke

    Full Text Available So far how hepatitis C virus (HCV replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp infection and downregulated cell surface level of CD81, a critical HCV entry (coreceptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

  14. Inclusion bodies are a site of ebolavirus replication.

    Science.gov (United States)

    Hoenen, Thomas; Shabman, Reed S; Groseth, Allison; Herwig, Astrid; Weber, Michaela; Schudt, Gordian; Dolnik, Olga; Basler, Christopher F; Becker, Stephan; Feldmann, Heinz

    2012-11-01

    Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for other viruses that produce similar structures have suggested that inclusion bodies might be involved in genome replication and transcription. In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus polymerase L, which is found in inclusion bodies. The resulting L-mCherry fusion protein was functional in minigenome assays and incorporated into virus-like particles. Importantly, L-mCherry fluorescence in transfected cells was readily detectable and distributed in a punctate pattern characteristic for inclusion bodies. A recombinant ebolavirus encoding L-mCherry instead of L was rescued and showed virtually identical growth kinetics and endpoint titers to those for wild-type virus. Using this virus, we showed that the onset of inclusion body formation corresponds to the onset of viral genome replication, but that viral transcription occurs prior to inclusion body formation. Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that they can undergo dramatic reorganization during cell division. Finally, by labeling nascent RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthesis. Based on these data we conclude that, rather than being inert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structures and an important site at which viral RNA replication takes place.

  15. Early events in alphavirus replication determine the outcome of infection.

    Science.gov (United States)

    Frolov, Ilya; Akhrymuk, Maryna; Akhrymuk, Ivan; Atasheva, Svetlana; Frolova, Elena I

    2012-05-01

    Alphaviruses are a group of important human and animal pathogens. They efficiently replicate to high titers in vivo and in many commonly used cell lines of vertebrate origin. They have also evolved effective means of interfering with development of the innate immune response. Nevertheless, most of the alphaviruses are known to induce a type I interferon (IFN) response in vivo. The results of this study demonstrate that the first hours postinfection play a critical role in infection spread and development of the antiviral response. During this window, a balance is struck between virus replication and spread in vertebrate cells and IFN response development. The most important findings are as follows: (i) within the first 2 to 4 h postinfection, alphavirus-infected cells become unable to respond to IFN-β, and this occurs before the virus-induced decrease in STAT1 phosphorylation in response to IFN treatment. (ii) Most importantly, very low, subprotective doses of IFN-β, which do not induce the antiviral response in uninfected cells, have a very strong stimulatory effect on the cells' ability to express type I IFN and activate interferon-stimulated genes during subsequent infection with Sindbis virus (SINV). (iii) Small changes in SINV nsP2 protein affect its ability to inhibit cellular transcription and IFN release. Thus, the balance between type I IFN induction and the ability of the virus to develop further rounds of infection is determined in the first few hours of virus replication, when only low numbers of cells and infectious virus are involved.

  16. Eskişehir Devlet Demir Yolları Yerleşkesi Lojman Konutları Plan Tipolojileri Üzerine bir Çalışma

    Directory of Open Access Journals (Sweden)

    Berna Üstün

    2011-12-01

    Full Text Available Sanayi yapıları yalnızca makineleri barındıran binalar değil, yeni bir yaşam tarzının ve kültürünün topluma tanıtılmasının ve yayılmasının araçlarıdırlar. Sanayi yapıları, modern sanayinin ortaya çıkardığı sınıfsal yapıdan başlayarak, işyeri ilişkilerine uzanan toplumsal dönüşümlerin ortak mekânı olarak kabul edilebilir (Doğan, 2009:77. Bu kapsamda, İngiltere, Almanya ve ABD’de endüstri devrimi ile birlikte artan üretim mekânları ile yaygınlık kazanan, sanayi yapıları kurucuları, çalışanlardan daha etkin bir biçimde yararlanmak ve daha verimli şartlar sunma kaygısı ile Company Town’ları (Şirket Kentlerini oluşturmuşlardır.Sanayileşme, Batıda olduğu gibi Modern Türkiye’nin kurucu öğelerinden olmuş, bir yandan toplumu dönüştürüp farklılaştırırken, diğer yandan toplumu örgütlemenin ve onun iç dinamiklerine müdahale etmenin bir aracı olarak kullanılmıştır.  Aynı zamanda sanayi kuruluşları ile konut kurguları, kentin konut kültürünün anlaşılmasında önemli bir veri teşkil etmiştir. Bu kapsamda ele alınan, Eskişehir Devlet Demir Yolları (Tülomsaş Yerleşkesi; günümüz endüstriyel mirasının fonksiyonel ve mekânsal bağlamda öncü örneklerindendir. Eskişehir kenti için bir prototip olma özelliği taşıyan yerleşke; çalışanlarının çalışma dışında, barınma, sosyal, kültürel ve eğitime yönelik gereksinimlerini karşılayan mikro ölçekli bir kent modeli ortaya koyan ilk yapılanmalardan biri olma özelliği taşımaktadır. Eskişehir kenti için özellikle inşa edildiği dönemde ve sonrasında önemli bir ekonomik ve sosyal dinamik oluşturmuştur.Makale kapsamında; Batıda 1800’lü yıllarda ortaya çıkan Türkiye’de ise Cumhuriyetin ilanı ile örneklerini veren Şirket Kentlerinin gelişimi özetlenerek Eskişehir’de bir şirket kenti Company Town örneği olan Devlet Demir Yolları (T

  17. Tetrahydroberberine, a pharmacologically active naturally occurring alkaloid.

    Science.gov (United States)

    Pingali, Subramanya; Donahue, James P; Payton-Stewart, Florastina

    2015-04-01

    Tetrahydroberberine (systematic name: 9,10-dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the molecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core. The intermolecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole -CH2···OCH3 and -OCH3···OCH3 interactions between neighboring molecules.

  18. Pilomyxoid Astrocytoma Occurring in the Third Ventricle

    Directory of Open Access Journals (Sweden)

    Sanghyeon Kim

    2015-01-01

    Full Text Available Pilomyxoid astrocytoma (PMA is a rare central nervous system tumor that has been included in the 2007 World Health Organization Classification of Tumors of the Central Nervous System. Due to its more aggressive behavior, PMA is classified as Grade II neoplasm by the World Health Organization. PMA predominantly affects the hypothalamic/chiasmatic region and occurs in children (mean age of occurrence = 10 months. We report a case of a 24-year-old man who presented with headache, nausea, and vomiting. Brain CT and MRI revealed a mass occupying only the third ventricle. We performed partial resection. Histological findings, including monophasic growth with a myxoid background, and absence of Rosenthal fibers or eosinophilic granular bodies, as well as the strong positivity for glial fibrillary acidic protein were consistent with PMA.

  19. Detection of Harmonic Occurring using Kalman Filtering

    DEFF Research Database (Denmark)

    Hussain, Dil Muhammad Akbar; Shoro, Ghulam Mustafa; Imran, Raja Muhammed

    2014-01-01

    As long as the load to a power system is linear which has been the case before 80's, typically no harmonics are produced. However, the modern power electronic equipment for controlled power consumption produces harmonic disturbances, these devices/equipment possess nonlinear voltage/current chara...... using Kalman filter. This may be very useful for example to quickly switching on certain filters based on the harmonic present. We are using a unique technique to detect the occurrence of harmonics......./current characteristic. These harmonics are not to be allowed to grow beyond a certain limit to avoid any grave consequence to the customer’s main supply. Filters can be implemented at the power source or utility location to eliminate these harmonics. In this paper we detect the instance at which these harmonics occur...

  20. Mehmed Enisî Yalkı’nın Alman Ruhu Adlı Seyahatnamesine İmgebilimsel Bir Yaklaşım An Imagologist Approach To Mehmet Enisi Yalkı's Travelbook

    Directory of Open Access Journals (Sweden)

    Yılmaz DAŞCIOĞLU

    2012-12-01

    Full Text Available The period of second constitutional is very important in terms of providing transition between Reorganization and Republic period. Besides this, it is a pioneer period in that it encloses determinants which play an important role in bulding a new national identity. It is a clear fact that literary works take a crucial assignment in creation of a new national identity. In this respect, to asses that some literary works published during second contitutional had very important functions to build up western-type turkish identity which was systematized later by Republic period would not be wrong. In this research, one of abroad travelbook after second constitutional is scrutinized, using imagology as a method. Mehmed Enisi Yalkı, jounalist and writer from the time ofconstitutional, proposes German/Germany model in order to build up a newnation, a western type Turk, in his travelbook Alman Ruhu which is still nottranscripted from Arabic Alphabet to Latin. This model is analysed in terms ofimagery. Being resound as a background, the exclamations such as work like aGerman, immovable like a German, fortify your spirit like a German, run afterjustice like a German are the signs of proposing Germany as a model. At theend of research it is determined that ottoman intellectuals who experienced thecrisis of building a new nation wrote travelbook to educate and direct society, topresent an alternative life or culture for it rather than literary concern duringthe time from Reorganization to Republic. II. Meşrutiyet dönemi, Tanzimat ile Cumhuriyet arasındaki geçişi sağlaması yönüyle son derece önemli bir evre olduğu gibi, yeni bir ulusun kimliğinin oluşumunda rol oynayan etkenleri barındırması yönüyle de öncü bir dönemdir. Bir ulusun kimliğinin oluşmasında edebiyat eserlerinin çok önemli bir görev üstlendiği açık bir gerçektir. Bu bağlamda II. Meşrutiyet dönemi gibi kritik bir zaman zarfında ortaya konan kimi edebi eserlerin

  1. Estetik Bir Öğe Olarak Sinemada Ses Tasarımı Ve Örnek Bir Film Çözümlemesi Sound Design As An Aesthetical Element In Cinema And An Example Of A Film Analysis

    Directory of Open Access Journals (Sweden)

    Mustafa SÖZEN

    2013-09-01

    Full Text Available It is a well-known fact that the image itself, even in a film having the simplest story, does not provide enough message. Due to a spesific aesthetic predication of audio phonemena, the films, right from the beginning, started to be shown in accompany with sound. The soundelement in cinematography which produces the semantic expression asa parlance by means of images and sounds has its own ways of use.The sound universe of cinematography is composed of dialogs, effectsand music each having different ontologies. In today’s cinematography,all these three elements were given in. For all that, in some filmsproduced for certain aesthetic considerations and in limited numbersthe usage of effects and music are avoided. Looking at the elementsmaking up the universe of sound in a film from the perspective ofessential functions it is seen that the dialogs are used to provideinformation, effects to create a real spatial and temporal feeling, andmusic to conceive the ambiance required by narrative. By doing so,matching the sounds in harmony with images is achieved and so theenhancement of the narrative’s reality illusion is expected. Somedirectors on the other hand, by pushing the sound out of its basicfunctions, rendering images and sounds contrary oppose this approachgo in search of producing different and new meanings. This studyinvestigates the how the sound universe design of the film “Deli DeliOlma” directed by Murat Saracoğlu, as an aesthetic element ismanipulated. In analysis, sound universe has been assesed either bystructural or dramatic functional dimensions. En basit öyküye sahip bir filmde bile sadece görüntülerin yeteri kadar ileti sağlamadığı bilinen bir gerçekliktir. Ses olgusunun kendine özgü estetik bir yükleme sahip oluşundan ötürü, sinemanın ilk anlarından itibaren filmler ses eşliğinde gösterilmeye başlanmıştır. Bir dil olarak anlamsal ifadeyi görüntü ve sesler aracılığıyla üreten sinemada ses

  2. Turistlerin destinasyon seçiminde rol oynayan bir etken olarak yerel mutfaklar: İzmir Yarımadası’nı ziyaret eden turistlerin algılamaları üzerine bir araştırma

    OpenAIRE

    ZAĞRALI, Egem; AKBABA, Atilla

    2015-01-01

    Bu çalışmada İzmir Yarımada örneği üzerinde yerel yemeklerin turistler açısından ne derecede çekicilik unsuru oluşturduğu araştırılmıştır. Çalışma kapsamında İzmir Yarımadası’nı ziyaret eden yerli ve yabancı turistler üzerinde (n=430) bir alan araştırması yapılarak, turistlerin düşünceleri ve algılamaları çerçevesinde ortaya çıkan veriler irdelenmiştir. Çalışma sonucunda turistlerin Yarımada’yı tercihlerinde yerel yemeklerin belirleyici bir rol oynamadığı, ancak yerel yemekleri beğendikleri v...

  3. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    HAN Xin; ZHANG DeYuan

    2008-01-01

    Direct replication of creatural scarfskins to form biomimetic surfaces with relatively vivid morphology is a new attempt of the bio-replicated forming technology at animal body.Taking shark skins as the replication templates,and the micro-em-bossing and micro-molding as the material forming methods,the micro-replicating technology of the outward morphology on shark skins was demonstrated.The pre-liminary analysis on replication precision indicates that the bio-replicated forming technology can replicate the outward morphology of the shark scales with good precision,which validates the application of the bio-replicated forming technology in the direct morphology replication of the firm creatural scarfskins.

  4. The Role of the Transcriptional Response to DNA Replication Stress.

    Science.gov (United States)

    Herlihy, Anna E; de Bruin, Robertus A M

    2017-03-02

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

  5. A replication-time-controlling sequence element in Schizosaccharomyces pombe.

    Science.gov (United States)

    Tripathi, Vishnu P; Dubey, Dharani D

    2017-08-01

    Eukaryotic replication origins are highly variable in their activity and replication timing. The nature and role of cis-acting regulatory sequences that control chromosomal replication timing is not well defined. In the fission yeast, Schizosaccharomyces pombe, a 200-bp late-replication-enforcing element (LRE), has been shown to enforce late replication of ARS elements in plasmids. Here, we show that a short (133-bp) fragment of the LRE (shLRE) is required for causing late replication of adjoining origins in its native as well as in an ectopic early-replicating chromosomal location. Active from both sides of an early-replicating origin, the shLRE is a bona fide cis-acting regulatory element that imposes late replication timing in the chromosome.

  6. Birliktelik Kısıtları Altında Montaj Hattı Dengeleme Problemi İçin Bir Çözüm Yaklaşımı Önerisi ve Bir İşletmede Uygulama

    Directory of Open Access Journals (Sweden)

    Serkan Altuntaş

    2010-01-01

    Full Text Available Montaj Hattı Dengelemesinde, -çeşitli nedenlerle- belli iş elemanlarının birbirinden ayrılmaması ve aynı istasyona atanması istenebilir. Bu tür problemler, 'Birliktelik Kısıtları Altında Montaj Hattı Dengeleme (BKAMHD Problemi' olarak tanınmaktadır. Bu birliktelik kısıtı sayesinde, havaleli ürün imali, birlikte işlem görme gereği gibi özel isteklerden veya takım-kolaylık benzeri kaynakların ortak kullanımı düşüncesinden kaynaklanan 'konum ve bölge kısıtları' da karşılanabilmektedir. Bu tür hatlarda ayrıca, malzeme aktarma, takım ve kolaylık maliyetleri, yürüyüş mesafeleri, ayar süreleri ile tedarik süreleri de azalmaktadır. Uygulamada BKAMHD yapısındaki problemlerle yaygın olarak karşılaşılmasına karşın, bunlar üzerinde yapılan çalışmaların klasik montaj hattı dengeleme problemi ile ilgili yayınlara göre daha az olduğu görülmektedir. Bu çalışmanın amacı, özel konum kısıtları dolayısıyla-, bilinen Montaj Hattı Dengeleme yöntemlerinin uygulanamadığı büyük ölçekli bir montaj hattı için uygun bir hat dengeleme yöntemi geliştirmek ve bu yöntem ile söz konusu hattı dengelemek olmuştur. Çalışmanın başında, bu problemin çözümünde kullanılabilecek basit fakat etkili bir yol olarak tanınan 'En Büyük Aday' algoritmasında bazı değişiklikler yapılarak yeni bir yöntem geliştirilmiştir. Bu yöntemin uyarlanabilmesi için de montaj işlemlerinin yapıldığı atölyede çok yoğun bir metot ve zaman etüdü çalışması yürütmek gerekmiştir. Bu çalışma sonucunda derlenen verilerin geliştirilen yönteme uyarlanması sonucunda türetilen seçenekler değerlendirilerek karar vericiye sunulmuştur.

  7. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  8. Exploiting features of adenovirus replication to support mammalian kinase production.

    Science.gov (United States)

    Cotten, Matt; Stegmueller, Kerstin; Eickhoff, Jan; Hanke, Miriam; Herzberger, Katrin; Herget, Thomas; Choidas, Axel; Daub, Henrik; Godl, Klaus

    2003-11-01

    Faced with the current wealth of genomic data, it is essential to have robust and reliable methods of converting DNA sequences into their functional gene products. We demonstrate here that when conditions are established that take advantage of the replication-associated virus amplification, the virus-induced shutdown of host protein synthesis as well as the activation of signalling pathways that normally occur during virus replication, adenovirus biology can be exploited to generate a potent kinase expression system. Residual virus in the protein production has always been a limitation for adenovirus systems and we describe a DNA intercalator/ultraviolet light treatment that eliminates residual adenovirus in protein preparations that has no deleterious effect on enzyme activity. The use of mammalian cells in combination with adenovirus generated a variety of active enzymes which could not be produced in Escherichia coli or baculovirus-infected insect cells. Thus, the utility of adenovirus-mediated enzyme expression as a versatile alternative to established protein production technologies is demonstrated.

  9. Myc localizes to histone locus bodies during replication in Drosophila.

    Directory of Open Access Journals (Sweden)

    Kaveh Daneshvar

    Full Text Available Myc is an important protein at the center of multiple pathways required for growth and proliferation in animals. The absence of Myc is lethal in flies and mice, and its over-production is a potent inducer of over-proliferation and cancer. Myc protein is localized to the nucleus where it executes its many functions, however the specific sub-nuclear localization of Myc has rarely been reported. The work we describe here began with an observation of unexpected, punctate spots of Myc protein in certain regions of Drosophila embryos. We investigated the identity of these puncta and demonstrate that Myc is co-localized with coilin, a marker for sub-nuclear organelles known as Cajal Bodies (CBs, in embryos, larvae and ovaries. Using antibodies specific for U7 snRNP component Lsm11, we show that the majority of Myc and coilin co-localization occurs in Histone Locus Bodies (HLBs, the sites of histone mRNA transcription and processing. Furthermore, Myc localizes to HLBs only during replication in mitotic and endocycling cells, suggesting that its role there relates to replication-dependent canonical histone gene transcription. These results provide evidence that sub-nuclear localization of Myc is cell-cycle dependent and potentially important for histone mRNA production and processing.

  10. The hexameric structure of the human mitochondrial replicative helicase Twinkle.

    Science.gov (United States)

    Fernández-Millán, Pablo; Lázaro, Melisa; Cansız-Arda, Şirin; Gerhold, Joachim M; Rajala, Nina; Schmitz, Claus-A; Silva-Espiña, Cristina; Gil, David; Bernadó, Pau; Valle, Mikel; Spelbrink, Johannes N; Solà, Maria

    2015-04-30

    The mitochondrial replicative helicase Twinkle is involved in strand separation at the replication fork of mitochondrial DNA (mtDNA). Twinkle malfunction is associated with rare diseases that include late onset mitochondrial myopathies, neuromuscular disorders and fatal infantile mtDNA depletion syndrome. We examined its 3D structure by electron microscopy (EM) and small angle X-ray scattering (SAXS) and built the corresponding atomic models, which gave insight into the first molecular architecture of a full-length SF4 helicase that includes an N-terminal zinc-binding domain (ZBD), an intermediate RNA polymerase domain (RPD) and a RecA-like hexamerization C-terminal domain (CTD). The EM model of Twinkle reveals a hexameric two-layered ring comprising the ZBDs and RPDs in one layer and the CTDs in another. In the hexamer, contacts in trans with adjacent subunits occur between ZBDs and RPDs, and between RPDs and CTDs. The ZBDs show important structural heterogeneity. In solution, the scattering data are compatible with a mixture of extended hexa- and heptameric models in variable conformations. Overall, our structural data show a complex network of dynamic interactions that reconciles with the structural flexibility required for helicase activity.

  11. Betulin-derived compounds as inhibitors of alphavirus replication.

    Science.gov (United States)

    Pohjala, Leena; Alakurtti, Sami; Ahola, Tero; Yli-Kauhaluoma, Jari; Tammela, Päivi

    2009-11-01

    This paper describes inhibition of Semliki Forest virus (SFV) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical modifications were made to OH groups at C-3 and C-28 and to the C-20-C-29 double bond. A set of heterocyclic betulin derivatives was also assayed. A free or acetylated OH group at C-3 was identified as an important structural contributor for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent derivative (IC50 value 9.1 microM). Betulinic acid (13), 28-O-tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 microM, respectively. The latter three compounds also had significant synergistic effects against SFV when combined with 3'-amino-3'-deoxyadenosine. In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase. The efficacy was also shown to be independent of external guanosine supplementation.

  12. Single molecule analysis of Trypanosoma brucei DNA replication dynamics.

    Science.gov (United States)

    Calderano, Simone Guedes; Drosopoulos, William C; Quaresma, Marina Mônaco; Marques, Catarina A; Kosiyatrakul, Settapong; McCulloch, Richard; Schildkraut, Carl L; Elias, Maria Carolina

    2015-03-11

    Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis of Trypanosoma brucei, the etiological agent of sleeping sickness, localized its replication origins to the boundaries of multigenic transcription units. To better understand genomic replication in this organism, we examined replication by single molecule analysis of replicated DNA. We determined the average speed of replication forks of procyclic and bloodstream form cells and we found that T. brucei DNA replication rate is similar to rates seen in other eukaryotes. We also analyzed the replication dynamics of a central region of chromosome 1 in procyclic forms. We present evidence for replication terminating within the central part of the chromosome and thus emanating from both sides, suggesting a previously unmapped origin toward the 5' extremity of chromosome 1. Also, termination is not at a fixed location in chromosome 1, but is rather variable. Importantly, we found a replication origin located near an ORC1/CDC6 binding site that is detected after replicative stress induced by hydroxyurea treatment, suggesting it may be a dormant origin activated in response to replicative stress. Collectively, our findings support the existence of more replication origins in T. brucei than previously appreciated.

  13. High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

    Directory of Open Access Journals (Sweden)

    Michelle Hawkins

    2013-11-01

    Full Text Available Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.

  14. Mevlana’nın Menkıbeleri Üzerine Folklorik Bir İnceleme A Folkloric Analysis on the Legends of Mevlana

    Directory of Open Access Journals (Sweden)

    Gülay KARAMAN

    2012-09-01

    article these topics are determined in Menâkıbu’l-Ârifîn to analysis: Places, occupations, belongings, manner of dressing, food and drinks, custom and traditions, medical treatments. Arapça bir kelime olan menkabe sözlükte övünülecek güzel iş, davranış anlamına gelmektedir. Çoğulu menâkıb olan kelime bu anlamıyla ilk defa, IX. yüzyıldan itibaren yazılıp derlenmeye başlayan hadis külliyatlarında Hz. Peygamber ve ashabının faziletlerini anlatmak için kullanılmıştır. Bundan başka tarihî şahsiyetlerin hal tercümeleri, önemli kişilerin övülecek işleri ve hatta bazı mukaddes şehirlerin tasvirinden ibaret yazılara da menâkıb denilmiştir. Başlangıçta, Hz. Peygamber ve sahabelerinin üstün ahlâkını ve yaşantılarını anlatmak üzere oluşturulan menâkıbnâmeler daha sonraları tasavvuf ve tarikat erbabının hayatlarını da konu edinmişlerdir. Türk menâkıbnâme edebiyatının bilinen ilk örneği Karahanlı dönemine ait Tezkire-i Satuk Buğra Han isimli eserdir. Tezkire-i Satuk Buğra Han’la başlayan Türk menâkıbnâme edebiyatı, göçlerle Anadolu’ya gelip yerleşen Müslüman Türkler arasında hızlı bir biçimde yayılmaya devam etmiştir. Yazar kendi toplumunun bir üyesi olduğu için doğal olarak eser de kendi çağının sosyal, kültürel ekonomik, politik yaşamına ayna olacaktır. Velilerin olağanüstü hayat hikâyelerini anlatan menâkıbnâmeler bu sebepten dolayı; özellikle tarih, kültür, halkbilimi ve edebiyat için çok önemli bilgi kaynaklarıdır. Menkıbeler üzerinde yapılacak dikkatli çalışmalar sonucunda çok zengin bir bilgi kaynağına ulaşmak mümkün olacaktır. Türkiye’de menâkıbnâmelerin bilimsel çalışmalarda kullanılmasına dikkat çeken ilk isim Türk Edebiyatında İlk Mutasavvıflar adlı eseriyle Fuad Köprülü’dür. Bu çalışmada Mevlana ve diğer Mevlevi büyüklerinin menkıbelerini anlatan bir menâkıbnâme olan Men

  15. mRNA decay factor AUF1 binds the internal ribosomal entry site of enterovirus 71 and inhibits virus replication.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lin

    Full Text Available AU-rich element binding factor 1 (AUF1 has a role in the replication cycles of different viruses. Here we demonstrate that AUF1 binds the internal ribosome entry site (IRES of enterovirus 71 (EV71 and negatively regulates IRES-dependent translation. During EV71 infection, AUF1 accumulates in the cytoplasm where viral replication occurs, whereas AUF1 localizes predominantly in the nucleus in mock-infected cells. AUF1 knockdown in infected cells increases IRES activity and synthesis of viral proteins. Taken together, the results suggest that AUF1 interacts with the EV71 IRES to negatively regulate viral translation and replication.

  16. Rapid Exchange of Bound ADP on the Staphylococcus aureus Replication Initiation Protein DnaA*

    OpenAIRE

    2009-01-01

    In Escherichia coli, regulatory inactivation of the replication initiator DnaA occurs after initiation as a result of hydrolysis of bound ATP to ADP, but it has been unknown how DnaA is controlled to coordinate cell growth and chromosomal replication in Gram-positive bacteria such as Staphylococcus aureus. This study examined the roles of ATP binding and its hydrolysis in the regulation of the S. aureus DnaA activity. In vitro, S. aureus DnaA melted S. aureus oriC in the presence of ATP but n...

  17. Restoring chromatin after replication: How new and old histone marks come together

    DEFF Research Database (Denmark)

    Jasencakova, Zusana; Groth, Anja

    2010-01-01

    replication and chromatin assembly processes in time and space. Dynamic recycling and de novo deposition of histones are fundamental for chromatin restoration. Histone post-translational modifications (PTMs) are thought to have a causal role in establishing distinct chromatin structures. Here we discuss PTMs...... present on new and parental histones and how they influence genome stability and restoration of epigenetically defined domains. Newly deposited histones must change their signature in the process of chromatin restoration, this may occur in a step-wise fashion involving replication-coupled processes...... and information from recycled parental histones....

  18. Introduction to naturally occurring radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Egidi, P.

    1997-08-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose

  19. Introduction to naturally occurring radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Egidi, P.

    1997-08-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose

  20. Novel Mutant AAV2 Rep Proteins Support AAV2 Replication without Blocking HSV-1 Helpervirus Replication

    Science.gov (United States)

    Seyffert, Michael; Glauser, Daniel L.; Schraner, Elisabeth M.; de Oliveira, Anna-Paula; Mansilla-Soto, Jorge; Vogt, Bernd; Büning, Hildegard; Linden, R. Michael; Ackermann, Mathias; Fraefel, Cornel

    2017-01-01

    As their names imply, parvoviruses of the genus Dependovirus rely for their efficient replication on the concurrent presence of a helpervirus, such as herpesvirus, adenovirus, or papilloma virus. Adeno-associated virus 2 (AAV2) is such an example, which in turn can efficiently inhibit the replication of each helpervirus by distinct mechanisms. In a previous study we have shown that expression of the AAV2 rep gene is not compatible with efficient replication of herpes simplex virus 1 (HSV-1). In particular, the combined DNA-binding and ATPase/helicase activities of the Rep68/78 proteins have been shown to exert opposite effects on the replication of AAV2 and HSV-1. While essential for AAV2 DNA replication these protein activities account for the Rep-mediated inhibition of HSV-1 replication. Here, we describe a novel Rep mutant (Rep-D371Y), which displayed an unexpected phenotype. Rep-D371Y did not block HSV-1 replication, but still supported efficient AAV2 replication, at least when a double-stranded AAV2 genome template was used. We also found that the capacity of Rep-D371Y to induce apoptosis and a Rep-specific DNA damage response was significantly reduced compared to wild-type Rep. These findings suggest that AAV2 Rep-helicase subdomains exert diverging activities, which contribute to distinct steps of the AAV2 life cycle. More important, the novel AAV2 mutant Rep-D371Y may allow deciphering yet unsolved activities of the AAV2 Rep proteins such as DNA second-strand synthesis, genomic integration or packaging, which all involve the Rep-helicase activity. PMID:28125695

  1. Mapping and Use of a Sequence that Targets DNA Ligase I to Sites of DNA Replication In Vivo

    OpenAIRE

    Cardoso, M. Cristina; Joseph, Cuthbert; Rahn, Hans-Peter; Reusch, Regina; Nadal-Ginard, Bernardo; Leonhardt, Heinrich

    1997-01-01

    The mammalian nucleus is highly organized, and nuclear processes such as DNA replication occur in discrete nuclear foci, a phenomenon often termed “functional organization” of the nucleus. We describe the identification and characterization of a bipartite targeting sequence (amino acids 1–28 and 111–179) that is necessary and sufficient to direct DNA ligase I to nuclear replication foci during S phase. This targeting sequence is located within the regulatory, NH2-terminal domain of the protei...

  2. Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase

    Science.gov (United States)

    Lõoke, Marko; Maloney, Michael F.; Bell, Stephen P.

    2017-01-01

    Activation of the Mcm2–7 replicative DNA helicase is the committed step in eukaryotic DNA replication initiation. Although Mcm2–7 activation requires binding of the helicase-activating proteins Cdc45 and GINS (forming the CMG complex), an additional protein, Mcm10, drives initial origin DNA unwinding by an unknown mechanism. We show that Mcm10 binds a conserved motif located between the oligonucleotide/oligosaccharide fold (OB-fold) and A subdomain of Mcm2. Although buried in the interface between these domains in Mcm2–7 structures, mutations predicted to separate the domains and expose this motif restore growth to conditional-lethal MCM10 mutant cells. We found that, in addition to stimulating initial DNA unwinding, Mcm10 stabilizes Cdc45 and GINS association with Mcm2–7 and stimulates replication elongation in vivo and in vitro. Furthermore, we identified a lethal allele of MCM10 that stimulates initial DNA unwinding but is defective in replication elongation and CMG binding. Our findings expand the roles of Mcm10 during DNA replication and suggest a new model for Mcm10 function as an activator of the CMG complex throughout DNA replication. PMID:28270517

  3. Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation

    Directory of Open Access Journals (Sweden)

    Sallie Richard

    2005-02-01

    Full Text Available Abstract Hepatitis C (HCV, hepatitis B (HBV, the human immunodeficiency viruses (HIV, and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide. These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical. This paper presents the hypothesis, and evidence, that viruses capable of persistent infection autoregulate replication and the likely mechanism mediating autoregulation – Replicative Homeostasis – is described. Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses. More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression.

  4. Can human autonomic classical conditioning occur without contingency awareness? The critical importance of the trial sequence.

    Science.gov (United States)

    Singh, Kulwinder; Dawson, Michael E; Schell, Anne M; Courtney, Christopher G; Payne, Andrew F H

    2013-04-01

    Most evidence suggests that awareness of the CS-US contingency is necessary for human autonomic conditioning. However, Schultz and Helmstetter (2010) reported unaware skin conductance conditioning using difficult-to-discriminate visual CSs. We sought to replicate these findings with procedures nearly identical to Schultz and Helmstetter among 66 participants. Results replicated the findings of significantly greater autonomic responding to CS+ than CS-; however, participants also demonstrated greater expectancy of shock to CS+ than CS- despite being classified as unaware. The differential expectancy and conditioning occurred only on trials that followed a CS+/CS- alternating sequence. On non-alternating trials, there was significantly higher expectancy and skin conductance responding to CS- compared to CS+. These results indicate that what initially appeared to be unaware differential conditioning was likely due to differential expectancy arising from a predictable trial sequence. These results underscore the critical importance of controlling for trial sequence effects in the study of learning.

  5. Escalation of error catastrophe for enzymatic self-replicators

    Science.gov (United States)

    Obermayer, B.; Frey, E.

    2009-11-01

    It is a long-standing question in origin-of-life research whether the information content of replicating molecules can be maintained in the presence of replication errors. Extending standard quasispecies models of non-enzymatic replication, we analyze highly specific enzymatic self-replication mediated through an otherwise neutral recognition region, which leads to frequency-dependent replication rates. We find a significant reduction of the maximally tolerable error rate, because the replication rate of the fittest molecules decreases with the fraction of functional enzymes. Our analysis is extended to hypercyclic couplings as an example for catalytic networks.

  6. İki Lazer Demeti İle Zamana-Bağlı Etkileşim Altındaki Üç-Düzeyli Bir Tuzaklanmış İyonun Kuantum Dinamiği ve Kuantum Dolaşıklığı

    OpenAIRE

    Deveci, Bekir

    2013-01-01

    Bir üniter transformasyon kullanılan sunumunda iki lazer demeti ile etkileşen üç düzeyli bir iyonun zamana bağlı hamiltonyeni hesaplandı. Kullanılan üniter transformasyon metot titreşen fonon geçişleri için sunumunun bir dönüşümüdür. Grafiklerdeki beli bir zaman periyodunda Lamb-Dicke rejimine ulaştıktan sonra olasılık genlikleri için analitik sonuçlarımız tamdı. Bu işlemden sonra iyon-fonon sisteminde meydana gelen kuantum dolaşıklık incelendi. Zamandan bağımsız daha önceden yapılmış b...

  7. Physically Embedded Minimal Self-Replicating Systems

    DEFF Research Database (Denmark)

    Fellermann, Harold

    Self-replication is a fundamental property of all living organisms, yet has only been accomplished to limited extend in manmade systems. This thesis is part of the ongoing research endeavor to bridge the two sides of this gap. In particular, we present simulation results of a minimal life......-like, artificial, molecular aggregate (i.e. protocell) that has been proposed by Steen Rasussen and coworkers and is currently pursued both experimentally and computationally in interdisciplinary international research projects. We develop a space-time continuous physically motivated simulation framework based...... computational models. This allows us to address key issues of the replicating subsystems – container, genome, and metabolism – both individually and in mutual coupling. We analyze each step in the life-cycle of the molecular aggregate, and a final integrated simulation of the entire life-cycle is prepared. Our...

  8. Choreography of bacteriophage T7 DNA replication.

    Science.gov (United States)

    Lee, Seung-Joo; Richardson, Charles C

    2011-10-01

    The replication system of phage T7 provides a model for DNA replication. Biochemical, structural, and single-molecule analyses together provide insight into replisome mechanics. A complex of polymerase, a processivity factor, and helicase mediates leading strand synthesis. Establishment of the complex requires an interaction of the C-terminal tail of the helicase with the polymerase. During synthesis the complex is stabilized by other interactions to provide for a processivity of 5 kilobase (kb). The C-terminal tail also interacts with a distinct region of the polymerase to captures dissociating polymerase to increase the processivity to >17kb. The lagging strand is synthesized discontinuously within a loop that forms and resolves during each cycle of Okazaki fragment synthesis. The synthesis of a primer as well as the termination of a fragment signal loop resolution.

  9. Surface micro topography replication in injection moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf

    , the topography itself, and other factors were also investigated. The experimental work is based on a multi-purpose experimental injection mould with a collection of test surface inserts manufactured by EDM (electrical discharge machining). Experimental production took place with an injection moulding machine......Thermoplastic injection moulding is a widely used industrial process that involves surface generation by replication. The surface topography of injection moulded plastic parts can be important for aesthetical or technical reasons. With the emergence of microengineering and nanotechnology additional...... in a clean room environment. The mould and the injection moulding machine were fitted with transducers for subsequent process analysis. A total of 13 different plastic material grades were applied. Topographical characterisation was performed with an optical laser focus detection instrument. Replication...

  10. Entropy involved in fidelity of DNA replication

    CERN Document Server

    Arias-Gonzalez, J Ricardo

    2012-01-01

    Information has an entropic character which can be analyzed within the Statistical Theory in molecular systems. R. Landauer and C.H. Bennett showed that a logical copy can be carried out in the limit of no dissipation if the computation is performed sufficiently slowly. Structural and recent single-molecule assays have provided dynamic details of polymerase machinery with insight into information processing. We introduce a rigorous characterization of Shannon Information in biomolecular systems and apply it to DNA replication in the limit of no dissipation. Specifically, we devise an equilibrium pathway in DNA replication to determine the entropy generated in copying the information from a DNA template in the absence of friction. Both the initial state, the free nucleotides randomly distributed in certain concentrations, and the final state, a polymerized strand, are mesoscopic equilibrium states for the nucleotide distribution. We use empirical stacking free energies to calculate the probabilities of incorpo...

  11. The Solution to Science's Replication Crisis

    CERN Document Server

    Knuteson, Bruce

    2016-01-01

    The solution to science's replication crisis is a new ecosystem in which scientists sell what they learn from their research. In each pairwise transaction, the information seller makes (loses) money if he turns out to be correct (incorrect). Responsibility for the determination of correctness is delegated, with appropriate incentives, to the information purchaser. Each transaction is brokered by a central exchange, which holds money from the anonymous information buyer and anonymous information seller in escrow, and which enforces a set of incentives facilitating the transfer of useful, bluntly honest information from the seller to the buyer. This new ecosystem, capitalist science, directly addresses socialist science's replication crisis by explicitly rewarding accuracy and penalizing inaccuracy.

  12. Experimental Replication of an Aeroengine Combustion Instability

    Science.gov (United States)

    Cohen, J. M.; Hibshman, J. R.; Proscia, W.; Rosfjord, T. J.; Wake, B. E.; McVey, J. B.; Lovett, J.; Ondas, M.; DeLaat, J.; Breisacher, K.

    2000-01-01

    Combustion instabilities in gas turbine engines are most frequently encountered during the late phases of engine development, at which point they are difficult and expensive to fix. The ability to replicate an engine-traceable combustion instability in a laboratory-scale experiment offers the opportunity to economically diagnose the problem (to determine the root cause), and to investigate solutions to the problem, such as active control. The development and validation of active combustion instability control requires that the causal dynamic processes be reproduced in experimental test facilities which can be used as a test bed for control system evaluation. This paper discusses the process through which a laboratory-scale experiment was designed to replicate an instability observed in a developmental engine. The scaling process used physically-based analyses to preserve the relevant geometric, acoustic and thermo-fluid features. The process increases the probability that results achieved in the single-nozzle experiment will be scalable to the engine.

  13. Competition and cooperation in dynamic replication networks.

    Science.gov (United States)

    Dadon, Zehavit; Wagner, Nathaniel; Alasibi, Samaa; Samiappan, Manickasundaram; Mukherjee, Rakesh; Ashkenasy, Gonen

    2015-01-07

    The simultaneous replication of six coiled-coil peptide mutants by reversible thiol-thioester exchange reactions is described. Experimental analysis of the time dependent evolution of networks formed by the peptides under different conditions reveals a complex web of molecular interactions and consequent mutant replication, governed by competition for resources and by autocatalytic and/or cross-catalytic template-assisted reactions. A kinetic model, first of its kind, is then introduced, allowing simulation of varied network behaviour as a consequence of changing competition and cooperation scenarios. We suggest that by clarifying the kinetic description of these relatively complex dynamic networks, both at early stages of the reaction far from equilibrium and at later stages approaching equilibrium, one lays the foundation for studying dynamic networks out-of-equilibrium in the near future.

  14. Replicative DNA polymerase mutations in cancer.

    Science.gov (United States)

    Heitzer, Ellen; Tomlinson, Ian

    2014-02-01

    Three DNA polymerases - Pol α, Pol δ and Pol ɛ - are essential for DNA replication. After initiation of DNA synthesis by Pol α, Pol δ or Pol ɛ take over on the lagging and leading strand respectively. Pol δ and Pol ɛ perform the bulk of replication with very high fidelity, which is ensured by Watson-Crick base pairing and 3'exonuclease (proofreading) activity. Yeast models have shown that mutations in the exonuclease domain of Pol δ and Pol ɛ homologues can cause a mutator phenotype. Recently, we identified germline exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to 'polymerase proofreading associated polyposis' (PPAP), a disease characterised by multiple colorectal adenomas and carcinoma, with high penetrance and dominant inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable and show an 'ultramutator' phenotype, with a dramatic increase in base substitutions.

  15. Replicating and understanding successful innovations: Implementing tutorials in introductory physics

    Directory of Open Access Journals (Sweden)

    S. J. Pollock

    2005-09-01

    Full Text Available We report a detailed study of the implementation of Tutorials in Introductory Physics at a large-scale research institution. Based on two successive semesters of evaluation, we observe students’ improved conceptual mastery (force and motion concept evaluation median normalized gain 0.77, N=336 , albeit with some student discontent. We replicate the results of original studies of tutorial effectiveness and document how and why these results occur. Additionally, using the Colorado Learning Attitudes about Science Survey we measure the support of students’ expertlike beliefs about learning physics in our environment. We examine this implementation from a viewpoint that emphasizes varying contextual levels of this implementation, from students’ engagement in individual tasks, to the situations in which these tasks are embedded, to the broader classroom, departmental, and educational structures. We document both obvious and subtle features that help ensure the successful implementation of these reforms.

  16. DNA ligase I, the replicative DNA ligase.

    Science.gov (United States)

    Howes, Timothy R L; Tomkinson, Alan E

    2012-01-01

    Multiple DNA ligation events are required to join the Okazaki fragments generated during lagging strand DNA synthesis. In eukaryotes, this is primarily carried out by members of the DNA ligase I family. The C-terminal catalytic region of these enzymes is composed of three domains: a DNA binding domain, an adenylation domain and an OB-fold domain. In the absence of DNA, these domains adopt an extended structure but transition into a compact ring structure when they engage a DNA nick, with each of the domains contacting the DNA. The non-catalytic N-terminal region of eukaryotic DNA ligase I is responsible for the specific participation of these enzymes in DNA replication. This proline-rich unstructured region contains the nuclear localization signal and a PCNA interaction motif that is critical for localization to replication foci and efficient joining of Okazaki fragments. DNA ligase I initially engages the PCNA trimer via this interaction motif which is located at the extreme N-terminus of this flexible region. It is likely that this facilitates an additional interaction between the DNA binding domain and the PCNA ring. The similar size and shape of the rings formed by the PCNA trimer and the DNA ligase I catalytic region when it engages a DNA nick suggest that these proteins interact to form a double-ring structure during the joining of Okazaki fragments. DNA ligase I also interacts with replication factor C, the factor that loads the PCNA trimeric ring onto DNA. This interaction, which is regulated by phosphorylation of the non-catalytic N-terminus of DNA ligase I, also appears to be critical for DNA replication.

  17. Advanced Patient Data Replication and Recovery

    Science.gov (United States)

    2010-10-01

    able to “dial” the bandwidth back down to the 10Mbps range to reduce 8 the cost of the data link back to EMC. EMC2 Centera replication is the...automation robot (which fills pharmacy orders) and the drug dispensing kiosks located near the nurse stations in the hospital. These systems have...with appropriate workspaces, including telephone and internet service, for several weeks if needed. 11. Hotels must be available within 15

  18. Standart Türkçeye Bir Katkı: us+(uk- A Contribution To The Literary Turkish: us+(uk-

    Directory of Open Access Journals (Sweden)

    İ. Gülsel SEV

    2013-07-01

    Full Text Available A language has two dimensions namely colloquial and literary. Dialects within the colloquial language have important places. Literary language, which is static and resistant to changes, improves and gets richer with the help of dialects. The best examples of this process wereobserved during the language revolution when words, notions andterms were transferred to the literary language from with collectionsfrom dialects.The focus of the present study is the usuk- verb which means‘become wise, to get silent, to calm down’ in the dialects of Turkish.usuk- was derived with the deverbal suffix +(Ik- from the noun us‘wisdom’. Us is related both u- which means to understand and -ū whichmeans ‘to be able to, to have the power’.The suffix +(Ik- is not widely used in Turkish, there are a fewexamples such as acık-, birik-, gecik-, gözük-. However, there are manyexamples of this suffix in the historical and modern dialects.us-(uk- or with the forms in dialects as usukmak ve usuhmah hasseveral meanings such as ‘to get wise, to calm down after an offence oranger, to get silent because of astonishment, not to be able to talk, toget calm’. It is stated in the article that usuk whose implied meaningwere nor encountered in the historical dialects must be transferred tothe literary language with the meanings of ‘to get wise, to get silent andto calm down’. Besides, it is expected to take a step to increase thenumber of example verbs derived with +(Ik-, considering the examplesin the historical dialects. Dilin yazı dili ve konuşma dili olmak üzere iki yönü vardır. Konuşma dili içerisinde yer alan ağızlar apayrı bir yere sahiptir. Kolay kolay değişmeyen, durgun bir yapıya sahip olan yazı dili; canlı, gelişime ve değişime açık ağızlardan beslenerek gelişir ve zenginleşir. Bunun en güzel örneklerini dil devrimi sırasında halk ağızlarından yapılan derlemelerin, sözcük, terim ve kavram olarak yazı diline kazand

  19. Hatay’da Entelektüel Bir Kadro Hareketi Olarak Hatay Halkevi Dergisi Journal of Intellectual Community Center in Hatay Hatay as a Squad Movement

    Directory of Open Access Journals (Sweden)

    Haktan BİRSEL

    2013-03-01

    Full Text Available The Turkish cultural struggle and the activities to be a part ofTurkey were carried out by an intellectual group of people in Sanjak ofIskenderun, Turkey. In the post-rule phase, the same intellectual groupplayed an important role in execution and coordination of the struggle,this time within the Community Center.Hatay Community Center has continued its studies after Sanjakhas joined the Mainland to both spread the Turkish culture and othergroups to appropriate the Turkish culture.In this framework, the journal, “Hatay”, published by theCommunity Center has played a critical role in adaptation of the localcommunity in Hatay to the Turkish culture. The journal was publishedfor about a year and then was stopped. However, important means ofinformation was shared throughout this short timeframe of publication.The journal of Hatay Community Center is acknowledged in Hatayas a carrier of the revolution movement accepted by Modern Turkey.This mission has caused a reconstruction of almost every aspect of lifein Hatay and has shaped an educational path as well as a culturalrevolution within the new era. The Community Journal, that constitutean important field for the intellectuals of Hatay, played a substantialrole in gaining public awareness and educating the local communitythrough articles on contemporary and modern life. The journal of HatayCommunity Center and Misak-I Milli have progressed activities to voicethe identity of Hatay by publishing Hatay’s iconic history throughKemalist ideology and through Ataturk’s reforms. İskenderun Sancağı’nda, Sancağın Bağımsızlık, Türk kültürmücadelesi ve Türkiye’ye iltihakın gerçekleşmesi yönünde faaliyetlerentelektüel bir kadro tarafından yürütülmüştür. Bu mücadelelerinyürütülmesinde ve koordine edilmesinde İltihak sonrası süreçte aynıentelektüel kadro bu defa Hatay Halk Evi bünyesinde önemli bir rolüstlenmiştir.Hatay Halk Evi, faaliyetlerine Sancak b

  20. II.Abdülhamid Döneminde Zirai Eğitime Bir Bakış An Outlook on Agricultural Education in The Reign of Abdulhamid II

    Directory of Open Access Journals (Sweden)

    Özgür YILDIZ

    2012-12-01

    ülhamid’in saltanatı uzun ve sıkıntılarla dolu bir siyasi yaşamın yansıması olarak görülmektedir. Padişah büyük siyasi sorunlarla uğraşırken ülkenin kalkınması ve modernleşmesi için de çaba harcamıştır.II. Abdülhamid eğitimle yakından ilgilenen bir padişahtır. Yönetimde kaldığı süre içinde eğitimin her alanında yenilikler yaptığı bilinmektedir. Padişah II. Abdülhamid’in şehzadeliği döneminde ziraat işleriyle meşgul olması ve çiftlik sahibi olarak servet elde etmesi ziraat eğitimiyle de doğrudan ilgilenmesine neden olmuştur.Osmanlı Devleti’nin çeşitli vilayetlerinde ziraat mektebi açmak suretiyle Sultan II. Abdülhamid bu konudaki hassasiyetini göstermiştir. İstanbul, Selanik ve Bursa’da açtırdığı ziraat okulları modern tarımın gelişmesinde etkili olmuştur.Ziraat mekteplerine öğrenci seçimi, sınavlarda merkezi sınav uygulanması hatta merkezi sınavdan sonra da öğrencilerin okul öğretmenleri tarafından tekrar bir sınava tabi tutulmaları da dönemin eğitim anlayışı hakkında ipuçları vermektedir.Öğrencilere ödül verilerek eğitimin özendirilmesi, sınavların çok sıkı kuralarla göre yapılması, eğitimin uygulamalı olması, öğretmenlerin de özenle seçilmesi ziraat eğitimine verilen önem ve değeri ortaya koymaktadır.1884 tarihli nizamname ve diğer arşiv belgeleri ışığında hazırlanan araştırmanın giriş bölümünde; II. Abdülhamid döneminde eğitim anlayışına kısa bir şekilde yer verilmiştir. Birinci bölümde; II. Abdülhamid döneminde ziraat meselesine bakış, ziraat mekteplerinin teşkili ve mekteplere öğrenci seçim usullerine değinilmiştir. İkinci bölümde; ziraat okullarında talim ve tedris hakkında bilgi verilmiş, üçüncü bölümde; ziraat mekteplerinin idaresi ve mektepte çalışan diğer memurlar hakkında bilgi verilerek II. Abdülhamid döneminde ziraat eğitimi hakkında bir değerlendirme yapılmaya çalışılmıştır.

  1. Ultrastructural Characterization of Zika Virus Replication Factories

    Directory of Open Access Journals (Sweden)

    Mirko Cortese

    2017-02-01

    Full Text Available A global concern has emerged with the pandemic spread of Zika virus (ZIKV infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs. Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton.

  2. The molecular biology of Bluetongue virus replication.

    Science.gov (United States)

    Patel, Avnish; Roy, Polly

    2014-03-01

    The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses which are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at a molecular and structural level. The complex nature of the virion structure has been well characterised at high resolution along with the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell as well as the protein and genome sequestration required for it; and the role of host proteins in virus entry and virus release. More recent developments of Reverse Genetics and Cell-Free Assembly systems have allowed integration of the accumulated structural and molecular knowledge to be tested at meticulous level, yielding higher insight into basic molecular virology, from which the rational design of safe efficacious vaccines has been possible. This article is centred on the molecular dissection of BTV with a view to understanding the role of each protein in the virus replication cycle. These areas are important in themselves for BTV replication but they also indicate the pathways that related viruses, which includes viruses that are pathogenic to man and animals, might also use providing an informed starting point for intervention or prevention.

  3. Continuously Cumulating Meta-Analysis and Replicability.

    Science.gov (United States)

    Braver, Sanford L; Thoemmes, Felix J; Rosenthal, Robert

    2014-05-01

    The current crisis in scientific psychology about whether our findings are irreproducible was presaged years ago by Tversky and Kahneman (1971), who noted that even sophisticated researchers believe in the fallacious Law of Small Numbers-erroneous intuitions about how imprecisely sample data reflect population phenomena. Combined with the low power of most current work, this often leads to the use of misleading criteria about whether an effect has replicated. Rosenthal (1990) suggested more appropriate criteria, here labeled the continuously cumulating meta-analytic (CCMA) approach. For example, a CCMA analysis on a replication attempt that does not reach significance might nonetheless provide more, not less, evidence that the effect is real. Alternatively, measures of heterogeneity might show that two studies that differ in whether they are significant might have only trivially different effect sizes. We present a nontechnical introduction to the CCMA framework (referencing relevant software), and then explain how it can be used to address aspects of replicability or more generally to assess quantitative evidence from numerous studies. We then present some examples and simulation results using the CCMA approach that show how the combination of evidence can yield improved results over the consideration of single studies.

  4. Early steps of retrovirus replicative cycle

    Directory of Open Access Journals (Sweden)

    Saïb Ali

    2004-05-01

    Full Text Available Abstract During the last two decades, the profusion of HIV research due to the urge to identify new therapeutic targets has led to a wealth of information on the retroviral replication cycle. However, while the late stages of the retrovirus life cycle, consisting of virus replication and egress, have been partly unraveled, the early steps remain largely enigmatic. These early steps consist of a long and perilous journey from the cell surface to the nucleus where the proviral DNA integrates into the host genome. Retroviral particles must bind specifically to their target cells, cross the plasma membrane, reverse-transcribe their RNA genome, while uncoating the cores, find their way to the nuclear membrane and penetrate into the nucleus to finally dock and integrate into the cellular genome. Along this journey, retroviruses hijack the cellular machinery, while at the same time counteracting cellular defenses. Elucidating these mechanisms and identifying which cellular factors are exploited by the retroviruses and which hinder their life cycle, will certainly lead to the discovery of new ways to inhibit viral replication and to improve retroviral vectors for gene transfer. Finally, as proven by many examples in the past, progresses in retrovirology will undoubtedly also provide some priceless insights into cell biology.

  5. Inhibition of HIV-1 replication by balsamin, a ribosome inactivating protein of Momordica balsamina.

    Science.gov (United States)

    Kaur, Inderdeep; Puri, Munish; Ahmed, Zahra; Blanchet, Fabien P; Mangeat, Bastien; Piguet, Vincent

    2013-01-01

    Ribosome-inactivating proteins (RIPs) are endowed with several medicinal properties, including antiviral activity. We demonstrate here that the recently identified type I RIP from Momordica balsamina also possesses antiviral activity, as determined by viral growth curve assays and single-round infection experiments. Importantly, this activity is at play even as doses where the RIP has no cytotoxic effect. In addition, balsamin inhibits HIV-1 replication not only in T cell lines but also in human primary CD4(+) T cells. This antiviral compound exerts its activity at a viral replicative step occurring later than reverse-transcription, most likely on viral protein translation, prior to viral budding and release. Finally, we demonstrate that balsamin antiviral activity is broad since it also impedes influenza virus replication. Altogether our results demonstrate that type I RIP can exert a potent anti-HIV-1 activity which paves the way for new therapeutic avenues for the treatment of viral infections.

  6. Information Needs While A Disaster Is Occurring

    Science.gov (United States)

    Perry, S. C.

    2010-12-01

    that rainfall intensity at their homes might be less than the intensity up in the mountains where the debris flows would start. Nor did they know that debris flows travel too quickly to be outrun. These and many other examples indicate need for social and natural scientists to increase awareness of what to expect when the disaster strikes. This information must be solidly understood before the event occurs - while a disaster is unfolding there are no teachable moments. Case studies indicate that even those who come into a disaster well educated about the phenomenon can struggle to apply what they know when the real situation is at hand. In addition, psychological studies confirm diminished ability to comprehend information at times of stress.

  7. Üstün Yetenekli Dijital Yerlilerin Sosyal Medya Kullanımları Üzerine Nitel Bir Çalışma

    Directory of Open Access Journals (Sweden)

    İbrahim Şamil Köroğlu

    2015-08-01

    Full Text Available Ağ neslinin yeni medya teknolojilerine ilişkin algısına ve teknolojiyi kullanma motivasyonuna ilişkin yapılan nicel çalışmalar dijital antropoloji alanına ilgi duyanlar için ufuk açıcı niteliktedir. Ağ neslinin özellikli bir grubunu teşkil eden üstün yetenekli dijital yerliler ise interneti ve mobil iletişim teknolojilerini bir dil gibi kullanabilen, içerik üretimi ve paylaşımı konusunda katılımcı, bilgi edinme, eğlenme ve sosyalleşme amacıyla birincil kaynak olarak sanal ortamı gören üstün yetenekli çocuklardır. Üstün yetenekli dijital yerlilerin sosyal medya kullanım motivasyonlarını Kullanımlar ve Doyumlar Yaklaşımı ile inceleyen bu çalışma, betimsel nitelikli tarama modelinde bir araştırmadır. Araştırma grubu, 2012-2013 eğitim yılında İstanbul Bilim ve Sanat Merkezi, Beşiktaş Bilim ve Sanat Merkezi ve Beyazıt Ford Otosan İlköğretim Okulu’nda öğrenim gören 401 üstün yetenekli öğrencidir. Grupta yer alan üstün yeteneklilerin 231’i (%57,6 9–11; 148’i (%36,9 12–14; 22’si (%5,5 ise 15–17 yaş grubundadır. Araştırmaya katılan üstün yeteneklilerin 247’si erkek (%61,6; 154’ü (%38,4 kız öğrencilerden oluşmaktadır. Çalışmada üstün yetenekli dijital yerlilerin sosyal medya kullanım sıklıkları; internet kullanım amaçları ile sosyal medya kullanım amaçları ve sık kullandıkları sosyal medya sitelerinin hangileri olduğu incelenmiştir. Çalışmada elde edilen bulgular üstün yetenekli dijital yerlilerin sosyal medya kullanım sıklığının akranlarına oranla Türkiye ortalamasının altında kaldığını; internet kullanım amaçlarıyla sosyal medya kullanım amaçlarının örtüştüğünü, ayrıca YouTube, Facebook ve Twitter’ın üstün yetenekli dijital yerlilerin en sık kullandıkları sosyal medya siteleri olduğunu ortaya koymaktadır.

  8. Sosyolojinin Peşinde Geçen Bir Ömür: Prof. Dr. Sami ŞENER ile Söyleşi

    Directory of Open Access Journals (Sweden)

    Mine Doğan

    2012-07-01

    Full Text Available Sosyoloji Bölümünün temel problemlerine çözüm önerileri üretmeye çalışan 3. Ulusal Sosyoloji Çalıştayı bu sene Karabük Üniversitesi Sosyoloji Bölümü tarafından düzenlendi. Çalıştayın oturum başkanlarından Sakarya Üniversitesi Bölüm Başkanı Prof. Dr Sami Şener’e, Türkiye’deki sosyoloji çalışmalarına bakışı ile sosyolojinin temel problemlerini teşhis etme ve çözüm yolları üretme konusundaki düşüncelerinin neler olduğu konusunda sorular sorduk. Sosyoloji eğitiminin kalitesini yükseltebilmek için neler yapılabileceği üzerinde konuşan ŞENER hoca: “Türk üniversitelerinde eğitim alan sosyoloji öğrencilerinin, hem pratik bir çalışma ve iş üretme yeteneğine nasıl sahip olacakları ve hem de hükümetin karşı karşıya geldiği sosyal problemlerin çözümünde neden sosyologlardan daha fazla yararlanılmadığının gün yüzüne çıkarılması için bu çalıştayların yapılması gerekmektedir” dedi. Bu konuda önemli adımlardan birini atan Prof Dr. Sami ŞENER hocamız Türkiye’deki sosyologları birleştirici bir faaliyet içerisine girerek SOSYODER’i (Sosyologlar Derneğini kurmuştur. Dernek yakın bir tarihte kurulmasına rağmen ŞENER hocanın ve çok sayıda değerli akademisyenin destekleri ile Türkiye’de sesini duyurmayı başarmıştır. The 3rd National Sociology Workshop, which tries to find answers to major problems of the Sociology Department, has been held this year by the department of sociology at Karabuk University. Some questions have been addressed to Prof. Dr. Sami Şener, the head of the department of Sociology at Sakarya University, concerning his point of view on sociology, together with identifying the basic problems in the field of sociology and then determining the ways of solutions. Having proposed the way to increase the efficiency of the quality of sociology education, Prof. Dr. Sami Sener has said: “The sociology students that

  9. A problem peculiar to women: Mental health in menopauseKadına özgü bir sorun: Menopozda ruh sağlığı

    Directory of Open Access Journals (Sweden)

    Şükran Ertekin Pınar

    2015-09-01

    Full Text Available Menopause ranked among reproductive health is one of the issues that requires special consideration because of the position of women. In terms of the elimination of inequalities in gender-related health, it is important to investigate this issue in a holistic approach. Today with the increasing length of life, the time that spent in menopause period is increasing too. Accepted physiological event menopause leads to changes in physiological, mental, social and sexual ways. Changes in the levels of reproductive hormones lead to menstrual cycle disruption, vasomotor symptoms, sleep disorders and mood changes. As menopause period develops with pathological events which threaten life, impair quality of life and affect marriage relationship, it is an important period needs to be addressed by health professionals. In this context, identifying mental problems gone through in menopause period is important in terms of holistic approach. Women in menopause periods should be addressed in the biopsychosocial and cultural integrity and health professionals should determine women who are at risk of mental problems at an early stage and should provide support in a mental aspect.   Özet Üreme sağlığı içinde yer alan menopoz, kadınların konumlarından dolayı özel yaklaşım gerektiren konulardan biridir. Cinsiyete bağlı sağlıkta eşitsizlik durumunun ortadan kaldırması açısından bütüncül yaklaşım içerisinde bu konunun araştırılmış olması önemlidir. Günümüzde yaşam süresinin uzaması ile birlikte menopoz döneminde geçirilen süre de artmaktadır. Fizyolojik bir olay olarak kabul edilen menopoz kadında fizyolojik, mental, sosyal ve cinsel yönden birçok değişimler yaşanmasına neden olmaktadır. Üreme hormonlarının düzeylerindeki değişiklikler sonucu adet döngüsünde bozulma, vazomotor belirtiler, uyku bozuklukları, duygu durum değişiklikleri görülebilmektedir. Menopoz dönemi yaşamı tehdit edici, ya

  10. Yükseköğretim öğrencilerinin işlevsel yazma becerilerinin geliştirilmesine yönelik bir eylem araştırması

    OpenAIRE

    Nohutçu, Ufuk

    2015-01-01

    Bireylerin üniversitelere gitme sebeplerine bakıldığında ilk sırada herhangi bir devlet kurumunda ya da özel kurum ve kuruluşlarda iş sahibi olabilmek amacı yer almaktadır. Her yıl ülkemizin farklı yerlerinden binlerce öğrenci bu amacına ulaşabilmek için üniversitelere girmektedir. Bu öğrencilerin günlük ve meslek hayatlarında onlara katkı sağlayacak olan işlevsel yazma türlerinden resmi yazışma türlerini iyi bir şekilde bilmeleri gerekmektedir. Bu amaçla hangi bölüm olursa olsun her üniversi...

  11. Taklit ve esinlenme ambalajın tüketici satın alma kararları üzerindeki etkisi ve Karaman’da bir uygulama

    OpenAIRE

    Öz, Murat; Kazak, Mustafa

    2016-01-01

    Ambalaj insanoğlunun yiyecek, içecek ve kullanım nesnelerini korumak, saklamak ve taşımak için geliştirdiği bir malzemedir. Gelişimi esnasında yeni malzemelerin bulunmasıyla farklı biçimler kazanmış ve gelişen teknoloji sayesinde Sanayi Devrimi ile seri üretime geçmiştir. Sanayi Devrimi’nden sonra rekabet ortamı ve gelişen ihtiyaçlar doğrultusunda modern ambalaj tasarımı kavramı ortaya çıkmış, son yıllarda çok önemli bir hale gelmiştir. Ambalajlamanın günümüzdeki önemi, self-servis sistemi il...

  12. Theoretical models for the regulation of DNA replication in fast-growing bacteria

    Science.gov (United States)

    Creutziger, Martin; Schmidt, Mischa; Lenz, Peter

    2012-09-01

    Growing in always changing environments, Escherichia coli cells are challenged by the task to coordinate growth and division. In particular, adaption of their growth program to the surrounding medium has to guarantee that the daughter cells obtain fully replicated chromosomes. Replication is therefore to be initiated at the right time, which is particularly challenging in media that support fast growth. Here, the mother cell initiates replication not only for the daughter but also for the granddaughter cells. This is possible only if replication occurs from several replication forks that all need to be correctly initiated. Despite considerable efforts during the last 40 years, regulation of this process is still unknown. Part of the difficulty arises from the fact that many details of the relevant molecular processes are not known. Here, we develop a novel theoretical strategy for dealing with this general problem: instead of analyzing a single model, we introduce a wide variety of 128 different models that make different assumptions about the unknown processes. By comparing the predictions of these models we are able to identify the key quantities that allow the experimental discrimination of the different models. Analysis of these quantities yields that out of the 128 models 94 are not consistent with available experimental data. From the remaining 34 models we are able to conclude that mass growth and DNA replication need either to be truly coupled, by coupling DNA replication initiation to the event of cell division, or to the amount of accumulated mass. Finally, we make suggestions for experiments to further reduce the number of possible regulation scenarios.

  13. USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

    Science.gov (United States)

    Hernández-Pérez, Santiago; Cabrera, Elisa; Amoedo, Hugo; Rodríguez-Acebes, Sara; Koundrioukoff, Stephane; Debatisse, Michelle; Méndez, Juan; Freire, Raimundo

    2016-10-01

    DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested.

  14. Replicative intermediates of maize streak virus found during leaf development.

    Science.gov (United States)

    Erdmann, Julia B; Shepherd, Dionne N; Martin, Darren P; Varsani, Arvind; Rybicki, Edward P; Jeske, Holger

    2010-04-01

    Geminiviruses of the genera Begomovirus and Curtovirus utilize three replication modes: complementary-strand replication (CSR), rolling-circle replication (RCR) and recombination-dependent replication (RDR). Using two-dimensional gel electrophoresis, we now show for the first time that maize streak virus (MSV), the type member of the most divergent geminivirus genus, Mastrevirus, does the same. Although mastreviruses have fewer regulatory genes than other geminiviruses and uniquely express their replication-associated protein (Rep) from a spliced transcript, the replicative intermediates of CSR, RCR and RDR could be detected unequivocally within infected maize tissues. All replicative intermediates accumulated early and, to varying degrees, were already present in the shoot apex and leaves at different maturation stages. Relative to other replicative intermediates, those associated with RCR increased in prevalence during leaf maturation. Interestingly, in addition to RCR-associated DNA forms seen in other geminiviruses, MSV also apparently uses dimeric open circular DNA as a template for RCR.

  15. On the scattering of DNA replication completion times

    Science.gov (United States)

    Meilikhov, E. Z.; Farzetdinova, R. M.

    2015-07-01

    Stochasticity of Eukaryotes' DNA replication should not lead to large fluctuations of replication times, which could result in mitotic catastrophes. Fundamental problem that cells face is how to be ensured that entire genome is replicated on time. We develop analytic approach of calculating DNA replication times, that being simplified and approximate, leads, nevertheless, to results practically coincident with those that were obtained by some sophisticated methods. In the framework of that model we consider replication times' scattering and discuss the influence of repair stopping on kinetics of DNA replication. Our main explicit formulae for DNA replication time t r ∝ ( N is the total number of DNA base pairs) is of general character and explains basic features of DNA replication kinetics.

  16. Arap Dili Fonetiğinde Bazı Kavramların Yansıttığı ‘Ses Üretiminde Süre’ Olgusu Üzerine Bir Deneme

    Directory of Open Access Journals (Sweden)

    Yrd.Doç.Dr. Nazife İnce

    2016-06-01

    Full Text Available Dünya üzerindeki hemen hemen bütün diller dil çalışmalarında fonetiğe bir şekilde yer ayırmıştır. Arap dilinin fonetiğe gösterdiği ihtimam ise birçok dile nazaran daha fazla olmuştur. Fonetik incelemeler umumiyetle seslerin artikülasyon nitelikleri yani mahreç ve sıfatlar üzerinde yoğunlaşır. Buna mukabil gerek sıfat gerçeğinin ima ettiği her bir ses için farklı güç ihtiyacı düşüncesi gerekse ünlü seslerin uzatmaya elverişli oluşu ses-süre ilişkisini de zihinlere getirmektedir. Bu çalışmada Arap dili geleneğinde artikülasyon sürelerini ifade eden kavramların ve buna benzer verilerin yardımıyla konuyu ele alan disiplinlerin ses miktarı konusundaki tutumunu aydınlatmayı amaçladık. Çalışmamızın sonunda bazı tecvit eserlerinin yer verdiği ve seslerin ölçülerini korumayı işleyen bölümlerde kullandığı kavramlardan ve diğer olgulardan hareketle en azından uygulama hedefi olarak ses sürelerinin korunması ile ses niteliklerinin korunmasına yönelik dengeli bir bakışın olduğu neticesine ulaştık.

  17. Replication of plasmids in gram-negative bacteria.

    OpenAIRE

    1989-01-01

    Replication of plasmid deoxyribonucleic acid (DNA) is dependent on three stages: initiation, elongation, and termination. The first stage, initiation, depends on plasmid-encoded properties such as the replication origin and, in most cases, the replication initiation protein (Rep protein). In recent years the understanding of initiation and regulation of plasmid replication in Escherichia coli has increased considerably, but it is only for the ColE1-type plasmids that significant biochemical d...

  18. PCNA Modifications for Regulation of Post-Replication Repair Pathways

    OpenAIRE

    2008-01-01

    Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is ...

  19. Mathematical Framework for A Novel Database Replication Algorithm

    Directory of Open Access Journals (Sweden)

    Divakar Singh Yadav

    2013-10-01

    Full Text Available In this paper, the detailed overview of the database replication is presented. Thereafter, PDDRA (Pre-fetching based dynamic data replication algorithm algorithm as recently published is detailed. In this algorithm, further, modifications are suggested to minimize the delay in data replication. Finally a mathematical framework is presented to evaluate mean waiting time before a data can be replicated on the requested site.

  20. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F

    2003-11-27

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Pol{kappa}). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development.

  1. The plant cell cycle: Pre-Replication complex formation and controls.

    Science.gov (United States)

    Brasil, Juliana Nogueira; Costa, Carinne N Monteiro; Cabral, Luiz Mors; Ferreira, Paulo C G; Hemerly, Adriana S

    2017-01-01

    The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes.

  2. DNA replication and spindle checkpoints cooperate during S phase to delay mitosis and preserve genome integrity.

    Science.gov (United States)

    Magiera, Maria M; Gueydon, Elisabeth; Schwob, Etienne

    2014-01-20

    Deoxyribonucleic acid (DNA) replication and chromosome segregation must occur in ordered sequence to maintain genome integrity during cell proliferation. Checkpoint mechanisms delay mitosis when DNA is damaged or upon replication stress, but little is known on the coupling of S and M phases in unperturbed conditions. To address this issue, we postponed replication onset in budding yeast so that DNA synthesis is still underway when cells should enter mitosis. This delayed mitotic entry and progression by transient activation of the S phase, G2/M, and spindle assembly checkpoints. Disabling both Mec1/ATR- and Mad2-dependent controls caused lethality in cells with deferred S phase, accompanied by Rad52 foci and chromosome missegregation. Thus, in contrast to acute replication stress that triggers a sustained Mec1/ATR response, multiple pathways cooperate to restrain mitosis transiently when replication forks progress unhindered. We suggest that these surveillance mechanisms arose when both S and M phases were coincidently set into motion by a unique ancestral cyclin-Cdk1 complex.

  3. Plasticity of DNA replication initiation in Epstein-Barr virus episomes.

    Directory of Open Access Journals (Sweden)

    Paolo Norio

    2004-06-01

    Full Text Available In mammalian cells, the activity of the sites of initiation of DNA replication appears to be influenced epigenetically, but this regulation is not fully understood. Most studies of DNA replication have focused on the activity of individual initiation sites, making it difficult to evaluate the impact of changes in initiation activity on the replication of entire genomic loci. Here, we used single molecule analysis of replicated DNA (SMARD to study the latent duplication of Epstein-Barr virus (EBV episomes in human cell lines. We found that initiation sites are present throughout the EBV genome and that their utilization is not conserved in different EBV strains. In addition, SMARD shows that modifications in the utilization of multiple initiation sites occur across large genomic regions (tens of kilobases in size. These observations indicate that individual initiation sites play a limited role in determining the replication dynamics of the EBV genome. Long-range mechanisms and the genomic context appear to play much more important roles, affecting the frequency of utilization and the order of activation of multiple initiation sites. Finally, these results confirm that initiation sites are extremely redundant elements of the EBV genome. We propose that these conclusions also apply to mammalian chromosomes.

  4. Histone H4 acetylation required for chromatin decompaction during DNA replication.

    Science.gov (United States)

    Ruan, Kun; Yamamoto, Takaharu G; Asakawa, Haruhiko; Chikashige, Yuji; Kimura, Hiroshi; Masukata, Hisao; Haraguchi, Tokuko; Hiraoka, Yasushi

    2015-07-30

    Faithful DNA replication is a prerequisite for cell proliferation. Several cytological studies have shown that chromosome structures alter in the S-phase of the cell cycle. However, the molecular mechanisms behind the alteration of chromosome structures associated with DNA replication have not been elucidated. Here, we investigated chromatin structures and acetylation of specific histone residues during DNA replication using the meiotic nucleus of the fission yeast Schizosaccharomyces pombe. The S. pombe meiotic nucleus provides a unique opportunity for measuring the levels of compaction of chromatin along the chromosome in a defined orientation. By direct measurement of chromatin compaction in living cells, we demonstrated that decompaction of chromatin occurs during meiotic DNA replication. This chromatin decompaction was suppressed by depletion of histone acetyltransferase Mst1 or by arginine substitution of specific lysine residues (K8 and K12) of histone H4. These results suggest that acetylation of histone H4 residues K8 and K12 plays a critical role in loosening chromatin structures during DNA replication.

  5. The fork and the kinase: a DNA replication tale from a CHK1 perspective.

    Science.gov (United States)

    González Besteiro, Marina A; Gottifredi, Vanesa

    2015-01-01

    Replication fork progression is being continuously hampered by exogenously introduced and naturally occurring DNA lesions and other physical obstacles. Checkpoint kinase 1 (Chk1) is activated at replication forks that encounter damaged DNA. Subsequently, Chk1 inhibits the initiation of new replication factories and stimulates the firing of dormant origins (those in the vicinity of stalled forks). Chk1 also avoids fork collapse into DSBs (double strand breaks) and promotes fork elongation. At the molecular level, the current model considers stalled forks as the site of Chk1 activation and the nucleoplasm as the location where Chk1 phosphorylates target proteins. This model certainly serves to explain how Chk1 modulates origin firing, but how Chk1 controls the fate of stalled forks is less clear. Interestingly, recent reports demonstrating that Chk1 phosphorylates chromatin-bound proteins and even holds kinase-independent functions might shed light on how Chk1 contributes to the elongation of damaged DNA. Indeed, such findings have unveiled a puzzling connection between Chk1 and DNA lesion bypass, which might be central to promoting fork elongation and checkpoint attenuation. In summary, Chk1 is a multifaceted and versatile signaling factor that acts at ongoing forks and replication origins to determine the extent and quality of the cellular response to replication stress.

  6. The replication of beta cells in normal physiology, in disease and for therapy.

    Science.gov (United States)

    Butler, Peter C; Meier, Juris J; Butler, Alexandra E; Bhushan, Anil

    2007-11-01

    Replication of beta cells is an important source of beta-cell expansion in early childhood. The recent linkage of type 2 diabetes with several transcription factors involved in cell cycle regulation implies that growth of the beta-cell mass in early childhood might be an important determinant of risk for type 2 diabetes. Under some circumstances, including obesity and pregnancy, the beta-cell mass is adaptively increased in adult humans. The mechanisms by which this adaptive growth occurs and the relative contributions of beta-cell replication or of mechanisms independent of beta-cell replication are unknown. Also, although there is interest in the potential for beta-cell regeneration as a therapeutic approach in both type 1 and 2 diabetes, little is yet known about the potential sources of new beta cells in adult humans. In common with other cell types, replicating beta cells have an increased vulnerability to apoptosis, which is likely to limit the therapeutic value of inducing beta-cell replication in the proapoptotic environment of type 1 and 2 diabetes unless applied in conjunction with a strategy to suppress increased apoptosis.

  7. 3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle

    KAUST Repository

    Knodel, Markus

    2017-10-02

    Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures-namely the ER surface and the membranous webs-based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.

  8. Sol-gel replicated optics made from single point diamond turned masters exhibit fractal surface roughness

    Energy Technology Data Exchange (ETDEWEB)

    Bernacki, B.E.; Miller, A.C. Jr.; Evans, B.M. III [Oak Ridge National Lab., TN (United States); Moreshead, W.V.; Nogues, J.L.R. [GELTECH, Inc., Alachua, FL (United States)

    1996-05-01

    Deterministic optics manufacturing, notably single point diamond turning (SPDT) has matured such that the current generation of machines is capable of producing refractive and reflective optics for the visible wavelength region that are quite acceptable for many applications. However, spiral tool marks are still produced that result in unwanted diffractive scattering from grating-like features having a spatial frequency determined by the machine feed, tool radius, and other influences such as vibration and material removal effects. Such regular artifacts are the characteristic of deterministic manufacturing methods such as SPDT. The authors present some initial findings suggesting that fractal, or non-deterministic surfaces can be produced by SPDT through sol-gel replication. The key is the large isotropic shrinkage that occurs through monolithic sol-gel replication (a factor of 2.5) that results in all features, including tooling marks, being reduced by that amount. The large shrinkage itself would be a laudable-enough feature of the replication process. However, by an as-yet-not understood manner, the replication process itself seems to alter the roughness character of the replicated surface such that it appears to be fractal when analyzed using contact profilometry and the power spectrum approach.

  9. Replication slippage of the thermophilic DNA polymerases B and D from the Euryarchaeota Pyrococcus abyssi.

    Science.gov (United States)

    Castillo-Lizardo, Melissa; Henneke, Ghislaine; Viguera, Enrique

    2014-01-01

    Replication slippage or slipped-strand mispairing involves the misalignment of DNA strands during the replication of repeated DNA sequences, and can lead to genetic rearrangements such as microsatellite instability. Here, we show that PolB and PolD replicative DNA polymerases from the archaeal model Pyrococcus abyssi (Pab) slip in vitro during replication of a single-stranded DNA template carrying a hairpin structure and short direct repeats. We find that this occurs in both their wild-type (exo+) and exonuclease deficient (exo-) forms. The slippage behavior of PabPolB and PabPolD, probably due to limited strand displacement activity, resembles that observed for the high fidelity P. furiosus (Pfu) DNA polymerase. The presence of PabPCNA inhibited PabPolB and PabPolD slippage. We propose a model whereby PabPCNA stimulates strand displacement activity and polymerase progression through the hairpin, thus permitting the error-free replication of repetitive sequences.

  10. Replication slippage of the thermophilic DNA polymerases B and D from the Euryarchaeota Pyrococcus abyssi

    Directory of Open Access Journals (Sweden)

    Melissa G. eCastillo-Lizardo

    2014-08-01

    Full Text Available Replication slippage or slipped-strand mispairing involves the misalignment of DNA strands during the replication of repeated DNA sequences, and can lead to genetic rearrangements such as microsatellite instability. Here, we show that PolB and PolD replicative DNA polymerases from the archaeal model Pyrococcus abyssi (Pab slip in vitro during replication of a single-stranded DNA template carrying a hairpin structure and short direct repeats. We find that this occurs in both their wild-type (exo+ and exonuclease deficient (exo- forms. The slippage behavior of PabPolB and PabPolD, probably due to limited strand displacement activity, resembles that observed for the high fidelity Pyrococcus furiosus (Pfu DNA polymerase. The presence of PabPCNA inhibited PabPolB and PabPolD slippage. We propose a model whereby PabPCNA stimulates strand displacement activity and polymerase progression through the hairpin, thus permitting the error-free replication of repetitive sequences.

  11. Maksimum Yagıslar için Süreden Bagımsız Bir Bölgesel Model Yaklasımı

    Directory of Open Access Journals (Sweden)

    Ömer Levend AŞIKOĞLU

    2009-04-01

    Full Text Available Bu çalısmada, Ege Bölgesi örneginde belli tekerrürlü standart süreli yıllık maksimum yagıs (SSMY tahmininde kullanılabilecek, Lognormal tabanlı bir bölgesel model gelistirilmistir. Bölgesel modellerin temel amacı, proje alanına yakın birkaç istasyondaki noktasal veri ve bilgilerin proje alanına aktarılması ile ortaya çıkacak sakıncaları en aza indirmektir. Ayrıca, bölgesel modeller yardımıyla plüvyografsız istasyon bulunan veya hiç istasyon bulunmayan proje alanlarına da bilgi aktarma olanagı mevcuttur. Çalısmada, Lognormal dagılım fonksiyonunun tanımlanması için gerekli olan degiskenlik katsayısının yagıs süresinden bagımsız oldugu belirlenmis, tüm bölge için süreden bagımsız bir "bölgesel degiskenlik katsayısı" kullanılmıstır. Bölgesel degiskenlik katsayısının kullanımıyla gelistirilen "boyutsuz bölgesel tekerrür egrisi", proje alanında ortalama yagıs yüksekligi bilinen her noktada verilen tekerrüre karsılık gelecek yagıs yüksekliginin hesaplanmasını saglayacaktır. Böylelikle bölgede daha etkin boyutsuz yagıs tahminleri yapılabilmesine imkan verecektir. Bu model, yagıs ölçüm istasyonlarının standart süreli yagısları Lognormal frekans dagılım modeline uyan bölgelerde, bölgesel model kurma açısından büyük kolaylıklar getirecektir.

  12. Systematic determination of replication activity type highlights interconnections between replication, chromatin structure and nuclear localization.

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

    Full Text Available DNA replication is a highly regulated process, with each genomic locus replicating at a distinct time of replication (ToR. Advances in ToR measurement technology enabled several genome-wide profiling studies that revealed tight associations between ToR and general genomic features and a remarkable ToR conservation in mammals. Genome wide studies further showed that at the hundreds kb-to-megabase scale the genome can be divided into constant ToR regions (CTRs in which the replication process propagates at a faster pace due to the activation of multiple origins and temporal transition regions (TTRs in which the replication process propagates at a slower pace. We developed a computational tool that assigns a ToR to every measured locus and determines its replication activity type (CTR versus TTR. Our algorithm, ARTO (Analysis of Replication Timing and Organization, uses signal processing methods to fit a constant piece-wise linear curve to the measured raw data. We tested our algorithm and provide performance and usability results. A Matlab implementation of ARTO is available at http://bioinfo.cs.technion.ac.il/people/zohar/ARTO/. Applying our algorithm to ToR data measured in multiple mouse and human samples allowed precise genome-wide ToR determination and replication activity type characterization. Analysis of the results highlighted the plasticity of the replication program. For example, we observed significant ToR differences in 10-25% of the genome when comparing different tissue types. Our analyses also provide evidence for activity type differences in up to 30% of the probes. Integration of the ToR data with multiple aspects of chromosome organization characteristics suggests that ToR plays a role in shaping the regional chromatin structure. Namely, repressive chromatin marks, are associated with late ToR both in TTRs and CTRs. Finally, characterization of the differences between TTRs and CTRs, with matching ToR, revealed that TTRs are

  13. Chromatin Dynamics During DNA Replication and Uncharacterized Replication Factors determined by Nascent Chromatin Capture (NCC) Proteomics

    Science.gov (United States)

    Alabert, Constance; Bukowski-Wills, Jimi-Carlo; Lee, Sung-Bau; Kustatscher, Georg; Nakamura, Kyosuke; de Lima Alves, Flavia; Menard, Patrice; Mejlvang, Jakob; Rappsilber, Juri; Groth, Anja

    2014-01-01

    SUMMARY To maintain genome function and stability, DNA sequence and its organization into chromatin must be duplicated during cell division. Understanding how entire chromosomes are copied remains a major challenge. Here, we use Nascent Chromatin Capture (NCC) to profile chromatin proteome dynamics during replication in human cells. NCC relies on biotin-dUTP labelling of replicating DNA, affinity-purification and quantitative proteomics. Comparing nascent chromatin with mature post-replicative chromatin, we provide association dynamics for 3995 proteins. The replication machinery and 485 chromatin factors like CAF-1, DNMT1, SUV39h1 are enriched in nascent chromatin, whereas 170 factors including histone H1, DNMT3, MBD1-3 and PRC1 show delayed association. This correlates with H4K5K12diAc removal and H3K9me1 accumulation, while H3K27me3 and H3K9me3 remain unchanged. Finally, we combine NCC enrichment with experimentally derived chromatin probabilities to predict a function in nascent chromatin for 93 uncharacterized proteins and identify FAM111A as a replication factor required for PCNA loading. Together, this provides an extensive resource to understand genome and epigenome maintenance. PMID:24561620

  14. Building up and breaking down: mechanisms controlling recombination during replication.

    Science.gov (United States)

    Branzei, Dana; Szakal, Barnabas

    2017-08-01

    The complete and faithful duplication of the genome is an essential prerequisite for proliferating cells to maintain genome integrity. This objective is greatly challenged by DNA damage encountered during replication, which causes fork stalling and in certain cases, fork breakage. DNA damage tolerance (DDT) pathways mitigate the effects on fork stability induced by replication fork stalling by mediating damage-bypass and replication fork restart. These DDT mechanisms, largely relying on homologous recombination (HR) and specialized polymerases, can however contribute to genome rearrangements and mutagenesis. There is a profound connection between replication and recombination: recombination proteins protect replication forks from nuclease-mediated degradation of the nascent DNA strands and facilitate replication completion in cells challenged by DNA damage. Moreover, in case of fork collapse and formation of double strand breaks (DSBs), the recombination factors present or recruited to the fork facilitate HR-mediated DSB repair, which is primarily error-free. Disruption of HR is inexorably linked to genome instability, but the premature activation of HR during replication often leads to genome rearrangements. Faithful replication necessitates the downregulation of HR and disruption of active RAD51 filaments at replication forks, but upon persistent fork stalling, building up of HR is critical for the reorganization of the replication fork and for filling-in of the gaps associated with discontinuous replication induced by DNA lesions. Here we summarize and reflect on our understanding of the mechanisms that either suppress recombination or locally enhance it during replication, and the principles that underlie this regulation.

  15. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

    Yardimci, Hasan; Loveland, Anna B.; Habuchi, Satoshi; van Oijen, Antoine M.; Walter, Johannes C.

    2010-01-01

    The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes.

  16. Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

    NARCIS (Netherlands)

    Tanner, Nathan A.; Loparo, Joseph J.; Oijen, Antoine M. van

    2009-01-01

    We describe a simple fluorescence microscopy-based real-time method for observing DNA replication at the single-molecule level. A circular, forked DNA template is attached to a functionalized glass coverslip and replicated extensively after introduction of replication proteins and nucleotides. The

  17. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

    Yardimci, Hasan; Loveland, Anna B.; Habuchi, Satoshi; van Oijen, Antoine M.; Walter, Johannes C.

    2010-01-01

    The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes. So

  18. Geminin: a major DNA replication safeguard in higher eukaryotes

    DEFF Research Database (Denmark)

    Melixetian, Marina; Helin, Kristian

    2004-01-01

    Eukaryotes have evolved multiple mechanisms to restrict DNA replication to once per cell cycle. These mechanisms prevent relicensing of origins of replication after initiation of DNA replication in S phase until the end of mitosis. Most of our knowledge of mechanisms controlling prereplication...

  19. Anaphase onset before complete DNA replication with intact checkpoint responses

    DEFF Research Database (Denmark)

    Torres-Rosell, Jordi; De Piccoli, Giacomo; Cordon-Preciado, Violeta

    2007-01-01

    Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast smc5-smc6 mutants, which are related to cohesin and condensin, replication is delayed, most...

  20. Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

    NARCIS (Netherlands)

    Tanner, Nathan A.; Loparo, Joseph J.; Oijen, Antoine M. van

    2009-01-01

    We describe a simple fluorescence microscopy-based real-time method for observing DNA replication at the single-molecule level. A circular, forked DNA template is attached to a functionalized glass coverslip and replicated extensively after introduction of replication proteins and nucleotides. The g

  1. Geminin: a major DNA replication safeguard in higher eukaryotes

    DEFF Research Database (Denmark)

    Melixetian, Marina; Helin, Kristian

    2004-01-01

    Eukaryotes have evolved multiple mechanisms to restrict DNA replication to once per cell cycle. These mechanisms prevent relicensing of origins of replication after initiation of DNA replication in S phase until the end of mitosis. Most of our knowledge of mechanisms controlling prereplication...

  2. Replication NAND gate with light as input and output.

    Science.gov (United States)

    Samiappan, Manickasundaram; Dadon, Zehavit; Ashkenasy, Gonen

    2011-01-14

    Logic operations can highlight information transfer within complex molecular networks. We describe here the design of a peptide-based replication system that can be detected by following its fluorescence quenching. This process is used to negate the signal of light-activated replication, and thus to prepare the first replication NAND gate.

  3. RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells.

    Science.gov (United States)

    Im, Jun-Sub; Park, Soon-Young; Cho, Won-Ho; Bae, Sung-Ho; Hurwitz, Jerard; Lee, Joon-Kyu

    2015-01-01

    Though RecQL4 was shown to be essential for the initiation of DNA replication in mammalian cells, its role in initiation is poorly understood. Here, we show that RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical interactions and association with replication origins are controlled by the concerted action of both CDK and DDK activities. Although RecQL4-dependent binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre-replicative complex, their association with replication origins requires the presence of the pre-replicative complex and CDK and DDK activities. Their association with replication origins and physical interactions are also targets of the DNA damage checkpoint pathways which prevent initiation of DNA replication at replication origins. Taken together, the RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells.

  4. Kitap İncelemesi: Thomas Piketty'nin 21. YY'da Eşitsizlik Dinamiklerini Bir Kıt'a Avrupası Bakış Açısından Değerlendirmesi

    OpenAIRE

    2014-01-01

    Thomas Piketty’nin, “21.yy’da Sermaye” başlıklı kitabı dünya ekonomi literatüründe çok ses getirdi. Uzun zamandan beri Anglosakson hâkimiyetinde olan ekonomi literatüründe bir Kıt’a Avrupası bakış açısının ses getirmesi dikkat çekicidir. Yazarın Fransız olması ve ağırlıklı olarak Fransız ekolünden gelmesi kitabı ayrıcalıklı kılan bir nedendir. Fransız ekolünden gelen bir akademisyen olarak kitabı orijinal dili olan Fransızca okuma ayrıcalığına sahip oldum. Bu yazı, “Thomas Piketty, Le Capital...

  5. İstanbul’daki 5 Yıldızlı Otellerde Kültürel Zeka Ölçeğine İlişkin Bir Uygulama

    OpenAIRE

    Aslan, Sevinç; ASLAN, Özgür

    2017-01-01

    Dünya artık daha fazla kültürün etkileşim içinde olduğu bir yer haline gelmektedir. Bu durum, örgütlerin ve çalışanların bu değişim karşısında stratejik bir unsur olarak, kültürel anlamda daha yetkin ve başarılı olmaya çalışmaları gerekliliğini ortaya koymaktadır. İşletmeleri başarıya ulaştıracak bu stratejik unsurlardan bir tanesi de çalışanların kültürel zeka seviyeleridir. Bu çalışmada da belirtildiği üzere yüksek kültürel zekaya sahip çalışanlar işletmeye önemli katkılar sağlamaktadırlar....

  6. Research Methods Used in Library and Information Science Theses: An Evaluation Kütüphanecilik ve Bilgi Bilim Tezlerinde Kullanılan Bilimsel Araştırma Yöntemleri : Bir Değerlendirme

    Directory of Open Access Journals (Sweden)

    S. Serap Kurbanoğlu

    1996-12-01

    Full Text Available A literature analysis and an evaluation are made on the findings of researches which examine the research methods employed in library science and information science dissertations. The data suggest some changes regarding to research methods used in library science dissertations. Separate examinations of library science dissertations and information science dissertations suggest that there are differences as much assimilarities between these sister disciplines. Kütüphanecilik ve bilgi bilim tezlerinde kullanılan araştırma yöntemleri konusunda yapılan araştırmaların bulguları üzerine bir literatür çalışması ve bir değerlendirme yapılmıştır. Bulgular kütüphanecilik tezlerinde kullanılan araştırma yöntemleri konusunda zaman içinde bir çeşitlenme olduğunu göstermektedir. Kütüphanecilik ve bilgi bilim tezleri üzerinde ayrı ayrı yürütülen incelemeler ise bu iki kardeş disiplin arasında benzerlikler kadar farklılıklar da olduğunu ortaya koymaktadır.

  7. Assembling semiconductor nanocomposites using DNA replication technologies.

    Energy Technology Data Exchange (ETDEWEB)

    Heimer, Brandon W.; Crown, Kevin K.; Bachand, George David

    2005-11-01

    Deoxyribonucleic acid (DNA) molecules represent Nature's genetic database, encoding the information necessary for all cellular processes. From a materials engineering perspective, DNA represents a nanoscale scaffold with highly refined structure, stability across a wide range of environmental conditions, and the ability to interact with a range of biomolecules. The ability to mass-manufacture functionalized DNA strands with Angstrom-level resolution through DNA replication technology, however, has not been explored. The long-term goal of the work presented in this report is focused on exploiting DNA and in vitro DNA replication processes to mass-manufacture nanocomposite materials. The specific objectives of this project were to: (1) develop methods for replicating DNA strands that incorporate nucleotides with ''chemical handles'', and (2) demonstrate attachment of nanocrystal quantum dots (nQDs) to functionalized DNA strands. Polymerase chain reaction (PCR) and primer extension methodologies were used to successfully synthesize amine-, thiol-, and biotin-functionalized DNA molecules. Significant variability in the efficiency of modified nucleotide incorporation was observed, and attributed to the intrinsic properties of the modified nucleotides. Noncovalent attachment of streptavidin-coated nQDs to biotin-modified DNA synthesized using the primer extension method was observed by epifluorescence microscopy. Data regarding covalent attachment of nQDs to amine- and thiol-functionalized DNA was generally inconclusive; alternative characterization tools are necessary to fully evaluate these attachment methods. Full realization of this technology may facilitate new approaches to manufacturing materials at the nanoscale. In addition, composite nQD-DNA materials may serve as novel recognition elements in sensor devices, or be used as diagnostic tools for forensic analyses. This report summarizes the results obtained over the course of this 1-year

  8. Lack of a unique termination site for the first round of bacteriophage lambda DNA replication

    Energy Technology Data Exchange (ETDEWEB)

    Valenzuela, M.S. (Brandeis Univ., Waltham, MA); Freifelder, D.; Inman, R.B.

    1976-01-01

    From previous data on the first round of bacteriophage lambdacIIcIII DNA replication (Schnos and Inman, 1970) it is possible to estimate, by extrapolation, the position on circular lambda DNA where bidirectional growing points meet. In the present study we have investigated whether this position occurs at a genetically defined site. To this end, replicative intermediates of lambda mutants containing either deletions to the left of the replication origin, or one deletion plus a duplication to the right, were analyzed in the electron microscope. Our results indicate that (i) leftward growing points can traverse the extrapolated termination point calculated from the lambdacIIcIII data, (ii) no discontinuity of either right or leftward growing fork position is observed, and (iii) the extrapolated termination points for these mutants are well removed from those calculated for lambdacIIcIII DNA. From these data we conclude that there is probably no unique termination site for the first round of lambda DNA replication and that termination occurs simply by collision of the growing forks.

  9. Cnr interferes with dimerization of the replication protein alpha in phage-plasmid P4.

    Science.gov (United States)

    Tocchetti, A; Serina, S; Oliva, I; Dehò, G; Ghisotti, D

    2001-01-15

    DNA replication of phage-plasmid P4 in its host Escherichia coli depends on its replication protein alpha. In the plasmid state, P4 copy number is controlled by the regulator protein Cnr (copy number regulation). Mutations in alpha (alpha(cr)) that prevent regulation by Cnr cause P4 over-replication and cell death. Using the two-hybrid system in Saccharomyces cerevisiae and a system based on lambda immunity in E.coli for in vivo detection of protein-protein interactions, we found that (i) alpha protein interacts with Cnr, whereas alpha(cr) proteins do not; (ii) both alpha-alpha and alpha(cr)-alpha(cr) interactions occur and the interaction domain is located within the C-terminal of alpha; (iii) Cnr-Cnr interaction also occurs. Using an in vivo competition assay, we found that Cnr interferes with both alpha-alpha and alpha(cr)-alpha(cr) dimerization. Our data suggest that Cnr and alpha interact in at least two ways, which may have different functional roles in P4 replication control.

  10. Human herpesvirus 8-associated neoplasms: the roles of viral replication and antiviral treatment.

    Science.gov (United States)

    Gantt, Soren; Casper, Corey

    2011-08-01

    In this review, we highlight the importance of human herpesvirus 8 (HHV-8) lytic replication and the potential for antiviral therapies to prevent or treat HHV-8-related neoplasms. Diseases caused by HHV-8 infection include Kaposi sarcoma, multicentric Castleman disease (MCD), and primary effusion lymphoma (PEL), which occur primarily in patients with HIV infection. Kaposi sarcoma is the most common AIDS-associated malignancy worldwide. MCD and PEL occur less commonly but, like Kaposi sarcoma, are associated with poor treatment outcomes. Like all herpesviruses, HHV-8 is capable of either latent or lytic infection of cells. Although HHV-8 infection of tumor cells is predominately latent, accumulating data point to the importance of both lytic phase viral gene products and production of infectious virus. Antiviral agents that target herpesvirus DNA synthesis, such as ganciclovir, inhibit HHV-8 lytic replication and can prevent Kaposi sarcoma. Several HIV protease inhibitors may interfere with tumor growth and angiogenesis, and one protease inhibitor, nelfinavir, directly inhibits HHV-8 replication in vitro. Controlled trials are indicated to determine the clinical utility of antiviral suppression of HHV-8 replication, and identify the optimal antiretroviral regimens, for the prevention and treatment of Kaposi sarcoma.

  11. Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication

    Science.gov (United States)

    Jia, Tony Z.; Fahrenbach, Albert C.; Kamat, Neha P.; Adamala, Katarzyna P.; Szostak, Jack W.

    2016-10-01

    The non-enzymatic replication of RNA is thought to have been a critical process required for the origin of life. One unsolved difficulty with non-enzymatic RNA replication is that template-directed copying of RNA results in a double-stranded product. After strand separation, rapid strand reannealing outcompetes slow non-enzymatic template copying, which renders multiple rounds of RNA replication impossible. Here we show that oligoarginine peptides slow the annealing of complementary oligoribonucleotides by up to several thousand-fold; however, short primers and activated monomers can still bind to template strands, and template-directed primer extension can still occur, all within a phase-separated condensed state, or coacervate. Furthermore, we show that within this phase, partial template copying occurs even in the presence of full-length complementary strands. This method to enable further rounds of replication suggests one mechanism by which short non-coded peptides could have enhanced early cellular fitness, and potentially explains how longer coded peptides, that is, proteins, came to prominence in modern biology.

  12. Role of viral replication in extrahepatic syndromes related to hepatitis B virus infection.

    Science.gov (United States)

    Mason, A

    2006-03-01

    Approximately 20% of patients with hepatitis B virus (HBV) infection may experience extrahepatic disease. These manifestations include a viral prodrome with a serum sickness-like syndrome, polyarteritis nodosa, glomerulonephritis, as well as various neurological and dermatologic diseases amongst other manifestations. The viral pathogenesis is not well understood and has been difficult to study due to the lack of an animal model of HBV-related extrahepatic disease. Deposition of immune complexes and activation of the complement cascade has been most widely studied. However, circulating immune complexes are physiologic and occur more frequently than extrahepatic disease. Also, HBV-related extrahepatic syndromes occur in the absence of immune complex formation. Several studies support the notion that HBV replication in extrahepatic tissues may also precipitate disease but extrahepatic replication has commonly been observed without any apparent cytopathic or immune related tissue damage. It is clear that suppression of viral replication with antiviral therapy or spontaneous viral clearance positively correlates with resolution of extrahepatic disease. The use of continuous immunosuppressive therapy has largely been abandoned with the advent of robust antiviral strategies to manage disease. These data support the notion that a combination of factors including inadequate clearance immune complexes and viral replication in extrahepatic tissues play an important role in the pathogenesis. This conceptual framework is potentially significant as it emphasizes the importance of antiviral treatment in the management of extrahepatic disease.

  13. The IFITMs Inhibit Zika Virus Replication

    Directory of Open Access Journals (Sweden)

    George Savidis

    2016-06-01

    Full Text Available Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.

  14. Multiscale modeling of virus replication and spread.

    Science.gov (United States)

    Kumberger, Peter; Frey, Felix; Schwarz, Ulrich S; Graw, Frederik

    2016-07-01

    Replication and spread of human viruses is based on the simultaneous exploitation of many different host functions, bridging multiple scales in space and time. Mathematical modeling is essential to obtain a systems-level understanding of how human viruses manage to proceed through their life cycles. Here, we review corresponding advances for viral systems of large medical relevance, such as human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV). We will outline how the combination of mathematical models and experimental data has advanced our quantitative knowledge about various processes of these pathogens, and how novel quantitative approaches promise to fill remaining gaps.

  15. Accounting for PDMS shrinkage when replicating structures

    DEFF Research Database (Denmark)

    Madsen, Morten Hannibal; Feidenhans'l, Nikolaj Agentoft; Hansen, Poul-Erik

    2014-01-01

    are seldom applied to counteract the shrinkage of PDMS. Also, to perform metrological measurements using replica techniques one has to take the shrinkage into account. Thus we report a study of the shrinkage of PDMS with several different mixing ratios and curing temperatures. The shrinkage factor, with its...... associated uncertainty, for PDMS in the range 40 to 120 °C is provided. By applying this correction factor, it is possible to replicate structures with a standard uncertainty of less than 0.2% in lateral dimensions using typical curing temperatures and PDMS mixing ratios in the range 1:6 to 1:20 (agent:base)....

  16. Replication of DNA during barley endosperm development

    DEFF Research Database (Denmark)

    Giese, H.

    1992-01-01

    The incorporation of [6-H-3]-thymidine into DNA of developing barley end sperm was examined by autoradiography of cross sections of seeds and DNA analysis. The majority of nuclear divisions took place in the very young endosperm, but as late as 25 days after anthesis there was evidence for DNA...... replication. The DNA content of the endosperm increases during development and in response to nitrogen application in parallel to the storage protein synthesis profile. The hordein genes were hypersensitive to DNase I treatment throughout development....

  17. The Nature of Stability in Replicating Systems

    Directory of Open Access Journals (Sweden)

    Addy Pross

    2011-02-01

    Full Text Available We review the concept of dynamic kinetic stability, a type of stability associated specifically with replicating entities, and show how it differs from the well-known and established (static kinetic and thermodynamic stabilities associated with regular chemical systems. In the process we demonstrate how the concept can help bridge the conceptual chasm that continues to separate the physical and biological sciences by relating the nature of stability in the animate and inanimate worlds, and by providing additional insights into the physicochemical nature of abiogenesis.

  18. Simulation Studies in Data Replication Strategies

    Institute of Scientific and Technical Information of China (English)

    HarveyB.Newman; IosifC.Legrand

    2001-01-01

    The aim of this work is to present the simulation studies in evaluating different data replication strategies between Regional Centers.The simulation Framework developed within the "Models of Networked Analysis at Rgional Centers”(MONARC) project,as a design and optimization tool for large scale distributed systems,has been used for these modeling studies.Remote client-serer access to database servers as well as ftp-like data transfers have been ralistically simulated and the performance and limitations are presented as a function of the characteristics of the protocol used and the network parameters.

  19. Microbial Toluene Removal in Hypoxic Model Constructed Wetlands Occurs Predominantly via the Ring Monooxygenation Pathway.

    Science.gov (United States)

    Martínez-Lavanchy, P M; Chen, Z; Lünsmann, V; Marin-Cevada, V; Vilchez-Vargas, R; Pieper, D H; Reiche, N; Kappelmeyer, U; Imparato, V; Junca, H; Nijenhuis, I; Müller, J A; Kuschk, P; Heipieper, H J

    2015-09-01

    In the present study, microbial toluene degradation in controlled constructed wetland model systems, planted fixed-bed reactors (PFRs), was queried with DNA-based methods in combination with stable isotope fractionation analysis and characterization of toluene-degrading microbial isolates. Two PFR replicates were operated with toluene as the sole external carbon and electron source for 2 years. The bulk redox conditions in these systems were hypoxic to anoxic. The autochthonous bacterial communities, as analyzed by Illumina sequencing of 16S rRNA gene amplicons, were mainly comprised of the families Xanthomonadaceae, Comamonadaceae, and Burkholderiaceae, plus Rhodospirillaceae in one of the PFR replicates. DNA microarray analyses of the catabolic potentials for aromatic compound degradation suggested the presence of the ring monooxygenation pathway in both systems, as well as the anaerobic toluene pathway in the PFR replicate with a high abundance of Rhodospirillaceae. The presence of catabolic genes encoding the ring monooxygenation pathway was verified by quantitative PCR analysis, utilizing the obtained toluene-degrading isolates as references. Stable isotope fractionation analysis showed low-level of carbon fractionation and only minimal hydrogen fractionation in both PFRs, which matches the fractionation signatures of monooxygenation and dioxygenation. In combination with the results of the DNA-based analyses, this suggests that toluene degradation occurs predominantly via ring monooxygenation in the PFRs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Examining a DNA Replication Requirement for Bacteriophage λ Red- and Rac Prophage RecET-Promoted Recombination in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Lynn C. Thomason

    2016-09-01

    Full Text Available Recombineering, in vivo genetic engineering with bacteriophage homologous recombination systems, is a powerful technique for making genetic modifications in bacteria. Two systems widely used in Escherichia coli are the Red system from phage λ and RecET from the defective Rac prophage. We investigated the in vivo dependence of recombineering on DNA replication of the recombining substrate using plasmid targets. For λ Red recombination, when DNA replication of a circular target plasmid is prevented, recombination with single-stranded DNA oligonucleotides is greatly reduced compared to that under replicating conditions. For RecET recombination, when DNA replication of the targeted plasmid is prevented, the recombination frequency is also reduced, to a level identical to that seen for the Red system in the absence of replication. The very low level of oligonucleotide recombination observed in the absence of any phage recombination functions is the same in the presence or absence of DNA replication. In contrast, both the Red and RecET systems recombine a nonreplicating linear dimer plasmid with high efficiency to yield a circular monomer. Therefore, the DNA replication requirement is substrate dependent. Our data are consistent with recombination by both the Red and RecET systems occurring predominately by single-strand annealing rather than by strand invasion.

  1. Replication of M13 single—stranded DNA bearing a sitespecific ethenocytosine lesion by Escherichia coil cell extracts

    Institute of Scientific and Technical Information of China (English)

    WANGGE; PAULMDUNMAN; 等

    1997-01-01

    Previous investigation on the mutagenic effects of 3,N4-Ethenocytosine (εC),a nonpairing DNA lesion,revealed the existence of a novel SOS-independent inducible mutagenic mechanism in E.coli termed UVM for UV modulation of mutagenesis.To investigate whether UVM is mediated by an alteration of DNA replication,we have set up an in vitro replication system in which phage M13 viral single-stranded DNA bearing a single site-specific (εC) residue is replicated by soluble protein extracts from E.coli cells.Replication products were analyzed by agarose gel electrophoresis and the frequency of translesion synthesis was determined by restriction endonuclease analyses.Our data indicate that DNA replication is strongly inhibited by εC,but that translesion DNA synthesis does occur in about 14% of the replicated DNA molecules.These results are very similar to those observed previously in vivo,and suggest that this experimental system may be suitable for evaluating alterations in DNA replication in UVM-induced cells.

  2. Break-seq reveals hydroxyurea-induced chromosome fragility as a result of unscheduled conflict between DNA replication and transcription.

    Science.gov (United States)

    Hoffman, Elizabeth A; McCulley, Andrew; Haarer, Brian; Arnak, Remigiusz; Feng, Wenyi

    2015-03-01

    We have previously demonstrated that in Saccharomyces cerevisiae replication, checkpoint inactivation via a mec1 mutation leads to chromosome breakage at replication forks initiated from virtually all origins after transient exposure to hydroxyurea (HU), an inhibitor of ribonucleotide reductase. Here we sought to determine whether all replication forks containing single-stranded DNA gaps have equal probability of producing double-strand breaks (DSBs) when cells attempt to recover from HU exposure. We devised a new methodology, Break-seq, that combines our previously described DSB labeling with next generation sequencing to map chromosome breaks with improved sensitivity and resolution. We show that DSBs preferentially occur at genes transcriptionally induced by HU. Notably, different subsets of the HU-induced genes produced DSBs in MEC1 and mec1 cells as replication forks traversed a greater distance in MEC1 cells than in mec1 cells during recovery from HU. Specifically, while MEC1 cells exhibited chromosome breakage at stress-response transcription factors, mec1 cells predominantly suffered chromosome breakage at transporter genes, many of which are the substrates of those transcription factors. We propose that HU-induced chromosome fragility arises at higher frequency near HU-induced genes as a result of destabilized replication forks encountering transcription factor binding and/or the act of transcription. We further propose that replication inhibitors can induce unscheduled encounters between replication and transcription and give rise to distinct patterns of chromosome fragile sites.

  3. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

  4. Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes.

    Science.gov (United States)

    Shen, Li; Inoue, Azusa; He, Jin; Liu, Yuting; Lu, Falong; Zhang, Yi

    2014-10-02

    With the exception of imprinted genes and certain repeats, DNA methylation is globally erased during preimplantation development. Recent studies have suggested that Tet3-mediated oxidation of 5-methylcytosine (5mC) and DNA replication-dependent dilution both contribute to global paternal DNA demethylation, but demethylation of the maternal genome occurs via replication. Here we present genome-scale DNA methylation maps for both the paternal and maternal genomes of Tet3-depleted and/or DNA replication-inhibited zygotes. In both genomes, we found that inhibition of DNA replication blocks DNA demethylation independently from Tet3 function and that Tet3 facilitates DNA demethylation largely by coupling with DNA replication. For both genomes, our data indicate that replication-dependent dilution is the major contributor to demethylation, but Tet3 plays an important role, particularly at certain loci. Our study thus defines the respective functions of Tet3 and DNA replication in paternal DNA demethylation and reveals an unexpected contribution of Tet3 to demethylation of the maternal genome.

  5. Examining a DNA Replication Requirement for Bacteriophage λ Red- and Rac Prophage RecET-Promoted Recombination in Escherichia coli

    Science.gov (United States)

    Thomason, Lynn C.; Costantino, Nina

    2016-01-01

    ABSTRACT Recombineering, in vivo genetic engineering with bacteriophage homologous recombination systems, is a powerful technique for making genetic modifications in bacteria. Two systems widely used in Escherichia coli are the Red system from phage λ and RecET from the defective Rac prophage. We investigated the in vivo dependence of recombineering on DNA replication of the recombining substrate using plasmid targets. For λ Red recombination, when DNA replication of a circular target plasmid is prevented, recombination with single-stranded DNA oligonucleotides is greatly reduced compared to that under replicating conditions. For RecET recombination, when DNA replication of the targeted plasmid is prevented, the recombination frequency is also reduced, to a level identical to that seen for the Red system in the absence of replication. The very low level of oligonucleotide recombination observed in the absence of any phage recombination functions is the same in the presence or absence of DNA replication. In contrast, both the Red and RecET systems recombine a nonreplicating linear dimer plasmid with high efficiency to yield a circular monomer. Therefore, the DNA replication requirement is substrate dependent. Our data are consistent with recombination by both the Red and RecET systems occurring predominately by single-strand annealing rather than by strand invasion. PMID:27624131

  6. Bloom syndrome complex promotes FANCM recruitment to stalled replication forks and facilitates both repair and traverse of DNA interstrand crosslinks.

    Science.gov (United States)

    Ling, Chen; Huang, Jing; Yan, Zhijiang; Li, Yongjiang; Ohzeki, Mioko; Ishiai, Masamichi; Xu, Dongyi; Takata, Minoru; Seidman, Michael; Wang, Weidong

    2016-01-01

    The recruitment of FANCM, a conserved DNA translocase and key component of several DNA repair protein complexes, to replication forks stalled by DNA interstrand crosslinks (ICLs) is a step upstream of the Fanconi anemia (FA) repair and replication traverse pathways of ICLs. However, detection of the FANCM recruitment has been technically challenging so that its mechanism remains exclusive. Here, we successfully observed recruitment of FANCM at stalled forks using a newly developed protocol. We report that the FANCM recruitment depends upon its intrinsic DNA translocase activity, and its DNA-binding partner FAAP24. Moreover, it is dependent on the replication checkpoint kinase, ATR; but is independent of the FA core and FANCD2-FANCI complexes, two essential components of the FA pathway, indicating that the FANCM recruitment occurs downstream of ATR but upstream of the FA pathway. Interestingly, the recruitment of FANCM requires its direct interaction with Bloom syndrome complex composed of BLM helicase, Topoisomerase 3α, RMI1 and RMI2; as well as the helicase activity of BLM. We further show that the FANCM-BLM complex interaction is critical for replication stress-induced FANCM hyperphosphorylation, for normal activation of the FA pathway in response to ICLs, and for efficient traverse of ICLs by the replication machinery. Epistasis studies demonstrate that FANCM and BLM work in the same pathway to promote replication traverse of ICLs. We conclude that FANCM and BLM complex work together at stalled forks to promote both FA repair and replication traverse pathways of ICLs.

  7. Etkin bir yönetim için vizyoner liderliğin önemi: Hatay'daki kamu kurumları üzerinde bir uygulama/Importance Of Vısıonary Leadershıp For An Actıve Admınıstratıon: An Applıcaton In Publıc Instıtutıons In Hatay

    OpenAIRE

    Bulut, Yakup BULUT; uygun, serdar vural

    2014-01-01

    Özet Liderlik, insanlık tarihi kadar eski bir kavram olmakla beraber, bu konudaki çalışmaların sanayi devrimi sonrasında hız kazandığı görülmektedir. Günümüze kadar bu konuda birçok araştırmalar yapılmış, ulaşılan bulgular yorumlanmış ve kavramla ilgili çeşitli teoriler ortaya atılmıştır. Değişen yönetim anlayışları, beraberinde yeni yönetici ve lider tiplemelerini de getirmiştir. Vizyoner liderlik, diğer yönetim tiplemelerinden farklı olarak, son dönemde ortaya çıkan yeni bir anlayıştır. Bu ...

  8. Replication intermediate analysis confirms that chromosomal replication origin initiates from an unusual intergenic region in Caulobacter crescentus.

    Science.gov (United States)

    Brassinga, A K; Marczynski, G T

    2001-11-01

    The alpha-proteobacterium Caulobacter crescentus possesses a developmental cell cycle that restricts chromosome replication to a stalked cell type. The proposed C.crescentus chromosome replication origin (Cori) lies between hemE and RP001, an unusual intergenic region not previously associated with bacterial replication origins, although a similar genomic arrangement is also present at the putative replication origin in the related bacterium Rickettsia prowazekii. The cloned Cori supports autonomous plasmid replication selectively in the stalked cell type implying that replication of the entire chromosome also initiates between hemE and RP001. To confirm this location, we applied the 2-D (N/N) agarose gel electrophoresis technique to resolve and identify chromosome replication intermediates throughout a 30 kb region spanning Cori. Replication initiation in Cori was uniquely characterized by an 'origin bubble and Y-arc' pattern and this observation was supported by simple replication fork 'Y-arc' patterns that characterized the regions flanking Cori. These replication forks originated bi-directionally from within Cori as determined by the fork direction assay. Therefore, chromosomal replication initiates from the unusual hemE/RP001 intergenic region that we propose represents a new class of replication origins.

  9. Method of producing an item with enhanced wetting properties by fast replication and replication tool used in the method

    DEFF Research Database (Denmark)

    2016-01-01

    The invention relates to a replication tool (1) for producing an item (4) with enhanced wetting properties by fast replication, such as injection moulding or extrusion coating. The replication tool (1) comprises a tool surface (2a, 2b) defining a general shape of the item (4). The tool surface (2a...

  10. The DNA replication program is altered at the FMR1 locus in fragile X embryonic stem cells.

    Science.gov (United States)

    Gerhardt, Jeannine; Tomishima, Mark J; Zaninovic, Nikica; Colak, Dilek; Yan, Zi; Zhan, Qiansheng; Rosenwaks, Zev; Jaffrey, Samie R; Schildkraut, Carl L

    2014-01-09

    Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the FMR1 gene that appears to occur during oogenesis and during early embryogenesis. One model proposes that repeat instability depends on the replication fork direction through the repeats such that (CNG)n hairpin-like structures form, causing DNA polymerase to stall and slip. Examining DNA replication fork progression on single DNA molecules at the endogenous FMR1 locus revealed that replication forks stall at CGG repeats in human cells. Furthermore, replication profiles of FXS human embryonic stem cells (hESCs) compared to nonaffected hESCs showed that fork direction through the repeats is altered at the FMR1 locus in FXS hESCs, such that predominantly the CCG strand serves as the lagging-strand template. This is due to the absence of replication initiation that would typically occur upstream of FMR1, suggesting that altered replication origin usage combined with fork stalling promotes repeat instability during early embryonic development.

  11. Materials Chemistry and Performance of Silicone-Based Replicating Compounds.

    Energy Technology Data Exchange (ETDEWEB)

    Brumbach, Michael T.; Mirabal, Alex James; Kalan, Michael; Trujillo, Ana B; Hale, Kevin

    2014-11-01

    Replicating compounds are used to cast reproductions of surface features on a variety of materials. Replicas allow for quantitative measurements and recordkeeping on parts that may otherwise be difficult to measure or maintain. In this study, the chemistry and replicating capability of several replicating compounds was investigated. Additionally, the residue remaining on material surfaces upon removal of replicas was quantified. Cleaning practices were tested for several different replicating compounds. For all replicating compounds investigated, a thin silicone residue was left by the replica. For some compounds, additional inorganic species could be identified in the residue. Simple solvent cleaning could remove some residue.

  12. DNA replication origin activation in space and time.

    Science.gov (United States)

    Fragkos, Michalis; Ganier, Olivier; Coulombe, Philippe; Méchali, Marcel

    2015-06-01

    DNA replication begins with the assembly of pre-replication complexes (pre-RCs) at thousands of DNA replication origins during the G1 phase of the cell cycle. At the G1-S-phase transition, pre-RCs are converted into pre-initiation complexes, in which the replicative helicase is activated, leading to DNA unwinding and initiation of DNA synthesis. However, only a subset of origins are activated during any S phase. Recent insights into the mechanisms underlying this choice reveal how flexibility in origin usage and temporal activation are linked to chromosome structure and organization, cell growth and differentiation, and replication stress.

  13. ClIfford Geertz’e Göre Kültürel Bir Sistem Olarak Din Religion as a Cultural System by Clifford Geertz

    OpenAIRE

    HASANOV, BEHRAM

    2015-01-01

    ÖZETBu makale Clifford Geertz’in, dini kültürel bir sistem olarak incelemek üzere geliştirdiğikendi tanım ve metotlarına dayanan görüşlerini ele almaktadır. Makale Geertz’inyorumlayıcı yaklaşımını ve kültürü yorumlama yöntemi üzerine yoğunlaşmaktadır.Çalışma aynı zamanda Geertz’in dine nasıl yaklaştığını ve dinle toplumsal hayatı nasılilişkilendirdiğini incelemektedir. Makalede Geertz’in düşüncelerinin ve metodolojisininönemi ve dini yorumlamada başarısız olduğu noktalar da genel hatlarıyla b...

  14. Çocuk Kitaplarına Yeni Bir Yaklaşım: İnternet'te Resimli Çocuk Kitapları (e-books

    Directory of Open Access Journals (Sweden)

    Mübeccel Gönen

    2002-06-01

    Full Text Available Elektronik kitaplar (e-books yurtdışında oldukça yaygın bir biçimde kullanılmakta ve kullanıcı sayısı da giderek artmaktadır. İnternette yer alan bu kitaplar, her yaştaki insanın ilgi alanına hizmet edecek kadar çok ve çeşitlidir. Bu tür kitaplara internette yer alan kütüphanelerden, yayınevlerinden ve yazarlardan ulaşılmaktadır. Çocuk edebiyatı ile ilgili sitelerden de her konuda resimli çocuk kitaplarına ulaşılabilir. İnternette Türkçe resimli çocuk kitapları ve çocuk edebiyatı ile ilgili sitelere rastlanmamaktadır. Ancak elektronik çocuk kitaplarına yabancı sitelerden ulaşılabilir ve bazı sitelerden ücretsiz olarak da temin edilebilir. Bu yeni uygulama ile ülkemizde bulunan yayınevleri ve yazarların, iletişim ve bilgi teknolojisinden yararlanarak daha fazla aileye, okul ve çocuğa hizmet götürebileceği düşünülmektedir.

  15. Iznīqī and Jābir, Sirr and Miftāḥ: Two Authors, Four Titles, One Alchemical Treatise

    Directory of Open Access Journals (Sweden)

    Paola Carusi

    2017-03-01

    Full Text Available An alchemical Arabic treatise alternatively entitled Miftāḥ al-ḥikma, Miftāḥ jannāt al-khuld, Sirr al-asrār and Sirr al-sārr wa-sirr al-asrār is attributed in its manuscripts to two different authors: al-Iznīqī and Jābir b. Ḥayyān. In this article I briefly discuss some characteristic aspects of the treatise and its significance for the history of alchemy. These aspects include its ancient and important sources, such as the Muṣḥaf al-jamā‛a (Turba philosophorum and the Kitāb al-Ḥabīb, and its connection with the tradition of the artists and the activity of the workshop and laboratory, which first comes to the fore in Greek alchemy and later in Islamic alchemy. Furthermore, the work includes references to alchemical physical theories in which the influence of Islamic theology may perhaps be traced. This article, which summarises the results of investigations carried out over the last few years, could be considered as a kind of introduction to the edition and translation of the text currently in progress.

  16. Optimal Allocation of Replicates for Measurement Evaluation Studies

    Institute of Scientific and Technical Information of China (English)

    Stanislav O.Zakharkin; Kyoungmi Kim; Alfred A.Bartolucci; Grier P.Page; David B.Allison

    2006-01-01

    Optimal experimental design is important for the efficient use of modern highthroughput technologies such as microarrays and proteomics. Multiple factors including the reliability of measurement system, which itself must be estimated from prior experimental work, could influence design decisions. In this study, we describe how the optimal number of replicate measures (technical replicates) for each biological sample (biological replicate) can be determined. Different allocations of biological and technical replicates were evaluated by minimizing the variance of the ratio of technical variance (measurement error) to the total variance (sum of sampling error and measurement error). We demonstrate that if the number of biological replicates and the number of technical replicates per biological sample are variable, while the total number of available measures is fixed, then the optimal allocation of replicates for measurement evaluation experiments requires two technical replicates for each biological replicate. Therefore, it is recommended to use two technical replicates for each biological replicate if the goal is to evaluate the reproducibility of measurements.

  17. The Genomic Replication of the Crenarchaeal Virus SIRV2

    DEFF Research Database (Denmark)

    Martinez Alvarez, Laura

    of the crenarchaeal virus SIRV2, a model among archaeal viruses. SIRV2 was found to employ multiple replication mechanisms, with DNA synthesis starting by a strand-displacement mode that later derived in a rolling-circle replication from a circular intermediate. Interestingly, evidence for a secondary, bidirectional...... reinitiation events may partially explain the branched topology of the viral replication intermediates. We also analyzed the intracellular location of viral replication, showing the formation of viral peripheral replication centers in SIRV2-infected cells, where viral DNA synthesis and replication......-related proteins are concentrated. Our data indicates that the host DNA polymerase Dpo1 is also the viral replicative polymerase. Moreover, additional data suggests that other processes, such as translation, are also reorganized after infection. Based on our results, a model for the organization of viral...

  18. Regulation of replication fork progression through histone supply and demand

    DEFF Research Database (Denmark)

    Groth, Anja; Corpet, Armelle; Cook, Adam J L

    2007-01-01

    DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone...... chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf......1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork...

  19. Replication, falsification, and the crisis of confidence in social psychology

    Directory of Open Access Journals (Sweden)

    Brian D. Earp

    2015-05-01

    Full Text Available The (latest crisis in confidence in social psychology has generated much heated discussion about the importance of replication, including how such replication should be carried out as well as interpreted by scholars in the field. What does it mean if a replication attempt fails—does it mean that the original results, or the theory that predicted them, have been falsified? And how should failed replications affect our belief in the validity of the original research? In this paper, we consider the replication debate from a historical and philosophical perspective, and provide a conceptual analysis of both replication and falsification as they pertain to this important discussion. Along the way, we introduce a Bayesian framework for assessing failed replications in terms of how they should affect our confidence in purported findings.

  20. Replication, falsification, and the crisis of confidence in social psychology.

    Science.gov (United States)

    Earp, Brian D; Trafimow, David

    2015-01-01

    The (latest) crisis in confidence in social psychology has generated much heated discussion about the importance of replication, including how it should be carried out as well as interpreted by scholars in the field. For example, what does it mean if a replication attempt "fails"-does it mean that the original results, or the theory that predicted them, have been falsified? And how should "failed" replications affect our belief in the validity of the original research? In this paper, we consider the replication debate from a historical and philosophical perspective, and provide a conceptual analysis of both replication and falsification as they pertain to this important discussion. Along the way, we highlight the importance of auxiliary assumptions (for both testing theories and attempting replications), and introduce a Bayesian framework for assessing "failed" replications in terms of how they should affect our confidence in original findings.