Sample records for arsenite-induced replication lesions

  1. Arsenite-induced autophagy is associated with proteotoxicity in human lymphoblastoid cells

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    Bolt, Alicia M.; Zhao, Fei; Pacheco, Samantha; Klimecki, Walter T., E-mail:


    Epidemiological studies of arsenic-exposed populations have provided evidence that arsenic exposure in humans is associated with immunosuppression. Previously, we have reported that arsenite-induced toxicity is associated with the induction of autophagy in human lymphoblastoid cell lines (LCL). Autophagy is a cellular process that functions in the degradation of damaged cellular components, including protein aggregates formed by misfolded or damaged proteins. Accumulation of misfolded or damaged proteins in the endoplasmic reticulum (ER) lumen causes ER stress and activates the unfolded protein response (UPR). In an effort to investigate the mechanism of autophagy induction by arsenite in the LCL model, we examined the potential contribution of ER stress and activation of the UPR. LCL exposed to sodium arsenite for 8-days induced expression of UPR-activated genes, including CHOP and GRP78, at the RNA and the protein level. Evidence for activation of the three arms of the UPR was observed. The arsenite-induced activation of the UPR was associated with an accumulation of protein aggregates containing p62 and LC3, proteins with established roles in the sequestration and autophagic clearance of protein aggregates. Taken together, these data provide evidence that arsenite-induced autophagy is associated with the generation of ER stress, activation of the UPR, and formation of protein aggregates that may be targeted to the lysosome for degradation. -- Highlights: ► Arsenite induces endoplasmic reticulum stress and the unfolded protein response. ► Arsenite induces the formation of protein aggregates that contain p62 and LC3-II. ► Time-course data suggests that arsenite-induced autophagy precedes ER stress.

  2. Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells

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    Xu, Yuan; Zhao, Yue; Xu, Wenchao; Luo, Fei; Wang, Bairu; Li, Yuan; Pang, Ying; Liu, Qizhan, E-mail:


    Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis. - Highlights: • Arsenite induces inflammation. • Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α. • Inflammation is involved in arsenite-induced carcinogenesis.

  3. The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction. (United States)

    Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai


    The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

  4. Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction. (United States)

    Kaur, Tajpreet; Goel, Rajesh Kumar; Balakumar, Pitchai


    The present study has been designed to investigate the effect of rosiglitazone, a peroxisome proliferator activated receptor gamma agonist in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. The rats were administered sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) to induce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum nitrite/nitrate concentration. Further, the integrity of the aortic endothelium was assessed histologically using haematoxylin-eosin staining. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances, aortic reactive oxygen species and reduced form of glutathione. The administration of sodium arsenite produced VED by impairing acetylcholine-induced endothelium dependent relaxation, diminishing the integrity of vascular endothelium and decreasing the serum nitrite/nitrate concentration. In addition, sodium arsenite was noted to produce oxidative stress as it increased serum thiobarbituric acid reactive substances and aortic reactive oxygen species and consequently decreased glutathione. Treatment with rosiglitazone (3 mg/kg/day, p.o., 2 weeks and 5 mg/kg/day, p.o., 2 weeks) significantly prevented sodium arsenite-induced VED by enhancing acetylcholine-induced endothelium dependent relaxation, improving the integrity of vascular endothelium, increasing the nitrite/nitrate concentration and decreasing the oxidative stress. However, the vascular protective effect of rosiglitazone was markedly abolished by co-administration of nitric oxide synthase inhibitor, N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME) (25 mg/kg/day, i.p., 2 weeks). Thus, it may be concluded that rosiglitazone reduces oxidative stress, activates eNOS and enhances the generation of nitric oxide to prevent sodium arsenite-induced VED in rats.

  5. Acute Sodium Arsenite-Induced Hematological and Biochemical Changes in Wistar Rats: Protective Effects of Ethanol Extract of Ageratum conyzoides (United States)

    Ola-Davies, Olufunke Eunice; Akinrinde, Akinleye Stephen


    Background: Ageratum conyzoides L. (Asteraceae) is an annual herbaceous plant used in folklore medicine for the treatment of a wide range of diseases. Objective: To investigate the protective effect of the ethanol leaf extract of A. conyzoides (EEAC) against hematological, serum biochemical and histological alterations induced by Sodium arsenite administration to Wistar rats. Materials and Methods: Twenty male Wistar rats were randomly assigned into four groups of five rats each. Group I received propylene glycol and Group II rats were given the (EEAC, 100 mg/kg b.w.) orally for 7 days. Group III were given a single oral dose of sodium arsenite (NaAsO2, 2.5 mg/kg b.w.). Animals in Group IV were pretreated with 100 mg/kg EEAC for 7 days followed by a single oral dose of sodium arsenite. Results: Arsenic exposure resulted in significant reductions (P produced significant reversal of the reduction in the erythrocytic indices (packed cell volume, red blood cell, and Hb) caused by sodium arseniteSodium arsenite-induced slight elevations in serum aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), correlating with the histopathological lesions observedAgeratum conyzoides produced only slight reductions in AST, ALT, and ALP compared to the sodium arsenite group, but significantly reduced the severity of histopathological lesions. Abbreviations Used: EEAC: Ethanol extract of Ageratum conyzoides; RBC: Red blood cell; WBC: White blood cell; Hb: Hemoglobin; ALT: Alanine transaminase; AST: Aspartate transaminase or Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transferase. PMID:27114688

  6. Possible vasculoprotective role of linagliptin against sodium arsenite-induced vascular endothelial dysfunction. (United States)

    Jyoti, Uma; Kansal, Sunil Kumar; Kumar, Puneet; Goyal, Sandeep


    Vascular endothelial dysfunction (VED) interrupts the integrity and function of endothelial lining through enhanced markers of oxidative stress and decrease endothelial nitric oxide synthase (eNOS) expression. The main aim of the present study has been designed to investigate the possible vasculoprotective role of linagliptin against sodium arsenite-induced VED. Sodium arsenite (1.5 mg/kg, i.p., 2 weeks) abrogated the acetylcholine-induced, endothelium-dependent vasorelaxation by depicting the decrease in serum nitrite/nitrate concentration, reduced glutathione level, and simultaneously enhance the thiobarbituric acid reactive substances (TBARS) level, superoxide level, and tumor necrosis factor-alpha. These elevated markers interrupt the integrity of endothelial lining of thoracic aorta which was assessed histologically. The study elicits dose dependent effect of linagliptin (1.5 mg/kg, i.p. and 3 mg/kg, i.p.) or atorvastatin (30 mg/kg, p.o.) treatment, improved the endothelium-dependent independent relaxation, improve the integrity of endothelium lining which was assessed histologically by enhancing the serum nitrite/nitrate level, reduced glutathione level and simultaneously decreasing the TBARS level, superoxide anion level and tumor necrosis factor-alpha (TNF-α) level. L-NAME (25 mg/kg, i.p.), eNOS inhibitor, abrogated the ameliorative potential of linagliptin. However, the ameliorative potential of linagliptin has been enhanced by l-arginine (200 mg/kg, i.p.) which elicits that ameliorative potential of linagliptin was through eNOS signaling cascade and it may be concluded that linagliptin 3 mg/kg, i.p. has more significantly activated the eNOS and decreased the oxidative markers than linagliptin 1.5 mg/kg, i.p. and prevented sodium arsenite-induced VED.

  7. Aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) protect against sodium arsenite-induced hepatotoxicity in Wistar rats. (United States)

    Gbadegesin, M A; Odunola, O A


    We evaluated the effects of aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) on sodium arsenite-induced hepatotoxicity in Wistar rats. We observed that treatment of the animals with the extracts before or just after sodium arsenite administration significantly (p basilicum before the administration of sodium arsenite resulted in the attenuation of the sodium arsenite-induced aspartate and alanine aminotransferase activities: ALT (from 282.6% to 167.7% and 157.8%), AST (from 325.1% to 173.5% and 164.2%) for the group administered sodium arsenite alone, the aqueous extracts plus sodium arsenite, and ethanolic extracts plus sodium arsenite respectively, expressed as percentage of the negative control. These findings support the presence of hepatoprotective activity in the O.basilicum extracts.

  8. Crystal Structure of a Replicative DNA Polymerase Bound to the Oxidized Guanine Lesion Guanidinohydantoin

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    Aller, Pierre; Ye, Yu; Wallace, Susan S.; Burrows, Cynthia J.; Doubli, Sylvie (Vermont); (Utah)


    The oxidation of guanine generates one of the most common DNA lesions, 8-oxo-7,8-dihydroguanine (8-oxoG). The further oxidation of 8-oxoG can produce either guanidinohydantoin (Gh) in duplex DNA or spiroiminodihydantoin (Sp) in nucleosides and ssDNA. Although Gh can be a strong block for replicative DNA polymerases such as RB69 DNA polymerase, this lesion is also mutagenic: DNA polymerases bypass Gh by preferentially incorporating a purine with a slight preference for adenine, which results in G {center_dot} C {yields} T {center_dot} A or G {center_dot} C {yields} C {center_dot} G transversions. The 2.15 {angstrom} crystal structure of the replicative RB69 DNA polymerase in complex with DNA containing Gh reveals that Gh is extrahelical and rotated toward the major groove. In this conformation Gh is no longer in position to serve as a templating base for the incorporation of an incoming nucleotide. This work also constitutes the first crystallographic structure of Gh, which is stabilized in the R configuration in the two polymerase/DNA complexes present in the crystal asymmetric unit. In contrast to 8-oxoG, Gh is found in a high syn conformation in the DNA duplex and therefore presents the same hydrogen bond donor and acceptor pattern as thymine, which explains the propensity of DNA polymerases to incorporate a purine opposite Gh when bypass occurs.

  9. The novel role of fenofibrate in preventing nicotine- and sodium arsenite-induced vascular endothelial dysfunction in the rat. (United States)

    Kaur, Jagdeep; Reddy, Krishna; Balakumar, Pitchai


    The present study investigated the effect of fenofibrate, an agonist of PPAR-alpha, in nicotine- and sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) and sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) were administered to produce VED in rats. The scanning electron microscopy study in thoracic aorta revealed that administration of nicotine or sodium arsenite impaired the integrity of vascular endothelium. Further, administration of nicotine or sodium arsenite significantly decreased serum and aortic concentrations of nitrite/nitrate and subsequently reduced acetylcholine-induced endothelium-dependent relaxation. Moreover, nicotine or sodium arsenite produced oxidative stress by increasing serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide generation. However, treatment with fenofibrate (30 mg/kg/day, p.o.) or atorvastatin (30 mg/kg/day p.o., a standard agent) significantly prevented nicotine- and sodium arsenite-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentrations of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium-dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Conversely, co-administration of L-NAME (25 mg/kg/day, i.p.), an inhibitor of nitric oxide synthase, markedly attenuated these vascular protective effects of fenofibrate. The administration of nicotine or sodium arsenite altered the lipid profile by increasing serum cholesterol and triglycerides and consequently decreasing high-density lipoprotein levels, which were significantly prevented by treatment with fenofibrate or atorvastatin. It may be concluded that fenofibrate improves the integrity and function of vascular endothelium, and the vascular protecting potential of fenofibrate in preventing the development of nicotine- and sodium arsenite-induced VED may be attributed to its

  10. 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)



    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.

  11. Stress-induced Start Codon Fidelity Regulates Arsenite-inducible Regulatory Particle-associated Protein (AIRAP) Translation* (United States)

    Zach, Lolita; Braunstein, Ilana; Stanhill, Ariel


    Initial steps in protein synthesis are highly regulated processes as they define the reading frame of the translation machinery. Eukaryotic translation initiation is a process facilitated by numerous factors (eIFs), aimed to form a “scanning” mechanism toward the initiation codon. Translation initiation of the main open reading frame (ORF) in an mRNA transcript has been reported to be regulated by upstream open reading frames (uORFs) in a manner of re-initiation. This mode of regulation is governed by the phosphorylation status of eIF2α and controlled by cellular stresses. Another mode of translational initiation regulation is leaky scanning, and this regulatory process has not been extensively studied. We have identified arsenite-inducible regulatory particle-associated protein (AIRAP) transcript to be translationally induced during arsenite stress conditions. AIRAP transcript contains a single uORF in a poor-kozak context. AIRAP translation induction is governed by means of leaky scanning and not re-initiation. This induction of AIRAP is solely dependent on eIF1 and the uORF kozak context. We show that eIF1 is phosphorylated under specific conditions that induce protein misfolding and have biochemically characterized this site of phosphorylation. Our data indicate that leaky scanning like re-initiation is responsive to stress conditions and that leaky scanning can induce ORF translation by bypassing poor kozak context of a single uORF transcript. PMID:24898249

  12. Replication and recombination factors contributing to recombination-dependent bypass of DNA lesions by template switch.

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    Fabio Vanoli


    Full Text Available Damage tolerance mechanisms mediating damage-bypass and gap-filling are crucial for genome integrity. A major damage tolerance pathway involves recombination and is referred to as template switch. Template switch intermediates were visualized by 2D gel electrophoresis in the proximity of replication forks as X-shaped structures involving sister chromatid junctions. The homologous recombination factor Rad51 is required for the formation/stabilization of these intermediates, but its mode of action remains to be investigated. By using a combination of genetic and physical approaches, we show that the homologous recombination factors Rad55 and Rad57, but not Rad59, are required for the formation of template switch intermediates. The replication-proficient but recombination-defective rfa1-t11 mutant is normal in triggering a checkpoint response following DNA damage but is impaired in X-structure formation. The Exo1 nuclease also has stimulatory roles in this process. The checkpoint kinase, Rad53, is required for X-molecule formation and phosphorylates Rad55 robustly in response to DNA damage. Although Rad55 phosphorylation is thought to activate recombinational repair under conditions of genotoxic stress, we find that Rad55 phosphomutants do not affect the efficiency of X-molecule formation. We also examined the DNA polymerase implicated in the DNA synthesis step of template switch. Deficiencies in translesion synthesis polymerases do not affect X-molecule formation, whereas DNA polymerase δ, required also for bulk DNA synthesis, plays an important role. Our data indicate that a subset of homologous recombination factors, together with DNA polymerase δ, promote the formation of template switch intermediates that are then preferentially dissolved by the action of the Sgs1 helicase in association with the Top3 topoisomerase rather than resolved by Holliday Junction nucleases. Our results allow us to propose the choreography through which different

  13. Human Adipose-Derived Stem Cells Expanded Under Ambient Oxygen Concentration Accumulate Oxidative DNA Lesions and Experience Procarcinogenic DNA Replication Stress. (United States)

    Bétous, Rémy; Renoud, Marie-Laure; Hoede, Claire; Gonzalez, Ignacio; Jones, Natalie; Longy, Michel; Sensebé, Luc; Cazaux, Christophe; Hoffmann, Jean-Sébastien


    Adipose-derived stem cells (ADSCs) have led to growing interest in cell-based therapy because they can be easily harvested from an abundant tissue. ADSCs must be expanded in vitro before transplantation. This essential step causes concerns about the safety of adult stem cells in terms of potential transformation. Tumorigenesis is driven in its earliest step by DNA replication stress, which is characterized by the accumulation of stalled DNA replication forks and activation of the DNA damage response. Thus, to evaluate the safety of ADSCs during ex vivo expansion, we monitored DNA replication under atmospheric (21%) or physiologic (1%) oxygen concentration. Here, by combining immunofluorescence and DNA combing, we show that ADSCs cultured under 21% oxygen accumulate endogenous oxidative DNA lesions, which interfere with DNA replication by increasing fork stalling events, thereby leading to incomplete DNA replication and fork collapse. Moreover, we found by RNA sequencing (RNA-seq) that culture of ADSCs under atmospheric oxygen concentration leads to misexpression of cell cycle and DNA replication genes, which could contribute to DNA replication stress. Finally, analysis of acquired small nucleotide polymorphism shows that expansion of ADSCs under 21% oxygen induces a mutational bias toward deleterious transversions. Overall, our results suggest that expanding ADSCs at a low oxygen concentration could reduce the risk for DNA replication stress-associated transformation, as occurs in neoplastic tissues. Stem Cells Translational Medicine 2017;6:68-76.

  14. Marek's disease virus infection in the eye: chronological study of the lesions, virus replication, and vaccine-induced protection. (United States)

    Pandiri, Arun K R; Cortes, Aneg L; Lee, Lucy F; Gimeno, I M


    Marek's disease virus (MDV) infection in the eye was studied chronologically after inoculating 1-day-old chickens with a very virulent MDV strain, Md5. The ocular lesions could be classified as early lesions (6-11 days postinoculation [dpi]) and late lesions (26 and 56 dpi), based upon the location and severity of the lesions. The early lesions involved iris, ciliary body, and choroid layer, and were characterized by endothelial cell hypertrophy, vasculitis, and infiltration of lymphocytes (mainly CD8+), plasma cells, macrophages, and heterophils. Expression of early MDV-antigen pp38 in the cells infiltrating choroid layer was detected as early as 11 dpi. Late lesions consisted of severe lymphohistiocytic uveitis, keratitis, pectenitis, vitreitis, retinitis, and segmental to diffuse retinal necrosis. Cell infiltration included macrophages, granulocytes, plasma cells, and both CD4+ and CD8+ cells of various sizes. Expression of early MDV-antigen pp38 was readily found within the retina, uveal tract, and corneal epithelium. No expression of late-antigen gB or oncoprotein meq was detected in any of the eyes examined. A second experiment was conducted to study the effect of vaccination on the development of ocular lesions. Both HVT and CVI988 were able to protect against the development of early ocular lesions in chickens infected with very virulent plus strain MDV 648A. However, only CVI988 conferred complete protection against the development of late ocular lesions. HVT conferred partial protection, as it reduced the frequency and severity of the late ocular lesions. These results enhance our understanding of the nature and pattern of MDV infection in the eye.

  15. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress

    DEFF Research Database (Denmark)

    Lukas, Claudia; Savic, Velibor; Bekker-Jensen, Simon;


    Completion of genome duplication is challenged by structural and topological barriers that impede progression of replication forks. Although this can seriously undermine genome integrity, the fate of DNA with unresolved replication intermediates is not known. Here, we show that mild replication...... bodies shield chromosomal fragile sites sequestered in these compartments against erosion. Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations....... increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear...

  16. Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation. (United States)

    Gao, Ming; Li, Xiaoguang; Dong, Wen; Jin, Rui; Ma, Hanghang; Yang, Pingxun; Hu, Meiru; Li, Yi; Hao, Yi; Yuan, Shengtao; Huang, Junjian; Song, Lun


    The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination and degradation in vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting in GADD45α accumulation to activate JNKs cell death pathway, thereby revealing a novel mechanism for the cellular GADD45α functional regulation. But the factors involved in GADD45α stability modulations are unidentified. Here, we demonstrated that MDM2 was an E3 ubiquitin ligase for GADD45α. One of MDM2-binding partner, ribosomal protein S7, interacted with and stabilized GADD45α through preventing the ubiquitination and degradation of GADD45α mediated by MDM2. This novel function of S7 is unrelated to p53 but seems to depend on S7/MDM2 interaction, for the S7 mutant lacking MDM2-binding ability lost its function to stabilize GADD45α. Further investigations indicated that arsenite treatment enhanced S7-MDM2 interaction, resulting in attenuation of MDM2-dependent GADD45α ubiquitination and degradation, thereby leading to GADD45α-dependent cell death pathway activation. Silencing S7 expression suppressed GADD45α-dependent cytotoxicity induced by arsenite. Our findings thus identify a novel function of S7 in control of GADD45α stabilization under both basal and stress conditions and its significance in mediating arsenite-induced cellular stress.

  17. Lesion of the olfactory epithelium accelerates prion neuroinvasion and disease onset when prion replication is restricted to neurons.

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    Jenna Crowell

    Full Text Available Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain.

  18. Involvement of NO in sodium arsenite-induced yeast cell death%NO参与亚砷酸钠诱导酵母细胞死亡的调控

    Institute of Scientific and Technical Information of China (English)

    吴丽华; 仪慧兰; 张虎芳


    sodium arsenite exposure decreased cell viability in a dose-and time-dependent manner. Exposure to 1 to 7 mmol· L^-1 arsenite for 3 to 24 h significantly induced cell death. Dead cells showed some typical features of apoptosis, such as nuclear condensation and fragmentation. Caspase inhibitor Z-Asp-CH2-DCB (2 μmol · L^-1 ) significantly blocked arsenite-induced cell death. The characteristic features of apoptosis and the blockade by apoptosis inhibitor suggested a process of programmed cell death in arsenite-treated yeast cells. Arsenite exposure induced significant cell death and also an obvious increase of intercellular NO levels. Moreover, when either NO scavenger c-PTIO (0.2 mmol·L^ - 1 ) or NR inhibitor NaN3 ( 1 mmol· L^ - 1 ) was used to block intracellular NO increase, arsenite-induced cell death significantly decreased. These results clearly demonstrated that arsenite-caused cell death is associated with an increase of the intercellular NO levels. Increased NO triggered arsenite-induced cell death, and may also contribute to arsenite-induced programmed cell death. Our results suggest that arsenite-induced cell death may have dual effects on the organism, since apoptosis is programmed cell death for the good of the organism, but other kinds of cell death may be harmful to the body.

  19. ATR-Chk1-APC/C-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

    DEFF Research Database (Denmark)

    Yamada, M.; Watanabe, K.; Mistrik, M.;


    Cdc7 kinase regulates DNA replication. However, its role in DNA repair and recombination is poorly understood. Here we describe a pathway that stabilizes the human Cdc7-ASK (activator of S-phase kinase; also called Dbf4), its regulation, and its function in cellular responses to compromised DNA...... replication. Stalled DNA replication evoked stabilization of the Cdc7-ASK (Dbf4) complex in a manner dependent on ATR-Chk1-mediated checkpoint signaling and its interplay with the anaphase-promoting complex/cyclosomeCdh1 (APC/C) ubiquitin ligase. Mechanistically, Chk1 kinase inactivates APC/C through......) with RAD18 disables foci formation by RAD18 and hinders chromatin loading of translesion DNA polymerase h. These findings define a novel mechanism that orchestrates replication checkpoint signaling and ubiquitin-proteasome machinery with the DNA damage bypass pathway to guard against replication collapse...

  20. A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary artery lesion in Kawasaki disease.

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    Ho-Chang Kuo

    Full Text Available Single-nucleotide polymorphisms (SNPs in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC, rs28493229 and caspase-3 (CASP3, rs113420705 are associated with susceptibility to KD in Japanese and Taiwanese populations. This study was conducted to investigate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG resistance and coronary artery lesion (CAL in Taiwanese population. A total of 340 KD patients were subjected to assess by the identification of 2-locus genes model. A combinatorial association between ITPKC (rs28493229 and CASP3 (rs113420705 was found in CAL formation (P = 0.0227, OR: 3.06. KD patients with high-risk genotype had a trend of overrepresentation in IVIG resistance compared with individual SNPs. Our findings suggest the existence of genetic factors affecting patients' risk for CAL formation and IVIG responsiveness in a Taiwanese population.

  1. Database Replication

    CERN Document Server

    Kemme, Bettina


    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

  2. Lesiones laborales



    Las lesiones laborales se producen por un esfuerzo repetitivo, cuando un exceso de presión se ejerce sobre una parte del cuerpo provocando lesiones óseas, articulares, musculares y daños en los tejidos. Los accidentes laborales también pueden producir una lesión en el organismo y esto sumado a diversos factores es un problema para la reinserción laboral de los trabajadores de la energía eléctrica. Objetivo: Establecer cuáles son las lesiones más frecuentes que afectan a los ...

  3. Archaeal DNA replication. (United States)

    Kelman, Lori M; Kelman, Zvi


    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.

  4. Pink lesions. (United States)

    Giacomel, Jason; Zalaudek, Iris


    Dermoscopy (dermatoscopy or surface microscopy) is an ancillary dermatologic tool that in experienced hands can improve the accuracy of diagnosis of a variety of benign and malignant pigmented skin tumors. The early and more accurate diagnosis of nonpigmented, or pink, tumors can also be assisted by dermoscopy. This review focuses on the dermoscopic diagnosis of pink lesions, with emphasis on blood vessel morphology and pattern. A 3-step algorithm is presented, which facilitates the timely and more accurate diagnosis of pink tumors and subsequently guides the management for such lesions.

  5. DNA replication and cancer

    DEFF Research Database (Denmark)

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


    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...... to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby...... 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....

  6. Mechanism of chromosomal DNA replication initiation and replication fork stabilization in eukaryotes. (United States)

    Wu, LiHong; Liu, Yang; Kong, DaoChun


    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.

  7. Parasellar lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ruscalleda, J. [Hospital Sant Pau, Radiology Department, Neuroradiology, Barcelona (Spain)


    The sellar and parasellar region is an anatomically complex area that represents a crucial crossroad of important adjacent structures, e.g. orbits, cavernous sinus and its content, polygon of Willis, hypothalamus through the pituitary stalk and dural reflections forming the diaphragm sellae and the walls of the cavernous sinuses. Although the cavernous sinus represents the most relevant parasellar structure, from the practical and clinical point of view all the structures that surround the sella turcica can be included in the parasellar region. CT and, mainly, MRI are the imaging modalities to study and characterise the normal anatomy and the majority of processes in this region. We present a practical short review of the most relevant CT and MRI characteristics, such as location, nature of contrast enhancement and presence of cystic components, together with clinical findings, which permit differentiation of the most frequent and less common lesions found in the parasellar region. Learning objectives: A short review of the anatomy and clinical symptoms related to the parasellar region. Radiological characterisation, mainly by MRI, of the many lesions that alter the structure and function of sellar and parasellar anatomy. Description of the MRI features that permit differentiation among less common lesions. (orig.)

  8. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney


    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.

  9. Modeling DNA Replication. (United States)

    Bennett, Joan


    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)

  10. Abiotic self-replication. (United States)

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


    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

  11. Adenovirus DNA Replication


    Hoeben, Rob C.; Uil, Taco G.


    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...

  12. Minichromosome replication in vitro: inhibition of re-replication by replicatively assembled nucleosomes. (United States)

    Krude, T; Knippers, R


    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.

  13. 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.


    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.

  14. Hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)


    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.

  15. Psychology, replication & beyond. (United States)

    Laws, Keith R


    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.

  16. DNA replication origins in archaea


    Zhenfang eWu; Jingfang eLiu; Haibo eYang; Hua eXiang


    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 ...

  17. Replication studies in longevity

    DEFF Research Database (Denmark)

    Varcasia, O; Garasto, S; Rizza, T;


    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...

  18. Coronavirus Attachment and Replication (United States)


    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

  19. Reversible Switching of Cooperating Replicators (United States)

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


    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.

  20. Unique psoriatic lesion versus multiple lesions

    Directory of Open Access Journals (Sweden)

    Anca Chiriac


    Full Text Available Aim: To evaluate the number of lesions of psoriasis and to find risk factors for multiple lesions. Material and Methods: 1,236 patients (male 54.13%, female 45.87% with psoriasis were seen over a period of 8 years in an Outpatient Clinic. Patients filled out questionnaires containing age at onset, number of lesions and location at the beginning of the disease, gender, type and localization of psoriasis at the time of clinical examination, psoriasis family history, previous treatment, comorbidities, and social status. Results: The number of psoriasis lesions correlates with: onset age of psoriasis (F=8.902, p=0.0029; age at the moment of clinical examination (F=8.902, p=0.0029; residence in rural area (χ2=8.589, p=0.00338, 95%CI; alcohol intake (χ2=16.47, p=0.00005, 95%CI; smoking (χ2=8.408, p=0.00373, 95%CI; occupation: workers/pupils/students (χ2=14.11, p=0.0069, 95%CI. Conclusions: There is a correlation between number of psoriatic lesions and some factors. Multiple lesions were observed in older patients, smokers and drinkers, coming from rural area and social active (workers and pupils/students. No correlation was statistically proved between number of lesions and gender, comorbidities and family history of psoriasis.

  1. PCNA-Dependent Cleavage and Degradation of SDE2 Regulates Response to Replication Stress


    Jo, Ukhyun; Cai, Winson; Wang, Jingming; Kwon,Yoojin; D’Andrea, Alan D.; Kim, Hyungjin


    Maintaining genomic integrity during DNA replication is essential for cellular survival and for preventing tumorigenesis. Proliferating cell nuclear antigen (PCNA) functions as a processivity factor for DNA replication, and posttranslational modification of PCNA plays a key role in coordinating DNA repair against replication-blocking lesions by providing a platform to recruit factors required for DNA repair and cell cycle control. Here, we identify human SDE2 as a new genome surveillance fact...

  2. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja


    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...

  3. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja


    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...

  4. Initiation of adenovirus DNA replication.


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


    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 ...

  5. Replication Research and Special Education (United States)

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


    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…

  6. Replication data collection highlights value in diversity of replication attempts (United States)

    DeSoto, K. Andrew; Schweinsberg, Martin


    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

  7. 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.

  8. Initiation of Replication in Escherichia coli

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob

    of initiation, which leads to hyperinitiation, results in double-strand breaks when replication forks encounters single-stranded DNA lesions generated while removing oxidized bases, primarily 8-oxoG, from the DNA. Thus, the number of replication forks can only increase when ROS formation is reduced or when...... that the cell needs a copy of both DARS1 and DARS2 for proper regulation of initiation; i.e. DARS1 is a poor replacement for DARS2 and vice versa. Last we suggest that transcription has a negative effect of the activity of the non-coding regions....

  9. Lesion activity assessment

    DEFF Research Database (Denmark)

    Ekstrand, K R; Zero, D T; Martignon, S;


    . The literature suggests that there is a fair agreement between visual/tactile external scripts of caries and the severity/depth of the lesion. The reproducibility of the different systems is, in general, substantial. No single clinical predictor is able to reliably assess activity. However, a combination......This chapter focusses on the probability of a caries lesion detected during a clinical examination being active (progressing) or arrested. Visual and tactile methods to assess primary coronal lesions and primary root lesions are considered. The evidence level is rated as low (R...... in response to cariogenic plaque as well as lesion arrest. Based on this understanding, different clinical scoring systems have been developed to assess the severity/depth and activity of lesions. A recent system has been devised by the International Caries Detection and Assessment System Committee...

  10. Ghost cell lesions

    Directory of Open Access Journals (Sweden)

    E Rajesh


    Full Text Available Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms.

  11. Replicated Spectrographs in Astronomy

    CERN Document Server

    Hill, Gary J


    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...

  12. 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: [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)


    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.

  13. Herpes simplex virus type 1 ribonucleotide reductase null mutants induce lesions in guinea pigs. (United States)

    Turk, S R; Kik, N A; Birch, G M; Chiego, D J; Shipman, C


    Two herpes simplex virus type 1 ribonucleotide reductase null mutants, hrR3 and ICP6 delta, produced cutaneous lesions in guinea pigs as severe as those of wild-type strains. The lesions induced by hrR3 resulted from in vivo replication of the mutant virus, suggesting that this virus-encoded enzyme is nonessential for virus replication in guinea pigs.

  14. Efficient usage of Adabas replication

    CERN Document Server

    Storr, Dieter W


    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

  15. Solving the Telomere Replication Problem (United States)

    Maestroni, Laetitia; Matmati, Samah; Coulon, Stéphane


    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

  16. More forks on the road to replication stress recovery

    Institute of Scientific and Technical Information of China (English)

    Chris Allen; Amanda K. Ashley; Robert Hromas; Jac A. Nickoloff


    High-fidelity replication of DNA, and its accurate segregation to daughter cells, is critical for maintaining genome stability and suppressing cancer. DNA replication forks are stalled by many DNA lesions, activating checkpoint proteins that stabilize stalled forks.Stalled forks may eventually collapse, producing a broken DNA end. Fork restart is typically mediated by proteins initially identified by their rotes in homologous recombination repair of DNA double-strand breaks (DSBs). In recent years, several proteins involved in DSB repair by non-homologous end joining (NHEJ) have been implicated in the replication stress response, including DNA-PKcs, Ku,DNA Ligase IV-XRCC4, Artemis, XLF and Metnase. It is currently unclear whether NHEJ proteins are involved in the replication stress response through indirect (signaling) roles, and/or direct roles involving DNA end joining. Additional complexity in the replication stress response centers around RPA, which undergoes significant post-translational modification after stress, and RAD52, a conserved HR protein whose role in DSB repair may have shifted to another protein in higher eukaryotes, such as BRCA2, but retained its rote in fork restart. Most cancer therapeutic strategies create DNA reputation stress. Thus, it is imperative to gain a better understanding of replication stress response proteins and pathways to improve cancer therapy.

  17. Human brain lesion-deficit inference remapped. (United States)

    Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev


    Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

  18. Intraosseous osteolytic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Adler, C.P.; Wenz, W.


    Any pathological damage occurring in a bone will produce either an osteolytic or osteosclerotic lesion which can be seen in the macroscopic specimen as well as in the roentgenogram. Various bone lesions may lead to local destructions of the bone. An osteoma or osteoplastic osteosarcoma produces an osteosclerotic lesion showing a dense mass in the roentgenogram; a chondroblastoma or an osteoclastoma, on the other hand, induces an osteolytic focal lesion. This paper presents examples of different osteolytic lesions of the humerus. An osteolytic lesion seen in the roentgenogram may be either produced by an underlying non-ossifying fibroma of the bone, by fibrous dysplasia, osteomyelitis or Ewing's sarcoma. Differential diagnostic considerations based on the radiological picture include eosinophilic bone granuloma, juvenile or aneurysmal bone cyst, multiple myeloma or bone metastases. Serious differential diagnostic problems may be involved in case of osteolytic lesions occurring in the humerus. Cases of this type involving complications have been reported and include the presence of an teleangiectatic osteosarcoma as well as that of a hemangiosarcoma of the bone.

  19. Charter School Replication. Policy Guide (United States)

    Rhim, Lauren Morando


    "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…

  20. Inhibition of simian virus 40 DNA replication by ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Edenberg, H.J.


    The effects of ultraviolet light (uv) upon SV40 DNA synthesis in monkey cells were examined to determine whether replication forks were halted upon encountering lesions in the DNA, or alternatively whether lesions were rapidly bypassed. Ultraviolet light inhibits elongation of nascent DNA strands; the extent of incorporation of (/sup 3/H)deoxythymidine ((/sup 3/H)dT) into DNA decreases with increasing uv fluence. Inhibition begins within minutes of irradiation, and becomes more pronounced with increasing time after irradiation. The synthesis of form I (covalently closed) molecules is inhibited even more severely than is total incorporation: post-uv incorporation is predominantly into replication intermediates. In contrast to previous reports, we find that replication intermediates labeled after uv resemble those in unirradiated cells, and contain covalently closed parental strands. DNA strands made after uv are approximately the size of parental DNA which has been cleaved at pyrimidine dimers by a uv endonuclease, indicating that they do not extend past dimers. The hypothesis that replication forks are halted upon encountering pyrimidine dimers in the template strand is consistent with these data.

  1. Genome-wide alterations of the DNA replication program during tumor progression (United States)

    Arneodo, A.; Goldar, A.; Argoul, F.; Hyrien, O.; Audit, B.


    Oncogenic stress is a major driving force in the early stages of cancer development. Recent experimental findings reveal that, in precancerous lesions and cancers, activated oncogenes may induce stalling and dissociation of DNA replication forks resulting in DNA damage. Replication timing is emerging as an important epigenetic feature that recapitulates several genomic, epigenetic and functional specificities of even closely related cell types. There is increasing evidence that chromosome rearrangements, the hallmark of many cancer genomes, are intimately associated with the DNA replication program and that epigenetic replication timing changes often precede chromosomic rearrangements. The recent development of a novel methodology to map replication fork polarity using deep sequencing of Okazaki fragments has provided new and complementary genome-wide replication profiling data. We review the results of a wavelet-based multi-scale analysis of genomic and epigenetic data including replication profiles along human chromosomes. These results provide new insight into the spatio-temporal replication program and its dynamics during differentiation. Here our goal is to bring to cancer research, the experimental protocols and computational methodologies for replication program profiling, and also the modeling of the spatio-temporal replication program. To illustrate our purpose, we report very preliminary results obtained for the chronic myelogeneous leukemia, the archetype model of cancer. Finally, we discuss promising perspectives on using genome-wide DNA replication profiling as a novel efficient tool for cancer diagnosis, prognosis and personalized treatment.


    Directory of Open Access Journals (Sweden)

    Hendro Nindito


    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.

  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


    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. 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


    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.

  5. The hydantoin lesions formed from oxidation of 7,8-dihydro-8-oxoguanine are potnt sources of replication errors in vivo; Henderson, P.T.; Delaney, J.C.; Muller, J. G.; Neeley, W.L.; Tannenbaum, S.R.; Burrows, C.J.; Essigmann, J.M. Biochemistry (accelerate

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, P; Delaney, J; Muller, J; Neeley, W; Tannenbaum, S; Burrows, C; Essigmann, J


    Single-stranded DNA genomes have been constructed that site-specifically contain the 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG) oxidation products guanidinohyndantoin (Gh), and the two stable stereoisomers of spiroiminodihydantoin (Sp1 and Sp2). The circular viral genomes were transfected into wild-type AB1157 Escherichia coli and the efficiency of lesion bypass by DNA polymerase(s) was assessed. Viral progeny were analyzed for mutation frequency and type using the recently developed restriction endonuclease and post-labeling (REAP) assay. Gh was bypassed nearly as efficiently as the parent 8-oxoG, but was highly mutagenic, causing almost exclusive G{yields}C transversions. The stereoisomers Sp1 and Sp2 were, in comparison, much stronger blocks to DNA polymerase extension, and caused a mixture of G{yields}T and G{yields}C transversions. The ratio of G{yields}T to G{yields}C mutations for each Sp lesion was dependent on the stereochemical configuration of the base. All observed mutation frequencies were at least an order of magnitude higher than those caused by 8-oxoG. Were these lesions to be formed in vivo, our data show that they are absolutely miscoding, and may be refractory to repair after translesion synthesis.

  6. Managing Carious Lesions

    DEFF Research Database (Denmark)

    Schwendicke, F; Frencken, J E; Bjørndal, L


    The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental...

  7. Andersson Lesion in Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Manimegalai N, KrishnanKutty K, Panchapakesa Rajendran C, Rukmangatharajan S, Rajeswari S


    Full Text Available Andersson lesions are destructive foci that appear at the discovertebral junction in ankylosingspondylitis. We report three cases of ankylosing spondylitis with such lesions. These lesions simulatean infection and in our country, mimic spinal tuberculosis.

  8. The Psychology of Replication and Replication in Psychology. (United States)

    Francis, Gregory


    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.

  9. Meniscal Ramp Lesions (United States)

    Chahla, Jorge; Dean, Chase S.; Moatshe, Gilbert; Mitchell, Justin J.; Cram, Tyler R.; Yacuzzi, Carlos; LaPrade, Robert F.


    Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, and consequently, ramp lesions often go undiagnosed. Therefore, to rule out a ramp lesion, an arthroscopic evaluation with probing of the posterior horn of the medial meniscus should be performed. Several treatment options have been reported, including nonsurgical management, inside-out meniscal repair, or all-inside meniscal repair. In cases of isolated ramp lesions, a standard meniscal repair rehabilitation protocol should be followed. However, when a concomitant ACL reconstruction (ACLR) is performed, the rehabilitation should follow the designated ACLR postoperative protocol. The purpose of this article was to review the current literature regarding meniscal ramp lesions and summarize the pertinent anatomy, biomechanics, diagnostic strategies, recommended treatment options, and postoperative protocol. PMID:27504467

  10. Nucleotide Metabolism and DNA Replication. (United States)

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


    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.

  11. Plasmid Rolling-Circle Replication. (United States)

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


    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.

  12. Lesiones deportivas Sports injuries



    El estrés generado por la práctica deportiva ha originado una mayor probabilidad de que los atletas presenten lesiones agudas y crónicas. En el ámbito mundial existen diferentes investigaciones acerca de la incidencia de lesiones deportivas. La comparación de sus resultados es difícil por las diferencias en las características de la población y en la forma de reportar los datos, que varía ampliamente entre los estudios (proporciones o tasas de incidencia o tasas por cada 100 ó 1.000 participa...

  13. Genital lesions following bestiality

    Directory of Open Access Journals (Sweden)

    Mittal A


    Full Text Available A 48-year-old man presented with painful genital lesions with history of bestiality and abnor-mal sexual behaviour. Examination revealed multiple irregular tender ulcers and erosions, with phimosis and left sided tender inguinal adenopathy. VDRL, TPHA, HIV-ELISA were negative. He was treated with ciprofloxacin 500mg b.d. along with saline compresses with complete resolution.

  14. Immunopathology of skin lesions

    Directory of Open Access Journals (Sweden)

    Khan Nazoora


    Full Text Available A study was conducted on 130 patients suffering from skin lesions which included psoriasis, lichen planus, DLE, pemphigus, vitiligo and alopecia areata. Forty age-and-sex-matched healthy individuals served as control. Serum IgG, IgM, and circulating immune complexes (CIC were estimated. Significant increase in serum IgG (1937.2 ± 1030.43 mg% and IgM (232.12 ± 136.98 mg% was observed in all the skin lesions when compared with controls except in lichen planus where they were significantly lowered, values being 580.61± 77.35 mg% and 66.88 ± 6.59mg% respectively. CIC levels were significantly raised (P<0.00 1 in various skin lesions (40.49±23.29 when compared with controls (17.68± 3.21, but no significance was observed in lichen planus( 17.72 ± 4.28. Serum IgG, IgM and CIC were statistically significantly altered depending on the extent of the lesion and lowered significantly to almost normal values following treatment, thereby confirming the role of immunity in the pathogenesis of these skin disorders.

  15. Traumatic plexus lesion.

    NARCIS (Netherlands)

    Dongen, R.T.M. van; Cohen, S.P.; Kleef, M. van; Mekhail, N.; Huygen, F.


    Pain, motor, and sensory deficits characterize patients with a traumatic lesion of the brachial plexus. Frequently, more severe injuries co-exist that require immediate surgical attention. Early rehabilitation and physical therapy are the cornerstones of treatment. Pharmacological management can be

  16. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C;


    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants...

  17. Morel-Lavallee lesion

    Institute of Scientific and Technical Information of China (English)

    Li Hui; Zhang Fangjie; Lei Guanghua


    Objective To review current knowledge of the Morel-Lavallee lesion (MLL) to help clinicians become familiar with this entity.Familiarization may decrease missed diagnoses and misdiagnoses.It could also help steer the clinician to the proper treatment choice.Data sources A search was performed via PubMed and EMBASE from 1966 to July 2013 using the following keywords:Morel-Lavallee lesion,closed degloving injury,concealed degloving injury,Morel-Lavallee effusion,Morel-Lavallee hematoma,posttraumatic pseudocyst,posttraumatic soft tissue cyst.Study selection Chinese and English language literatures relevant to the subject were collected.Their references were also reviewed.Results Morel-Lavallee lesion is a relatively rare condition involving a closed degloving injury.It is characterized by a filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia.Apart from the classic location over the region of the greater trochanter,MLLs have been described in other parts of the body.The natural history of MLL has not yet been established.The lesion may decrease in volume,remain stable,enlarge progressively or show a recurrent pattern.Diagnosis of MLL was often missed or delayed.Ultrasonography,computed tomography,and magnetic resonance imaging have great value in the diagnosis of MLL.Treatment of MLL has included compression,local aspiration,open debridement,and sclerodesis.No standard treatment has been established.Conclusions A diagnosis of MLL should be suspected when a soft,fluctuant area of skin or chronic recurrent fluid collection is found in a region exposed to a previous shear injury.Clinicians and radiologists should be aware of both the acute and chronic appearances to make the correct diagnosis.Treatment decisions should base on association with fractures,the condition of the lesion,symptom and desire of the patient.

  18. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis


    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...

  19. Shell Separation for Mirror Replication (United States)


    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.

  20. Defects of mitochondrial DNA replication. (United States)

    Copeland, William C


    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.

  1. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan


    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...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  2. Personality and Academic Motivation: Replication, Extension, and Replication (United States)

    Jones, Martin H.; McMichael, Stephanie N.


    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…

  3. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul


    Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to adapt...... 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...

  4. 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...

  5. [Managing focal incidental renal lesions]. (United States)

    Nicolau, C; Paño, B; Sebastià, C


    Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy.

  6. Lesiones en el deporte

    Directory of Open Access Journals (Sweden)

    Rubio Gimeno, Silvio


    Full Text Available Not available

    El incremento de la actividad física y del deporte, en las sociedades llamadas desarrolladas, ha traído consigo beneficios claros para la salud, reflejados en diferentes indicadores de salud. Simultáneamente, el deporte de competición obliga a una dedicación diaria a intensidad de entrenamiento, con objeto de obtener los elevados requerimientos físicos que exige la competición. Todo ello ha traído consigo la aparición de numerosas lesiones, fundamentalmente del sistema músculo- esquelético.
    Se exponen en este trabajo consideraciones históricas, la epidemiología de la lesión deportiva y se describen, concisamente, algunas de las lesiones más habituales y significativas que afectan a músculos, tendones y sistema esquelético.

  7. Meniscal Ramp Lesions



    Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, ...

  8. 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.

  9. Cellular Responses to Replication Problems

    NARCIS (Netherlands)

    M. Budzowska (Magdalena)


    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

  10. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss


    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

  11. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo;


    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class...

  12. Acute periodontal lesions. (United States)

    Herrera, David; Alonso, Bettina; de Arriba, Lorenzo; Santa Cruz, Isabel; Serrano, Cristina; Sanz, Mariano


    This review provides updates on acute conditions affecting the periodontal tissues, including abscesses in the periodontium, necrotizing periodontal diseases and other acute conditions that cause gingival lesions with acute presentation, such as infectious processes not associated with oral bacterial biofilms, mucocutaneous disorders and traumatic and allergic lesions. A periodontal abscess is clinically important because it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth and bacteria within the abscess can spread and cause infections in other body sites. Different types of abscesses have been identified, mainly classified by their etiology, and there are clear differences between those affecting a pre-existing periodontal pocket and those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, while an evaluation of the need for systemic antimicrobial therapy will be made for each case, based on local and systemic factors. The definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal diseases present three typical clinical features: papilla necrosis, gingival bleeding and pain. Although the prevalence of these diseases is not high, their importance is clear because they represent the most severe conditions associated with the dental biofilm, with very rapid tissue destruction. In addition to bacteria, the etiology of necrotizing periodontal disease includes numerous factors that alter the host response and predispose to these diseases, namely HIV infection, malnutrition, stress or tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in nonresponding conditions, being the first option metronidazole. Once the acute

  13. Replication-Uncoupled Histone Deposition during Adenovirus DNA Replication


    Komatsu, Tetsuro; Nagata, Kyosuke


    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...

  14. A disappearing neonatal skin lesion.

    LENUS (Irish Health Repository)

    Hawkes, Colin Patrick


    A preterm baby girl was noted at birth to have a firm, raised, non-tender skin lesion located over her right hip. She developed three similar smaller lesions on her ear, buttock and right knee. All lesions had resolved by 2 months of age.

  15. The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery. (United States)

    O'Driscoll, Mark


    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.

  16. Lesiones deportivas Sports injuries

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Gallego Ching


    Full Text Available El estrés generado por la práctica deportiva ha originado una mayor probabilidad de que los atletas presenten lesiones agudas y crónicas. En el ámbito mundial existen diferentes investigaciones acerca de la incidencia de lesiones deportivas. La comparación de sus resultados es difícil por las diferencias en las características de la población y en la forma de reportar los datos, que varía ampliamente entre los estudios (proporciones o tasas de incidencia o tasas por cada 100 ó 1.000 participantes o tasas por horas de juego o por número de partidos jugados. Las tasas varían entre 1,7 y 53 lesiones por 1.000 horas de práctica deportiva, entre 0,8 y 90,9 por 1.000 horas de entrenamiento, entre 3,1 y 54,8 por 1.000 horas de competición y de 6,1 a 10,9 por 100 juegos. La gran variación entre las tasas de incidencia se explica por las diferencias existentes entre los deportes, los países, el nivel competitivo, las edades y la metodología empleada en los estudios. Se ha definido la lesión deportiva como la que ocurre cuando los atletas están expuestos a la práctica del deporte y se produce alteración o daño de un tejido, afectando el funcionamiento de la estructura. Los deportes de contacto generan mayor riesgo de presentar lesiones; se destacan al respecto los siguientes: fútbol, rugby, baloncesto, balonmano, artes marciales y jockey. Las lesiones ocurren con mayor probabilidad en las competencias que en el entrenamiento. Stress generated by sports practice has increased the probability that athletes suffer from acute and chronic injuries. Worldwide, there have been many different investigations concerning the incidence of sport injuries. The different ways in which results have been presented makes it difficult to compare among them. Rates of sports injuries vary between 1.7 and 53 per 1.000 hours of sports practice; 0.8 and 90.9 per 1.000 hours of training; 3.1 and 54.8 per 1.000 hours of competition, and 6.1 and 10.9 per 100

  17. Atrichia with Papular Lesions


    Bansal, Manish; Manchanda, Kajal; Lamba, Sachin; Pandey, SS


    Atrichia with papular lesions (APL) is a rare autosomal recessive form of irreversible alopecia with onset at few months of age with papular keratin cysts over the body. It is associated with mutation in the Zinc finger domain of the human hairless gene on chromosome region 8p12. An eleven-year-old male presented with extensive alopecia starting at six months of age refractory to the treatment along with keratotic papules on the face and trunk. Biopsy from a papule showed mid-dermal keratin c...

  18. Lesiones en corredores amateurs


    Natale, Vanesa


    Se realizó un estudio tomando como muestra a 100 corredores amateurs de la ciudad de Mar del Plata, en la cual el objetivo general fue determinar cuáles son las patologías más frecuentes en corredores. Correr no es solo un deporte en si mismo sino que tiene elementos de otras actividades deportivas, es decir, que las lesiones de los corredores también son comunes en otros tipos de deportes. El número de deportistas aumenta diariamente y al mismo tiempo aumentan el número de per...

  19. Lesiones en el deporte



    Not available

    El incremento de la actividad física y del deporte, en las sociedades llamadas desarrolladas, ha traído consigo beneficios claros para la salud, reflejados en diferentes indicadores de salud. Simultáneamente, el deporte de competición obliga a una dedicación diaria a intensidad de entrenamiento, con objeto de obtener los elevados requerimientos físicos que exige la competición. Todo ello ha traído consigo la aparición de numerosas lesiones, fundamentalmen...

  20. Klatskin-Like Lesions

    Directory of Open Access Journals (Sweden)

    M. P. Senthil Kumar


    Full Text Available Hilar cholangiocarcinoma, also known as Klatskin tumour, is the commonest type of cholangiocarcinoma. It poses unique problems in the diagnosis and management because of its anatomical location. Curative surgery in the form of major hepatic resection entails significant morbidity. About 5–15% of specimens resected for presumed Klatskin tumour prove not to be cholangiocarcinomas. There are a number of inflammatory, infective, vascular, and other pathologies, which have overlapping clinical and radiological features with a Klatskin tumour, leading to misinterpretation. This paper aims to summarise the features of such Klatskin-like lesions that have been reported in surgical literature.

  1. Klatskin-like lesions. (United States)

    Senthil Kumar, M P; Marudanayagam, R


    Hilar cholangiocarcinoma, also known as Klatskin tumour, is the commonest type of cholangiocarcinoma. It poses unique problems in the diagnosis and management because of its anatomical location. Curative surgery in the form of major hepatic resection entails significant morbidity. About 5-15% of specimens resected for presumed Klatskin tumour prove not to be cholangiocarcinomas. There are a number of inflammatory, infective, vascular, and other pathologies, which have overlapping clinical and radiological features with a Klatskin tumour, leading to misinterpretation. This paper aims to summarise the features of such Klatskin-like lesions that have been reported in surgical literature.

  2. Cystic Lesions of the Mediastinum. (United States)

    Vargas, Daniel; Suby-Long, Thomas; Restrepo, Carlos S


    Cystic lesions are commonly seen in the mediastinum, and they may arise from virtually any organ. The vast majority of these lesions are benign and result in no symptoms. When large, cysts may produce symptoms related to compression of adjacent structures. The most common mediastinal cysts are pericardial and foregut duplication cysts. Both computed tomography and magnetic resonance are routinely used to evaluate these lesions. Although computed tomography offers superior spatial resolution, magnetic resonance is useful in differentiating cysts that contain proteinaceous material from solid lesions. Occasionally, cysts arise from solid lesions, such as thymoma or teratoma. Although cysts are alike in appearance, location helps narrowing the differential diagnoses.

  3. Alphavirus polymerase and RNA replication. (United States)

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


    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.

  4. Therapeutic targeting of replicative immortality


    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


    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...

  5. Dynamic replication of Web contents

    Institute of Scientific and Technical Information of China (English)


    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.

  6. Protective effect of Juglans nigra on sodium arsenite-induced toxicity in rats

    Directory of Open Access Journals (Sweden)

    Solomon E Owumi


    Full Text Available Background: Consumption of arsenic contaminated water has been implicated in metalloid-induced carcinogenesis. Dietary intake of certain plant products with chemoprotective properties may protect against the onset of diseases and promote maintenance of health. Objectives: We investigated the outcome of black walnut Juglans nigra (JN consumption on sodium arsenite (SA-induced toxicity in rats. Materials and Methods: Wister albino rats were treated as follows: Control, SA only (positive control (2.5 mg/kg body weight, JN only (100 mg/kg weight, and JN+SA coadministered. After 5 weeks animals were sacrificed whole blood, femur, liver and testis harvested were assessed for hepatic transaminases and clastogenicity. Histology of the liver, sperm morphology and quality were also assessed. Data were analyzed (ANOVA and expressed as means ±SD. Results: SA treatment elevated hepatic transaminases level in serum (P < 0.05, induced histological changes in liver: fibroplasia and periportal hepatocytes infiltration by mononuclear cells. These changes were ameliorated by JN (P < 0.05 coadministration. SA induced micronuclei formation (P < 0.05. Again JN decreased (P < 0.05 micronuclei formation by 50%. Sperm count and motility decreased (P < 0.05 in all groups compared to control. Conclusion: JN showed no protection against arsenite effect on sperm quality. Hepatoprotective and anticlastogenic effects were apparent suggesting a chemopreventive potential active against arsenite genotoxicity and chromosomal instability which have implication for metalloid-induced carcinogenesis.

  7. Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of curcumin. (United States)

    Yousef, Mokhtar I; El-Demerdash, Fatma M; Radwan, Fatma M E


    The present study was undertaken to evaluate the therapeutic efficacy of curcumin in terms of normalization of altered biochemical parameters following sodium arsenite treatment in rats. Animals were divided into four groups. The first group was used as control. While, groups 2, 3 and 4 were orally treated with curcumin (Cur, 15 mg/kg BW), sodium arsenite (Sa, 5 mg/kg BW) and sodium arsenite plus curcumin, respectively. Results showed that the activities of transaminases and phosphatases were significantly decreased in liver due to Sa administration, whereas increased in plasma. The activity of brain and plasma acetylcholinesterase (AChE) was decreased in rats treated with Sa. Also, Sa significantly decreased plasma total protein (TP), albumin (Alb) and high density lipoprotein-cholesterol (HDL-c), while increased glucose, urea, creatinine, bilirubin, total lipid (TL), cholesterol, triglyceride (TG) and low density lipoprotein-cholesterol (LDL-c). Curcumin alone decreased the levels of glucose, urea, creatinine, TL, cholesterol, TG and LDL-c. Curcumin reduced Sa-induced transaminases, phosphatases, glucose, urea, creatinine, bilirubin, TL, cholesterol and TG. Moreover, curcumin induced Sa-reduced liver transaminases and phosphatases, plasma and brain AChE, and the levels of TP and Alb. Experimental results, therefore suggested that curcumin protects arsenic induced biochemical alterations in rats.

  8. In Vitro Protective Potentials of Annona muricata Leaf Extracts Against Sodium Arsenite-induced Toxicity. (United States)

    George, Vazhappilly Cijo; Kumar, Devanga Ragupathi Naveen; Suresh, Palamadai Krishnan; Kumar, Rangasamy Ashok


    Sodium arsenite (NaAsO2) is a metalloid which is present widely in the environment and its chronic exposure can contribute to the induction of oxidative stress, resulting in disturbances in various metabolic functions including liver cell death. Hence, there is a need to develop drugs from natural sources, which can reduce arsenic toxicity. While there have been reports regarding the antioxidant and protective potentials of Annona muricataleaf extracts, our study is the first ofits kind to extend these findings by specifically evaluating its ability to render protection against sodium arsenite (NaAsO2) induced toxicity (10 μM) in WRL-68 (human hepatic cells) and human erythrocytes by employing XTT and haemolysis inhibition assays respectively. The methanolic extract exhibited higher activity than the aqueous extract in both assays. The results showed a dose-dependent decrease in arsenic toxicity in both WRL-68 cells and erythrocytes, suggesting the protective nature of Annona muricatato mitigate arsenic toxicity. Hence the bioactive extracts can further be scrutinized for the identification and characterization of their principal contributors.

  9. Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Rong-Nan Huang; I-Ching Ho; Ling-Hui Yih [Institute of Biomedical Sciences, Taiwan (China)] [and others


    Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 {mu}M) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplication in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity. 61 refs., 6 figs., 2 tabs.

  10. Arsenite induced oxidative damage in mouse liver is associated with increased cytokeratin 18 expression

    Energy Technology Data Exchange (ETDEWEB)

    Gonsebatt, M.E. [UNAM, Ciudad Universitaria, Dept. Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Mexico (Mexico); Razo, L.M. del; Sanchez-Pena, L.C. [Seccion de Toxicologia, CINVESTAV, Mexico (Mexico); Cerbon, M.A. [Facultad de Quimica, UNAM, Departamento de Biologia, Mexico (Mexico); Zuniga, O.; Ramirez, P. [Facultad de Estudios Superiores Cuautitlan, UNAM, Laboratorio de Toxicologia Celular, Coordinacion General de Estudios de Posgrado e Investigacion, Cuautitlan Izcalli, Estado de Mexico (Mexico)


    Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously observed that sodium arsenite (SA) induced the synthesis of CK18 protein and promotes a dose-related disruption of cytoplasmic CK18 filaments in a human hepatic cell line. Both abnormal gene expression and disturbance of structural organization are toxic effects that are likely to cause liver disease by interfering with normal hepatocyte function. To investigate if a disruption in the CK18 expression pattern is associated with arsenite liver damage, we investigated CK18 mRNA and protein levels in liver slices treated with low levels of SA. Organotypic cultures were incubated with 0.01, 1 and 10 {mu}M of SA in the absence and presence of N-acetyl cysteine (NAC). Cell viability and inorganic arsenic metabolism were determined. Increased expression of CK18 was observed after exposure to SA. The addition of NAC impeded the oxidative effects of SA exposure, decreasing the production of thiobarbituric acid-reactive substances and significantly diminishing the up regulation of CK18 mRNA and protein. Liver arsenic levels correlated with increased levels of mRNA. Mice treated with intragastric single doses of 2.5 and 5 mg/kg of SA showed an increased expression of CK18. Results suggest that CK18 expression may be a sensible early biomarker of oxidative stress and damage induced by arsenite in vitro and in vivo. Then, during SA exposure, altered CK expression may compromise liver function. (orig.)

  11. Replication of micro and nano surface geometries

    DEFF Research Database (Denmark)

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


    The paper describes the state-of-the-art in replication of surface texture and topography at micro and nano scale. The description includes replication of surfaces in polymers, metals and glass. Three different main technological areas enabled by surface replication processes are presented......: 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....

  12. Evaluating replicability of laboratory experiments in economics. (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


    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.

  13. Adenovirus sequences required for replication in vivo.


    Wang, K.; Pearson, G D


    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...

  14. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard


    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. Replication Origin Specification Gets a Push. (United States)

    Plosky, Brian S


    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.

  16. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases. (United States)

    Barnes, Ryan; Eckert, Kristin


    Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize "difficult to replicate" genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.


    Directory of Open Access Journals (Sweden)

    Kiran H. S


    Full Text Available BACKGROUND Cancer of the breast is the second most common cause of cancer in women. Benign or malignant lesions presenting as mass in the breast causes anxiety to the patients and the family members. AIMS AND OBJECTIVES OF THE STUDY 1. To classify different types of lesions of breast, both benign and malignant. 2. Histomorphological study of various types of benign and malignant breast lesions. 3. To study spectrum of lesions associated with benign and malignant breast diseases. SETTING AND DESIGN All the breast biopsies, lumpectomies, and mastectomy specimens presenting to Department of Pathology of our institution between June 2012 to June 2014. MATERIALS AND METHODS A sample size of 100 cases are included in this study. Clinical details are taken from records. The specimens of breast sent to the Department of Pathology are processed by routine histopathological techniques. Histopathological features are studied on haematoxylin and eosin-stained sections. STATISTICAL ANALYSIS Statistically, the test of proportion is used to obtain the frequency of all lesions. Chi-square test, which is used to find the association between the spectrum of lesions showed a p value of 0.0438 and hence the study was considered significant. RESULTS In our study, out of 100 cases, malignant breast lesions constituted the majority of the lesions comprising of 49 cases (49%, followed by benign lesions comprising 46 cases (46% and the inflammatory lesions comprising 5 cases (5%. Among benign lesions, fibrocystic disease was the predominant lesion comprising of 39 cases (41%, followed by fibroadenoma comprising 26 cases (28%, which is followed by 13 cases (14% of fibrocystic disease with columnar cell change and 8 cases (9% of sclerosing adenosis. Among malignant lesions, invasive ductal carcinoma (NST type was the most common lesion comprising 31 cases (61% followed by 11 cases (21% of invasive lobular carcinoma. Invasive papillary carcinoma and medullary carcinoma

  18. DNA ligase I and Nbs1 proteins associate in a complex and colocalize at replication factories. (United States)

    Vago, Riccardo; Leva, Valentina; Biamonti, Giuseppe; Montecucco, Alessandra


    DNA ligase I is the main DNA ligase activity involved in eukaryotic DNA replication acting in the joining of Okazaki fragments. This enzyme is also implicated in nucleotide excision repair and in the long-patch base excision repair while its role in the recombinational repair pathways is poorly understood. DNA ligase I is phosphorylated during cell cycle at several serine and threonine residues that regulate its participation in different DNA transactions by modulating the interaction with different protein partners. Here we use an antibody-based array method to identify novel DNA ligase-interacting partners. We show that DNA ligase I participates in several multiprotein complexes with proteins involved in DNA replication and repair, cell cycle control, and protein modification. In particular we demonstrate that DNA ligase I complexes with Nbs1, a core component of the MRN complex critical for detection, processing and repair of double-stranded DNA breaks. The analysis of epitope tagged DNA ligase I mutants demonstrates that the association is mediated by the catalytic fragment of the enzyme. DNA ligase I and Nbs1 colocalize at replication factories during unperturbed replication and after treatment with DNA damaging agents. Since MRN complex is involved in the repair of double-stranded DNA breaks by homologous recombination at stalled replication forks our data support the notion that DNA ligase I participates in homology dependent pathways that deal with replication-associated lesions generated when replication fork encounters DNA damage.

  19. Replication of prions in differentiated muscle cells. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS


    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  1. Radio-induced brain lesions

    Directory of Open Access Journals (Sweden)

    Gorgan Mircea Radu


    Full Text Available Introduction : Radiotherapy, an important tool in multimodal oncologic treatment, can cause radio-induced brain lesion development after a long period of time following irradiation.

  2. DNA replication stress: causes, resolution and disease. (United States)

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


    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.

  3. Replication Stress: A Lifetime of Epigenetic Change

    Directory of Open Access Journals (Sweden)

    Simran Khurana


    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.

  4. The fork and the kinase: a DNA replication tale from a CHK1 perspective. (United States)

    González Besteiro, Marina A; Gottifredi, Vanesa


    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.

  5. Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity. (United States)

    Dickey, Jennifer S; Baird, Brandon J; Redon, Christophe E; Avdoshina, Valeriya; Palchik, Guillermo; Wu, Junfang; Kondratyev, Alexei; Bonner, William M; Martin, Olga A


    Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by γ-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-β and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo.

  6. Self-replication of DNA rings (United States)

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


    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.

  7. Structural Basis for Error-free Replication of Oxidatively Damaged DNA by Yeast DNA Polymerase eta

    Energy Technology Data Exchange (ETDEWEB)

    T Silverstein; R Jain; R Johnson; L Prakash; S Prakash; A Aggarwal


    7,8-dihydro-8-oxoguanine (8-oxoG) adducts are formed frequently by the attack of oxygen-free radicals on DNA. They are among the most mutagenic lesions in cells because of their dual coding potential, where, in addition to normal base-pairing of 8-oxoG(anti) with dCTP, 8-oxoG in the syn conformation can base pair with dATP, causing G to T transversions. We provide here for the first time a structural basis for the error-free replication of 8-oxoG lesions by yeast DNA polymerase {eta} (Pol{eta}). We show that the open active site cleft of Pol{eta} can accommodate an 8-oxoG lesion in the anti conformation with only minimal changes to the polymerase and the bound DNA: at both the insertion and post-insertion steps of lesion bypass. Importantly, the active site geometry remains the same as in the undamaged complex and provides a basis for the ability of Pol to prevent the mutagenic replication of 8-oxoG lesions in cells.

  8. "Hybrid" lesion of the maxilla

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    S Sankaranarayanan


    Full Text Available Juvenile ossifying fibroma is an uncommon benign but aggressive fibroosseous lesion that affects the craniofacial skeleton. Their distinct clinical and histopathological features warrant the lesion to be considered as a separate entity from other fibro-osseous group of lesions such as fibrous dysplasia and cemento ossifying fibroma. Concomitant development of secondary aneurysmal bone cyst may rarely occur, which makes the lesion more aggressive and difficult to treat. We report a case of a 6 year old girl who was diagnosed with aneurysmal bone cyst during her earlier presentation at a private hospital and was treated for the same. The lesion recurred within 6 months. The second incisional biopsy specimen revealed features of trabecular variant of juvenile ossifying fibroma along with areas of aneurysmal bone cyst.

  9. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases

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    Ryan Barnes


    Full Text Available Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize “difficult to replicate” genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.

  10. DNA Replication via Entanglement Swapping

    CERN Document Server

    Pusuluk, Onur


    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.

  11. Pain in osteochondral lesions. (United States)

    Wiewiorski, Martin; Pagenstert, Geert; Rasch, Helmut; Jacob, Augustinus Ludwig; Valderrabano, Victor


    Pain is the key symptom of patients suffering from osteochondral lesions (OCLs) of the ankle joint. Routine radiographic imaging methods for diagnosis and staging of OCL fail to visualize the pain-inducing focus within the joint. SPECT-CT (Single-photon emission computed tomography-computed tomography) is a new hybrid imaging technique allowing exact digital fusion of scintigraphic and computer tomographic images. This allows precise localization and size determination of an OCL within the joint. Using this novel imaging method, we conducted a study to evaluate the correlation between pathological uptake within an OCL and pain experienced by patients suffering from this condition; 15 patients were assessed in the orthopaedic ambulatory clinic for unilateral OCL of the ankle joint. Pain status was measured with the Visual Analogue Scale (VAS). A SPECT-CT was performed. All patients underwent CT-guided ankle injection with a local anesthetic and iodine contrast medium. The VAS score assessed immediately postinfiltration was compared with the preinterventional VAS score obtained in the outpatient clinic. Pain relief was defined as a reduction of the VAS score to ≤50% of the preinterventional score, if expected immediately after infiltration. Pain relief was found in all 15 patients. The results of our study show that there is a highly significant correlation between pain and pathological uptake seen on SPECT-CT, indicating that pathologically remodeled bone tissue is an important contributor to pain in OCL. Adequate addressing of involved bone tissue needs to be taken into consideration when choosing a surgical treatment method.

  12. Chromosome replication and segregation in bacteria. (United States)

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


    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.

  13. Regulation of Unperturbed DNA Replication by Ubiquitylation

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    Sara Priego Moreno


    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.

  14. Semiconservative replication in the quasispecies model (United States)

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


    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.

  15. Replicating chromatin: a tale of histones

    DEFF Research Database (Denmark)

    Groth, Anja


    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...... framework of chromatin and carry information to specify higher-order organization and gene expression. When replication forks traverse the chromosomes, nucleosomes are transiently disrupted, allowing the replication machinery to gain access to DNA. Histone recycling, together with new deposition, ensures...... reassembly on nascent DNA strands. The aim of this review is to discuss how histones - new and old - are handled at the replication fork, highlighting new mechanistic insights and revisiting old paradigms....

  16. Regulation of chromosomal replication in Caulobacter crescentus. (United States)

    Collier, Justine


    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.

  17. 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 (United States)

    Tannenbaum, Emmanuel


    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.

  18. Analysis of unassisted translesion replication by the DNA polymerase III holoenzyme. (United States)

    Tomer, G; Livneh, Z


    DNA damage-induced mutations are formed when damaged nucleotides present in single-stranded DNA are replicated. We have developed a new method for the preparation of gapped plasmids containing site-specific damaged nucleotides, as model DNA substrates for translesion replication. Using these substrates, we show that the DNA polymerase III holoenzyme from Escherichia coli can bypass a synthetic abasic site analogue with high efficiency (30% bypass in 16 min), unassisted by other proteins. The theta and tau subunits of the polymerase were not essential for bypass. No bypass was observed when the enzyme was assayed on a synthetic 60-mer oligonucleotide carrying the same lesion, and bypass on a linear gapped plasmid was 3-4-fold slower than on a circular gapped plasmid. There was no difference in the bypass when standing-start and running-start replication were compared. A comparison of translesion replication by DNA polymerase I, DNA polymerase II, the DNA polymerase III core, and the DNA polymerase III holoenzyme clearly showed that the DNA polymerase III holoenzyme was by far the most effective in performing translesion replication. This was not only due to the high processivity of the pol III holoenzyme, because increasing the processivity of pol II by adding the gamma complex and beta subunit, did not increase bypass. These results support the model that SOS regulation was imposed on a fundamentally constitutive translesion replication reaction to achieve tight control of mutagenesis.


    Directory of Open Access Journals (Sweden)

    M. Rasoolinejad


    Full Text Available Phaeohyphomycosis is an amalgam of clinical diseases caused by a wide variety of dematiaceous fungi. We are reporting on a 16 year-old patient from Amol with subcutaneous cervical nodes and nasopharyngeal lesions of phaeohypho"nmycosis that were confirmed by pathological examination, direct smear, and culture. After treatment with an oral triazole (Itraconazole for 4 months, all nodes and lesions disappeared and treatment was stopped A new lesion appeared on his chest wall 8 months, therapy with itraconazole was restarted and commuted for a long time.

  20. Factitious lesions of the hand

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    Ricardo Kaempf de Oliveira


    Full Text Available OBJECTIVE: The presence of a lesion with atypical presentation, obscure clinical history, which does not improve with classic treatments, shall raise the red flag of the medical team. In such cases, the hypothesis of a factitious lesion shall be considered. Many times the correct diagnosis on the initial assessment may avoid high-cost diagnostic tests, unnecessary treatments, and time consumption of the medical team. We present here two classic cases of factitious lesions that, similar to those described in the literature, is difficult to diagnose and difficult to treat.

  1. Lesiones debido a un rayo


    Soraia Oliveira; Andriy Bal


    Lesiones debido a un rayo Mujer de 72 años, fue admitida en urgências con dolor abdominal y lipotimia después de ser golpeada por un rayo mientras abría una ventana. En la exploracion presentaba lesiones, localizadas en el tronco, dolorosas a la palpación. Las lesiones abdominales en forma de estrella eran muy sugestivas de imágenes de Lichtenberg (figura A), mientras en la región pélvica (figura B) y en la nalga derecha (figura C) eran más lineales y compatibles con quemaduras de pri...

  2. Biochemical analysis of DNA polymerase η fidelity in the presence of replication protein A.

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    Samuel C Suarez

    Full Text Available DNA polymerase η (pol η synthesizes across from damaged DNA templates in order to prevent deleterious consequences like replication fork collapse and double-strand breaks. This process, termed translesion synthesis (TLS, is an overall positive for the cell, as cells deficient in pol η display higher mutation rates. This outcome occurs despite the fact that the in vitro fidelity of bypass by pol η alone is moderate to low, depending on the lesion being copied. One possible means of increasing the fidelity of pol η is interaction with replication accessory proteins present at the replication fork. We have previously utilized a bacteriophage based screening system to measure the fidelity of bypass using purified proteins. Here we report on the fidelity effects of a single stranded binding protein, replication protein A (RPA, when copying the oxidative lesion 7,8-dihydro-8-oxo-guanine(8-oxoG and the UV-induced cis-syn thymine-thymine cyclobutane pyrimidine dimer (T-T CPD. We observed no change in fidelity dependent on RPA when copying these damaged templates. This result is consistent in multiple position contexts. We previously identified single amino acid substitution mutants of pol η that have specific effects on fidelity when copying both damaged and undamaged templates. In order to confirm our results, we examined the Q38A and Y52E mutants in the same full-length construct. We again observed no difference when RPA was added to the bypass reaction, with the mutant forms of pol η displaying similar fidelity regardless of RPA status. We do, however, observe some slight effects when copying undamaged DNA, similar to those we have described previously. Our results indicate that RPA by itself does not affect pol η dependent lesion bypass fidelity when copying either 8-oxoG or T-T CPD lesions.

  3. Lesions of the avian pancreas. (United States)

    Schmidt, Robert E; Reavill, Drury R


    Although not well described, occasional reports of avian exocrine and endocrine pancreatic disease are available. This article describes the lesions associated with common diseases of the avian pancreas reported in the literature and/or seen by the authors.

  4. Pediatric sellar and suprasellar lesions. (United States)

    Schroeder, Jason W; Vezina, L Gilbert


    Masses arising in the sella turcica and the suprasellar region are common in children. The type and frequency of the various lesions encountered in childhood differ from the adult presentation. This article reviews the embryology of the pituitary gland and its normal appearance in childhood as well as the imaging and clinical findings of the common and some of the uncommon lesions arising in the sella turcica, the pituitary stalk, the suprasellar cistern and the lower third ventricle in the pediatric population.

  5. Premalignant Lesions in the Kidney

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    Ziva Kirkali


    Full Text Available Renal cell carcinoma (RCC is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1 morphological similarity; (2 spatial association; (3 development of microinvasive carcinoma; (4 higher frequency, severity, and extent then invasive carcinoma; (5 progression to invasive cancer; and (6 similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

  6. Border preserving skin lesion segmentation (United States)

    Kamali, Mostafa; Samei, Golnoosh


    Melanoma is a fatal cancer with a growing incident rate. However it could be cured if diagnosed in early stages. The first step in detecting melanoma is the separation of skin lesion from healthy skin. There are particular features associated with a malignant lesion whose successful detection relies upon accurately extracted borders. We propose a two step approach. First, we apply K-means clustering method (to 3D RGB space) that extracts relatively accurate borders. In the second step we perform an extra refining step for detecting the fading area around some lesions as accurately as possible. Our method has a number of novelties. Firstly as the clustering method is directly applied to the 3D color space, we do not overlook the dependencies between different color channels. In addition, it is capable of extracting fine lesion borders up to pixel level in spite of the difficulties associated with fading areas around the lesion. Performing clustering in different color spaces reveals that 3D RGB color space is preferred. The application of the proposed algorithm to an extensive data-base of skin lesions shows that its performance is superior to that of existing methods both in terms of accuracy and computational complexity.

  7. Simulation of spiculated breast lesions (United States)

    Elangovan, Premkumar; Alrehily, Faisal; Pinto, R. Ferrari; Rashidnasab, Alaleh; Dance, David R.; Young, Kenneth C.; Wells, Kevin


    Virtual clinical trials are a promising new approach increasingly used for the evaluation and comparison of breast imaging modalities. A key component in such an assessment paradigm is the use of simulated pathology, in particular, simulation of lesions. Breast mass lesions can be generally classified into two categories based on their appearance; nonspiculated masses and spiculated masses. In our previous work, we have successfully simulated non-spiculated masses using a fractal growth process known as diffusion limited aggregation. In this new work, we have extended the DLA model to simulate spiculated lesions by using features extracted from patient DBT images containing spiculated lesions. The features extracted included spicule length, width, curvature and distribution. This information was used to simulate realistic looking spicules which were attached to the surface of a DLA mass to produce a spiculated mass. A batch of simulated spiculated masses was inserted into normal patient images and presented to an experienced radiologist for review. The study yielded promising results with the radiologist rating 60% of simulated lesions in 2D and 50% of simulated lesions in DBT as realistic.

  8. Unusual lesions of the mediastinum

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    Fatima Shamsuddin


    Full Text Available Objectives: To study unusual lesions in the mediastinum, which do not originate from the thymus, lymph nodes, neural tissues or germ cells, and tissues that normally engender pathologic lesions in the mediastinum. Materials and Methods: Of the 65 cases seen, 12 unusual lesion were encountered in a 5½ year period from 2006 to 2011. Results: Two cases of nodular colloid goiter and one each of the mediastinal cyst, undifferentiated carcinoma, and Langerhans cell histiocytosis (LCH affected the anterosuperior mediastinum. In the middle mediastinum, one case each of the mesothelioma, malignant gastrointestinal stromal tumor (GIST, squamous cell carcinoma (SCC, solitary fibrous tumor (SFT, and pleomorphic sarcoma (PS was seen. One case of meningeal melanocytoma (Mme and primary pleural liposarcoma (PL involved the posterior mediastinum. Persistent disease was seen in LCH after 2 years. Of all the cases with malignant lesions, only the patient with SCC was alive after 1 year. Conclusion: The cases of primary and SCC, LCH, melanocytoma, liposarcoma and PS, and GIST are unexpected and very rarely have paradigms in the mediastinum. Radiologic impression and knowledge of the compartment where these lesions arose from hardly assisted in arriving at a definitive opinion as the lesions were not typical of this location. A high index of suspicion and the immunohistochemical profile facilitated the final diagnosis.

  9. Completion of DNA replication in Escherichia coli. (United States)

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


    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.

  10. Replication and Robustness in Developmental Research (United States)

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


    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…

  11. How frog embryos replicate their DNA reliably (United States)

    Bechhoefer, John; Marshall, Brandon


    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.

  12. Characterization of metabolically quiescent Leishmania parasites in murine lesions using heavy water labeling.

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    Joachim Kloehn


    Full Text Available Information on the growth rate and metabolism of microbial pathogens that cause long-term chronic infections is limited, reflecting the absence of suitable tools for measuring these parameters in vivo. Here, we have measured the replication and physiological state of Leishmania mexicana parasites in murine inflammatory lesions using 2H2O labeling. Infected BALB/c mice were labeled with 2H2O for up to 4 months, and the turnover of parasite DNA, RNA, protein and membrane lipids estimated from the rate of deuterium enrichment in constituent pentose sugars, amino acids, and fatty acids, respectively. We show that the replication rate of parasite stages in these tissues is very slow (doubling time of ~12 days, but remarkably constant throughout lesion development. Lesion parasites also exhibit markedly lower rates of RNA synthesis, protein turnover and membrane lipid synthesis than parasite stages isolated from ex vivo infected macrophages or cultured in vitro, suggesting that formation of lesions induces parasites to enter a semi-quiescent physiological state. Significantly, the determined parasite growth rate accounts for the overall increase in parasite burden indicating that parasite death and turnover of infected host cells in these lesions is minimal. We propose that the Leishmania response to lesion formation is an important adaptive strategy that minimizes macrophage activation, providing a permissive environment that supports progressive expansion of parasite burden. This labeling approach can be used to measure the dynamics of other host-microbe interactions in situ.

  13. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

    DEFF Research Database (Denmark)

    Syed, Salahuddin; Madsen, Claus Desler; Rasmussen, Lene J.;


    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N......-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor......-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each...

  14. A New Replication Norm for Psychology

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    Etienne P LeBel


    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.

  15. Inferring Where and When Replication Initiates from Genome-Wide Replication Timing Data (United States)

    Baker, A.; Audit, B.; Yang, S. C.-H.; Bechhoefer, J.; Arneodo, A.


    Based on an analogy between DNA replication and one dimensional nucleation-and-growth processes, various attempts to infer the local initiation rate I(x,t) of DNA replication origins from replication timing data have been developed in the framework of phase transition kinetics theories. These works have all used curve-fit strategies to estimate I(x,t) from genome-wide replication timing data. Here, we show how to invert analytically the Kolmogorov-Johnson-Mehl-Avrami model and extract I(x,t) directly. Tests on both simulated and experimental budding-yeast data confirm the location and firing-time distribution of replication origins.

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

    Directory of Open Access Journals (Sweden)

    Richard A. Klein


    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.

  17. Role of pre-replication and post-replication processes in mutation induction in Haemophilus influenzae by N-methyl-N'-nitro-N-nitrosoguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Kimball, R.F.; Perdue, S.W.; Boling, M.E.


    Studies were carried out on the repair and fixation of premutational damage induced in Haemophilus influenzae by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The studies employed a temperature-sensitive DNA elongation mutant (dna9) and its combinations with mutants defective in pyrimidine dimer excision (uvr1, uvr2) and in recombination (rec1). The dna9 mutant is shown to be leaky, allowing about 1% of the normal rate of DNA synthesis at the restrictive temperature. Repair of premutational lesions was detected by a decline in mutation frequency with increasing delay in DNA replication in dna9 at the restrictive temperature. This repair is unaffected by the pyrimidine dimer excision system. Mutation fixation was detected by the ability of DNA from treated and then lysed cells to transfer mutants to recipient cells by transformation. Some fixation occurred at the restrictive temperature but much less than at the non-restrictive temperature suggesting that an appreciable minority of the mutations resulted from lesions introduced near the replication fork but that the majority of mutations arise from lesions introduced at some distance from the fork, perhaps randomly. The DNA synthesized immediately after MNNG treatment is of lower molecular weight than normal and returns to normal with time. This return is blocked in the rec1 mutant, suggesting that recombination is involved. The possible role of this process in MNNG mutagenesis is discussed.

  18. Nodular lesions and mesangiolysis in diabetic nephropathy. (United States)

    Wada, Takashi; Shimizu, Miho; Yokoyama, Hitoshi; Iwata, Yasunori; Sakai, Yoshio; Kaneko, Shuichi; Furuichi, Kengo


    Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions.

  19. A quantitative model of DNA replication in Xenopus embryos: reliable replication despite stochasticity (United States)

    Cheng-Hsin Yang, Scott; Bechhoefer, John


    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.

  20. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang


    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.

  1. Targeting DNA Replication Stress for Cancer Therapy (United States)

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


    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

  2. Oncogene v-jun modulates DNA replication. (United States)

    Wasylyk, C; Schneikert, J; Wasylyk, B


    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.

  3. [Percutaneous diagnostic angioscopy. Primary lesions]. (United States)

    Carlier, C; Foucart, H; Baudrillard, J C; Cécile, J P


    Efficacy of percutaneous treatments of arterial affections requires the correct choice of indications, necessitating precise knowledge of elementary arterial lesions. Arterial endoscopy appears to be more specific than angiography for this use, since it allows direct vision in vivo of the lesion, a histopathologic approach compared with the non univocal images produced by angiography (for example, an arterial obstruction can result from varied causes). Different accidents to the endothelial surface can be observed: golden yellow atheromatous elevations on a straw yellow background, intimal flaps, mobile intra-luminal vegetations. Established atheromatous stenosis are smooth and regular, or on the contrary ulcerated and edged with irregular flaps capable of provoking an eccentric residual lumen. The vegetating atheromatous lesions may project into the lumen, often as calcified and thus pearly white scales adhering to the wall, or as larger occlusive lesions. When capable of being isolated, a thrombus often completes the stenosis: its recognition is therefore fundamental since its removal exposes the subjacent lesions to be treated. The fresh clot is coral shaped, bright red and mobile in the blood flow. Established clots are compact and greenish brown. At an advanced stage of atheroma the surface of the occluding clot is covered with a regular straw yellow endothelium. In the presence of a dissecting vessel the fibroscope may be introduced into the false channel, no longer showing typical endothelium but a coagulated mass interspersed with fibrous bands. Prosthetic stenosis result from either intimal hyperplasia or a suturing fault with plication.

  4. Spectroscopic Detection of Caries Lesions

    Directory of Open Access Journals (Sweden)

    Mika Ruohonen


    Full Text Available Background. A caries lesion causes changes in the optical properties of the affected tissue. Currently a caries lesion can be detected only at a relatively late stage of development. Caries diagnosis also suffers from high interobserver variance. Methods. This is a pilot study to test the suitability of an optical diffuse reflectance spectroscopy for caries diagnosis. Reflectance visible/near-infrared spectroscopy (VIS/NIRS was used to measure caries lesions and healthy enamel on extracted human teeth. The results were analysed with a computational algorithm in order to find a rule-based classification method to detect caries lesions. Results. The classification indicated that the measured points of enamel could be assigned to one of three classes: healthy enamel, a caries lesion, and stained healthy enamel. The features that enabled this were consistent with theory. Conclusions. It seems that spectroscopic measurements can help to reduce false positives at in vitro setting. However, further research is required to evaluate the strength of the evidence for the method’s performance.

  5. A whole genome RNAi screen identifies replication stress response genes. (United States)

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


    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.

  6. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)


    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.

  7. Replicated Data Management for Mobile Computing

    CERN Document Server

    Douglas, Terry


    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

  8. Pediatric Knee Osteochondritis Dissecans Lesions. (United States)

    Cruz, Aristides I; Shea, Kevin G; Ganley, Theodore J


    Osteochondritis dissecans (OCD) can cause knee pain and dysfunction in children. The etiology of OCD remains unclear; theories on causes include inflammation, ischemia, ossification abnormalities, genetic factors, and repetitive microtrauma. Most OCD lesions in skeletally immature patients will heal with nonoperative treatment. The success of nonoperative treatment decreases once patients reach skeletal maturity. The goals of surgical treatment include maintenance of articular cartilage congruity, rigid fixation of unstable fragments, and repair of osteochondral defects with cells or tissues that can adequately replace lost or deficient cartilage. Unsalvageable OCD lesions can be treated with various surgical techniques.

  9. Lesiones frecuentes en atletas profesionales


    Doyel, Crevecoer


    Durante la práctica del atletismo frecuentemente ocurren lesiones, afectando principalmente a los miembros inferiores. Las causas que las originan son muy diversas y tienen diferentes características de acuerdo al tipo de modalidad realizada dentro del atletismo. Objetivo: Analizar las características de las lesiones más frecuentes en miembros inferiores, en atletas corredores profesionales, de diferentes distancias, de ambos sexos, de entre 18 y 40 años de edad, que practican atletismo en...

  10. A transcription and translation-coupled DNA replication system using rolling-circle replication. (United States)

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


    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.

  11. H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex

    Energy Technology Data Exchange (ETDEWEB)

    Saredi, Giulia; Huang, Hongda; Hammond, Colin M.; Alabert, Constance; Bekker-Jensen, Simon; Forne, Ignasi; Reverón-Gómez, Nazaret; Foster, Benjamin M.; Mlejnkova, Lucie; Bartke, Till; Cejka, Petr; Mailand, Niels; Imhof, Axel; Patel, Dinshaw J.; Groth, Anja [UCopenhagen; (MSKCC); (ICL); (LMU); (Zurich)


    Here, we report that after DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. In this paper we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L1, 2, 3, 4 homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark post-replicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL–MMS22L binds new histones H3–H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL–MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Finally, together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Krysan, P.J.


    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.

  13. Bypass of a 5',8-cyclopurine-2'-deoxynucleoside by DNA polymerase β during DNA replication and base excision repair leads to nucleotide misinsertions and DNA strand breaks. (United States)

    Jiang, Zhongliang; Xu, Meng; Lai, Yanhao; Laverde, Eduardo E; Terzidis, Michael A; Masi, Annalisa; Chatgilialoglu, Chryssostomos; Liu, Yuan


    5',8-Cyclopurine-2'-deoxynucleosides including 5',8-cyclo-dA (cdA) and 5',8-cyclo-dG (cdG) are induced by hydroxyl radicals resulting from oxidative stress such as ionizing radiation. 5',8-cyclopurine-2'-deoxynucleoside lesions are repaired by nucleotide excision repair with low efficiency, thereby leading to their accumulation in the human genome and lesion bypass by DNA polymerases during DNA replication and base excision repair (BER). In this study, for the first time, we discovered that DNA polymerase β (pol β) efficiently bypassed a 5'R-cdA, but inefficiently bypassed a 5'S-cdA during DNA replication and BER. We found that cell extracts from pol β wild-type mouse embryonic fibroblasts exhibited significant DNA synthesis activity in bypassing a cdA lesion located in replication and BER intermediates. However, pol β knock-out cell extracts exhibited little DNA synthesis to bypass the lesion. This indicates that pol β plays an important role in bypassing a cdA lesion during DNA replication and BER. Furthermore, we demonstrated that pol β inserted both a correct and incorrect nucleotide to bypass a cdA at a low concentration. Nucleotide misinsertion was significantly stimulated by a high concentration of pol β, indicating a mutagenic effect induced by pol β lesion bypass synthesis of a 5',8-cyclopurine-2'-deoxynucleoside. Moreover, we found that bypass of a 5'S-cdA by pol β generated an intermediate that failed to be extended by pol β, resulting in accumulation of single-strand DNA breaks. Our study provides the first evidence that pol β plays an important role in bypassing a 5',8-cyclo-dA during DNA replication and repair, as well as new insight into mutagenic effects and genome instability resulting from pol β bypassing of a cdA lesion.

  14. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

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


    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...

  15. LHCb Data Replication During SC3

    CERN Multimedia

    Smith, A


    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.

  16. Disseminated paracoccidioidomycosis diagnosis based on oral lesions

    Directory of Open Access Journals (Sweden)

    Liana Preto Webber


    Full Text Available Paracoccidioidomycosis (PCM is a deep mycosis with primary lung manifestations that may present cutaneous and oral lesions. Oral lesions mimic other infectious diseases or even squamous cell carcinoma, clinically and microscopically. Sometimes, the dentist is the first to detect the disease, because lung lesions are asymptomatic, or even misdiagnosed. An unusual case of PCM with 5 months of evolution presenting pulmonary, oral, and cutaneous lesions that was diagnosed by the dentist based on oral lesions is presented and discussed.

  17. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

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


    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. Mycobacterium tuberculosis replicates within necrotic human macrophages (United States)

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


    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

  19. Commercial Building Partnerships Replication and Diffusion

    Energy Technology Data Exchange (ETDEWEB)

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


    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. Imaging inflammatory acne: lesion detection and tracking (United States)

    Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos


    It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

  1. The beta subunit sliding DNA clamp is responsible for unassisted mutagenic translesion replication by DNA polymerase III holoenzyme. (United States)

    Tomer, G; Reuven, N B; Livneh, Z


    The replication of damaged nucleotides that have escaped DNA repair leads to the formation of mutations caused by misincorporation opposite the lesion. In Escherichia coli, this process is under tight regulation of the SOS stress response and is carried out by DNA polymerase III in a process that involves also the RecA, UmuD' and UmuC proteins. We have shown that DNA polymerase III holoenzyme is able to replicate, unassisted, through a synthetic abasic site in a gapped duplex plasmid. Here, we show that DNA polymerase III*, a subassembly of DNA polymerase III holoenzyme lacking the beta subunit, is blocked very effectively by the synthetic abasic site in the same DNA substrate. Addition of the beta subunit caused a dramatic increase of at least 28-fold in the ability of the polymerase to perform translesion replication, reaching 52% bypass in 5 min. When the ssDNA region in the gapped plasmid was extended from 22 nucleotides to 350 nucleotides, translesion replication still depended on the beta subunit, but it was reduced by 80%. DNA sequence analysis of translesion replication products revealed mostly -1 frameshifts. This mutation type is changed to base substitution by the addition of UmuD', UmuC, and RecA, as demonstrated in a reconstituted SOS translesion replication reaction. These results indicate that the beta subunit sliding DNA clamp is the major determinant in the ability of DNA polymerase III holoenzyme to perform unassisted translesion replication and that this unassisted bypass produces primarily frameshifts.

  2. Cystic Lesions in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Macarena Gompertz


    Full Text Available Autoimmune pancreatitis (AIP can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

  3. Self-inflicted skin lesions

    DEFF Research Database (Denmark)

    Ring, Hans Christian; Smith, Matthias Nybro; Jemec, Gregor B E


    The current literature on the management of self-inflicted skin lesions points to an overall paucity of treatments with a high level of evidence (randomized controlled trials, controlled trials, or meta-analyses). In order to improve the communication between dermatologists and mental health...

  4. SLAP lesions: a treatment algorithm. (United States)

    Brockmeyer, Matthias; Tompkins, Marc; Kohn, Dieter M; Lorbach, Olaf


    Tears of the superior labrum involving the biceps anchor are a common entity, especially in athletes, and may highly impair shoulder function. If conservative treatment fails, successful arthroscopic repair of symptomatic SLAP lesions has been described in the literature particularly for young athletes. However, the results in throwing athletes are less successful with a significant amount of patients who will not regain their pre-injury level of performance. The clinical results of SLAP repairs in middle-aged and older patients are mixed, with worse results and higher revision rates as compared to younger patients. In this population, tenotomy or tenodesis of the biceps tendon is a viable alternative to SLAP repairs in order to improve clinical outcomes. The present article introduces a treatment algorithm for SLAP lesions based upon the recent literature as well as the authors' clinical experience. The type of lesion, age of patient, concomitant lesions, and functional requirements, as well as sport activity level of the patient, need to be considered. Moreover, normal variations and degenerative changes in the SLAP complex have to be distinguished from "true" SLAP lesions in order to improve results and avoid overtreatment. The suggestion for a treatment algorithm includes: type I: conservative treatment or arthroscopic debridement, type II: SLAP repair or biceps tenotomy/tenodesis, type III: resection of the instable bucket-handle tear, type IV: SLAP repair (biceps tenotomy/tenodesis if >50 % of biceps tendon is affected), type V: Bankart repair and SLAP repair, type VI: resection of the flap and SLAP repair, and type VII: refixation of the anterosuperior labrum and SLAP repair.

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

    DEFF Research Database (Denmark)

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


    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...... RAD52 facilitates repair of collapsed DNA replication forks in cancer cells.......RNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian...

  6. Petrous apex lesions in the pediatric population

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, Rupa [University of Cincinnati College of Medicine, Department of Radiology, Cincinnati, OH (United States); Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Son, Hwa Jung [University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Cincinnati, OH (United States); Koch, Bernadette L. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)


    A variety of abnormal imaging findings of the petrous apex are encountered in children. Many petrous apex lesions are identified incidentally while images of the brain or head and neck are being obtained for indications unrelated to the temporal bone. Differential considerations of petrous apex lesions in children include ''leave me alone'' lesions, infectious or inflammatory lesions, fibro-osseous lesions, neoplasms and neoplasm-like lesions, as well as a few rare miscellaneous conditions. Some lesions are similar to those encountered in adults, and some are unique to children. Langerhans cell histiocytosis (LCH) and primary and metastatic pediatric malignancies such as neuroblastoma, rhabomyosarcoma and Ewing sarcoma are more likely to be encountered in children. Lesions such as petrous apex cholesterol granuloma, cholesteatoma and chondrosarcoma are more common in adults and are rarely a diagnostic consideration in children. We present a comprehensive pictorial review of CT and MRI appearances of pediatric petrous apex lesions. (orig.)

  7. Imaging of Chest Wall Lesions in Children

    Directory of Open Access Journals (Sweden)

    A. Hekmatnia


    Full Text Available Chest wall lesions in childhood include a wide range of pathologies; Benign lesions include lipoma, neurofibroma, lymphangioma, hemangioma, and mesenchymal hamartoma."nMalignant lesions include Neuroblastoma, Rhabdo-myosarcoma, Ewing sarcoma, and Askin tumor."nSystemic diseases such as leukemia, lymphoma, Langerhans cell histiocytosis, and also infections such as tuberculosis, and actinomycosis may also cause chest wall lesions."nThe imaging characteristics of these lesions are re-viewed, but only a minority of the lesions shows diagnostic imaging features, and most of lesions re-quire biopsy and histopathological examination for "ndefinitive diagnosis."nThe role of different modalities is discussed with an emphasis on magnetic resonance imaging for demonstrating lesion morphology and local spread. Computed tomography and neuclear medicine being used mainly to assess remote disease."nIn this lecture, we discuss about imaging of chest wall lesions in children.

  8. Dynamics of Escherichia coli chromosome segregation during multifork replication. (United States)

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


    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.

  9. H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex

    DEFF Research Database (Denmark)

    Saredi, Giulia; Huang, Hongda; Hammond, Colin M;


    that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific...... is required for TONSL–MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Together, these data reveal a histone-reader-based mechanism...... for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy....

  10. 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.

  11. Spacetime replication of continuous variable quantum information (United States)

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


    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.

  12. A Self-Replicating Ligase Ribozyme (United States)

    Paul, Natasha; Joyce, Gerald F.


    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.

  13. Extremal dynamics in random replicator ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Kärenlampi, Petri P., E-mail:


    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.

  14. Implant periapical lesion. Case report

    Directory of Open Access Journals (Sweden)

    Gregory Venetis, Fotis Iordanidis, Paraskevi Giovani, Lambros Zouloumis


    Full Text Available Ιmplant periapical lesion (IPL is probably not a uniform entity in all cases presented in the literature. Asseptic bone necrosis may be a cause for some of the IPLs, whilst the presence of microorganisms is not always detectable with conventional methods. A case of IPL in a male patient who underwent an extraction of 12 tooth and an immediate implantation at this site is presented. Eight months postoperatively, an IPL was revealed on radiologic examination. After surgical exploration, the IPL was removed and examined histologically and microbiologically. The implant was replaced with a longer one and a bone regeneration procedure was simultaneously carried out. From the study of the lesion and the patient’s followup, infection cannot be considered as primary cause information of presented IPL, but literature data suggests that classic histology and microbiology cannot exclude infection from IPL causatives.

  15. Recombinational DNA repair is regulated by compartmentalization of DNA lesions at the nuclear pore complex

    DEFF Research Database (Denmark)

    Géli, Vincent; Lisby, Michael


    and colleagues shows that also physiological threats to genome integrity such as DNA secondary structure-forming triplet repeat sequences relocalize to the NPC during DNA replication. Mutants that fail to reposition the triplet repeat locus to the NPC cause repeat instability. Here, we review the types of DNA...... lesions that relocalize to the NPC, the putative mechanisms of relocalization, and the types of recombinational repair that are stimulated by the NPC, and present a model for NPC-facilitated repair....

  16. Os Odontoideum: Rare Cervical Lesion (United States)


    the articulation between C1 and the os odontoideum on flexion imaging. The remainder of his cervical vertebral bodies had normal alignment with no...appears normal. Figure 3. Flexion view of plain cervical spine. This image shows abnormal translation of the articulation between C1 and the C2 os...worldwide. Peer Reviewed Title: Os Odontoideum: Rare Cervical Lesion Journal Issue: Western Journal of Emergency Medicine, 12(4) Author: Robson

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


    Smith, Owen K.; Aladjem, Mirit I.


    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 ...

  18. Automatic segmentation of psoriasis lesions (United States)

    Ning, Yang; Shi, Chenbo; Wang, Li; Shu, Chang


    The automatic segmentation of psoriatic lesions is widely researched these years. It is an important step in Computer-aid methods of calculating PASI for estimation of lesions. Currently those algorithms can only handle single erythema or only deal with scaling segmentation. In practice, scaling and erythema are often mixed together. In order to get the segmentation of lesions area - this paper proposes an algorithm based on Random forests with color and texture features. The algorithm has three steps. The first step, the polarized light is applied based on the skin's Tyndall-effect in the imaging to eliminate the reflection and Lab color space are used for fitting the human perception. The second step, sliding window and its sub windows are used to get textural feature and color feature. In this step, a feature of image roughness has been defined, so that scaling can be easily separated from normal skin. In the end, Random forests will be used to ensure the generalization ability of the algorithm. This algorithm can give reliable segmentation results even the image has different lighting conditions, skin types. In the data set offered by Union Hospital, more than 90% images can be segmented accurately.

  19. Follicular-patterned thyroid lesions

    Directory of Open Access Journals (Sweden)



    Full Text Available Aim: Our aim is to determine the minimal cytopathologic criteria needed to make differential diagnosis in follicular-patterned lesions of the thyroid gland.Materials and Methods: We reviewed 56 fine needle aspiration cytology specimens which were reported as “suspicious for follicular-patterned lesions of thyroid” between years 2001 and 2005 in our hospital and their histological slides. Parameters for cytopathologic assesment are cellularity, colloid formation, multilayered rosette formation, follicular cell rings, monolayered sheets, intact follicles, hyperplastic papillae, hyaline stromal fragments, intranuclear inclusions, nuclear grooves, angulated nuclei, nucleoli, cerebriform nuclei, nuclear size, macrophages, flame cells and Hurthle cells. Statistical analysis was performed using χ2 and Fisher's-exact tests and Kolmogorov-Simirnov test.Results: Four cytopathologic features–cerebriform nuclei, angulated nuclei, nuclear grooves and intranuclear inclusion- were constantly observed in the follicular variant of papillary carcinoma (p< 0.05. Diluted colloid, monolayered sheet, nuclear size, macrophage and nucleoli were frequently seen in nodular hyperplasia (p< 0.05. The nuclear size was the sole differential cytopathologic criteria between follicular adenoma and follicular carcinoma (p<0.05.Conclusion: Detailed cytopathologic examination was found to be important in differentiating follicular variant of papillary carcinoma from nodular hyperplasia. On the other hand, none of the cytopathologic findings were sufficient to distinguish follicular adenoma from follicular carcinoma. Therefore, cytopathologists should report such lesions as “follicular neoplasms”.

  20. GFLV replication in electroporated grapevine protoplasts. (United States)

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


    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.

  1. Content replication and placement in mobile networks

    CERN Document Server

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


    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 ...

  2. Replicating Cardiovascular Condition-Birth Month Associations (United States)

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


    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 (United States)

    Manturov, Alexey O.; Grigoryev, Anton V.


    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. Evolution of Database Replication Technologies for WLCG

    CERN Document Server

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


    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.

  5. Relationship between DNA damage response, initiated by camptothecin or oxidative stress, and DNA replication, analyzed by quantitative 3D image analysis. (United States)

    Berniak, K; Rybak, P; Bernas, T; Zarębski, M; Biela, E; Zhao, H; Darzynkiewicz, Z; Dobrucki, J W


    A method of quantitative analysis of spatial (3D) relationship between discrete nuclear events detected by confocal microscopy is described and applied in analysis of a dependence between sites of DNA damage signaling (γH2AX foci) and DNA replication (EdU incorporation) in cells subjected to treatments with camptothecin (Cpt) or hydrogen peroxide (H2O2). Cpt induces γH2AX foci, likely reporting formation of DNA double-strand breaks (DSBs), almost exclusively at sites of DNA replication. This finding is consistent with the known mechanism of induction of DSBs by DNA topoisomerase I (topo1) inhibitors at the sites of collisions of the moving replication forks with topo1-DNA "cleavable complexes" stabilized by Cpt. Whereas an increased level of H2AX histone phosphorylation is seen in S-phase of cells subjected to H2O2, only a minor proportion of γH2AX foci coincide with DNA replication sites. Thus, the increased level of H2AX phosphorylation induced by H2O2 is not a direct consequence of formation of DNA lesions at the sites of moving DNA replication forks. These data suggest that oxidative stress induced by H2O2 and formation of the primary H2O2-induced lesions (8-oxo-7,8-dihydroguanosine) inhibits replication globally and triggers formation of γH2AX at various distances from replication forks. Quantitative analysis of a frequency of DNA replication sites and γH2AX foci suggests also that stalling of replicating forks by Cpt leads to activation of new DNA replication origins. © 2013 International Society for Advancement of Cytometry.

  6. Suppression of Adenovirus Replication by Cardiotonic Steroids. (United States)

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


    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.

  7. Processing of DNA lesions by archaeal DNA polymerases from Sulfolobus solfataricus (United States)

    Grúz, Petr; Shimizu, Masatomi; Pisani, Francesca M.; Felice, Mariarita De; Kanke, Yusuke; Nohmi, Takehiko


    Spontaneous damage to DNA as a result of deamination, oxidation and depurination is greatly accelerated at high temperatures. Hyperthermophilic microorganisms constantly exposed to temperatures exceeding 80°C are endowed with powerful DNA repair mechanisms to maintain genome stability. Of particular interest is the processing of DNA lesions during replication, which can result in fixed mutations. The hyperthermophilic crenarchaeon Sulfolobus solfataricus has two functional DNA polymerases, PolB1 and PolY1. We have found that the replicative DNA polymerase PolB1 specifically recognizes the presence of the deaminated bases hypoxanthine and uracil in the template by stalling DNA polymerization 3–4 bases upstream of these lesions and strongly associates with oligonucleotides containing them. PolB1 also stops at 8-oxoguanine and is unable to bypass an abasic site in the template. PolY1 belongs to the family of lesion bypass DNA polymerases and readily bypasses hypoxanthine, uracil and 8-oxoguanine, but not an abasic site, in the template. The specific recognition of deaminated bases by PolB1 may represent an initial step in their repair while PolY1 may be involved in damage tolerance at the replication fork. Additionally, we reveal that the deaminated bases can be introduced into DNA enzymatically, since both PolB1 and PolY1 are able to incorporate the aberrant DNA precursors dUTP and dITP. PMID:12853619

  8. Replication, recombination, and repair: going for the gold. (United States)

    Klein, Hannah L; Kreuzer, Kenneth N


    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.

  9. Direct visualization of replication dynamics in early zebrafish embryos. (United States)

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


    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.

  10. Involvement of Autophagy in Coronavirus Replication

    Directory of Open Access Journals (Sweden)

    Paul Britton


    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.

  11. Chromatin challenges during DNA replication and repair

    DEFF Research Database (Denmark)

    Groth, Anja; Rocha, Walter; Verreault, Alain;


    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. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

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


    . 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....

  13. Regulation of eukaryotic DNA replication and nuclear structure

    Institute of Scientific and Technical Information of China (English)



    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.

  14. Spatial regulation and organization of DNA replication within the nucleus. (United States)

    Natsume, Toyoaki; Tanaka, Tomoyuki U


    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.

  15. Assembly of Slx4 signaling complexes behind DNA replication forks. (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


    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.

  16. Lesion Contrast Enhancement in Medical Ultrasound Imaging

    DEFF Research Database (Denmark)

    Stetson, Paul F.; Sommer, F.G.; Macovski, A.


    Methods for improving the contrast-to-noise ratio (CNR) of low-contrast lesions in medical ultrasound imaging are described. Differences in the frequency spectra and amplitude distributions of the lesion and its surroundings can be used to increase the CNR of the lesion relative to the background...

  17. The Middle East respiratory syndrome coronavirus (MERS-CoV does not replicate in Syrian hamsters.

    Directory of Open Access Journals (Sweden)

    Emmie de Wit

    Full Text Available In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters.

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



    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...

  19. The use of modified and non-natural nucleotides provide unique insights into pro-mutagenic replication catalyzed by polymerase eta. (United States)

    Choi, Jung-Suk; Dasari, Anvesh; Hu, Peter; Benkovic, Stephen J; Berdis, Anthony J


    This report evaluates the pro-mutagenic behavior of 8-oxo-guanine (8-oxo-G) by quantifying the ability of high-fidelity and specialized DNA polymerases to incorporate natural and modified nucleotides opposite this lesion. Although high-fidelity DNA polymerases such as pol δ and the bacteriophage T4 DNA polymerase replicating 8-oxo-G in an error-prone manner, they display remarkably low efficiencies for TLS compared to normal DNA synthesis. In contrast, pol η shows a combination of high efficiency and low fidelity when replicating 8-oxo-G. These combined properties are consistent with a pro-mutagenic role for pol η when replicating this DNA lesion. Studies using modified nucleotide analogs show that pol η relies heavily on hydrogen-bonding interactions during translesion DNA synthesis. However, nucleobase modifications such as alkylation to the N2 position of guanine significantly increase error-prone synthesis catalyzed by pol η when replicating 8-oxo-G. Molecular modeling studies demonstrate the existence of a hydrophobic pocket in pol η that participates in the increased utilization of certain hydrophobic nucleotides. A model is proposed for enhanced pro-mutagenic replication catalyzed by pol η that couples efficient incorporation of damaged nucleotides opposite oxidized DNA lesions created by reactive oxygen species. The biological implications of this model toward increasing mutagenic events in lung cancer are discussed.

  20. Representation dimension of m-replicated algebras

    Institute of Scientific and Technical Information of China (English)


    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.

  1. Multiseason occupancy models for correlated replicate surveys (United States)

    Hines, James; Nichols, James; Collazo, Jaime


    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.

  2. Are renal ciliopathies (replication) stressed out?

    NARCIS (Netherlands)

    Slaats, Gisela G; Giles, R


    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

  3. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

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


    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...

  4. Replication and Inhibitors of Enteroviruses and Parechoviruses

    Directory of Open Access Journals (Sweden)

    Lonneke van der Linden


    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.

  5. Chemistry: Small molecular replicators go organic (United States)

    Taylor, Annette F.


    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

  6. Replication of biotinylated human immunodeficiency viruses. (United States)

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


    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.

  7. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki


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

    Directory of Open Access Journals (Sweden)

    Yokochi Tomoki


    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 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

  9. Chlamydia Psittaci Strains from Broiler Chickens Induce Histopathological Lesions and Mortality in SPF Chickens

    Directory of Open Access Journals (Sweden)

    Yin Lizi


    Full Text Available A detailed study on histopathological lesions induced by two C. psittaci outer membrane protein A (ompA genotype B strains (10/423 and 10/525 and one genotype D strain (10/298 in experimentally infected (aerosol specific pathogen free (SPF chickens was performed. The strains were derived from Belgian and French commercially raised broilers with pneumonia. Both genotype B and D strains induced conjunctivitis, rhinitis, sinusitis, tracheitis, bronchitis, pneumonitis, airsacculitis, splenitis, hepatitis, nephritis, and enteritis in sequentially (days 2 to 34 post infection euthanized chickens. Inflammation of the ovaries was only observed in genotype D infected chickens. Overall, the genotype D strain caused more severe gross and histopathological lesions and mortality (54.5% early upon infection. The genotype D strain seemed to replicate faster as severity of the lesions increased more quickly. C. psittaci is a primary pathogen in chickens, and efficient monitoring and control of this emerging zoonotic pathogen is urgently needed.

  10. Solitary lucent epiphyseal lesions in children

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, D.J.; Azouz, E.M.


    We evaluated retrospectively the varying radiographic appearances of 15 solitary lucent epiphyseal lesions occurring in children. Imaging modalities used included plain films, conventional tomography, nuclear scintigraphy, and computed tomography. 40% of the lesions (6) were due to osteomyelitis. The remaining lesions included tuberculosis (1), foreign body granuloma (1), chondroblastoma (2), chondromyoxid fibroma (1), enchondroma (1), osteoid osteoma (2), and eosinophilic granuloma (1). Although the radiographic appearances of such lesions may be particularly characteristic, pathologic correlation is frequently necessary. The high incidence of osteomyelitis in our cases emphasizes its importance as a cause for a lucent epiphyseal lesion.

  11. Structure and mechanism for DNA lesion recognition

    Institute of Scientific and Technical Information of China (English)

    Wei Yang


    A fundamental question in DNA repair is how a lesion is detected when embedded in millions to billions of normal base pairs. Extensive structural and functional studies reveal atomic details of DNA repair protein and nucleic acid interactions. This review summarizes seemingly diverse structural motifs used in lesion recognition and suggests a general mechanism to recognize DNA lesion by the poor base stacking. After initial recognition of this shared struc-tural feature of lesions, different DNA repair pathways use unique verification mechanisms to ensure correct lesion identification and removal.

  12. Detection and monitoring of early caries lesions

    DEFF Research Database (Denmark)

    Pretty, I A; Ekstrand, K R


    AIM: To review the current evidence base of detecting and monitoring early carious lesions in children and adolescents and a rationale proposed to ensure that such lesions are identified and appropriately managed. METHODS: The systematic literature search identified initially a review by Gomez...... of existing visible and radiographical systems to monitor lesions over time. Using low-cost intra-oral cameras facilitates the recording of lesion appearance in the patient record and may be of significant benefit in monitoring early lesions over time following their detection. This benefit extends...

  13. Dieulafoy's lesion of duodenum: a case report

    Directory of Open Access Journals (Sweden)

    Wagholikar Gajanan D


    Full Text Available Abstract Background Dieulafoy's lesion is an uncommon but important cause of recurrent upper gastrointestinal bleeding. Extragastric location of Dieulafoy's lesion is rare. We report two cases of Dieulafoy's lesion of the duodenum and discuss the management of this extremely uncommon entity. Case presentation Two cases of massive upper gastro-intestinal bleeding in young adults due to Dieulafoy's lesion of the duodenum are reported. Endoscopic diagnosis was possible in both cases. Hemostasis was achieved successfully by endoscopic adrenaline injection. The endoscopic appearance, pitfalls in the diagnosis and management of this rare lesion are discussed. Conclusions Endoscopic diagnosis of extragastric Dieulafoy's lesion can be difficult because of the small size and obscure location of the lesion. Increased awareness and careful and early endoscopic evaluation following the bleeding episode are the key to accurate diagnosis. Adrenaline injection is one of the important endoscopic modalities for control of bleeding.

  14. Effect of UVM induction on mutation fixation at non-pairing and mispairing DNA lesions. (United States)

    Rahman, M S; Dunman, P M; Wang, G; Murphy, H S; Humayun, M Z


    Mutation fixation at an ethenocytosine (epsilon C) residue borne on transfected M13 single-stranded DNA is significantly enhanced in response to pretreatment of Escherichia coli cells with UV, alkylating agents or hydrogen peroxide, a phenomenon that we have called UVM for UV modulation of mutagenesis. The UVM response does not require the E. coli SOS or adaptive responses, and is observed in cells defective for oxyR, an oxidative DNA damage-responsive regulatory gene. UVM may represent either a novel DNA-repair phenomenon, or an unrecognized feature of DNA replication in damaged cells that affects a specific class of non-coding DNA lesions. To explore the range of DNA lesions subject to the UVM effect, we have examined mutation fixation at 3,N4-ethenocytosine and 1,N6-ethenoadenine, as well as at O6-methylguanine (O6mG). M13 viral single-stranded DNA constructs bearing a single mutagenic lesion at a specific site were transfected into cells pretreated with UV or 1-methyl-3-nitro-1-nitroso-guanidine (MNNG). Survival of transfected viral DNA was measured as transfection efficiency, and mutagenesis at the lesion site was analysed by a quantitative multiplex sequence analysis technology. The results suggest that the UVM effect modulates mutagenesis at the two etheno lesions, but does not appear to significantly affect mutagenesis at O6mG. Because the modulation of mutagenesis is observed in cells incapable of the SOS response, these data are consistent with the notion that UVM may represent a previously unrecognized DNA damage-inducible response that affects the fidelity of DNA replication at certain mutagenic lesions in Escherichia coli.

  15. The Role of the Transcriptional Response to DNA Replication Stress. (United States)

    Herlihy, Anna E; de Bruin, Robertus A M


    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.

  16. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    HAN Xin; ZHANG DeYuan


    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.

  17. Single molecule analysis of Trypanosoma brucei DNA replication dynamics. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Michelle Hawkins


    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.

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


    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

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

    Directory of Open Access Journals (Sweden)

    Sallie Richard


    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.

  1. Escalation of error catastrophe for enzymatic self-replicators (United States)

    Obermayer, B.; Frey, E.


    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.

  2. Reactive Hyperplastic Lesions of the Oral Cavity

    Directory of Open Access Journals (Sweden)

    Hamideh Kadeh


    Full Text Available Introduction: Peripheral reactive lesions of soft tissue are common oral lesions that dentists face during routine examinations. Diagnosis and development of a treatment plan is difficult if dentists are not aware of the prevalence and clinical symptoms of these lesions. The frequency of these lesions differs across various populations. The aim of this study was to determine the frequency and distribution of oral reactive lesions over a period of 7 years (2006–2012.   Materials and Methods: In this retrospective study, available records from the archives of the Department of Pathology, Dental School and the two main hospitals in southeast of Iran (Zahedan over a period of 7 years (2006–2012 were reviewed. Information relating to the type of reactive lesion, age, gender and location was extracted and recorded on data forms. Data were analyzed using SPSS statistical software (V.18 using the chi-square and Fisher’s exact test.   Results: Of 451 oral lesions, 91 cases (20.2% were reactive hyperplastic lesions. The most common lesions were pyogenic granuloma and irritation fibroma, respectively. These lesions were more frequent in women (60% than men (40%. The most common locations of involvement were the gingiva and alveolar mucosa of the mandible, and lesions were more common in the 21–40-year age group. The relationship between age group and reactive lesions was statistically significant (P=0.01.   Conclusion:  The major findings in this study are broadly similar to the results of previous studies, with differences observed in some cases. However, knowledge of the frequency and distribution of these lesions is beneficial when establishing a diagnosis and treatment plan in clinical practice.

  3. Lesion bypass in yeast cells: Pol η participates in a multi-DNA polymerase process (United States)

    Bresson, Anne; Fuchs, Robert P.P.


    Replication through (6–4)TT and G-AAF lesions was compared in Saccharomyces cerevisiae strains proficient and deficient for the RAD30-encoded DNA polymerase η (Pol η). In the RAD30 strain, the (6–4)TT lesion is replicated both inaccurately and accurately 60 and 40% of the time, respectively. Surprisingly, in a rad30Δ strain, the level of mutagenic bypass is essentially suppressed, while error-free bypass remains unchanged. Therefore, Pol η is responsible for mutagenic replication through the (6–4)TT photoproduct, while another polymerase mediates its error-free bypass. Deletion of the RAD30 gene also reduces the levels of both accurate and inaccurate bypass of AAF lesions within two different sequence contexts up to 8-fold. These data show that, in contrast to the accurate bypass by Pol η of TT cyclobutane dimers, it is responsible for the mutagenic bypass of other lesions. In conclusion, this paper shows that, in yeast, translesion synthesis involves the combined action of several polymerases. PMID:12110599

  4. The Solution to Science's Replication Crisis

    CERN Document Server

    Knuteson, Bruce


    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.

  5. Entropy involved in fidelity of DNA replication

    CERN Document Server

    Arias-Gonzalez, J Ricardo


    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...

  6. 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...

  7. Experimental Replication of an Aeroengine Combustion Instability (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.


    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.

  8. Choreography of bacteriophage T7 DNA replication. (United States)

    Lee, Seung-Joo; Richardson, Charles C


    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. Replicative DNA polymerase mutations in cancer. (United States)

    Heitzer, Ellen; Tomlinson, Ian


    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.

  10. Competition and cooperation in dynamic replication networks. (United States)

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


    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.

  11. Interplay between human high mobility group protein 1 and replication protein A on psoralen-cross-linked DNA

    DEFF Research Database (Denmark)

    Reddy, Madhava C; Christensen, Jesper; Vasquez, Karen M


    Human high mobility group box (HMGB) 1 and -2 proteins are highly conserved and abundant chromosomal proteins that regulate chromatin structure and DNA metabolism. HMGB proteins bind preferentially to DNA that is bent or underwound and to DNA damaged by agents such as cisplatin, UVC radiation......-DNA interstrand cross-link (ICL) to a specific site to determine the effect of HMGB proteins on recognition of these lesions. Our results reveal that human HMGB1 (but not HMGB2) binds with high affinity and specificity to psoralen ICLs, and interacts with the essential NER protein, replication protein A (RPA......), at these lesions. RPA, shown previously to bind tightly to these lesions, also binds in the presence of HMGB1, without displacing HMGB1. A discrete ternary complex is formed, containing HMGB1, RPA, and psoralen-damaged DNA. Thus, HMGB1 has the ability to recognize ICLs, can cooperate with RPA in doing so...

  12. DNA ligase I, the replicative DNA ligase. (United States)

    Howes, Timothy R L; Tomkinson, Alan E


    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.

  13. Imaging findings of various calvarial bone lesions witha focus on osteolytic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Yim, Young Hee; Moon, Won Jin; An, Hyeong Su; Cho, Joon [Konkuk University Medical Center, Konkuk University School of Medicine, Seoul (Korea, Republic of); Rho, Myung Ho [Dept. of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    In this review, we present computed tomography (CT) and magnetic resonance imaging (MRI) findings of various calvarial lesions on the basis of their imaging patterns and list the differential diagnoses of the lesions. We retrospectively reviewed 256 cases of calvarial lesion (122 malignant neoplasms, 115 benign neoplasms, and 19 non-neoplastic lesions) seen in our institutions, and classified them into six categories based on the following imaging features: generalized skull thickening, focal skull thickening, generalized skull thinning, focal skull thinning, single lytic lesion, and multiple lytic lesions. Although bony lesions of the calvarium are easily identified on CT, bone marrow lesions are better visualized on MRI including diffusion-weighted imaging or fat-suppressed T2-weighted imaging. Careful interpretation of calvarial lesions based on pattern recognition can effectively narrow a range of possible diagnoses.

  14. [Management of the meniscal lesion]. (United States)

    Baillon, B; Cermak, K; Vancabeke, M


    About 1,5 million arthroscopies are each year performed in the world, 50 % for meniscal affections. The menisci participate in the femoro-tibial load transmission and in the joint shock absorption; they contribute to the knee stability and play a role in the joint lubrication. The menisci are therefore important structures, and, in the case of a lesion, surgical abstention or repair should be favoured. When a meniscectomy has to be performed, it should be economical, preserving the meniscal wall. Meniscectomy is contra-indicated in the child and in the case of knee osteoarthrosis. Meniscal healing is compromised if the knee is unstable. If after total meniscectomy a patient presents symptomatic early osteoarthrosis, without marked loss of alignment, meniscal allografting is a therapeutic option, especially at the lateral compartment.

  15. The molecular biology of Bluetongue virus replication. (United States)

    Patel, Avnish; Roy, Polly


    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.

  16. Ultrastructural Characterization of Zika Virus Replication Factories

    Directory of Open Access Journals (Sweden)

    Mirko Cortese


    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.

  17. Continuously Cumulating Meta-Analysis and Replicability. (United States)

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


    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.

  18. Cutaneous lesions in new born

    Directory of Open Access Journals (Sweden)

    Sachdeva Meenakshi


    Full Text Available Five hundred unselected newborn babies delivered in the Department of Obstetrics and Gynaecology, Unit II of SGBT Hospital attached to Government Medical College, Amritsar during April 2000 to October 2000 were examined for cutaneous lesions daily for the first five days after birth. Different cutaneous lesions were seen in 474(94. 8% newborns. The physiological skin changes observed in order of frequency were Epstein pearls in 305(61%, Mongolian spot in 301(60. 2%, superficial cutaneous desquamation in 200(40%, icterus in 128(25. 6%, milia in 119(23. 8%, sebaceous gland hyperplasia in 107 (21. 4%, occipital alopecia in 94(18. 8%, lanugo in 72(14. 4%, peripheral cyanosis in 47(9. 4%, breast hypertrophy in 29(5. 8% and miniature puberty in 28(5. 6% newborns. Of the transient non-infective skin diseases, erythema toxicum neonatorum was observed most commonly in 105(21 %, followed by miliaria rubra in 103(20. 6% and acne neonatorum in 27(5. 4% newborns. The naevi and other developmental defects in the descending order were salmon patch in 69(13. 8%, congenital melanocytic noevi in 10(2%, accessory tragi in 3(0.6%, spina bifida in 2(0.4%, hydrocephalus in 1(0.2% and poliosis in 1(0.2% newborns. Cradle cap was the only dermatitis observed in 50(10% newborns. One (0.2% case each of Harlequin ichthyosis and labial cyst was seen.

  19. Protective effects of the dietary supplementation of turmeric (Curcuma longa L.) on sodium arsenite-induced biochemical perturbation in mice. (United States)

    Karim, Md Rezaul; Haque, Abedul; Islam, Khairul; Ali, Nurshad; Salam, Kazi Abdus; Saud, Zahangir Alam; Hossain, Ekhtear; Fajol, Abul; Akhand, Anwarul Azim; Himeno, Seiichiro; Hossain, Khaled


    The present study was undertaken to evaluate the protective effect of turmeric powder on arsenic toxicity through mice model. Swiss albino male mice were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were treated with turmeric powder (T, 50 mg/kg body weight/day), sodium arsenite (Sa, 10 mg/kg body weight/day) and turmeric plus Sa (T+Sa), respectively. Results showed that oral administration of Sa reduced the weight gain of the mice compared to the control group and food supplementation of turmeric prevented the reduction of weight gain. Turmeric abrogated the Sa-induced elevation of serum urea, glucose, triglyceride (TG) level and alanine aminotransferase (ALT) activity except the activity of alkaline phosphatase (ALP). Turmeric also prevented the Sa-induced perturbation of serum butyryl cholinesterase activity (BChE). Therefore, ameliorating effect of turmeric on Sa-treated mice suggested the future application of turmeric to reduce or to prevent arsenic toxicity in human.

  20. Auxin and its transport play a role in plant tolerance to arsenite-induced oxidative stress in Arabidopsis thaliana. (United States)

    Krishnamurthy, Aparna; Rathinasabapathi, Bala


    The role of auxin in plant development is well known; however, its possible function in root response to abiotic stress is poorly understood. In this study, we demonstrate a novel role of auxin transport in plant tolerance to oxidative stress caused by arsenite. Plant response to arsenite [As(III)] was evaluated by measuring root growth and markers for stress on seedlings treated with control or As(III)-containing medium. Auxin transporter mutants aux1, pin1 and pin2 were significantly more sensitive to As(III) than the wild type (WT). Auxin transport inhibitors significantly reduced plant tolerance to As(III) in the WT, while exogenous supply of indole-3-acetic acid improved As(III) tolerance of aux1 and not that of WT. Uptake assays using H(3) -IAA showed As(III) affected auxin transport in WT roots. As(III) increased the levels of H2 O2 in WT but not in aux1, suggesting a positive role for auxin transport through AUX1 on plant tolerance to As(III) stress via reactive oxygen species (ROS)-mediated signalling. Compared to the WT, the mutant aux1 was significantly more sensitive to high-temperature stress and salinity, also suggesting auxin transport influences a common element shared by plant tolerance to arsenite, salinity and high-temperature stress.

  1. Endo-periodontal lesion – endodontic approach


    Jivoinovici, R; Suciu, I; Dimitriu, B; Perlea, P; Bartok, R; Malita, M; C. Ionescu


    Endo-perio lesions might be interdependent because of the vascular and anatomic connections between the pulp and the periodontium. The aim of this study is to emphasise that primary endodontic lesion heals after a proper instrumentation, disinfection and sealing of the endodontic space. The primary endodontic lesion with a secondary periodontal involvement first requires an endodontic therapy and, in the second stage, a periodontal therapy. The prognosis is good, with an adequate root canal t...

  2. Hybrid Odontogenic Lesion: A Rare Entity

    Directory of Open Access Journals (Sweden)

    Reza Imani


    Full Text Available Hybrid tumors are very rare tumors composed of two different tumor entities, each of which conforms to an exactly defined tumor category. A 14-year-old boy was referred for an intraosseous painless lesion with a histopathological feature of multiple odontogenic lesions including calcifying odontogenic cyst, complex odontoma and ameloblastic fibro-odontoma. The final diagnosis considered to be a hybrid odontogenic lesion.

  3. The clinical spectrum of pigmented lesions. (United States)

    Schaffer, J V; Bolognia, J L


    This article presents the clinical features of a spectrum of pigmented lesions. It begins with benign lesions that may be confused with melanocytic nevi, such as lentigines, seborrheic keratoses, and dermatofibromas. The next section focuses on the various types of melanocytic nevi, including congenital, blue, and Spitz nevi. A description of atypical nevi is provided, followed by an outline of the clinical characteristics of each subtype of cutaneous melanoma. The clinical characteristics of various pigmented lesions are illustrated.

  4. Management of Anal Squamous Intraepithelial Lesions


    Pineda, Carlos E.; Welton, Mark L.


    Anal squamous intraepithelial lesions include both low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and are caused by chronic infection with the human papillomavirus (HPV). The disease is increasing in both incidence and prevalence, especially among patients with the following risk factors: homosexual men, acquired or iatrogenic immunosuppression, and presence of other HPV-related diseases. Although the natural history of the disease is ...

  5. On the scattering of DNA replication completion times (United States)

    Meilikhov, E. Z.; Farzetdinova, R. M.


    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.

  6. Replicative intermediates of maize streak virus found during leaf development. (United States)

    Erdmann, Julia B; Shepherd, Dionne N; Martin, Darren P; Varsani, Arvind; Rybicki, Edward P; Jeske, Holger


    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.

  7. Obstructive Lesions of the Pediatric Subglottis


    Ida, Jonathan B.; Guarisco, J. Lindhe; Rodriguez, Kimsey H.; Amedee, Ronald G.


    Purpose: To compile information regarding obstructive subglottic lesions in children, including anatomy, pathogenesis, prevention, evaluation, and treatment options, required for implementation of a multi-faceted treatment plan.

  8. Comet Lesions in Patients with Pseudoxanthoma Elasticum

    Directory of Open Access Journals (Sweden)

    Sinan Tatlıpınar


    Full Text Available Pseudoxanthoma elasticum (PXE is a genetic multisystemic disorder affecting the skin, eyes and cardiovascular system. Basic fundoscopic findings in PXE result from Bruch’s membrane involvement. The most important fundoscopic findings are angioid streaks. Other significant ocular findings are peau d’orange appearance, optic disc drusen, pattern dystrophy-like macular appearance, comet lesions, and choroidal neovascularization. Comet lesions are a pathognomonic ocular finding for PXE. The presence of both angioid streaks in the fundus and typical skin lesions should alert clinicians to PXE. Herein, we present two PXE cases with comet lesions.

  9. PCNA Modifications for Regulation of Post-Replication Repair Pathways



    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 ...

  10. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F


    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.

  11. Mathematical Framework for A Novel Database Replication Algorithm

    Directory of Open Access Journals (Sweden)

    Divakar Singh Yadav


    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.

  12. Replication of plasmids in gram-negative bacteria.



    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...

  13. CD57 expression and cytokine production by T cells in lesional and unaffected skin from patients with psoriasis.

    Directory of Open Access Journals (Sweden)

    Mariana D Batista

    Full Text Available BACKGROUND: The immunopathogenic mechanisms leading to psoriasis remain unresolved. CD57 is a marker of replicative inability and immunosenescence on CD8+ T cells and the proportion of CD57 expressing CD8+ T cells is increased in a number of inflammatory conditions. METHODOLOGY: We examined the expression of CD57 on T cells in the skin of patients affected with psoriasis, comparing lesional and unaffected skin. We also assessed functionality of the T cells by evaluating the secretion of several inflammatory cytokines (IL-17A, IFN-gamma, IL-2, IL-33, TNF-alpha, IL-21, IL-22, and IL-27, from cell-sorted purified CD4+ and CD8+ T cells isolated from lesional and unaffected skin biopsies of psoriasis patients. PRINCIPAL FINDINGS: We observed that the frequency of CD57+CD4+ and CD57+CD8+ T cells was significantly higher in unaffected skin of psoriasis patients compared to lesional skin. Sorted CD4+ T cells from psoriatic lesional skin produced higher levels of IL-17A, IL-22, and IFN-gamma compared to unaffected skin, while sorted CD8+ T cells from lesional skin produced higher levels of IL-17, IL-22, IFN-gamma, TNF-alpha, and IL-2 compared to unaffected skin. CONCLUSIONS/SIGNIFICANCE: These findings suggest that T cells in unaffected skin from psoriasis patients exhibit a phenotype compatible with replicative inability. As they have a lower replicative capacity, CD57+ T cells are less frequent in lesional tissue due to the high cellular turnover.

  14. 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 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

  15. Hepatitis C virus quasispecies in cancerous and noncancerous hepatic lesions: the core protein-encoding region.

    Directory of Open Access Journals (Sweden)

    Alam,Shahjalal S.


    Full Text Available We have shown that highly proofreading DNA polymerase is required for the polymerase chain reaction in the genetic analysis of hepatitis C virus (HCV. To clarify the status of HCV quasispecies in hepatic tissue using proofreading DNA polymerase, we performed a genetic analysis of the HCV core protein-encoding region in cancerous and noncancerous lesions derived from 4 patients with hepatocellular carcinoma. In contrast to the previously published data, we observed neither deletions nor stop codons in the analyzed region and no significant difference in the complexity of HCV quasispecies between cancerous and noncancerous lesions. This result suggests that the HCV core gene is never structurally defective in hepatic tissues, including cancerous lesions. However, in 3 of the patients, the consensus HCV species differed between cancerous and noncancerous lesions, suggesting that the predominant replicating HCV species differs between these 2 types of lesions. Moreover, during the course of the study, we obtained several interesting variants possessing a substitution at codon 9 of the core gene, whose substitution has been shown to induce the production of the F protein synthesized by a - 2/+1 ribosomal frameshift.

  16. Chromatin Dynamics During DNA Replication and Uncharacterized Replication Factors determined by Nascent Chromatin Capture (NCC) Proteomics (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


    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

  17. Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

    NARCIS (Netherlands)

    Tanner, Nathan A.; Loparo, Joseph J.; Oijen, Antoine M. van


    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

  18. Geminin: a major DNA replication safeguard in higher eukaryotes

    DEFF Research Database (Denmark)

    Melixetian, Marina; Helin, Kristian


    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


    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. Replication NAND gate with light as input and output. (United States)

    Samiappan, Manickasundaram; Dadon, Zehavit; Ashkenasy, Gonen


    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.

  1. DNA polymerase ζ-dependent lesion bypass in Saccharomyces cerevisiae is accompanied by error-prone copying of long stretches of adjacent DNA.

    Directory of Open Access Journals (Sweden)

    Olga V Kochenova


    Full Text Available Translesion synthesis (TLS helps cells to accomplish chromosomal replication in the presence of unrepaired DNA lesions. In eukaryotes, the bypass of most lesions involves a nucleotide insertion opposite the lesion by either a replicative or a specialized DNA polymerase, followed by extension of the resulting distorted primer terminus by DNA polymerase ζ (Polζ. The subsequent events leading to disengagement of the error-prone Polζ from the primer terminus and its replacement with an accurate replicative DNA polymerase remain largely unknown. As a first step toward understanding these events, we aimed to determine the length of DNA stretches synthesized in an error-prone manner during the Polζ-dependent lesion bypass. We developed new in vivo assays to identify the products of mutagenic TLS through a plasmid-borne tetrahydrofuran lesion and a UV-induced chromosomal lesion. We then surveyed the region downstream of the lesion site (in respect to the direction of TLS for the presence of mutations indicative of an error-prone polymerase activity. The bypass of both lesions was associated with an approximately 300,000-fold increase in the mutation rate in the adjacent DNA segment, in comparison to the mutation rate during normal replication. The hypermutated tract extended 200 bp from the lesion in the plasmid-based assay and as far as 1 kb from the lesion in the chromosome-based assay. The mutation rate in this region was similar to the rate of errors produced by purified Polζ during copying of undamaged DNA in vitro. Further, no mutations downstream of the lesion were observed in rare TLS products recovered from Polζ-deficient cells. This led us to conclude that error-prone Polζ synthesis continues for several hundred nucleotides after the lesion bypass is completed. These results provide insight into the late steps of TLS and show that error-prone TLS tracts span a substantially larger region than previously appreciated.

  2. Assembling semiconductor nanocomposites using DNA replication technologies.

    Energy Technology Data Exchange (ETDEWEB)

    Heimer, Brandon W.; Crown, Kevin K.; Bachand, George David


    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

  3. Cortical Lesions as Determinants of White Matter Lesion Formation and Cognitive Abnormalities in MS (United States)


    AWARD NUMBER: W81XWH-13-1-0098 TITLE: Cortical Lesions as Determinants of White Matter Lesion Formation and Cognitive Abnormalities in MS...2015 4. TITLE AND SUBTITLE Cortical Lesions as Determinants of White Matter Lesion Formation and Cognitive Abnormalities in MS 5a. CONTRACT developed for these maps will also be used to enhance tract-based FA and mean-diffusivity measurements in FSL, as originally proposed. The

  4. [Asterixis in focal brain lesions]. (United States)

    Velasco, F; Gomez, J C; Zarranz, J J; Lambarri, I; Ugalde, J


    Asterixis is a motor control disorder characterized by the presence of abnormal movements of the lower limbs in the vertical plane during posture maintenance. Asterixis is usually bilateral and associated with toxic-metabolic metabolic encephalopathies. Unilateral asterixis is less frequent and it normally indicates focal brain damage. We report the cases of four patients (two males/two females), aged 57 to 83 years, suffering from uni or bilateral asterixis associated with focal brain damage. All patients underwent CT brain scan and a neurophysiological study (parietal EMG and/or PES). In addition, any toxic-metabolic cause that could be produced by this clinical phenomenon was ruled out with the appropriate testing. Unilateral asterixis is a clinical symptom that may indicate the presence of focal brain damage. Often, it is ignored or overlooked during routine neurological examinations. On the other hand, the presence of a bilateral asterixis is not always indicative of a toxic-metabolic encephalopathy.Rarely, such as in one of the cases herein presented, bilateral asterixis can also appear associated with structural brain lesions. Although asterixis diagnosis is fundamentally clinical, the neurophysiological study contributes to verify the diagnosis.

  5. Children's cranial lesions from Neolithic. (United States)

    Shbat, A; Smrcka, V


    In skeletal material from the neolithic settlement at Makotrasy, county Kladno, were analysed two children's craniums (identification numbers Ao 8218 and Ao 4184) with pathological cases. Case 1 (Object 127, Ao 8218) is the individual about 4 to 5 years old. There is oval aperture with the diameter 25 x 20 mm in the area of anthropometrical point bregma, with vertical, multiple knurled edges. Bevelled and rounded segment in the left frontal part of the aperture with diameter 10 mm is imitating healing process. We suggest this case is the trephination with the marks of the healing process in the period of 1 to 2 weeks after the surgery took over. Case 2 (Pit 25, Ao 4184) is child with age determined about 4 years old. Cranium was found buried separately. There is oval defect located at os occipitale and os parietale sin and goes through sutura lambdoidea. Caudal part of defect is missing. The edge of the defect is sharp and inward bevelled with exposed diploe. Traces of any vital reaction were not identified. Diameter is around 50 mm. Perimortal trephination leading to death, or postmortal taking of the trephinational amulet must be considered. There were several pathological lesions on the same skull. Defect of oval shape sized 8 x 12 mm is located at the os parietale dex. Defect interferes mostly with lamina externa and less with lamina interna. Exposed diploe is without any vital reaction.

  6. Focal liver lesions found incidentally

    Institute of Scientific and Technical Information of China (English)

    Abdullah; A; Algarni; Abdullah; H; Alshuhri; Majed; M; Alonazi; Moustafa; Mabrouk; Mourad; Simon; R; Bramhal


    Incidentally found focal liver lesions are a commonfinding and a reason for referral to hepatobiliary service.They are often discovered in patients with history of liver cirrhosis,colorectal cancer,incidentally during work up for abdominal pain or in a trauma setting.Specific points should considered during history taking such as risk factors of liver cirrhosis;hepatitis,alcohol consumption,substance exposure or use of oral con-traceptive pills and metabolic syndromes.Full blood count,liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease.Imaging should start with B-mode ultrasound.If available,contrast enhanced ultrasound is a feasible,safe,cost effective option and increases the ability to reach a diagnosis.Contrast enhanced computed tomography should be considered next.It is more accurate in diagnosis and better to study anatomy for possible operation.Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity.If doubt still remains,the options are biopsy or surgical excision.

  7. Cerebral CT of ischaemic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Aulich, A.


    The diagnosis of stroke must first be established by clinical examination. CT has proved useful for confirmation of the diagnosis and provides a global intracranial picture of morphological changes in cerebral vascular diseases. A hemorrhage can be recognized with certainty at the first CT examination as the cause of the stroke, but in the detection of a lesion due to ischemia an important role is played by the correct choice of the time of examination, and in some cases also of the check-up with contrast medium. The differential diagnosis between infarct in the acute stage and encephalitis or gliomas of low-grade malignity can be difficult. A decision can often only be made after a series of examinations. Postmalacial conditions are often difficult to differentiate from defects due to other causes, such as hemorrhage, head injury, postoperative states and after encephalitis. A knowledge of the anamnesis and the clinical findings is indispensable for CT evaluation. In assessing the prognosis before vascular surgery on the extracranial brain-supplying vessels the performance of a CT examination should be advised. A warning is given against the use of CT as a screening method.

  8. [Mandibular lesions in multiple myeloma]. (United States)

    Scutellari, P N; Orzincolo, C


    A review was made of 237 cases of multiple myeloma seen at the Institute of Radiology and Hematology of the Ferrara University from 1984 through 1990. The results showed skeletal involvement of the mandible to be present in 25 patients (10.54%). The diagnosis of multiple myeloma was based on the following criteria: 1) increased number of abnormal, atypical or immature plasma cells in the bone marrow; 2) the presence of a monoclonal protein in the serum or urine; 3) bone lesions consistent with those of myeloma. Symptoms include pain and swelling of the oral cavity, tooth mobility and loss, numbness along the inferior dental nerve, and paresthesia of the lower lip. The typical radiographic appearance is a well-defined "punched-out" lytic defect, solitary or multiple; sometimes, the defect enlarges and appears "bubbly" or septated. Permeative lytic areas, with blurred outlines, are a rare pattern, which is radiologically indistinguishable from skeletal metastases. The involvement of the oral cavity and jaw in multiple myeloma has been often reported in literature: nevertheless, if radiographs of the jaws had been systematically taken in all the cases, its incidence would probably have been much higher than previously suspected.

  9. The IFITMs Inhibit Zika Virus Replication

    Directory of Open Access Journals (Sweden)

    George Savidis


    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.

  10. Replication of DNA during barley endosperm development

    DEFF Research Database (Denmark)

    Giese, H.


    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....

  11. Multiscale modeling of virus replication and spread. (United States)

    Kumberger, Peter; Frey, Felix; Schwarz, Ulrich S; Graw, Frederik


    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.

  12. Simulation Studies in Data Replication Strategies

    Institute of Scientific and Technical Information of China (English)

    HarveyB.Newman; IosifC.Legrand


    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.

  13. Method of producing an item with enhanced wetting properties by fast replication and replication tool used in the method

    DEFF Research Database (Denmark)


    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...

  14. Common oral lesions associated with HIV infection. (United States)

    Navazesh, M; Lucatorto, F


    More than 40 different lesions involving head and neck areas have been associated with HIV infection. The oral cavity may manifest the first sign of HIV infection. Early detection of these conditions can lead to early diagnosis of HIV infection and subsequent appropriate management. Signs, symptoms and management of the most common HIV-associated oral lesions are discussed.

  15. Principal component analysis of psoriasis lesions images

    DEFF Research Database (Denmark)

    Maletti, Gabriela Mariel; Ersbøll, Bjarne Kjær


    A set of RGB images of psoriasis lesions is used. By visual examination of these images, there seem to be no common pattern that could be used to find and align the lesions within and between sessions. It is expected that the principal components of the original images could be useful during future...

  16. Imaging granulomatous lesions with optical coherence tomography

    DEFF Research Database (Denmark)

    Banzhaf, Christina; Jemec, Gregor B E


    To investigate and compare the presentation of granulomatous lesions in optical coherence tomography (OCT) images and compare this to previous studies of nonmelanoma skin tumors.......To investigate and compare the presentation of granulomatous lesions in optical coherence tomography (OCT) images and compare this to previous studies of nonmelanoma skin tumors....

  17. The Post-Ureteroscopic Lesion Scale (PULS)

    DEFF Research Database (Denmark)

    Schoenthaler, Martin; Buchholz, Noor; Farin, Erik


    The Post-Ureteroscopic Lesion Scale (PULS) offers a simple grading system for the description of ureteral lesions after ureteroscopy. In this article, we present the results of a video-based multicenter evaluation of the inter-rater reliability of clinically important PULS grades 0-3....

  18. Pediatric multifocal liver lesions evaluated by MRI

    Directory of Open Access Journals (Sweden)

    Majed Almotairi


    Full Text Available Objective: The purpose of this study is to present our experience with MRI evaluation of multifocal liver lesions in children and describe the MRI characteristics of these lesions. Patients and Methods: A retrospective review of consecutive MRI exams performed for the evaluation of multiple liver lesions between 1 January 2007 and 31 December 2012 was done to note the number of lesions, the size of the largest lesion, MR signal characteristics, and background liver. Final diagnosis was assigned to each case based on pathology in the available cases and a combination of clinical features, imaging features, and follow-up in the remaining cases. Results: A total of 48 children (22 boys, 26 girls; age between 3 months and 18 years with average age 10.58 years and median age 11 years were included in the study. Totally 51 lesion diagnoses were seen in 48 children that included 17 focal nodular hyperplasia (FNH, 8 hemangiomas, 7 metastases, 6 regenerative nodules, 3 adenomas, 3 abscesses, and one each of angiomyolipoma, epithelioid hemangioendothelioma, focal fatty infiltration, hepatocellular carcinoma, hepatic infarction, nodular regenerative hyperplasia, and hepatic cyst. Background liver was normal in 33, cirrhotic in 10, fatty in 3, and siderotic in 2 children. Most FNH, hemangiomas, and regenerative nodules showed characteristic MRI features, while metastases were variable in signal pattern. Conclusion: Many commonly seen multifocal liver lesions in children have characteristic MRI features. MRI can help to arrive at reasonable differential diagnoses for multifocal liver lesions in children and guide further investigation and management.

  19. Pure Gerstmann's syndrome from a focal lesion. (United States)

    Roeltgen, D P; Sevush, S; Heilman, K M


    It is controversial whether a focal lesion can specifically induce Gerstmann's syndrome (dyscalculia, left-right disorientation, finger agnosia, and agraphia). Also, Gerstmann's tetrad has been attributed to other cerebral symptoms, particularly aphasia. We examined a patient who had all four symptoms of Gerstmann's syndrome, without other symptoms or signs, and who had a discrete left parietal lesion.

  20. Spindle cell melanocytic lesions: part II--an approach to intradermal proliferations and horizontally oriented lesions. (United States)

    Sade, Shachar; Al Habeeb, Ayman; Ghazarian, Danny


    Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes show a dendritic cytomorphology and territorial isolation, lesional nevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies, and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may either be a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either due to its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion due to a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified; however, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions may reliably be resolved through this standard approach, problem areas do exist for the surgical pathologist or dermatopathologist. With this review (part II of II), we complete our discussion of spindle cell melanocytic lesions, in order to: (1) model a systematic approach to such lesions; and (2) provide familiarity with those melanocytic lesions which either typically or occasionally display a spindled cytomorphology.

  1. DNA replication origin activation in space and time. (United States)

    Fragkos, Michalis; Ganier, Olivier; Coulombe, Philippe; Méchali, Marcel


    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.

  2. 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


    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.

  3. Oncocytic lesions of the ophthalmic region

    DEFF Research Database (Denmark)

    Østergaard, Jens; Prause, Jan U; Heegaard, Steffen


    Purpose: This study aimed to make a nationwide clinicopathological study of oncocytic lesions in the ophthalmic region and to characterize their cytokeratin (CK) expression. Methods: All histologically diagnosed oncocytic lesions in the ophthalmic region registered in Denmark over a 25-year period...... were collected and re-evaluated using a monoclonal antimitochondrial antibody (MU213-UC). Clinical data were registered. Immunohistochemical characterization was performed with a panel of anti-CK antibodies. Results: A total of 34 oncocytic lesions were identified and reviewed. The incidence...... that required surgical intervention in the Danish population could be approximated to 0.3 lesions per million capita per year. Patient ages ranged from 45 years to 89 years, with a peak incidence in the eighth decade. Female patients were twice as common as male. Lesions were typically described as red...

  4. 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


    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.

  5. Prevention of DNA re-replication in eukaryotic cells

    Institute of Scientific and Technical Information of China (English)

    Lan N. Truong; Xiaohua Wu


    DNA replication is a highly regulated process involving a number of licensing and replication factors that function in a carefully orchestrated manner to faithfully replicate DNA during every cell cycle. Loss of proper licensing control leads to deregulated DNA replication including DNA re-replication, which can cause genome instability and tumorigenesis. Eukaryotic organisms have established several conserved mechanisms to prevent DNA re-replication and to counteract its potentially harmful effects. These mechanisms include tightly controlled regulation of licensing factors and activation of cell cycle and DNA damage checkpoints.Deregulated licensing control and its associated compromised checkpoints have both been observed in tumor cells, indicating that proper functioning of these pathways is essential for maintaining genome stability. In this review, we discuss the regulatory mechanisms of licensing control, the deleterious consequences when both licensing and checkpoints are compromised, and present possible mechanisms to prevent re-replication in order to maintain genome stability.

  6. Eukaryotic Mismatch Repair in Relation to DNA Replication. (United States)

    Kunkel, Thomas A; Erie, Dorothy A


    Three processes act in series to accurately replicate the eukaryotic nuclear genome. The major replicative DNA polymerases strongly prevent mismatch formation, occasional mismatches that do form are proofread during replication, and rare mismatches that escape proofreading are corrected by mismatch repair (MMR). This review focuses on MMR in light of increasing knowledge about nuclear DNA replication enzymology and the rate and specificity with which mismatches are generated during leading- and lagging-strand replication. We consider differences in MMR efficiency in relation to mismatch recognition, signaling to direct MMR to the nascent strand, mismatch removal, and the timing of MMR. These studies are refining our understanding of relationships between generating and repairing replication errors to achieve accurate replication of both DNA strands of the nuclear genome.

  7. The Alleged Crisis and the Illusion of Exact Replication. (United States)

    Stroebe, Wolfgang; Strack, Fritz


    There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a "replication crisis" in psychology. Psychologists are encouraged to conduct more "exact" replications of published studies to assess the reproducibility of psychological research. This article argues that the alleged "crisis of replicability" is primarily due to an epistemological misunderstanding that emphasizes the phenomenon instead of its underlying mechanisms. As a consequence, a replicated phenomenon may not serve as a rigorous test of a theoretical hypothesis because identical operationalizations of variables in studies conducted at different times and with different subject populations might test different theoretical constructs. Therefore, we propose that for meaningful replications, attempts at reinstating the original circumstances are not sufficient. Instead, replicators must ascertain that conditions are realized that reflect the theoretical variable(s) manipulated (and/or measured) in the original study.

  8. Replication, falsification, and the crisis of confidence in social psychology

    Directory of Open Access Journals (Sweden)

    Brian D. Earp


    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.

  9. Replication, falsification, and the crisis of confidence in social psychology. (United States)

    Earp, Brian D; Trafimow, David


    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.

  10. Control of DNA replication by anomalous reaction-diffusion kinetics (United States)

    Bechhoefer, John; Gauthier, Michel


    DNA replication requires two distinct processes: the initiation of pre-licensed replication origins and the propagation of replication forks away from the fired origins. Experiments indicate that these origins are triggered over the whole genome at a rate I(t) (the number of initiations per unreplicated length per time) that increases throughout most of the synthesis (S) phase, before rapidly decreasing to zero at the end of the replication process. We propose a simple model for the control of DNA replication in which the rate of initiation of replication origins is controlled by protein-DNA interactions. Analyzing recent data from Xenopus frog embryos, we find that the initiation rate is reaction limited until nearly the end of replication, when it becomes diffusion limited. Initiation of origins is suppressed when the diffusion-limited search time dominates. To fit the experimental data, we find that the interaction between DNA and the rate-limiting protein must be subdiffusive.

  11. The Slx4-Dpb11 scaffold complex: coordinating the response to replication fork stalling in S-phase and the subsequent mitosis. (United States)

    Princz, Lissa N; Gritenaite, Dalia; Pfander, Boris


    Replication fork stalling at DNA lesions is a common problem during the process of DNA replication. One way to allow the bypass of these lesions is via specific recombination-based mechanisms that involve switching of the replication template to the sister chromatid. Inherent to these mechanisms is the formation of DNA joint molecules (JMs) between sister chromatids. Such JMs need to be disentangled before chromatid separation in mitosis and the activity of JM resolution enzymes, which is under stringent cell cycle control, is therefore up-regulated in mitosis. An additional layer of control is facilitated by scaffold proteins. In budding yeast, specifically during mitosis, Slx4 and Dpb11 form a cell cycle kinase-dependent complex with the Mus81-Mms4 structure-selective endonuclease, which allows efficient JM resolution by Mus81. Furthermore, Slx4 and Dpb11 interact even prior to joining Mus81 and respond to replication fork stalling in S-phase. This S-phase complex is involved in the regulation of the DNA damage checkpoint as well as in early steps of template switch recombination. Similar interactions and regulatory principles are found in human cells suggesting that Slx4 and Dpb11 may have an evolutionary conserved role organizing the cellular response to replication fork stalling.

  12. DNA instability in replicating Huntington's disease lymphoblasts

    Directory of Open Access Journals (Sweden)

    Frati Luigi


    Full Text Available Abstract Background The expanded CAG repeat in the Huntington's disease (HD gene may display tissue-specific variability (e.g. triplet mosaicism in repeat length, the longest mutations involving mitotic (germ and glial cells and postmitotic (neurons cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths. Results Although most lymphoblastoid cell lines (88% showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting in cis to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations. Conclusion Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.

  13. Le Chatelier's principle in replicator dynamics (United States)

    Allahverdyan, Armen E.; Galstyan, Aram


    The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.

  14. Why threefold-replication of families? (United States)

    Fitzpatrick, Gerald L.


    In spite of the many successes of the standard model of particle physics, the observed proliferation of matter-fields, in the form of ``replicated'' generations or families, is a major unsolved problem. In this paper, I explore some of the algebraic, geometric and physical consequences of a new organizing principle for fundamental fermions (quarks and leptons)(Gerald L. Fitzpatrick, phThe Family Problem--New Internal Algebraic and Geometric Regularities), Nova Scientific Press, Issaquah, Washington, 1997. Read more about this book (ISBN 0--9655695--0--0) and its subject matter at: and/or> The essence of the new organizing principle is the idea that the standard-model concept of scalar fermion numbers f can be generalized. In particular, a ``generalized fermion number,'' which consists of a 2× 2 matrix F that ``acts'' on an internal 2-space, instead of spacetime, is taken to describe certain internal properties of fundamental fermions. This generalization automatically introduces internal degrees of freedom that ``explain,'' among other things, family replication and the number (three) of families observed in nature.

  15. Replicative DNA polymerase mutations in cancer☆ (United States)

    Heitzer, Ellen; Tomlinson, Ian


    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. PMID:24583393

  16. Bacteriology of diabetic foot lesions. (United States)

    Yoga, R; Khairul, A; Sunita, K; Suresh, C


    Infection plays a pivotal role in enhancing a diabetic foot at risk toward amputation. Effective antibiotic therapy against the offending pathogens is an important component of treatment of diabetic foot infections. Recognition of the pathogen is always difficult as the representative deep tissue sample for culture is surrounded by ulcer surface harbouring colonies of organisms frequently labelled as skin commensals. The emergent of resistant strains represents a compounding problem standing against efforts to prevent amputation. This study was undertaken to identify the pathogens associated with diabetic foot infection in terms of their frequency and sensitivity against certain commonly used antibiotics. Forty-four consecutive patients with open diabetic foot infections had wound swab taken for culture and sensitivity testing. Cultures positive were observed in 89% of the cases with Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeroginosa encountered in 20%, 14% and 14% of cases respectively. Mixed growths were isolated in 6% of cultures. All Staphylcoccus aureus isolates were resistant to Penicillin but 80% were sensitive to Erythromycin and Co-trimoxazole. Klebsiella pneumoniae isolates were sensitive to Methicillin and Gentamycin in 80% and 60% of cases respectively, and resistant to Ampicillin and Ceftazidime in 83% and 50% respectively. All Pseudomonas aeroginosa isolates were sensitive to Amikacin and Ciprofloxacin but 50% were resistant to Gentamycin. There was no single antibiotic possessing good coverage for all common organisms isolated from diabetic foot lesions. Staphylococcus aureus remains the predominant cause of diabetic foot infections followed by Klebsiela pneumonia and Pseudomonas aeroginosa. Most infections are monomicrobial. The emergence of multiresistant organisms is a worrying feature in diabetic foot infections.

  17. Imperfect DNA lesion repair in the semiconservative quasispecies model: Derivation of the Hamming class equations and solution of the single-fitness peak landscape (United States)

    Tannenbaum, Emmanuel; Sherley, James L.; Shakhnovich, Eugene I.


    This paper develops a Hamming class formalism for the semiconservative quasispecies equations with imperfect lesion repair, first presented and analytically solved in Y. Brumer and E.I. Shakhnovich (q-bio.GN/0403018, 2004). Starting from the quasispecies dynamics over the space of genomes, we derive an equivalent dynamics over the space of ordered sequence pairs. From this set of equations, we are able to derive the infinite sequence length form of the dynamics for a class of fitness landscapes defined by a master genome. We use these equations to solve for a generalized single-fitness-peak landscape, where the master genome can sustain a maximum number of lesions and remain viable. We determine the mean equilibrium fitness and error threshold for this class of landscapes, and show that when lesion repair is imperfect, semiconservative replication displays characteristics from both conservative replication and semiconservative replication with perfect lesion repair. The work presented here provides a formulation of the model which greatly facilitates the analysis of a relatively broad class of fitness landscapes, and thus serves as a convenient springboard into biological applications of imperfect lesion repair.

  18. Replication regions of two pairs of incompatible lactococcal theta-replicating plasmids. (United States)

    Gravesen, A; von Wright, A; Josephsen, J; Vogensen, F K


    Incompatibility tests were performed employing 12 replicons belonging to a family of homologous lactococcal theta-replicating plasmids. Two pairs of incompatible plasmids were found, namely, pFV1001 and pFV1201, and pJW565 and pFW094. The replicons of plasmids pFV1001, pFV1201, pJW565, pJW566, and pFW094 were sequenced. Alignments were made of the replicational origins (repA) and putative replication proteins (RepB) of these and 11 related plasmid sequences. Comparison of the alignments with the incompatibility data indicated that the incompatibility determinant could be contained within the 22-bp tandem repeats DRII and/or the inverted repeat IR1 in repA. In support, the incompatibility determinant of pJW563 was localized to a 743-bp fragment encompassing repA. A stretch of 13 amino acids of RepB was proposed to be responsible for the plasmid-specific initiation of replication. This stretch is part of a domain containing features that are highly conserved within the proposed DNA binding regions of the initiation proteins from several well-characterized plasmids from Gram-negative bacteria, including pSC101, R6K, and mini-F.

  19. Late-replicating X-chromosome: replication patterns in mammalian females

    Directory of Open Access Journals (Sweden)

    Tunin Karen


    Full Text Available The GTG-banding and 5-BrdU incorporation patterns of the late-replicating X-chromosome were studied in female dogs and cattle, and compared to human female patterns. The replication patterns of the short arm of the X-chromosomes did not show any difference between human, dog and cattle females. As to the long arm, some bands showed differences among the three studied species regarding the replication kinetics pattern. These differences were observed in a restricted region of the X-chromosome, delimited by Xq11 -> q25 in humans, by Xq1 -> q8 in dogs, and by Xq12 -> q32 in cattle. In an attempt to find out if these differences in the replication kinetics could be a reflection of differences in the localization of genes in that region of the X-chromosome, we used the probe for the human androgen receptor gene (AR localized at Xq12, which is in the region where we observed differences among the three studied species. We did not, however, observe hybridization signals. Our study goes on, using other human probes for genes located in the region Xq11 -> Xq25.

  20. Assembly of alphavirus replication complexes from RNA and protein components in a novel trans-replication system in mammalian cells. (United States)

    Spuul, Pirjo; Balistreri, Giuseppe; Hellström, Kirsi; Golubtsov, Andrey V; Jokitalo, Eija; Ahola, Tero


    For positive-strand RNA viruses, the viral genomic RNA also acts as an mRNA directing the translation of the replicase proteins of the virus. Replication takes place in association with cytoplasmic membranes, which are heavily modified to create specific replication compartments. Here we have expressed by plasmid DNA transfection the large replicase polyprotein of Semliki Forest virus (SFV) in mammalian cells from a nonreplicating mRNA and provided a separate RNA containing the replication signals. The replicase proteins were able to efficiently and specifically replicate the template in trans, leading to accumulation of RNA and marker gene products expressed from the template RNA. The replicase proteins and double-stranded RNA replication intermediates localized to structures similar to those seen in SFV-infected cells. Using correlative light electron microscopy (CLEM) with fluorescent marker proteins to relocate those transfected cells, in which active replication was ongoing, abundant membrane modifications, representing the replication complex spherules, were observed both at the plasma membrane and in intracellular endolysosomes. Thus, replication complexes are faithfully assembled and localized in the trans-replication system. We demonstrated, using CLEM, that the replication proteins alone or a polymerase-negative polyprotein mutant together with the template did not give rise to spherule formation. Thus, the trans-replication system is suitable for cell biological dissection and examination in a mammalian cell environment, and similar systems may be possible for other positive-strand RNA viruses.

  1. Colon preneoplastic lesions in animal models. (United States)

    Suzui, Masumi; Morioka, Takamitsu; Yoshimi, Naoki


    The animal model is a powerful and fundamental tool in the field of biochemical research including toxicology, carcinogenesis, cancer therapeutics and prevention. In the carcinogenesis animal model system, numerous examples of preneoplastic lesions have been isolated and investigated from various perspectives. This may indicate that several options of endpoints to evaluate carcinogenesis effect or therapeutic outcome are presently available; however, classification of preneoplastic lesions has become complicated. For instance, these lesions include aberrant crypt foci (ACF), dysplastic ACF, flat ACF, β-catenin accumulated crypts, and mucin-depleted foci. These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments. Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions.

  2. Sport lesions caused by athletics practice

    Directory of Open Access Journals (Sweden)

    José Ernandes Feitoza


    Full Text Available Being a highly physical demanding sports, athletics depends on efficient training to overcome all physical demands without lesions. The aim of the present study was to analyze the types of lesions and their causes. The sample was constituted by forty-three athletes, sixteen males and twenty-seven females, 23.2 years of average age. A questionnaire containing five open questions and five closed questions was used as an instrument to determine the major lesions caused by athletics practice. The results showed that 84% of the athletes had already had some kind of lesions: 77% of which occurred during training and 23% during contest. The most frequent lesions were distension, tendinitis, twisting, contraction and inflammation. Legs were the most affected parts: 85% for jumpers, 85% for runners and 60% for throwers. When the lesions occurred, 76% of the jumpers, 84% of the runners and 85% of the throwers had no other health problem, but 52.7% of the athletes were in a state of anxiety before the contest and 13.8% had difficulties in concentrating on the contest. As for treatment 55.5% went to see a physiotherapist, and 16.6% went to see the medical doctor and the physiotherapist. The consequences of the lesions for the athletes’ performance were the following: 75% missed important contest events and 70% missed training for several months while they recuperated from their lesions. The results led to the conclusion that the best means to prevent lesions is to use adequate sites and equipments, efficient and individualized training coached by qualified specialists.

  3. Neurovestibular Compensation following Ototoxic Lesion and Labyrinthectomy

    Directory of Open Access Journals (Sweden)

    Yazdanshenas, Hamed


    Full Text Available Introduction Unilateral labyrinthectomy and intra-tympanic gentamycin have been employed in the treatment of Ménière's disease, but the efficacy of these techniques has not been well established. Objective The objective of this study is to measure the time course of recovery from a unilateral labyrinthectomy either after ipsilateral topical treatment with gentamicin to the inner ear or without the previous insult. Methods Twenty-nine adult Mongolian gerbils were randomized into two experimental groups. Group 1 (n = 17 received a right ear gentamicin drug-induced lesion by unilateral labyrinthectomy (UL. Group 2 (n = 12 only received a right unilateral labyrinthectomy lesion. We measured the horizontal vestibulo-ocular responses in gerbils before and after the lesion. The gerbils received an angular acceleration stimulus and their eye movements were recorded. Results The gentamicin lesion resulted in a quicker recovery. Experimental groups underwent a similar time course of recovery. Statistical analysis showed no significant difference between the two groups. Both groups displayed adaptation to the lesion by day 21, but long-term compensation did not completely revert to the original pre-lesion state. Conclusions In a lesion requiring both static and dynamic compensation as in UL, the need for a static compensation may alter pre-existing compensation from a previous dynamic insult and require a new compensation. A previous lesion and adaptation is not preserved for a second lesion and the subject has to re-compensate. Therefore, surgical treatment in Meniere's disease such as UL can be considered without prior gentamicin treatment. Static and dynamic compensations do not appear to be as independent as previous studies have suggested.

  4. Direct Visualization of DNA Replication Dynamics in Zebrafish Cells. (United States)

    Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Tamaru, Yutaka; Ogata, Shin; Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi


    Spatiotemporal regulation of DNA replication in the S-phase nucleus has been extensively studied in mammalian cells because it is tightly coupled with the regulation of other nuclear processes such as transcription. However, little is known about the replication dynamics in nonmammalian cells. Here, we analyzed the DNA replication processes of zebrafish (Danio rerio) cells through the direct visualization of replicating DNA in the nucleus and on DNA fiber molecules isolated from the nucleus. We found that zebrafish chromosomal DNA at the nuclear interior was replicated first, followed by replication of DNA at the nuclear periphery, which is reminiscent of the spatiotemporal regulation of mammalian DNA replication. However, the relative duration of interior DNA replication in zebrafish cells was longer compared to mammalian cells, possibly reflecting zebrafish-specific genomic organization. The rate of replication fork progression and ori-to-ori distance measured by the DNA combing technique were ∼ 1.4 kb/min and 100 kb, respectively, which are comparable to those in mammalian cells. To our knowledge, this is a first report that measures replication dynamics in zebrafish cells.

  5. Tibial cortical lesions: A multimodality pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Tyler, P.A., E-mail: [Department of Radiology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore HA7 4LP (United Kingdom); Mohaghegh, P., E-mail: [Department of Radiology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore HA7 4LP (United Kingdom); Foley, J., E-mail: [Department of Radiology, Glasgow Royal Infirmary, 16 Alexandra Parade, Glasgow G31 2ES (United Kingdom); Isaac, A., E-mail: [Department of Radiology, King' s College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Zavareh, A., E-mail: [Department of Radiology, North Bristol NHS Trust, Frenchay, Bristol BS16 1LE (United Kingdom); Thorning, C., E-mail: [Department of Radiology, East Surrey Hospital, Canada Avenue, Redhill, Surrey RH1 5RH (United Kingdom); Kirwadi, A., E-mail: [Department of Radiology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL (United Kingdom); Pressney, I., E-mail: [Department of Radiology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore HA7 4LP (United Kingdom); Amary, F., E-mail: [Department of Histopathology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore HA7 4LP (United Kingdom); Rajeswaran, G., E-mail: [Department of Radiology, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH (United Kingdom)


    Highlights: • Multimodality imaging plays an important role in the investigation and diagnosis of shin pain. • We review the multimodality imaging findings of common cortically based tibial lesions. • We also describe the rarer pathologies of tibial cortical lesions. - Abstract: Shin pain is a common complaint, particularly in young and active patients, with a wide range of potential diagnoses and resulting implications. We review the natural history and multimodality imaging findings of the more common causes of cortically-based tibial lesions, as well as the rarer pathologies less frequently encountered in a general radiology department.

  6. Dorsal hippocampal lesions disrupt Pavlovian delay conditioning and conditioned-response timing. (United States)

    Tam, Shu K E; Bonardi, Charlotte


    The involvement of the rat dorsal hippocampus (dhpc) in Pavlovian conditioning and timing of conditioned responding was examined in an appetitive preparation in which presentation of a relatively long, 40-s auditory conditioned stimulus (CS) was followed immediately by food delivery. Dorsal hippocampal lesions impaired Pavlovian conditioning in this task. They also produced a deficit in interval timing, replicating previous findings with short CSs. The conditioning and timing deficits observed are consistent with the findings from single-unit recording studies in other species, and suggest that the involvement of the dhpc in Pavlovian processes could be more general than is assumed by many of the current theories of hippocampal function.

  7. Security in a Replicated Metadata Catalogue

    CERN Document Server

    Koblitz, B


    The gLite-AMGA metadata has been developed by NA4 to provide simple relational metadata access for the EGEE user community. As advanced features, which will be the focus of this presentation, AMGA provides very fine-grained security also in connection with the built-in support for replication and federation of metadata. AMGA is extensively used by the biomedical community to store medical images metadata, digital libraries, in HEP for logging and bookkeeping data and in the climate community. The biomedical community intends to deploy a distributed metadata system for medical images consisting of various sites, which range from hospitals to computing centres. Only safe sharing of the highly sensitive metadata as provided in AMGA makes such a scenario possible. Other scenarios are digital libraries, which federate copyright protected (meta-) data into a common catalogue. The biomedical and digital libraries have been deployed using a centralized structure already for some time. They now intend to decentralize ...

  8. Entanglement Swapping Model of DNA Replication

    CERN Document Server

    Pusuluk, Onur


    Molecular biology explains function of molecules by their geometric and electronic structures which are mainly determined by utilization of quantum effects in chemistry. However, further quantum effects are not thought to play any significant role in the essential processes of life. On the contrary, consideration of quantum circuits/protocols and organic molecules as software and hardware of living systems that are co-optimized during evolution, may be useful to pass over the difficulties raised by biochemical complexity and to understand the physics of life. In this sense, we model DNA replication with a reliable qubit representation of the nucleotides: 1) molecular recognition of a nucleotide is assumed to trigger an intrabase entanglement corresponding to a superposition of different tautomer forms and 2) pairing of complementary nucleotides is described by swapping intrabase entanglements with interbase entanglements. We examine possible realizations of quantum circuits/protocols to be used to obtain intr...

  9. Replicator dynamics for optional public good games

    DEFF Research Database (Denmark)

    Hauert, C.; De Monte, Silvia; Hofbauer, J.;


    The public goods game represents a straightforward generalization of the prisoner's dilemma to an arbitrary number of players. Since the dominant strategy is to defect, both classical and evolutionary game theory predict the asocial outcome that no player contributes to the public goods....... In contrast to the compulsory public goods game, optional participation provides a natural way to avoid deadlocks in the state of mutual defection. The three resulting strategies-collaboration or defection in the public goods game, as well as not joining at all-are studied by means of a replicator dynamics...... participation makes cooperation feasible. But for each strategy, the average payoff value remains equal to the earnings of those not participating in the public goods game....

  10. Self-replicating alphavirus RNA vaccines. (United States)

    Ljungberg, Karl; Liljeström, Peter


    Recombinant nucleic acids are considered as promising next-generation vaccines. These vaccines express the native antigen upon delivery into tissue, thus mimicking live attenuated vaccines without having the risk of reversion to pathogenicity. They also stimulate the innate immune system, thus potentiating responses. Nucleic acid vaccines are easy to produce at reasonable cost and are stable. During the past years, focus has been on the use of plasmid DNA for vaccination. Now mRNA and replicon vaccines have come into focus as promising technology platforms for vaccine development. This review discusses self-replicating RNA vaccines developed from alphavirus expression vectors. These replicon vaccines can be delivered as RNA, DNA or as recombinant virus particles. All three platforms have been pre-clinically evaluated as vaccines against a number of infectious diseases and cancer. Results have been very encouraging and propelled the first human clinical trials, the results of which have been promising.

  11. Suggestibility and negative priming: two replication studies. (United States)

    David, Daniel; Brown, Richard J


    Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

  12. Dynamic combinatorial self-replicating systems. (United States)

    Moulin, Emilie; Giuseppone, Nicolas


    Thanks to their intrinsic network topologies, dynamic combinatorial libraries (DCLs) represent new tools for investigating fundamental aspects related to self-organization and adaptation processes. Very recently the first examples integrating self-replication features within DCLs have pushed even further the idea of implementing dynamic combinatorial chemistry (DCC) towards minimal systems capable of self-construction and/or evolution. Indeed, feedback loop processes - in particular in the form of autocatalytic reactions - are keystones to build dynamic supersystems which could possibly approach the roots of "Darwinian" evolvability at mesoscale. This topic of current interest also shows significant potentialities beyond its fundamental character, because truly smart and autonomous materials for the future will have to respond to changes of their environment by selecting and by exponentially amplifying their fittest constituents.

  13. Star Trek replicators and diatom nanotechnology. (United States)

    Drum, Ryan W; Gordon, Richard


    Diatoms are single celled algae, the 10(5)-10(6) species of which create a wide variety of three-dimensional amorphous silica shells. If we could get them to produce useful structures, perhaps by compustat selection experiments (i.e. forced evolution of development or evodevo), their exponential growth in suspension cultures could compete with the lithography techniques of present day nanotechnology, which have limited 3D capabilities. Alternatively, their fine detail could be used for templates for MEMS (micro electro mechanical systems), or their silica deposition systems isolated for guiding silica deposition. A recent paper has demonstrated that silica can be replaced atom for atom without change of shape--a step towards the Star Trek replicator.

  14. Replication Regulates Volume Weighting in Quantum Cosmology

    CERN Document Server

    Hartle, James


    Probabilities for observations in cosmology are conditioned both on the universe's quantum state and on local data specifying the observational situation. We show the quantum state defines a measure for prediction through such conditional probabilities that is well behaved for spatially large or infinite universes when the probabilities that our data is replicated are taken into account. In histories where our data are rare volume weighting connects top-down probabilities conditioned on both the data and the quantum state to the bottom-up probabilities conditioned on the quantum state alone. We apply these principles to a calculation of the number of inflationary e-folds in a homogeneous, isotropic minisuperspace model with a single scalar field moving in a quadratic potential. We find that volume weighting is justified and the top-down probabilities favor a large number of e-folds.

  15. [Telomerase activity in esophageal carcinoma and lesions unstained with Lugol's solution]. (United States)

    Yoneyama, K; Aoyama, N; Koizumi, H; Tamai, S


    Telomerase is a specific enzyme required for the replication of telomeres. Its activity is detected in almost human cancers. We examined in esophageal carcinoma and lesions unstained with Lugol's solution telomerase activity by using telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was detected in all 22 esophageal carcinomas, regardless of histopathological findings. In unstained lesions, telomerase activity was detected in 15 of 22; 10 squamous cell carcinomas, four dysplasia, one regenerative epithelium, no telomerase activity was found in seven; four normal esophageal epithelia, two Barrett's esophagi, one regenerative epithelium. These results suggest that telomerase activity may be a useful molecular marker for the diagnosis of esophageal carcinoma and of the early esophageal carcinoma in area unstained with Lugol's solution.

  16. Dengue virus binding and replication by platelets. (United States)

    Simon, Ayo Y; Sutherland, Michael R; Pryzdial, Edward L G


    Dengue virus (DENV) infection causes ∼200 million cases of severe flulike illness annually, escalating to life-threatening hemorrhagic fever or shock syndrome in ∼500,000. Although thrombocytopenia is typical of both mild and severe diseases, the mechanism triggering platelet reduction is incompletely understood. As a probable initiating event, direct purified DENV-platelet binding was followed in the current study by quantitative reverse transcription-polymerase chain reaction and confirmed antigenically. Approximately 800 viruses specifically bound per platelet at 37°C. Fewer sites were observed at 25°C, the blood bank storage temperature (∼350 sites), or 4°C, known to attenuate virus cell entry (∼200 sites). Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and heparan sulfate proteoglycan were implicated as coreceptors because only the combination of anti-DC-SIGN and low-molecular-weight heparin prevented binding. Interestingly, at 37°C and 25°C, platelets replicated the positive sense single-stranded RNA genome of DENV by up to ∼4-fold over 7 days. Further time course experiments demonstrated production of viral NS1 protein, which is known to be highly antigenic in patient serum. The infectivity of DENV intrinsically decayed in vitro, which was moderated by platelet-mediated generation of viable progeny. This was shown using a transcription inhibitor and confirmed by freeze-denatured platelets being incapable of replicating the DENV genome. For the first time, these data demonstrate that platelets directly bind DENV saturably and produce infectious virus. Thus, expression of antigen encoded by DENV is a novel consideration in the pathogen-induced thrombocytopenia mechanism. These results furthermore draw attention to the possibility that platelets may produce permissive RNA viruses in addition to DENV.

  17. Natural course of keratoacanthoma and related lesions after partial biopsy: clinical analysis of 66 lesions. (United States)

    Takai, Toshihiro; Misago, Noriyuki; Murata, Yozo


    There is some confusion regarding the classification of keratoacanthoma (KA) and related lesions that have crateriform architecture. We examined the clinical courses of 66 KA lesions and related lesions after a partial biopsy to clarify the nosological concept of KA. We histopathologically classified these lesions into five types: (i) KA at various stages (53 lesions); (ii) KA-like squamous cell carcinoma (SCC) (3 lesions); (iii) KA with malignant transformation (3 lesions); (iv) infundibular SCC (5 lesions); and (v) crateriform SCC arising from solar keratosis (2 lesions). We analyzed the clinical course in each group. The regression rate of KA was 98.1% and that of KA-like SCC/KA with malignant transformation was 33.3%. No regression was observed in either infundibular SCC or crateriform SCC arising from solar keratosis. Thus, KA is a distinct entity that should be distinguished from other types of SCC with crateriform architecture based on the high frequency of regression. The regression rate of 33.3% in KA-like SCC/KA with malignant transformation indicated that KA lesions with an SCC component still have the potential for regression. However, this result also indicated that KA is biologically unstable, and some KA tend to evolve into conventional SCC with a gradual loss of the capacity for the spontaneous regression. Infundibular SCC and crateriform SCC arising from solar keratosis are fundamentally different from KA, not only according to the histopathological findings but also based on the biological properties.

  18. Influence of SLAP lesions on chondral lesions of the glenohumeral joint. (United States)

    Patzer, Thilo; Lichtenberg, Sven; Kircher, Jörn; Magosch, Petra; Habermeyer, Peter


    From 2004 to 2008 we evaluated 431 SLAP lesions during 3,395 shoulder arthroscopies and compared two groups of patients, one with SLAP lesion as group I and one without SLAP lesions as group II. Exclusion of type I SLAP lesions, rotator cuff tears and history of dislocation of the shoulder in both groups left 182 cases in group I, and additionally, exclusion of all-type SLAP lesions left 251 patients in group II. In group I, SLAP lesion-associated chondral lesions were present in 20% at the humerus (4% group II, p = 0.005), 18% at the glenoid (5% in group II, p = 0.05) and 14% glenohumeral (3% group II, p = 0.04). We observed a pattern of typical localization of SLAP-associated chondral lesions at the humerus underneath the biceps tendon (78%) and at the anterior half of the glenoid (63%) in group I in contrast to the central region of the humerus (82%) and the central region at the glenoid (55%) in group II. The association of SLAP and chondral lesions was not influenced by the presence of trauma or age of the patients. SLAP lesions seem to be a risk factor for subsequent early onset of osteoarthritis either caused by a bicipital chondral print or glenohumeral instability or a combination of both.

  19. Causation and the origin of life. Metabolism or replication first? (United States)

    Pross, Addy


    The conceptual gulf that separates the 'metabolism first' and 'replication first' mechanisms for the emergence of life continues to cloud the origin of life debate. In the present paper we analyze this aspect of the origin of life problem and offer arguments in favor of the 'replication first' school. Utilizing Wicken's two-tier approach to causation we argue that a causal connection between replication and metabolism can only be demonstrated if replication would have preceded metabolism. In conjunction with existing empirical evidence and theoretical reasoning, our analysis concludes that there is no substantive evidence for a 'metabolism first' mechanism for life's emergence, while a coherent case can be made for the 'replication first' group of mechanisms. The analysis reaffirms our conviction that life is an extreme expression of kinetic control, and that the emergence of metabolic pathways can be understood by considering life as a manifestation of 'replicative chemistry'.

  20. Replication of Avocado Sunblotch Viroid in the Yeast Saccharomyces cerevisiae▿ (United States)

    Delan-Forino, Clémentine; Maurel, Marie-Christine; Torchet, Claire


    Viroids are the smallest known pathogenic agents. They are noncoding, single-stranded, closed-circular, “naked” RNAs, which replicate through RNA-RNA transcription. Viroids of the Avsunviroidae family possess a hammerhead ribozyme in their sequence, allowing self-cleavage during their replication. To date, viroids have only been detected in plant cells. Here, we investigate the replication of Avocado sunblotch viroid (ASBVd) of the Avsunviroidae family in a nonconventional host, the yeast Saccharomyces cerevisiae. We demonstrate that ASBVd RNA strands of both polarities are able to self-cleave and to replicate in a unicellular eukaryote cell. We show that the viroid monomeric RNA is destabilized by the nuclear 3′ and the cytoplasmic 5′ RNA degradation pathways. For the first time, our results provide evidence that viroids can replicate in other organisms than plants and that yeast contains all of the essential cellular elements for the replication of ASBVd. PMID:21270165

  1. An optimal replication strategy for data grid systems

    Institute of Scientific and Technical Information of China (English)

    JIANG Jianjin; YANG Guangwen


    Data access latency is an important metric of system performance in data grid.By means of efficient replication strategy,the amount of data transferred in a wide area network will decrease,and the average access latency of data will decrease ultimately.The motivation of our research is to solve the optimized replica distribution problem in a data grid;that is,the system should utilize many replicas for every data with storage constraints to minimize the average access latency of data.This paper proposes a model of replication strategy in federated data grid and gives the optimized solution.The analysis results and simulation results show that the optimized replication strategy proposed in this paper is superior to LRU caching strategy,uniform replication strategy,proportional replication strategy and square root replication strategy in terms of wide area network bandwidth requirement and in the average access latency of data.

  2. Approximate Lesion Localization in Dermoscopy Images

    CERN Document Server

    Celebi, M Emre; Schaefer, Gerald; Stoecker, William V; 10.1111/j.1600-0846.2009.00357.x


    Background: Dermoscopy is one of the major imaging modalities used in the diagnosis of melanoma and other pigmented skin lesions. Due to the difficulty and subjectivity of human interpretation, automated analysis of dermoscopy images has become an important research area. Border detection is often the first step in this analysis. Methods: In this article, we present an approximate lesion localization method that serves as a preprocessing step for detecting borders in dermoscopy images. In this method, first the black frame around the image is removed using an iterative algorithm. The approximate location of the lesion is then determined using an ensemble of thresholding algorithms. Results: The method is tested on a set of 428 dermoscopy images. The localization error is quantified by a metric that uses dermatologist determined borders as the ground truth. Conclusion: The results demonstrate that the method presented here achieves both fast and accurate localization of lesions in dermoscopy images.

  3. Post-mortal lesions in freshwater environment. (United States)

    Vanin, Stefano; Zancaner, Silvano


    Postmortem animal feeding activity may cause considerable damage to bodies resulting in the modification of wounds, loss of identifying features and injury. Certain postmortem lesions may appear inflicted or non-inflicted antemortem injuries. At present, apart from cases in sea water, no data are available about post mortal lesions performed by aquatic organisms. This note that represents the first report concerning colonisation of a dead body by crustaceans a few hours after death, describes injuries caused by the amphipod Niphargus elegans on the face, and in particular on the eye region, of a young man dead by drowning. The lesions recorded in this case are comparable with the lesions caused by ants. The high plasticity in the food choice can allow Amphipoda to colonise drowning bodies in every moment after dead, however the benthonic behaviour of these animals suggests a more important role in the colonisation during post-mortem submersion periods.


    Directory of Open Access Journals (Sweden)

    E. E. Achkasov


    Full Text Available The authors analyzed scientific literature in respect of various issues in treatment of athletes with peroneal muscles lesions starting from 1987 till 2016. Key search and publications selection was made in PubMed and russian national electronic scientific library eLIBRARY. Peroneal tendons pathology is not the major but the underestimated cause of pain in lateral and hindfoot as well as of foot dysfunction which is difficult to distinguish from lesions of lateral ligaments of the ankle joint. Untreated lesions of peroneal tendons can result in chronic ankle pain and significant functional disorders. The purpose of the present paper is to improve the current comprehension of anatomy, to identify factors contributing to pathology, to perform diagnostic evaluation of peroneal tendons and to review current treatment options of such lesions.

  5. [Traumatic and iatrogenic lesions of abdominal vessels]. (United States)

    Farah, I; Tarabula, P; Voirin, L; Magne, J L; Delannoy, P; Gattaz, F; Guidicelli, H


    Gravity of abdominal vessels traumatisms is secondary to multiple factors. It depends on the type of injured vessels, aetiology and associated lesions. Between September 1984 and March 1995, 22 abdominal vessel traumatisms in 16 patients (mean age: 39 years) were treated. At surgical exploration, 4 aortic and 2 renal vein lesions, 7 iliac artery and 3 renal artery contusions, 2 superior mesenteric artery dissections; 3 infra-renal vena cava ruptures and 1 superior mesenteric vein dilaceration were found. All lesions were caused by penetrant wounds secondary to firearm or blade injury or secondary to injuries due to ski or traffic accidents. In 5 cases, lesions were iatrogenic. There was no mortality in the post-operative period, 14 patients out of the 16 patients operated on have been followed during a period from 1 to 120 months.

  6. Keloidal granuloma faciale with extrafacial lesions

    Directory of Open Access Journals (Sweden)

    Verma Rajesh


    Full Text Available Granuloma faciale (GF is a rare cutaneous disorder characterized by one to several soft, erythematous to livid papules, plaques or nodules, usually occurring on the face. Extrafacial lesions are uncommon. A 52-year-old lady with multiple asymptomatic, variously sized brownish-black colored, firm, sharply circumscribed plaques resembling keloids on both cheeks and extrafacial lesions on the right arm and the right breast is presented for its unusual keloidal appearance and typical histopathological findings. She failed to respond to oral dapsone 100 mg daily administered for 3 months. Local infiltration of triamcinolone combined with cryotherapy led to only partial flattening of the lesions. All the skin lesions were excised surgically followed by flap transfer grafting on both cheeks. The cosmetic outcome was highly satisfactory.

  7. Self-inflicted lesions in dermatology

    DEFF Research Database (Denmark)

    Gieler, Uwe; Consoli, Sylvie G; Tomás-Aragones, Lucía;


    The terminology, classification, diagnosis and treatment of self-inflicted dermatological lesions are subjects of open debate. The present study is the result of various meetings of a task force of dermatologists, psychiatrists and psychologists, all active in the field of psychodermatology, aimed...... at clarifying the terminology related to these disorders. A flow chart and glossary of terms and definitions are presented to facilitate the classification and management of self-inflicted skin lesions. Several terms are critically discussed, including: malingering; factitious disorders; Münchausen's syndrome...... excoriations. Self-inflicted skin lesions are often correlated with mental disorders and/or patho-logical behaviours, thus it is important for dermatologists to become as familiar as possible with the psychiatric and psychological aspects underlying these lesions....

  8. Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome. (United States)

    Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Chen, Chun-Long; Arneodo, Alain; Goldar, Arach; d'Aubenton-Carafa, Yves; Thermes, Claude; Audit, Benjamin; Hyrien, Olivier


    Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general

  9. Detection of Helicobacter pylori in Oral Lesions


    Irani, Soussan; Monsef Esfahani, Alireza; Bidari Zerehpoush, Farahnaz


    Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC) and primary lymphoma. Materials and methods. A total of 228 bio...

  10. Elementary lesions in dermatological semiology: literature review* (United States)

    Cardili, Renata Nahas; Roselino, Ana Maria


    Discrepancies in the terminology of elementary lesions persist when texts from Dermatology and Semiology books are compared, which can cause some confusion in both the teaching of undergraduate medical students and the learning acquired by professionals in the field. This review aims to compare and clarify the differences in the description of elementary lesions by many authors, used as references for specialists in dermatology. PMID:27828637

  11. Puncture of thoracic lesions under sonographic guidance.


    Afschrift, M; Nachtegaele, P; Voet, D; Noens, L.; Van Hove, W; Van der Straeten, M; Verdonk, G


    Thirty-six punctures of thoracic lesions have been performed with a compound B-scanner or a real-time linear-array scanner for guidance. Twenty-three fluid collections were punctured and aspiration biopsies were performed on 13 echogenic lesions. All the punctures were successful at the first attempt. No complications occurred. The results confirm the usefulness of sonography for guiding punctures of thoracic fluid effusions and solid masses. Usually a static B-scanner is sufficient, but when...

  12. Lesions in the external auditory canal

    Directory of Open Access Journals (Sweden)

    Priyank S Chatra


    Full Text Available The external auditory canal is an S- shaped osseo-cartilaginous structure that extends from the auricle to the tympanic membrane. Congenital, inflammatory, neoplastic, and traumatic lesions can affect the EAC. High-resolution CT is well suited for the evaluation of the temporal bone, which has a complex anatomy with multiple small structures. In this study, we describe the various lesions affecting the EAC.

  13. Isolated plexiform neurofibroma mimicking a vascular lesion* (United States)

    Stefano, Paola Cecilia; Apa, Sebastian Nicolas; Lanoël, Agustina Maria; María, Josefina Sala; Sierre, Sergio; Pierini, Adrián Martin


    Plexiform neurofibromas are benign tumors originating from peripheral nerve sheaths, generally associated with Neurofibromatosis Type 1 (NF1). They are diffuse, painful and sometimes locally invasive, generating cosmetic problems. This report discusses an adolescent patient who presented with an isolated, giant plexiform neurofibroma on her leg that was confused with a vascular lesion due to its clinical aspects. Once the diagnosis was confirmed by surgical biopsy, excision of the lesion was performed with improvement of the symptoms. PMID:27192529

  14. Bone marrow lesions: A systematic diagnostic approach

    Directory of Open Access Journals (Sweden)

    Filippo Del Grande


    Full Text Available Bone marrow lesions on magnetic resonance (MR imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI, to achieve accurate final diagnosis has been highlighted.

  15. Acute hepatic encephalopathy with diffuse cortical lesions

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)


    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  16. Liver lesions in hepatitis B viral infection.


    Desmet, V J


    A review is made of the various histological lesions observed in hepatitis B virus-related liver diseases, including different forms of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The elementary lesions discussed include acidophil necrosis (apoptosis), confluent lytic necrosis in its different patterns, piecemeal necrosis, focal necrosis, and dysplastic hepatocytes. Their pathogenesis is explained in the framework of recent developments in the immunopathology of hepa...

  17. Supraorbital eyebrow approach to skull base lesions

    Directory of Open Access Journals (Sweden)

    Fernandes Yvens Barbosa


    Full Text Available We report our experience with a supraorbital eyebrow minicraniotomy. This technique is suitable to lesions situated in the region of the anterior fossa, suprasellar cisterns, parasellar region and Sylvian fissure. A 50 mm incision in the eyebrow and a supraorbital minicraniotomy is performed. Sixteem patients harboring different lesions were operated on with good postoperative and cosmetic results. We conclude that this approach is safe and useful in selected cases.

  18. SLAP lesions in the overhead athlete. (United States)

    Rokito, Steven E; Myers, Kevin R; Ryu, Richard K N


    The diagnosis and management of SLAP lesions in the overhead athlete remains a challenge for the sports medicine specialist due to variable anatomy, changes with aging, concomitant pathology, lack of dependable physical findings on examination, and lack of sensitivity and specificity with imaging studies. This article presents a comprehensive review of the epidemiology, relevant anatomy, proposed pathogenesis, diagnostic approach, and outcomes of nonoperative and operative management of SLAP lesions in the overhead athlete.

  19. Epigenetic control of DNA replication dynamics in mammals


    Casas Delucchi, Corella Susana


    One of the most critically important processes in any living organism, essential for development and reproduction, is that of the accurate replication of its genome before each cell division. The process of DNA replication can take place millions of times in a single organism and any mistake, if left unrepaired, is potentially transmitted into the next generation. Errors during replication can result in genetic mutations or karyotype aberrations, both of which can lead to disease or death. ...

  20. Texture feature based liver lesion classification (United States)

    Doron, Yeela; Mayer-Wolf, Nitzan; Diamant, Idit; Greenspan, Hayit


    Liver lesion classification is a difficult clinical task. Computerized analysis can support clinical workflow by enabling more objective and reproducible evaluation. In this paper, we evaluate the contribution of several types of texture features for a computer-aided diagnostic (CAD) system which automatically classifies liver lesions from CT images. Based on the assumption that liver lesions of various classes differ in their texture characteristics, a variety of texture features were examined as lesion descriptors. Although texture features are often used for this task, there is currently a lack of detailed research focusing on the comparison across different texture features, or their combinations, on a given dataset. In this work we investigated the performance of Gray Level Co-occurrence Matrix (GLCM), Local Binary Patterns (LBP), Gabor, gray level intensity values and Gabor-based LBP (GLBP), where the features are obtained from a given lesion`s region of interest (ROI). For the classification module, SVM and KNN classifiers were examined. Using a single type of texture feature, best result of 91% accuracy, was obtained with Gabor filtering and SVM classification. Combination of Gabor, LBP and Intensity features improved the results to a final accuracy of 97%.

  1. Lesion load in unprotected carotid artery stenting

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.Q.; Papanagiotou, P.; Roth, C.; Karp, K.; Krick, C.; Schieber, H.; Mueller, M.; Reith, W. [University of the Saarland, Department for Diagnostic and Interventional Neuroradiology, Homburg (Germany); Fassbender, K.; Haass, A. [University of the Saarland, Division of Neurology, Homburg (Germany)


    The purpose of the study was to determine the incidence of new ischemic lesions found on diffusion-weighted MR imaging (DWI) in nonselected patients after unprotected carotid artery stent placement. We retrospectively reviewed a nonrandomized cohort of 197 patients presenting with carotid occlusive disease who underwent unprotected carotid artery stent placement between 2003 and 2006. Mean degree of stenosis was 86.94% {+-} 9.72. In all patients, DWI was obtained before and 24 h after stent placement. New lesions were evaluated according to size and location. In 59 of 197 patients (29.9%), new ischemic lesions were found on DWI in the vessel dependent area. In 23 of 197 patients (11.7%), new ischemic lesions were found in the vessel independent area. Combined stroke/death rate was 3.63%. In our series of unprotected carotid angioplasty with stent, we found new DWI lesions in 34% of the patients. Further studies should now show in how far protection devices can reduce these lesions. (orig.)

  2. Bacillus subtilis strain deficient for the protein-tyrosine kinase PtkA exhibits impaired DNA replication

    DEFF Research Database (Denmark)

    Petranovic, Dina; Michelsen, Ole; Zahradka, K;


    in this study. We were unable to identify any striking phenotypes related to control of UDP-glucose dehydrogenases, natural competence and DNA lesion repair; however, a very strong phenotype of ΔptkA emerged with respect to DNA replication and cell cycle control, as revealed by flow cytometry and fluorescent...... microscopy. B. subtilis cells lacking the kinase PtkA accumulated extra chromosome equivalents, exhibited aberrant initiation mass for DNA replication and an unusually long D period.......A/PtpZ was previously shown to regulate the phosphorylation state of UDP-glucose dehydrogenases and single-stranded DNA-binding proteins. This promiscuity towards substrates is reminiscent of eukaryal kinases and has prompted us to investigate possible physiological effects of ptkA and ptpZ gene inactivations...

  3. Role of Fanconi Anemia FANCG in Preventing Double-Strand Breakage and Chromosomal Rearrangement during DNA Replication

    Energy Technology Data Exchange (ETDEWEB)

    Tebbs, R S; Hinz, J M; Yamada, N A; Wilson, J B; Jones, N J; Salazar, E P; Thomas, C B; Jones, I M; Thompson, L H


    The Fanconi anemia (FA) proteins overlap with those of homologous recombination through FANCD1/BRCA2, but the biochemical functions of other FA proteins are unknown. By constructing and characterizing a null fancg mutant of hamster CHO cells, we present several new insights for FA. The fancg cells show a broad sensitivity to genotoxic agents, not supporting the conventional concept of sensitivity to only DNA crosslinking agents. The aprt mutation rate is normal, but hprt mutations are reduced, which we ascribe to the lethality of large deletions. CAD and dhfr gene amplification rates are increased, implying excess chromosomal breakage during DNA replication, and suggesting amplification as a contributing factor to cancer-proneness in FA patients. In S-phase cells, both spontaneous and mutagen-induced Rad51 nuclear foci are elevated. These results support a model in which FancG protein helps to prevent collapse of replication forks by allowing translesion synthesis or lesion bypass through homologous recombination.

  4. Multifork chromosome replication in slow-growing bacteria (United States)

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


    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

  5. FBH1 Catalyzes Regression of Stalled Replication Forks

    DEFF Research Database (Denmark)

    Fugger, Kasper; Mistrik, Martin; Neelsen, Kai J;


    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...... a model whereby FBH1 promotes early checkpoint signaling by remodeling of stalled DNA replication forks....... 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...

  6. An antioxidant resveratrol significantly enhanced replication of hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    Mitsuyasu; Nakamura; Masanori; Ikeda; Ryota; Hokari; Nobuyuki; Kato; Toshifumi; Hibi; Soichiro; Miura


    AIM:To elucidate the effect of antioxidants,resveratrol (RVT)and astaxanthin(AXN),on hepatitis C virus(HCV) replication. METHODS:We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6.RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses.AXN is also a strong antioxidant.The replication of HCV RNA was assessed by the luciferase reporter assay.An additive effect of antioxidants on antiviral effects of inter...

  7. Common Chemical Inductors of Replication Stress:  Focus on Cell‐Based Studies

    Directory of Open Access Journals (Sweden)

    Eva Vesela


    Full Text Available DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS. Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research. These compounds act on replication by direct interaction with DNA causing DNA crosslinks and bulky lesions (cisplatin, chemical interference with the metabolism of deoxyribonucleotide triphosphates (hydroxyurea, direct inhibition of the activity of replicative DNA polymerases (aphidicolin and interference with enzymes dealing with topological DNA stress (camptothecin, etoposide. As a variety of mechanisms can induce RS, the responses of mammalian cells also vary. Here, we review the activity and mechanism of action of these compounds based on recent knowledge, accompanied by examples of induced phenotypes, cellular readouts and commonly used doses.

  8. Detection of low-contrast lesions in computed body tomography: an experimental study of simulated lesions. (United States)

    Meaney, T F; Raudkivi, U; McIntyre, W J; Gallagher, J H; Haaga, J R; Havrilla, T R; Reich, N E


    Observer accuracy in the identification of low-contrast objects in computed tomography (CT) was studied. Thresholds were established for detection of lesions of various sizes and attenuation differences in CT images produced at different radiation doses. Noise reduction was important in identifying certain types of lesions. Detection was not accurate when the standard deviation of the mean of an organ exceeded the difference in the means of the lesion and the surround region.

  9. Efficacy of rHuIFN-alpha2b and rFeIFN-omega on Feline Herpesvirus-1 Replication in vitro


    Siebeck, Nicola


    Feline herpesvirus-1 (FHV-1)-infection, also known as feline viral rhinotracheitis (FVR) is distributed world wide in the cat population, with a high incidence in colony cats (>70%). FHV-1 typically infects and replicates in epithelial tissue of the upper respiratory tract and conjunctiva causing cytopathic lesions. The virus is recognized as one of the most important pathogens of feline upper respiratory tract infections, conjunctivitis and keratitis in cats. Following primary infection over...

  10. The Cell Cycle Timing of Human Papillomavirus DNA Replication. (United States)

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


    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.

  11. Autophagy facilitates Salmonella replication in HeLa cells. (United States)

    Yu, Hong B; Croxen, Matthew A; Marchiando, Amanda M; Ferreira, Rosana B R; Cadwell, Ken; Foster, Leonard J; Finlay, B Brett


    Autophagy is a process whereby a double-membrane structure (autophagosome) engulfs unnecessary cytosolic proteins, organelles, and invading pathogens and delivers them to the lysosome for degradation. We examined the fate of cytosolic Salmonella targeted by autophagy and found that autophagy-targeted Salmonella present in the cytosol of HeLa cells correlates with intracellular bacterial replication. Real-time analyses revealed that a subset of cytosolic Salmonella extensively associates with autophagy components p62 and/or LC3 and replicates quickly, whereas intravacuolar Salmonella shows no or very limited association with p62 or LC3 and replicates much more slowly. Replication of cytosolic Salmonella in HeLa cells is significantly decreased when autophagy components are depleted. Eventually, hyperreplication of cytosolic Salmonella potentiates cell detachment, facilitating the dissemination of Salmonella to neighboring cells. We propose that Salmonella benefits from autophagy for its cytosolic replication in HeLa cells. IMPORTANCE As a host defense system, autophagy is known to target a population of Salmonella for degradation and hence restricting Salmonella replication. In contrast to this concept, a recent report showed that knockdown of Rab1, a GTPase required for autophagy of Salmonella, decreases Salmonella replication in HeLa cells. Here, we have reexamined the fate of Salmonella targeted by autophagy by various cell biology-based assays. We found that the association of autophagy components with cytosolic Salmonella increases shortly after initiation of intracellular bacterial replication. Furthermore, through a live-cell imaging method, a subset of cytosolic Salmonella was found to be extensively associated with autophagy components p62 and/or LC3, and they replicated quickly. Most importantly, depletion of autophagy components significantly reduced the replication of cytosolic Salmonella in HeLa cells. Hence, in contrast to previous reports, we propose

  12. Replicator-dynamics models of sexual conflict. (United States)

    Kimura, Mariko; Ihara, Yasuo


    Evolutionary conflict between the sexes has been studied in various taxa and in various contexts. When the sexes are in conflict over mating rates, natural selection favors both males that induce higher mating rates and females that are more successful at resisting mating attempts. Such sexual conflict may result in an escalating coevolutionary arms race between males and females. In this article, we develop simple replicator-dynamics models of sexual conflict in order to investigate its evolutionary dynamics. Two specific models of the dependence of a female's fitness on her number of matings are considered: in model 1, female fitness decreases linearly with increasing number of matings and in model 2, there is an optimal number of matings that maximizes female fitness. For each of these models, we obtain the conditions for a coevolutionary process to establish costly male and female traits and examine under what circumstances polymorphism is maintained at equilibrium. Then we discuss how assumptions in previous models of sexual conflict are translated to fit to our model framework and compare our results with those of the previous studies. The simplicity of our models allows us to consider sexual conflict in various contexts within a single framework. In addition, we find that our model 2 shows more complicated evolutionary dynamics than model 1. In particular, the population exhibits bistability, where the evolutionary outcome depends on the initial state, only in model 2.

  13. Factor Copula Models for Replicated Spatial Data

    KAUST Repository

    Krupskii, Pavel


    We propose a new copula model that can be used with replicated spatial data. Unlike the multivariate normal copula, the proposed copula is based on the assumption that a common factor exists and affects the joint dependence of all measurements of the process. Moreover, the proposed copula can model tail dependence and tail asymmetry. The model is parameterized in terms of a covariance function that may be chosen from the many models proposed in the literature, such as the Matérn model. For some choice of common factors, the joint copula density is given in closed form and therefore likelihood estimation is very fast. In the general case, one-dimensional numerical integration is needed to calculate the likelihood, but estimation is still reasonably fast even with large data sets. We use simulation studies to show the wide range of dependence structures that can be generated by the proposed model with different choices of common factors. We apply the proposed model to spatial temperature data and compare its performance with some popular geostatistics models.

  14. Energy Proportionality for Disk Storage Using Replication

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinoh; Rotem, Doron


    Energy saving has become a crucial concern in datacenters as several reports predict that the anticipated energy costs over a three year period will exceed hardware acquisition. In particular, saving energy for storage is of major importance as storage devices (and cooling them off) may contribute over 25 percent of the total energy consumed in a datacenter. Recent work introduced the concept of energy proportionality and argued that it is a more relevant metric than just energy saving as it takes into account the tradeoff between energy consumption and performance. In this paper, we present a novel approach, called FREP (Fractional Replication for Energy Proportionality), for energy management in large datacenters. FREP includes areplication strategy and basic functions to enable flexible energy management. Specifically, our method provides performance guarantees by adaptively controlling the power states of a group of disks based on observed and predicted workloads. Our experiments, using a set of real and synthetic traces, show that FREP dramatically reduces energy requirements with a minimal response time penalty.

  15. An Inadvertent Concurrent Replication: Same Roadmap, Different Journey (United States)

    Lemons, Christopher J.; King, Seth A.; Davidson, Kimberly A.; Berryessa, Teresa L.; Gajjar, Shimul A.; Sacks, Lia H.


    Replication is a critical aspect of scientific inquiry that presents a variety of challenges to researchers, even under the best of conditions. We conducted a review of replication rates in special education journals similar to the review conducted by Makel et al. in this issue. Unknowingly conducting independent reviews allowed for an unexpected…

  16. Regulation of replication fork progression through histone supply and demand

    DEFF Research Database (Denmark)

    Groth, Anja; Corpet, Armelle; Cook, Adam J L;


    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...

  17. Predicting Psychiatric Rehabilitation Outcome Using Demographic Characteristics: A Replication (United States)

    Anthony, William A.; Buell, Gregory J.


    Replication was undertaken of a recent study conducted by Buell and Anthony which had found that recidivism and posthospital employment could be predicted by a single demographic variable, number of previous hospitalizations and employment history, respectively. Results of the replication were consistent for posthospital employment but not for…

  18. Perfectionism in Gifted Adolescents: A Replication and Extension (United States)

    Margot, Kelly C.; Rinn, Anne N.


    To provide further generalizability for the results garnered by two previous studies, the authors conducted a methodological replication. In addition to adding to the body of replication research done with gifted students, the purpose of this study was to examine perfectionism differences among gifted adolescents in regards to gender, birth order,…

  19. Murine leukemia virus (MLV replication monitored with fluorescent proteins

    Directory of Open Access Journals (Sweden)

    Bittner Alexandra


    Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.

  20. The Alleged Crisis and the Illusion of Exact Replication

    NARCIS (Netherlands)

    Stroebe, Wolfgang; Strack, Fritz


    There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a replication crisis in psychology. Psychologists are encouraged to conduct more exact r

  1. Three attempts to replicate the moral licensing effect

    NARCIS (Netherlands)

    Blanken, I.; van de Ven, N.; Zeelenberg, M.; Meijers, M.H.C.


    The present work includes three attempts to replicate the moral licensing effect by Sachdeva, Iliev, and Medin (2009). The original authors found that writing about positive traits led to lower donations to charity and decreased cooperative behavior. The first two replication attempts (student sampl

  2. Focus Article: Replication in Second Language Writing Research (United States)

    Porte, Graeme; Richards, Keith


    This paper discusses the meaning and range of replication in L2 research from both quantitative and qualitative perspectives. In the first half of the paper, it will be argued that key quantitative studies need to be replicated to have their robustness and generalizability tested and that this is a requirement of scientific inquiry. Such research…

  3. Universal Temporal Profile of Replication Origin Activation in Eukaryotes (United States)

    Goldar, Arach


    The complete and faithful transmission of eukaryotic genome to daughter cells involves the timely duplication of mother cell's DNA. DNA replication starts at multiple chromosomal positions called replication origin. From each activated replication origin two replication forks progress in opposite direction and duplicate the mother cell's DNA. While it is widely accepted that in eukaryotic organisms replication origins are activated in a stochastic manner, little is known on the sources of the observed stochasticity. It is often associated to the population variability to enter S phase. We extract from a growing Saccharomyces cerevisiae population the average rate of origin activation in a single cell by combining single molecule measurements and a numerical deconvolution technique. We show that the temporal profile of the rate of origin activation in a single cell is similar to the one extracted from a replicating cell population. Taking into account this observation we exclude the population variability as the origin of observed stochasticity in origin activation. We confirm that the rate of origin activation increases in the early stage of S phase and decreases at the latter stage. The population average activation rate extracted from single molecule analysis is in prefect accordance with the activation rate extracted from published micro-array data, confirming therefore the homogeneity and genome scale invariance of dynamic of replication process. All these observations point toward a possible role of replication fork to control the rate of origin activation.

  4. Publication bias and the failure of replication in experimental psychology. (United States)

    Francis, Gregory


    Replication of empirical findings plays a fundamental role in science. Among experimental psychologists, successful replication enhances belief in a finding, while a failure to replicate is often interpreted to mean that one of the experiments is flawed. This view is wrong. Because experimental psychology uses statistics, empirical findings should appear with predictable probabilities. In a misguided effort to demonstrate successful replication of empirical findings and avoid failures to replicate, experimental psychologists sometimes report too many positive results. Rather than strengthen confidence in an effect, too much successful replication actually indicates publication bias, which invalidates entire sets of experimental findings. Researchers cannot judge the validity of a set of biased experiments because the experiment set may consist entirely of type I errors. This article shows how an investigation of the effect sizes from reported experiments can test for publication bias by looking for too much successful replication. Simulated experiments demonstrate that the publication bias test is able to discriminate biased experiment sets from unbiased experiment sets, but it is conservative about reporting bias. The test is then applied to several studies of prominent phenomena that highlight how publication bias contaminates some findings in experimental psychology. Additional simulated experiments demonstrate that using Bayesian methods of data analysis can reduce (and in some cases, eliminate) the occurrence of publication bias. Such methods should be part of a systematic process to remove publication bias from experimental psychology and reinstate the important role of replication as a final arbiter of scientific findings.

  5. Enzymes involved in organellar DNA replication in photosynthetic eukaryotes

    Directory of Open Access Journals (Sweden)

    Takashi eMoriyama


    Full Text Available Plastids and mitochondria possess their own genomes. Although the replication mechanisms of these organellar genomes remain unclear in photosynthetic eukaryotes, several organelle-localized enzymes related to genome replication, including DNA polymerase, DNA primase, DNA helicase, DNA topoisomerase, single-stranded DNA maintenance protein, DNA ligase, primer removal enzyme, and several DNA recombination-related enzymes, have been identified. In the reference Eudicot plant Arabidopsis thaliana, the replication-related enzymes of plastids and mitochondria are similar because many of them are dual targeted to both organelles, whereas in the red alga Cyanidioschyzon merolae, plastids and mitochondria contain different replication machinery components. The enzymes involved in organellar genome replication in green plants and red algae were derived from different origins, including proteobacterial, cyanobacterial, and eukaryotic lineages. In the present review, we summarize the available data for enzymes related to organellar genome replication in green plants and red algae. In addition, based on the type and distribution of replication enzymes in photosynthetic eukaryotes, we discuss the transitional history of replication enzymes in the organelles of plants.

  6. Replication stress activates DNA repair synthesis in mitosis

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Ying, Songmin; Bjerregaard, Victoria A


    mitosis serves as the trigger for completion of DNA replication at CFS loci in human cells. Given that this POLD3-dependent mitotic DNA synthesis is enhanced in aneuploid cancer cells that exhibit intrinsically high levels of chromosomal instability (CIN(+)) and replicative stress, we suggest...

  7. Stress responses and replication of plasmids in bacterial cells

    Directory of Open Access Journals (Sweden)

    Wegrzyn Alicja


    Full Text Available Abstract Plasmids, DNA (or rarely RNA molecules which replicate in cells autonomously (independently of chromosomes as non-essential genetic elements, play important roles for microbes grown under specific environmental conditions as well as in scientific laboratories and in biotechnology. For example, bacterial plasmids are excellent models in studies on regulation of DNA replication, and their derivatives are the most commonly used vectors in genetic engineering. Detailed mechanisms of replication initiation, which is the crucial process for efficient maintenance of plasmids in cells, have been elucidated for several plasmids. However, to understand plasmid biology, it is necessary to understand regulation of plasmid DNA replication in response to different environmental conditions in which host cells exist. Knowledge of such regulatory processes is also very important for those who use plasmids as expression vectors to produce large amounts of recombinant proteins. Variable conditions in large-scale fermentations must influence replication of plasmid DNA in cells, thus affecting the efficiency of recombinant gene expression significantly. Contrary to extensively investigated biochemistry of plasmid replication, molecular mechanisms of regulation of plasmid DNA replication in response to various environmental stress conditions are relatively poorly understood. There are, however, recently published studies that add significant data to our knowledge on relations between cellular stress responses and control of plasmid DNA replication. In this review we focus on plasmids derived from bacteriophage λ that are among the best investigated replicons. Nevertheless, recent results of studies on other plasmids are also discussed shortly.

  8. Alcoholism and the Armanni-Ebstein lesion. (United States)

    Parai, Jacqueline L; Kodikara, Sarathchandra; Milroy, Christopher M; Pollanen, Michael S


    The Armanni-Ebstein lesion is a histological change in the kidney consisting of sub-nuclear vacuolation of the proximal tubules. It has been most associated with diabetic ketoacidosis. The vacuoles have been reported to contain glycogen. More recent studies show them to contain fat. Recent papers have associated the Armanni-Ebstein lesion with non-diabetic ketoacidosis. We present 11 cases of alcoholic ketoacidosis where the Armanni-Ebstein lesion was identified. None had a history of diabetes mellitus and none showed any changes of diabetic nephropathy. All 11 cases had raised acetone levels (3-67 mg/100 mL (mean 17.9 mg/100 mL and median value of 16 mg/100 mL). In addition a case of isopropanol poisoning was found to have the Armanni-Ebstein lesion. Isopropanol is converted to acetone but is not associated with acidosis. These results indicate that the Armanni-Ebstein lesion is not specific to diabetes mellitus.

  9. Evaluation of various hepatic lesions with PET

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chul Ju


    When a liver lesion is found in a PET image, differential diagnosis and analysis of the lesion is very important. We tried to analyze hepatic lesions found in PET. 53 patients with focal liver lesions (13 patients with HCC, 8 patients with cholangiocarcinoma (CC), 20 patients with liver metastasis, 5 patients with hemangioma, 7 patients with liver abscess, including 1 patient with liver candidiasis) were examined. Definitely high FDG uptake pattern were observed in 54% (7/13) of HCC, 100% (8/8) of CC, 95% (19/20) of metastatic liver cancer and 100% (7/7) of liver abscess. Therefore, PET was partially useful in the diagnosis of HCC, but it was very useful in the diagnosis of CC or liver metastasis or liver abscess. The contrast between lesions and surrounding liver background was very conspicuous in PET images of CC or liver metastasis or liver abscess, which suggests that PET might be used for the follow up and assessment of treatment response of these diseases.

  10. Petrous apex lesions outcome in 21 cases

    Directory of Open Access Journals (Sweden)

    Hekmatara M


    Full Text Available Petrous apex lesions of temporal bone progress slowly. Most of the time not only destruct this area but also involve neighbouring element. The symptoms of the neighbouring neuro-vasculare involvement we can recognize these lesions. The most common symptoms of involvement of the petrous apex are: headache, conductive hearing loss or sensorineural type, paresthesia and anesthesia of the trigeminal nerve, paresia and paralysis of the facial nerve, abducent nerve. In retrospective study which has been in the ENT and HNS wards of Amiralam hospital, 148 patients have been operated due to temporal bone tumor; from these numbers, 21 (13.6% patients had petrous apex lesions of temporal bone. Eleven (52.9% patients of these 21 persons were men and the remaining 10 (47-6% were women. The average age of the patients was 37 years. The common pathology of these patients were glomus jugulare tumors, hemangioma, schwannoma, meningioma, congenital cholesteatoma, giant cell granuloma. The kind of operations that have been done on these patients were: infratemporal, translabyrinthine and middle fossa approaches. The conclusion of this study shows that petrous apex area is an occult site. The symptoms of this lesion are not characteristic, meticulous attention to the history and physical examination are very helpful to recognition of these lesions and it's extention.

  11. Venocentric lesions: an MRI marker of MS?

    Directory of Open Access Journals (Sweden)

    Matthew P. Quinn


    Full Text Available From the earliest descriptions of MS, the venocentric characteristic of plaques was noted. Recently, numerous MRI studies have proposed this finding as a prospective biomarker for MS, which might aid in differentiating MS from other diseases with similar MRI findings. High field MRI studies have shown that penetrating veins can be detected in most MS lesions using T2* weighted or susceptibility weighted imaging. Future studies must address the feasibility of imaging such veins in a clinically practical context. The specificity of this biomarker has been studied only in a limited capacity. Results in microangiopathic lesions are conflicting, whereas asymptomatic white matter hyperintensities as well as lesions of NMO are less frequently venocentric compared to MS plaques. Prospective studies have shown that the presence of venocentric lesions at an early clinical presentation is highly predictive of future MS diagnosis. This is very promising, but work remains to be done to confirm or exclude lesions of common MS mimics, such as ADEM, as venocentric. A number of technical challenges must be addressed before the introduction of this technique as a complementary tool in current diagnostic procedures.

  12. Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system. (United States)

    Jeffers-Francis, Liesl K; Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer


    BK polyomavirus (BKPyV) is a known kidney tropic virus that has been detected at high levels in HIV-associated salivary gland disease (HIV-SGD), one of the most important AIDS associated oral lesions. BKPyV has been detected in HIV-SGD patient saliva and replicates in salivary gland cells in vitro. BKPyV antivirals are currently in wide use to guard against BKPyV mediated organ rejection in kidney transplant recipients. The goal of this study was to investigate the inhibitory effects of three such antiviral agents, Ciprofloxacin, Cidofovir, and Leflunomide in BKPyV infected salivary gland cells. Human salivary gland cells, and Vero cells, were infected with BKPyV, treated with antiviral drugs and assessed for BKPyV gene expression and viral replication for up to 5 days post infection. The kinetics of BKPyV replication were different in salivary gland cells compared to kidney cells. Ciprofloxacin and Cidofovir had minimal effect on metabolic activity and host cell DNA replication, however, cell toxicity was detected at the protein level with Leflunomide treatment. Ciprofloxacin decreased BKV T Ag and VP1 mRNA expression by at least 50% in both cell types, and decreased T Ag protein expression at days 3 and 4 post infection. A 2.5-4 log decrease in intracellular DNA replication and a 2-3 log decrease in progeny release were detected with Ciprofloxacin treatment. Cidofovir and Leflunomide also inhibited BKPyV gene expression and DNA replication. The three drugs diminished progeny release by 30-90% and 2- to 6-fold decreases in infectious virus were detected post drug treatment by fluorescence focus assay. Additionally, three clinical BKPyV isolates were assessed for their responses to these agents in vitro. Cidofovir and Leflunomide, but not Ciprofloxacin treatment resulted in statistically significant inhibition of BKPyV progeny release from salivary gland cells infected with HIVSGD BKPyV isolates. All three drugs decreased progeny release from cells infected with a

  13. USP7 is a SUMO deubiquitinase essential for DNA replication

    DEFF Research Database (Denmark)

    Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia;


    Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment...... is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads...... to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7...

  14. USP7 is a SUMO deubiquitinase essential for DNA replication. (United States)

    Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia; Lopez-Contreras, Andres J; Ruppen, Isabel; Murga, Matilde; Muñoz, Javier; Mendez, Juan; Fernandez-Capetillo, Oscar


    Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7 inhibitors as anticancer agents.

  15. The sub-cellular localization of Sulfolobus DNA replication. (United States)

    Gristwood, Tamzin; Duggin, Iain G; Wagner, Michaela; Albers, Sonja V; Bell, Stephen D


    Analyses of the DNA replication-associated proteins of hyperthermophilic archaea have yielded considerable insight into the structure and biochemical function of these evolutionarily conserved factors. However, little is known about the regulation and progression of DNA replication in the context of archaeal cells. In the current work, we describe the generation of strains of Sulfolobus solfataricus and Sulfolobus acidocaldarius that allow the incorporation of nucleoside analogues during DNA replication. We employ this technology, in conjunction with immunolocalization analyses of replisomes, to investigate the sub-cellular localization of nascent DNA and replisomes. Our data reveal a peripheral localization of replisomes in the cell. Furthermore, while the two replication forks emerging from any one of the three replication origins in the Sulfolobus chromosome remain in close proximity, the three origin loci are separated.

  16. Mitochondrial biology. Replication-transcription switch in human mitochondria. (United States)

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


    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.

  17. NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. (United States)

    Bellelli, Roberto; Castellone, Maria Domenica; Guida, Teresa; Limongello, Roberto; Dathan, Nina Alayne; Merolla, Francesco; Cirafici, Anna Maria; Affuso, Andrea; Masai, Hisao; Costanzo, Vincenzo; Grieco, Domenico; Fusco, Alfredo; Santoro, Massimo; Carlomagno, Francesca


    NCOA4 is a transcriptional coactivator of nuclear hormone receptors that undergoes gene rearrangement in human cancer. By combining studies in Xenopus laevis egg extracts and mouse embryonic fibroblasts (MEFs), we show here that NCOA4 is a minichromosome maintenance 7 (MCM7)-interacting protein that is able to control DNA replication. Depletion-reconstitution experiments in Xenopus laevis egg extracts indicate that NCOA4 acts as an inhibitor of DNA replication origin activation by regulating CMG (CDC45/MCM2-7/GINS) helicase. NCOA4(-/-) MEFs display unscheduled origin activation and reduced interorigin distance; this results in replication stress, as shown by the presence of fork stalling, reduction of fork speed, and premature senescence. Together, our findings indicate that NCOA4 acts as a regulator of DNA replication origins that helps prevent inappropriate DNA synthesis and replication stress.

  18. Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates. (United States)

    Fenyö, E M; Morfeldt-Månson, L; Chiodi, F; Lind, B; von Gegerfelt, A; Albert, J; Olausson, E; Asjö, B


    According to their capacity to replicate in vitro, human immunodeficiency virus (HIV) isolates can be divided into two major groups, rapid/high and slow/low. Rapid/high viruses can easily be transmitted to a variety of cell lines of T-lymphoid (CEM, H9, and Jurkat) and monocytoid (U937) origin. In contrast, slow/low viruses replicate transiently, if at all, in these cell lines. Except for a few isolates, the great majority of slow/low viruses replicate in peripheral blood mononuclear cells and Jurkat-tatIII cells constitutively expressing the tatIII gene of HIV-1. The viruses able to replicate efficiently cause syncytium formation and are regularly isolated from immunodeficient patients. Poorly replicating HIV isolates, often obtained from individuals with no or mild disease, show syncytium formation and single-cell killing simultaneously or, with some isolates, cell killing only. Images PMID:2459416

  19. Replication Attack Mitigations for Static and Mobile WSN

    CERN Document Server

    Manjula, V; 10.5121/ijnsa.2011.3210


    Security is important for many sensor network applications. Wireless Sensor Networks (WSN) are often deployed in hostile environments as static or mobile, where an adversary can physically capture some of the nodes. once a node is captured, adversary collects all the credentials like keys and identity etc. the attacker can re-program it and replicate the node in order to eavesdrop the transmitted messages or compromise the functionality of the network. Identity theft leads to two types attack: clone and sybil. In particularly a harmful attack against sensor networks where one or more node(s) illegitimately claims an identity as replicas is known as the node replication attack. The replication attack can be exceedingly injurious to many important functions of the sensor network such as routing, resource allocation, misbehavior detection, etc. This paper analyzes the threat posed by the replication attack and several novel techniques to detect and defend against the replication attack, and analyzes their effect...

  20. Functional interactions of DNA topoisomerases with a human replication origin. (United States)

    Abdurashidova, Gulnara; Radulescu, Sorina; Sandoval, Oscar; Zahariev, Sotir; Danailov, Miltcho B; Demidovich, Alexander; Santamaria, Laura; Biamonti, Giuseppe; Riva, Silvano; Falaschi, Arturo


    The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. The topoisomerases interact in vivo and in vitro with precise bonds ahead of the start sites of bidirectional replication, within the pre-replicative complex region; topoisomerase I is bound in M, early G1 and G1/S border and topoisomerase II in M and the middle of G1. The Orc2 protein competes for the same sites of the origin bound by either topoisomerase in different moments of the cell cycle; furthermore, it interacts on the DNA with topoisomerase II during the assembly of the pre-replicative complex and with DNA-bound topoisomerase I at the G1/S border. Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation.

  1. Initiation and regulation of paramyxovirus transcription and replication. (United States)

    Noton, Sarah L; Fearns, Rachel


    The paramyxovirus family has a genome consisting of a single strand of negative sense RNA. This genome acts as a template for two distinct processes: transcription to generate subgenomic, capped and polyadenylated mRNAs, and genome replication. These viruses only encode one polymerase. Thus, an intriguing question is, how does the viral polymerase initiate and become committed to either transcription or replication? By answering this we can begin to understand how these two processes are regulated. In this review article, we present recent findings from studies on the paramyxovirus, respiratory syncytial virus, which show how its polymerase is able to initiate transcription and replication from a single promoter. We discuss how these findings apply to other paramyxoviruses. Then, we examine how trans-acting proteins and promoter secondary structure might serve to regulate transcription and replication during different phases of the paramyxovirus replication cycle.

  2. Proteasome activity is important for replication recovery, CHK1 phosphorylation and prevention of G2 arrest after low-dose formaldehyde

    Energy Technology Data Exchange (ETDEWEB)

    Ortega-Atienza, Sara; Green, Samantha E.; Zhitkovich, Anatoly, E-mail:


    Formaldehyde (FA) is a human carcinogen with numerous sources of environmental and occupational exposures. This reactive aldehyde is also produced endogenously during metabolism of drugs and other processes. DNA–protein crosslinks (DPCs) are considered to be the main genotoxic lesions for FA. Accumulating evidence suggests that DPC repair in high eukaryotes involves proteolysis of crosslinked proteins. Here, we examined a role of the main cellular proteolytic machinery proteasomes in toxic responses of human lung cells to low FA doses. We found that transient inhibition of proteasome activity increased cytotoxicity and diminished clonogenic viability of FA-treated cells. Proteasome inactivation exacerbated suppressive effects of FA on DNA replication and increased the levels of the genotoxic stress marker γ-H2AX in normal human cells. A transient loss of proteasome activity in FA-exposed cells also caused delayed perturbations of cell cycle, which included G2 arrest and a depletion of S-phase populations at FA doses that had no effects in control cells. Proteasome activity diminished p53-Ser15 phosphorylation but was important for FA-induced CHK1 phosphorylation, which is a biochemical marker of DPC proteolysis in replicating cells. Unlike FA, proteasome inhibition had no effect on cell survival and CHK1 phosphorylation by the non-DPC replication stressor hydroxyurea. Overall, we obtained evidence for the importance of proteasomes in protection of human cells against biologically relevant doses of FA. Biochemically, our findings indicate the involvement of proteasomes in proteolytic repair of DPC, which removes replication blockage by these highly bulky lesions. - Highlights: • Proteasome inhibition enhances cytotoxicity of low-dose FA in human lung cells. • Active proteasomes diminish replication-inhibiting effects of FA. • Proteasome activity prevents delayed G2 arrest in FA-treated cells. • Proteasome inhibition exacerbates replication stress by FA in

  3. Imaging caries lesions and lesion progression with polarization-sensitive optical coherence tomography (United States)

    Fried, Daniel; Xie, John; Shafi, Sahar; Featherstone, John D. B.; Breunig, Thomas; Le, Charles Q.


    New diagnostic tools are needed for the characterization of dental caries in the early stages of development. If carious lesions are detected early enough, they can be arrested without the need for surgical intervention. The objective of this study was to demonstrate that polarization sensitive optical coherence tomography (PS-OCT) can be used for the imaging of early caries lesions and for the monitoring of lesion progression over time. High-resolution polarization resolved images were acquired of natural caries lesions and simulated caries lesions of varying severity created over time periods of 1 to 14 days. Linearly polarized light was incident on the tooth samples and the reflected intensity in both orthogonal polarizations was measured. PS-OCT was invaluable for removing the confounding influence of surface reflections and native birefringence and for resolving the surface structure of caries lesions. This study demonstrated that PS-OCT is well suited for the resolution of interproximal and occlusal caries, early root caries, and secondary caries around composite fillings. Longitudinal measurements of lesion progression established a strong correlation (p<0.001) between the reflected light from the lesion area and the square root of time indicating that PS-OCT is well suited for monitoring changes in enamel mineralization over time.

  4. The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases

    Institute of Scientific and Technical Information of China (English)

    Scott D McCulloch; Thomas A Kunkel


    In their seminal publication describing the structure of the DNA double helix [1], Watson and Crick wrote what may be one of the greatest understatements in the scientific literature, namely that "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Half a century later, we more fully appreciate what a huge challenge it is to replicate six billion nucleotides with the accuracy needed to stably maintain the human genome over many generations. This challenge is perhaps greater than was realized 50 years ago, because subsequent studies have revealed that the genome can be destabilized not only by environmental stresses that generate a large number and variety of potentially cytotoxic and mutagenic lesions in DNA but also by various sequence motifs of normal DNA that present challenges to replication. Towards a better understanding of the many determinants of genome stability, this chapter reviews the fidelity with which undamaged and damaged DNA is copied, with a focus on the eukaryotic B- and Y-family DNA polymerases, and considers how this fidelity is achieved.

  5. CtIP is required to initiate replication-dependent interstrand crosslink repair.

    Directory of Open Access Journals (Sweden)

    Michelle L Duquette

    Full Text Available DNA interstrand crosslinks (ICLs are toxic lesions that block the progression of replication and transcription. CtIP is a conserved DNA repair protein that facilitates DNA end resection in the double-strand break (DSB repair pathway. Here we show that CtIP plays a critical role during initiation of ICL processing in replicating human cells that is distinct from its role in DSB repair. CtIP depletion sensitizes human cells to ICL inducing agents and significantly impairs the accumulation of DNA damage response proteins RPA, ATR, FANCD2, γH2AX, and phosphorylated ATM at sites of laser generated ICLs. In contrast, the appearance of γH2AX and phosphorylated ATM at sites of laser generated double strand breaks (DSBs is CtIP-independent. We present a model in which CtIP functions early in ICL repair in a BRCA1- and FANCM-dependent manner prior to generation of DSB repair intermediates.

  6. Focal cerebral lesions and painting abilities. (United States)

    Mazzucchi, Anna; Sinforiani, Elena; Boller, François


    Focal lesions such as strokes significantly affect painting production in the vast majority of artists. In particular, painters, when they resume painting, show changes in their painting style. In exceptional cases, there may be an apparent improvement in style, but in most cases, the changes represent nothing short of deterioration. This, however, varies according to the hemisphere affected. Painters with left-hemisphere lesions tend to show an inability to deal adequately with perspective and also tend to use simplified colors with fewer nuances. One often witnesses an evolution toward simpler, often "naïve" techniques, and at times rigid geometric repetitive features. Painters with right-hemisphere lesions also become unable to represent tridimensionality. In addition, their figures are often drawn in very summary fashion, with lack of coordination between volumes and space and a chromatic impoverishment; their main problem, however, is visuospatial, leading to neglect of the left side of the canvas.

  7. Scintigraphic localization of bone lesions during surgery

    Energy Technology Data Exchange (ETDEWEB)

    Harcke, H.T.; MacEwen, G.D.; Conway, J.J.; Tachdjian, M.O.; Dias, L.S.; Noble, H.B.; Weiss, S.


    Nuclear medicine provides several methods for increasing the accuracy of surgical removal of bone lesions with focally increased uptake. In this paper, three intraoperative procedures are discussed: remote control by imaging, intraoperative control by imaging, and intraoperative control by scintillation probe. All techniques require preoperative injection of bone imaging tracer. Remote operative control calls for a gamma camera to mark the skin over the lesion prior to surgery, providing optimal preoperative localization and imaging of the excised lesion to ensure complete removal. Intraoperative control procedures require that a portable camera or a scintillation probe be used in the operating room; these permit direct monitoring of localization and resection. Our experience with 18 procedures performed on 15 patients suggests that these techniques are worthy of continued use.

  8. Histopathologic Approach to Oral Cavity Lesions

    Directory of Open Access Journals (Sweden)

    Cuyan Demirkesen


    Full Text Available Diseases of the oral cavity may be either a reflection of system or cutaneous diseases or can be seen as a primary oral lesion. These lesions are inflammatory reactions due to miscellaneous mechanisms, ulceration or erosion, reactive proliferative nodules, precancerous or neoplastic diseases. In this study, microscopic features of the most common diseases, together with their differential diagnosis are discussed. Some of the diseases of the oral cavity have overlapping histopathological findings. In these conditions, ancillary methods such as immunoflourescence or immunohistochemistry can be performed. Deep biopsies from representative areas are essential for proper histopathological diagnosis. Moreover, informing the pathologist about the exact anatomic localization of the biopsy, as well as the clinical findings of the lesion is crucial for a better approach.

  9. Rare lesions of the cerebellopontine angle. (United States)

    Yilmaz, Cem; Altinors, Nur; Sonmez, Erkin; Gulsen, Salih; Caner, Hakan


    Vestibular schwannomas, meningiomas and epidermoids account for a vast majority of the lesions occurring in the cerebellopontine angle (CPA). Neoplastic and non-neoplastic pathologies other than these tumors constitute 1% of all lesions located in the CPA. The aim of this study was to reveal our experience in the treatment of the rare lesions of the CPA. We have retrospectively reviewed the medical files and radiological data of all patients who underwent surgery involving any kind of pathology in the CPA. We have excluded those patients with a histopathological diagnosis of meningioma, schwannoma and epidermoids. Our research revealed a case of craniopharyngioma, a case of chloroma, a case of solitary fibrous tumor, a case of pinealoblastoma, a case of atypical teratoid rhabdoid tumor, a case of an aneurysm, a case of hemorrhage and a case of abscess.

  10. Sellar lesion: Not always a pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Rao Shalinee


    Full Text Available Inflammatory lesions of the hypophysis account for 0.5% of all symptomatic diseases of the pituitary, which include lymphocytic hypophysitis, granulomatous hypophysitis with or without specific etiology and pituitary abscess. Sellar tuberculoma is a rare type of granulomatous hypophysitis. We document a case of a postmenopausal lady who presented with galactorrhea, headache and blurring of vision. Based on preliminary investigations, a clinical diagnosis of pituitary adenoma was made and the pituitary gland was surgically excised. Histopathological examination showed caseating granulomas, along with normal areas of preserved pituitary gland and a final diagnosis of tuberculous hypophysitis was made. This case is being documented due to the extremely rare involvement of the pituitary gland by granulomatous lesions such as tuberculosis and to emphasize the role of intraoperative consultation to obviate the need for radical surgery in such lesions.

  11. Hypotension and Environmental Noise: A Replication Study (United States)

    Lercher, Peter; Widmann, Ulrich; Thudium, Jürg


    Up to now, traffic noise effect studies focused on hypertension as health outcome. Hypotension has not been considered as a potential health outcome although in experiments some people also responded to noise with decreases of blood pressure. Currently, the characteristics of these persons are not known and whether this down regulation of blood pressure is an experimental artifact, selection, or can also be observed in population studies is unanswered. In a cross-sectional replication study, we randomly sampled participants (age 20–75, N = 807) from circular areas (radius = 500 m) around 31 noise measurement sites from four noise exposure strata (35–44, 45–54, 55–64, >64 Leq, dBA). Repeated blood pressure measurements were available for a smaller sample (N = 570). Standardized information on socio-demographics, housing, life style and health was obtained by door to door visits including anthropometric measurements. Noise and air pollution exposure was assigned by GIS based on both calculation and measurements. Reported hypotension or hypotension medication past year was the main outcome studied. Exposure-effect relationships were modeled with multiple non-linear logistic regression techniques using separate noise estimations for total, highway and rail exposure. Reported hypotension was significantly associated with rail and total noise exposure and strongly modified by weather sensitivity. Reported hypotension medication showed associations of similar size with rail and total noise exposure without effect modification by weather sensitivity. The size of the associations in the smaller sample with BMI as additional covariate was similar. Other important cofactors (sex, age, BMI, health) and moderators (weather sensitivity, adjacent main roads and associated annoyance) need to be considered as indispensible part of the observed relationship. This study confirms a potential new noise effect pathway and discusses potential patho-physiological routes of actions

  12. Hypotension and Environmental Noise: A Replication Study

    Directory of Open Access Journals (Sweden)

    Peter Lercher


    Full Text Available Up to now, traffic noise effect studies focused on hypertension as health outcome. Hypotension has not been considered as a potential health outcome although in experiments some people also responded to noise with decreases of blood pressure. Currently, the characteristics of these persons are not known and whether this down regulation of blood pressure is an experimental artifact, selection, or can also be observed in population studies is unanswered. In a cross-sectional replication study, we randomly sampled participants (age 20–75, N = 807 from circular areas (radius = 500 m around 31 noise measurement sites from four noise exposure strata (35–44, 45–54, 55–64, >64 Leq, dBA. Repeated blood pressure measurements were available for a smaller sample (N = 570. Standardized information on socio-demographics, housing, life style and health was obtained by door to door visits including anthropometric measurements. Noise and air pollution exposure was assigned by GIS based on both calculation and measurements. Reported hypotension or hypotension medication past year was the main outcome studied. Exposure-effect relationships were modeled with multiple non-linear logistic regression techniques using separate noise estimations for total, highway and rail exposure. Reported hypotension was significantly associated with rail and total noise exposure and strongly modified by weather sensitivity. Reported hypotension medication showed associations of similar size with rail and total noise exposure without effect modification by weather sensitivity. The size of the associations in the smaller sample with BMI as additional covariate was similar. Other important cofactors (sex, age, BMI, health and moderators (weather sensitivity, adjacent main roads and associated annoyance need to be considered as indispensible part of the observed relationship. This study confirms a potential new noise effect pathway and discusses potential patho

  13. POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies. (United States)

    Nicolas, Emmanuelle; Golemis, Erica A; Arora, Sanjeevani


    The evolutionarily conserved human polymerase delta (POLD1) gene encodes the large p125 subunit which provides the essential catalytic activities of polymerase δ (Polδ), mediated by 5'-3' DNA polymerase and 3'-5' exonuclease moieties. POLD1 associates with three smaller subunits (POLD2, POLD3, POLD4), which together with Replication Factor C and Proliferating Nuclear Cell Antigen constitute the polymerase holoenzyme. Polδ function is essential for replication, with a primary role as the replicase for the lagging strand. Polδ also has an important proofreading ability conferred by the exonuclease activity, which is critical for ensuring replicative fidelity, but also serves to repair DNA lesions arising as a result of exposure to mutagens. Polδ has been shown to be important for multiple forms of DNA repair, including nucleotide excision repair, double strand break repair, base excision repair, and mismatch repair. A growing number of studies in the past decade have linked germline and sporadic mutations in POLD1 and the other subunits of Polδ with human pathologies. Mutations in Polδ in mice and humans lead to genomic instability, mutator phenotype and tumorigenesis. The advent of genome sequencing techniques has identified damaging mutations in the proofreading domain of POLD1 as the underlying cause of some inherited cancers, and suggested that mutations in POLD1 may influence therapeutic management. In addition, mutations in POLD1 have been identified in the developmental disorders of mandibular hypoplasia, deafness, progeroid features and lipodystrophy and atypical Werner syndrome, while changes in expression or activity of POLD1 have been linked to senescence and aging. Intriguingly, some recent evidence suggests that POLD1 function may also be altered in diabetes. We provide an overview of critical Polδ activities in the context of these pathologic conditions.


    Directory of Open Access Journals (Sweden)

    V. V. Vasilenko


    Full Text Available Cameron syndrome is the ulcerative or erosive lesions of mucosal layer at the sac of hiatal hernia which can cause chronic occult or overt bleeding and iron-deficiency anemia. Hiatal hernia is a relatively frequent finding, which is in most cases asymptomatic or manifested by dyspeptic symptoms of varying severity. Despite of being a very important association of hiatal hernia Cameron syndrome is not widely represented in medical literature. That`s the reason of a lack of awareness among physicians, surgeons and endoscopists about that pathology. Cameron lesions are significant pathology because they can become a source of chronic occult as well as an acute life-threatening bleeding. Those lesions of upper gastrointestinal tract are often misinterpreted or overlooked during standard diagnostic procedures. It can lead to the misdiagnosis and false ways of treatment. The review focuses on the pathogenesis, main diagnostic problems and treatment options of that pathology. The diagnostics of the Cameron syndrome is difficult because sometimes the lesions can`t be seen on upper gastrointestinal tract endoscopy. The review describes the criteria by which the physician may suspect Cameron syndrome when endoscopy results are not certain. Clinical case represents an important problem which is often faced by the doctors — the severe iron-deficiency anemia refractory to the medication and blood transfusions in the patients with Cameron lesions. It`s very important for doctor to be aware of that complication to include Cameron syndrome into the diagnostic search for the sources of persistent blood loss. Cameron lesions can be asymptomatic as well as be manifested in the form of severe chronic anemia. And that`s the reason why there are an important issue about the proper treatment which have to be provided in each case. The review describes the effectiveness of different treatment options and makes the conclusion about the principles on which doctor can

  15. Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation

    Energy Technology Data Exchange (ETDEWEB)

    Eyre, Nicholas S., E-mail: [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Hampton-Smith, Rachel J.; Aloia, Amanda L. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Eddes, James S. [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Simpson, Kaylene J. [Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, East Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville (Australia); Hoffmann, Peter [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide (Australia); Beard, Michael R. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia)


    Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using ‘APEX2’-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIα) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIα. - Highlights: • NS5A residues Ser-222, Ser-235 and Thr-348 are phosphorylated during HCV infection. • Phosphorylation of Ser-235 is essential to HCV RNA replication. • Mutation of Ser-235 alters replication compartment localization and morphology. • Phosphatidylinositol-4 kinase III alpha is important for Ser-235 phosphorylation.

  16. Replication fork progression is paused in two large chromosomal zones flanking the DNA replication origin in Escherichia coli. (United States)

    Akiyama, Masahiro Tatsumi; Oshima, Taku; Chumsakul, Onuma; Ishikawa, Shu; Maki, Hisaji


    Although the speed of nascent DNA synthesis at individual replication forks is relatively uniform in bacterial cells, the dynamics of replication fork progression on the chromosome are hampered by a variety of natural impediments. Genome replication dynamics can be directly measured from an exponentially growing cell population by sequencing newly synthesized DNA strands that were specifically pulse-labeled with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). However, a short pulse labeling with BrdU is impracticable for bacteria because of poor incorporation of BrdU into the cells, and thus, the genomewide dynamics of bacterial DNA replication remain undetermined. Using a new thymidine-requiring Escherichia coli strain, eCOMB, and high-throughput sequencing, we succeeded in determining the genomewide replication profile in bacterial cells. We also found that fork progression is paused in two ~200-kb chromosomal zones that flank the replication origin in the growing cells. This origin-proximal obstruction to fork progression was overcome by an increased thymidine concentration in the culture medium and enhanced by inhibition of transcription. These indicate that DNA replication near the origin is sensitive to the impediments to fork progression, namely a scarcity of the DNA precursor deoxythymidine triphosphate and probable conflicts between replication and transcription machineries.

  17. Decoding diffusivity in multiple sclerosis: analysis of optic radiation lesional and non-lesional white matter.

    Directory of Open Access Journals (Sweden)

    Alexander Klistorner

    Full Text Available Diffusion tensor imaging (DTI has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterations in brain tissue diffusivity are not yet fully delineated. Tract-specific DTI analysis has previously been proposed in an attempt to alleviate this problem. Here, we extended this approach by segmenting a single tract into areas bound by seemingly similar pathological processes, which may better delineate the potential association between DTI metrics and underlying tissue damage.Several compartments were segmented in optic radiation (OR of 50 relapsing-remitting MS patients including T2 lesions, proximal and distal parts of fibers transected by lesion and fibers with no discernable pathology throughout the entire length of the OR.Asymmetry analysis between lesional and non-lesional fibers demonstrated a marked increase in Radial Diffusivity (RD, which was topographically limited to focal T2 lesions and potentially relates to the lesional myelin loss. A relative elevation of Axial Diffusivity (AD in the distal part of the lesional fibers was observed in a distribution consistent with Wallerian degeneration, while diffusivity in the proximal portion of transected axons remained normal. A moderate, but significant elevation of RD in OR non-lesional fibers was strongly associated with the global (but not local T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI.This study highlights the utility of the compartmentalization approach in elucidating the pathological substrates of diffusivity and demonstrates the presence of tissue-specific patterns of altered diffusivity in MS, providing further evidence that DTI is a sensitive marker of tissue damage in both lesions and NAWM. Our results suggest that, at

  18. Non-infectious inflammatory genital lesions. (United States)

    Andreassi, Lucio; Bilenchi, Roberta


    The genitalia may be the site of non-infectious inflammatory lesions that are generally manifested as balanoposthitis and vulvovaginitis. In men, these forms constitute 50% of all balanoposthitis forms, and in women, vulvovaginitis frequency is even higher. They consist of genital locations of general skin diseases, such as psoriasis, lichen planus, lichen sclerosus, and other clinical entities with their own physiognomy, such as Zoon's balanitis-vulvitis. Diagnosis of genital non-infectious inflammatory lesions is usually made on clinical criteria. A biopsy is only necessary for the identification of clinical conditions that may simulate inflammatory form but are actually premalignant processes.

  19. Computed tomography of the retrofascial space lesions

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Hiroko; Kohno, Atsushi; Tsuchiya, Fumiko (Tokyo Women' s Medical Coll. (Japan))


    CT offers a unique method to evaluate anatomy of the retrofascial space. Retrofascial space which mainly consist of psoas and quadratus lumborum muscles locates behind the transversalis fascia. CT findings of 10 lesions, five with abscess and five with hematoma were reviewed. CT provided clinically useful information regarding the presence, size, extent and composition of the lesions and also their effects on adjacent structures. Abscesses revealed a well-defined low density with enhanced rim in the enlarged muscle. Hematoma showed an ill-defined low density area within the enlarged muscle. Abscesses can not be differentiated from hematomas and other retrofascial tumors by CT alone.

  20. Multispectral recordings and analysis of psoriasis lesions

    DEFF Research Database (Denmark)

    Clemmensen, Line Katrine Harder; Ersbøll, Bjarne Kjær


    An objective method to evaluate the severeness of psoriasis lesions is proposed. In order to obtain objectivity multi-spectral imaging is used. The multi-spectral images give rise to a large p, small n problem which is solved by use of elastic net model selection. The method is promising for furt......An objective method to evaluate the severeness of psoriasis lesions is proposed. In order to obtain objectivity multi-spectral imaging is used. The multi-spectral images give rise to a large p, small n problem which is solved by use of elastic net model selection. The method is promising...

  1. Annular, erythematous skin lesions in a neonate

    Directory of Open Access Journals (Sweden)

    Aparna Palit


    Full Text Available A 7-day-old premature female infant presented with rapidly progressive, erythematous, annular skin lesions from the 5 th day of life. She was diagnosed provisionally as a case of neonatal lupus erythematosus and was investigated accordingly. Histopathological examination of the skin biopsy specimen revealed presence of hyphae of dermatophytes in the stratum corneum, and the diagnosis was changed to tinea corporis. Differential diagnosis of the annular erythema of infancy has been discussed and the importance of scraping a scaly lesion for KOH preparation in the diagnostic work-up of such a patient has been highlighted.

  2. Assessing Elementary Lesions in Gout by Ultrasound

    DEFF Research Database (Denmark)

    Terslev, Lene; Gutierrez, Marwin; Christensen, Robin;


    OBJECTIVE: To test the reliability of the consensus-based ultrasound (US) definitions of elementary gout lesions in patients. METHODS: Eight patients with microscopically proven gout were evaluated by 16 sonographers for signs of double contour (DC), aggregates, erosions, and tophi in the first......, respectively. The best reliability was seen for erosions (κ 0.74, 95% CI 0.65-0.81) and lowest for aggregates (κ 0.21, 95% CI 0.04-0.37). CONCLUSION: This is the first step to test consensus-based US definitions on elementary lesions in patients with gout. High intraobserver reliability was found when applying...

  3. Detection of pathological lesions in slaughtered rabbits

    Directory of Open Access Journals (Sweden)

    Guido Grilli


    Full Text Available The slaughterhouse is considered an important control point for the monitoring of rabbit diseases. In our study, 59,440 rabbit carcasses were examined, but only 1% of pathological lesions were recorded at postmortem inspection. Mainly affected were tegumentary, digestive and urinary systems. The most consistent lesion was the subcutaneous abscess; nephritis, probably caused by Encephalitozoon cuniculi, was also frequent. Pathological alterations of the liver, classified as “necrotizing hepatitis” and localized at the caudate lobe, were observed for the first time.

  4. Computed tomography of sellar and parasellar lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Mitsunori; Aoki, Hideo (Yamaguchi Univ., Ube (Japan). School of Medicine)


    Neuroradiological modalities, particularly CT, for sellar and parasellar lesions were reviewed. Although accurate preoperative diagnosis is sometimes difficult, CT diagnosed 83% as far as pituitary adenoma, craniopharyngioma and meningioma were concerned and demonstrated abnormal findings in 95% of parasellar tumors. At the authors' department, CT visualized abnormalities in all cases, with the exception of suprasellar arachnoid cyst, but a histological diagnosis was possible only in 84%. Since lesions including tumors cannot be completely denied even if CT shows normal images, findings by modalities such as plain craniography, cerebral tomography, cerebral angiography and cisternography should be judged comprehensively.

  5. Infiltrating/sealing proximal caries lesions

    DEFF Research Database (Denmark)

    Martignon, S; Ekstrand, K R; Gomez, J


    This randomized split-mouth controlled clinical trial aimed at assessing the therapeutic effects of infiltration vs. sealing for controlling caries progression on proximal surfaces. Out of 90 adult students/patients assessed at university clinics and agreeing to participate, 39, each with 3...... differences in lesion progression between infiltration and placebo (P = 0.0012) and between sealing and placebo (P = 0.0269). The study showed that infiltration and sealing are significantly better than placebo treatment for controlling caries progression on proximal lesions. No significant difference...

  6. Deficits of musical timbre perception after unilateral temporal-lobe lesion revealed with multidimensional scaling. (United States)

    Samson, Séverine; Zatorre, Robert J; Ramsay, James O


    Thirty patients with unilateral temporal lobe excisions and 15 normal control subjects were tested in a task involving judgements of timbre dissimilarity in single tone and melodic conditions. Perceptual correlates of spectral and temporal parameters resulting from changing the number of harmonics and rise-time duration, respectively, were investigated by using a multidimensional scaling technique. The results of subjects with left temporal lobe lesion suggest that they were able to use the spectral and temporal envelopes of tones independently in making perceptual judgements of single tones. In the melodic condition, their results were significantly different from those of normal control subjects, suggesting that left temporal lesions do affect subtle aspects of timbre perception, despite these patients' preserved ability to make discrimination judgements using traditional paradigms. The major finding of this study concerns perceptual ratings obtained by subjects with right temporal lobe lesion, which revealed a disturbed perceptual space in both conditions. The most distorted results were obtained with single tones, in which the temporal parameter was less prominent. Tones were grouped according to their spectral content, but the results did not reflect a coherent underlying perceptual dimension. In general, the data from both patient groups (left lesions and right lesions) showed that the extraction of temporal cues was easier in the melodic than in the single tone condition, suggesting that the different durations and frequencies heard in a musical phrase enhance the importance of certain physical parameters. The findings of the present study replicate and extend previous results showing that timbre perception depends mainly upon the integrity of right neocortical structures, although a contribution of left temporal regions is also apparent. These data also demonstrate that multidimensional techniques are sensitive to more subtle perceptual disturbances that

  7. Claspin as a biomarker of human papillomavirus-related high grade lesions of uterine cervix

    Directory of Open Access Journals (Sweden)

    Benevolo Maria


    Full Text Available Abstract Background Claspin is a nuclear protein involved in DNA replication and damage response and is a key mediator for the S-phase checkpoint. Claspin expression is significantly high in several human solid tumors. Furthermore, high levels of claspin have been found in cervical cancer cell lines. Nevertheless, no data are available regarding claspin expression in cervical tissues. Methods In order to investigate whether claspin immunoreactivity is related to the lesion severity and High-Risk (HR HPV infection, we analyzed claspin expression by immunohistochemistry in a series of cervical biopsies which represent the steps occurring during cervical carcinogenesis (normal tissues, Cervical Intraepithelial Neoplasias 1, 2 and 3, Squamous Cell Carcinomas. All patients also had a cervico-vaginal sample for HPV testing, collected immediately before the colposcopy-guided biopsy. The HR-HPV DNA detection was performed by the HR-HPV Hybrid Capture 2 test. HPV genotyping was performed using the Linear Array HPV Genotyping Test. Results Our results evidenced a constant and significant increase of the rate of claspin positivity from the normal tissues to carcinomas (pχ2trend 2  Conclusions Our findings indicate that in vivo claspin expression is significantly related to HR-HPV infection and lesion grade both in histological and cytological samples. Therefore, the analysis of claspin expression could be clinically relevant in the diagnosis of HPV-related cervical lesions, in particular when applied to cervico-vaginal cytology. Moreover, giving information on the proliferation rate of each lesion, claspin immunostaining may contribute to the evaluation of progression risk, thus being helpful in patient management. Nevertheless, only large prospective studies may clarify the true clinical usefulness of claspin expression in distinguishing lesions with different progression potential.

  8. Human papillomavirus in oral lesions Virus papiloma humano en lesiones orales

    Directory of Open Access Journals (Sweden)

    Joaquín V. Gónzalez


    Full Text Available Growing evidence suggests a role for human papillomavirus (HPV in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases; the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.Crecientes evidencias sugieren que el virus Papiloma humano (HPV tiene un rol en el cáncer oral; sin embargo su participación es todavía controvertida. Este estudio evalúa la frecuencia de ADN de HPV en una variedad de lesiones orales de pacientes de Argentina. Se seleccionaron 77 muestras de tejido oral de 66 pacientes (casos; el diagnóstico histo-patológico correspondió a: 11 lesiones benignas asociadas a HPV, 8 lesiones benignas no asociadas a HPV, 33 lesiones premalignas y 25 cánceres. Como controles se usaron 60 muestras de células exfoliadas de mucosa oral normal. La

  9. The wide spectrum of hyperechoic lesions of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Linda, A., E-mail: [Institute of Diagnostic Radiology, University of Udine, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine (Italy); Zuiani, C.; Lorenzon, M.; Furlan, A.; Londero, V. [Institute of Diagnostic Radiology, University of Udine, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine (Italy); Machin, P. [Institute of Pathology, Ospedale De Gironcoli, Conegliano (Italy); Bazzocchi, M. [Institute of Diagnostic Radiology, University of Udine, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine (Italy)


    Although breast lesions are commonly detected because of their hypoechogenicity, some lesions may present with hyperechogenicity due to their histological components. Hyperechogenicity has been shown to be highly predictive of benignity; however, hyperechoic lesions can occasionally be malignant. This article reviews hyperechoic lesions of the breast, describes the underlying histological causes associated with hyperechogenicity, and the sonographic features useful for the differential diagnosis between benign and malignant hyperechoic lesions.

  10. Panero et al. (2016): Failure to replicate methods caused the failure to replicate results. (United States)

    Kidd, David Comer; Castano, Emanuele


    Contrary to Kidd and Castano (2013), Panero et al. (2016) fail to find that reading literary fiction improves performance on an advanced test of theory of mind (ToM), the Reading the Mind in the Eyes Test. However, this commentary shows that the findings presented in Panero et al. (2016) are not reliable due to two striking threats to the internal validity of their studies that were not clearly disclosed or discussed in the manuscript or supplementary materials. First, no effective strategy was implemented to ensure that participants read their assigned texts, and examination of the data revealed many participants whose reading times indicate that they were not exposed to the manipulation. Second, further examination shows that two of the largest studies contributing to Panero et al. (2016) are not valid experiments due to a clear failure of random assignment to conditions. These threats to experimental internal validity make the conclusions presented in Panero et al. (2016) untenable. After removing cases in which participants were not exposed to the manipulation and the data from the two studies without random assignment, an analysis reveals that reading literary fiction improves ToM compared to reading popular genre fiction. This result is consistent with prior studies and indicates that a failure to carefully replicate the methods of Kidd and Castano (2013) led to the failure to replicate Kidd and Castano's (2013) results. (PsycINFO Database Record

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

    Directory of Open Access Journals (Sweden)

    Bazilė Ravoitytė


    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. SMARCAL1 maintains telomere integrity during DNA replication. (United States)

    Poole, Lisa A; Zhao, Runxiang; Glick, Gloria G; Lovejoy, Courtney A; Eischen, Christine M; Cortez, David


    The SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) DNA translocase is one of several related enzymes, including ZRANB3 (zinc finger, RAN-binding domain containing 3) and HLTF (helicase-like transcription factor), that are recruited to stalled replication forks to promote repair and restart replication. These enzymes can perform similar biochemical reactions such as fork reversal; however, genetic studies indicate they must have unique cellular activities. Here, we present data showing that SMARCAL1 has an important function at telomeres, which present an endogenous source of replication stress. SMARCAL1-deficient cells accumulate telomere-associated DNA damage and have greatly elevated levels of extrachromosomal telomere DNA (C-circles). Although these telomere phenotypes are often found in tumor cells using the alternative lengthening of telomeres (ALT) pathway for telomere elongation, SMARCAL1 deficiency does not yield other ALT phenotypes such as elevated telomere recombination. The activity of SMARCAL1 at telomeres can be separated from its genome-maintenance activity in bulk chromosomal replication because it does not require interaction with replication protein A. Finally, this telomere-maintenance function is not shared by ZRANB3 or HLTF. Our results provide the first identification, to our knowledge, of an endogenous source of replication stress that requires SMARCAL1 for resolution and define differences between members of this class of replication fork-repair enzymes.

  13. Replication timing: a fingerprint for cell identity and pluripotency.

    Directory of Open Access Journals (Sweden)

    Tyrone Ryba


    Full Text Available Many types of epigenetic profiling have been used to classify stem cells, stages of cellular differentiation, and cancer subtypes. Existing methods focus on local chromatin features such as DNA methylation and histone modifications that require extensive analysis for genome-wide coverage. Replication timing has emerged as a highly stable cell type-specific epigenetic feature that is regulated at the megabase-level and is easily and comprehensively analyzed genome-wide. Here, we describe a cell classification method using 67 individual replication profiles from 34 mouse and human cell lines and stem cell-derived tissues, including new data for mesendoderm, definitive endoderm, mesoderm and smooth muscle. Using a Monte-Carlo approach for selecting features of replication profiles conserved in each cell type, we identify "replication timing fingerprints" unique to each cell type and apply a k nearest neighbor approach to predict known and unknown cell types. Our method correctly classifies 67/67 independent replication-timing profiles, including those derived from closely related intermediate stages. We also apply this method to derive fingerprints for pluripotency in human and mouse cells. Interestingly, the mouse pluripotency fingerprint overlaps almost completely with previously identified genomic segments that switch from early to late replication as pluripotency is lost. Thereafter, replication timing and transcription within these regions become difficult to reprogram back to pluripotency, suggesting these regions highlight an epigenetic barrier to reprogramming. In addition, the major histone cluster Hist1 consistently becomes later replicating in committed cell types, and several histone H1 genes in this cluster are downregulated during differentiation, suggesting a possible instrument for the chromatin compaction observed during differentiation. Finally, we demonstrate that unknown samples can be classified independently using site

  14. Systematic pathogenesis and replication of avian hepatitis E virus in specific-pathogen-free adult chickens. (United States)

    Billam, P; Huang, F F; Sun, Z F; Pierson, F W; Duncan, R B; Elvinger, F; Guenette, D K; Toth, T E; Meng, X J


    Hepatitis E virus (HEV) is an important human pathogen. Due to the lack of a cell culture system and a practical animal model for HEV, little is known about its pathogenesis and replication. The discovery of a strain of HEV in chickens, designated avian HEV, prompted us to evaluate chickens as a model for the study of HEV. Eighty-five 60-week-old specific-pathogen-free chickens were randomly divided into three groups. Group 1 chickens (n=28) were each inoculated with 5 x 10(4.5) 50% chicken infectious doses of avian HEV by the oronasal route, group 2 chickens (n=29) were each inoculated with the same dose by the intravenous (i.v.) route, and group 3 chickens (n=28) were not inoculated and were used as controls. Two chickens from each group were necropsied at 1, 3, 5, 7, 10, 13, 16, 20, 24, 28, 35, and 42 days postinoculation (dpi), and the remaining chickens were necropsied at 56 dpi. Serum, fecal, and various tissue samples, including liver and spleen samples, were collected at each necropsy for pathological and virological testing. By 21 dpi, all oronasally and i.v. inoculated chickens had seroconverted. Fecal virus shedding was detected variably from 1 to 20 dpi for the i.v. group and from 10 to 56 dpi for the oronasal group. Avian HEV RNA was detected in serum, bile, and liver samples from both i.v. and oronasally inoculated chickens. Gross liver lesions, characterized by subcapsular hemorrhages or enlargement of the right intermediate lobe, were observed in 7 of 28 oronasally and 7 of 29 i.v. inoculated chickens. Microscopic liver lesions were mainly lymphocytic periphlebitis and phlebitis. The lesion scores were higher for oronasal (P=0.0008) and i.v. (P=0.0029) group birds than for control birds. Slight elevations of the plasma liver enzyme lactate dehydrogenase were observed in infected chickens. The results indicated that chickens are a useful model for studying HEV replication and pathogenesis. This is the first report of HEV transmission via its natural

  15. Precancerous Lesions of the Oral Mucosa

    Directory of Open Access Journals (Sweden)

    Oya Gürbüz


    Full Text Available In this review of oral precancerous lesions, leukoplakia, erythroleukoplakia/erythroplakia and the least common variant proliferative verrucous leukoplakia will be focused with their clinical characteristics and their potential to develop oral squamous cell carcinoma and related factors will be discussed.

  16. Differential diagnosis of small solid pancreatic lesions

    DEFF Research Database (Denmark)

    Dietrich, Christoph Frank; Sahai, Anand Vasante; D'Onofrio, Mirko


    BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage. Little is known about the incidental finding of early-stage PDAC. The aim of the current study was to determine the etiology of small solid pancreatic lesions (≤15 mm) to optimize clinical managem...

  17. Scoliosis secondary to an unusual rib lesion.

    LENUS (Irish Health Repository)

    Burke, N G


    Tumours of the chest wall are uncommon and are usually malignant. A bone haemangioma is a rare benign vascular neoplasm, which more commonly occurs in middle-aged patients. We present the case of a scoliosis caused by a rib haemangioma in an adolescent male. Other causes of scoliosis secondary to rib lesions are discussed.

  18. Gamma knife radiosurgery for midline lesions

    Energy Technology Data Exchange (ETDEWEB)

    Legat, J.; Mokry, M.; Leber, K.; Schroettner, O.; Pendl, G. [Karl-Franzens Univ., Graz (Austria)


    Surgery of midline lesions is difficult in many cases and often only partial removal is possible. Between May 1992 and April 1997, 81 patients with midline lesions were treated radiosurgically. The lesions were located in the hypothalamic region (25), thalamus (20), third ventricle (2), quadrigeminal plate (9), pons (13), fourth ventricle (4), pineal region (4) and other locations (4). Forty-eight patients were male and 33 were female. Histologically, there were 56 benign cases (13 arteriovenous malformations, 11 low grade gliomas, 20 craniopharyngiomas, 5 meningiomas, 3 hamartomas, 4 miscellaneous) and 25 malignant cases (10 metastases, 10 high grade gliomas, 2 medulloblastomas, 3 miscellaneous). Clinical and radiological follow-up was obtained in 71 patients (88%). In all patients the treatment was well tolerated. Radiographic response could be achieved in 39 of 68 tumor patients (57%). A complete obliteration was seen in 6 arteriovenous malformations (60%) 2 years after radiosurgery. A second radiosurgical procedure was necessary in 2 patients because of incomplete obliteration after 3 years. According to our experience, we can conclude that radiosurgery appears to be effective as adjuvant treatment or midline lesions. (author)

  19. MRI of fetal acquired brain lesions

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail:; Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna (Austria); Helmer, Hanns [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Dietrich, Wolfgang [Department of Neurosurgery, Medical University of Vienna (Austria); Eppel, Wolfgang [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Langer, Martin [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria)


    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

  20. Otoendoscopic treatment of hidden lesions in otomastoiditis

    Institute of Scientific and Technical Information of China (English)

    LIU Yang; SUN Jian-jun; LIN Yong-sheng; ZHAO Dan-heng; ZHAO Jing; LEI Fei


    Background Surgical treatments for chronic suppurative and cholesteatoma otitis media have been discussed for several decades, but recurrences still occur because of the complex dissection required and hidden lesions associated with otomastoiditis. This study investigated the technology and strategy behind the use of otoendoscopic-assisted otosurgery.Methods We reported on hidden lesions in 32 ears of patients with otomastoiditis between November 2006 and January 2009. All the patients were treated with the aid of an otoendoscope. The advantages of otoendoscopy, including multi-angle light scattering, aperture illumination, and magnification of the local operative field, were utilized in otologic microsurgery, and otoendoscopic operative techniques were introduced for operative sites such as the epitympanum, aditus of the antrum, facial recess, sinus tympani and the mastoid tip.Results All patients were followed up from 3 months to 2 years after surgery. All patients recovered well within 3 months following surgery, except for one case of epithelialization of the mastoid cavity occurring 6 months after surgery for cholesteatoma on the cerebellar surface and another case with Bezold's abscess, hyperplastic granulation tissue developed at the antrum.Conclusions Otoendoscopy can overcome the technical deficiency of rectilinearity of the visual axis associated with otomicroscopic illumination, which presents a problem when dealing with otomastoiditis lesions in hidden areas. This technique allows such lesions within the complex three-dimensional structure to be visualized and cleaned. Otoendoscopy thus has significant potential for improving the quality of surgery and reducing the risk of postoperative recurrence.

  1. Dermoscopic Features of Facial Pigmented Skin Lesions (United States)

    Goncharova, Yana; Attia, Enas A. S.; Souid, Khawla; Vasilenko, Inna V.


    Four types of facial pigmented skin lesions (FPSLs) constitute diagnostic challenge to dermatologists; early seborrheic keratosis (SK), pigmented actinic keratosis (AK), lentigo maligna (LM), and solar lentigo (SL). A retrospective analysis of dermoscopic images of histopathologically diagnosed clinically-challenging 64 flat FPSLs was conducted to establish the dermoscopic findings corresponding to each of SK, pigmented AK, LM, and SL. Four main dermoscopic features were evaluated: sharp demarcation, pigment pattern, follicular/epidermal pattern, and vascular pattern. In SK, the most specific dermoscopic features are follicular/epidermal pattern (cerebriform pattern; 100% of lesions, milia-like cysts; 50%, and comedo-like openings; 37.50%), and sharp demarcation (54.17%). AK and LM showed a composite characteristic pattern named “strawberry pattern” in 41.18% and 25% of lesions respectively, characterized by a background erythema and red pseudo-network, associated with prominent follicular openings surrounded by a white halo. However, in LM “strawberry pattern” is widely covered by psewdonetwork (87.5%), homogenous structureless pigmentation (75%) and other vascular patterns. In SL, structureless homogenous pigmentation was recognized in all lesions (100%). From the above mentioned data, we developed an algorithm to guide in dermoscopic features of FPSLs. PMID:23431466

  2. Missed Massive Morel-Lavallee Lesion

    Directory of Open Access Journals (Sweden)

    Shunsuke Takahara


    Full Text Available A Morel-Lavallee lesion (MLL involves posttraumatic fluid collection around the greater trochanter. Many cases of MLL are missed at the initial evaluation, and the treatment of MLL is not well established. We present two cases in which MLL was missed at the initial evaluation. Case 1. A 65-year-old man was run over by a parade float. There was subcutaneous hematoma around the left greater trochanter, and no fracture was found. We diagnosed this injury as MLL on the 7th day after the trauma. Although we performed percutaneous drainage, the injured area was infected. Case 2. A 57-year-old man was hit by a train in a factory. There was an iliac wing fracture, but an MLL was not initially recognized. On the 6th day after the trauma, when performing open reduction and internal fixation for the iliac fracture, we recognized the lesion and performed percutaneous drainage simultaneously. This lesion also became infected. In these two cases, the wounds finally healed after a long duration of treatment. We suggest that it is important to keep this injury in mind and debride the lesion early and completely in the treatment course.

  3. Oral lichenoid lesions - A review and update

    Directory of Open Access Journals (Sweden)

    Venkatesh Vishwanath Kamath


    Full Text Available Background: Oral lichenoid lesions or reactions (OLLs/OLRs are clinical and histological contemporaries of the classical oral lichen planus (OLP that have generated a lot of debate in literature. In contrast to the idiopathic nature of OLP, OLLs are often associated with a known identifiable inciting factor. A superficial examination of these lesions clinically and histologically often reveals many similarities with OLP, but recent data indicate that distinguishable features do exist and form the basis of most classifications. Aims and Objectives: This paper attempts to collate available data in English literature on OLLs, highlight distinguishing features clinically and histologically and reflect on the malignant transformation potential and treatment modalities of the condition. Materials and Methods: A comprehensive search of medical and dental databases including PubMed, Ovid, Cochrane, Pubget, Researchgate, and non-medical search engines were utilized for the review. The search words included "oral lichen planus", "oral lichenoid lesions", "oral drug reactions", "lichenoid dysplasia", and "adverse effects of dental materials". Review Results: OLLs seem to grossly underrated and most cases were clubbed as OLP. Definite clinical and histological features were uncovered to establish the identity of this lesion. Associations with dental restorative materials, drugs, and medications have been conclusively proven in the etiology of this condition. Specific markers are being utilized to diagnose the condition and monitor its progress. Conclusion: Substantial differentiating features were uncovered to delineate OLLs as a separate entity with definite etiology, pathogenesis, and a high malignant transformation rate compared with OLP.

  4. [Longitudinal stent deformation during bifurcation lesion treatment]. (United States)

    Mami, Z; Monsegu, J


    Longitudinal stent deformation is defined as a compression of stent length after its implantation. It's a rare complication but dangerous seen with several stents. We reported a case of longitudinal stent deformation during bifurcation lesion treatment with a Promus Element(®) and we perform a short review of this complication.

  5. Roentgenologic diagnostics of capsular ligament lesions

    Energy Technology Data Exchange (ETDEWEB)

    Wirth, C.J.; Jaeger, M.


    The X-ray diagnostic is of obvious importance and relevance in the detection of acute or old capsular ligament lesions of the limb joint. On the one hand it serves as the plain radiograph (roentgenogram without contrast medium) for the assessment of osseous secondary lesions, for the documentation of luxationary positions of the joint partners, and in old capsular ligament lesions for the detection of an already existing arthrosis. On the other hand the X-ray images are of main importance, which are made from the hand-held limb in order to permit a comparison of the two sides, and which beyond the clinical detection of a joint instability indicate the extent and the direction of this instability and which also document it, and which allow in adolescents to recognize a separation of the epiphysis as an alternative to the capsular ligament rupture. Only in particular cases arthrography can provide some additional information, so for example in the case of an isolated syndesmosis rupture, ruptures of the rosette of the rotator muscle or of a damaged triangular disk in the hand. Angiography is only required in cases of traumatic luxations of the knee in order to exclude an intimal lesion of the popliteal artery.

  6. International Consensus for ultrasound lesions in gout

    DEFF Research Database (Denmark)

    Gutierrez, Marwin; Schmidt, Wolfgang A; Thiele, Ralf G


    elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability. RESULTS: A total of 32 participants responded to the questionnaires. Good agreement (>80%) was obtained for US definitions on DC, tophus, aggregates and erosion in the Delphi exercise after three rounds...

  7. Remineralization of caries lesions extending into dentin. (United States)

    ten Cate, J M


    Remineralization is one aspect of the overall process of tooth decay. However, it is primarily studied in shallow lesions. The aim of this study was to explore whether caries lesions in enamel and extending into the dentin can be remineralized. A single-section model was developed for the longitudinal and non-destructive monitoring of changes in enamel and dentin. Lesions at least 200 microm into dentin were formed in undersaturated acetate buffers. Next, the lesions were divided into groups (three treatment and one control) and remineralized. The treatments were: weekly immersion in 1,000 ppm fluoride, single treatment with methanehydroxybisphosphonate, and a constant level of 1 ppm fluoride. De- and remineralization was assessed by transverse microradiography. Remineralization was observed in enamel, but also in dentin, indicating that, deep into dentin, the pores become supersaturated to apatite formation. Treatments affected remineralization only in the outer part of enamel. Both findings are explained by a relatively fast diffusion of mineral ions, with precipitation being rate-limiting. The results suggest that dentin remineralization, underneath enamel, can be achieved and could possibly be used in clinical treatment strategies.

  8. Review of squamous premalignant vulvar lesions.

    NARCIS (Netherlands)

    Nieuwenhof, H.P. van de; Avoort, I.A.M. van der; Hullu, J.A. de


    Vulvar squamous cell carcinoma (SCC) develops following two different pathways, which have their own premalignant lesions. In the absence of human papilloma virus (HPV), vulvar SCC can develop in a background of lichen sclerosus (LS), differentiated vulvar intraepithelial neoplasia (VIN) or both. Th

  9. Pleural Mass Lesion Containing Calcium Sludge

    Directory of Open Access Journals (Sweden)

    Can Kurkcuoglu


    Full Text Available   A 30 year-old man was admitted with of chest pain. Had a x-ray and computed tomography showed calcified pleural mass . Lesions in the white-colored, dense mud was the consistency of the material.

  10. IDUS for Biliary and Pancreatic Duct Lesions

    Institute of Scientific and Technical Information of China (English)

    Takao ltoi


    @@ In the recent decade, wire-guided intraductal US(IDUS), which can be passed through the working channel of standard duodenoscopes to provide high-frequency ultrasound images, has been developed as a newly diagnostic tool for biliary and pancreatic duct lesions.


    Directory of Open Access Journals (Sweden)



    Full Text Available BACKGROUND : Breast lump is fairly common complaint in females for which patient seeks medical advice and becomes anxious about the diagnosis. Quick diagnosis by Fine needle aspiration cytology (FNAC relieves patient’s anxiety and assists in their pre - operative management a nd overall treatment . AIMS : To study the cytological spectrum of breast lesions in correlation with histological appearances to evaluate the utility of FNAC in the diagnosis of palpable breast lesions. MATERIALS AND METHODS : Total of 180 cases were studied by FNAC of which 42 cases specimen was received for histopathology examination (HPE. Diagnostic accuracy was studied by statistical analysis. RESULTS : In this study of 42 cases of correlation , maximum cases were obtained for fibroadenoma followed by malignancy. FNAC diagnosis was consistent with HPE in 41 cases and inconsistent in one case. CONCLUSION : FNAC can reliably distinguish between benign and malignant conditions , neoplastic and non - neoplastic conditions. The result compared with other studies substantiate the findings of the series that FNAC of breast is a sensitive and specific modality that assist in diagnosis and management of breast lesions. KEYWORDS: FNAC ; breast lesions; HPE.

  12. Oral White Lesions Associated with Chewing Khat

    Directory of Open Access Journals (Sweden)

    Gorsky Meir


    Full Text Available Abstract Introduction Khat is a cultivated plant whose leaves when chewed elevate mood. Unlike the chewing of betel nut, no association between the white oral mucosal lesions in khat users and oral malignancies has been reported. Chewing of khat has been documented in many countries and has increased with worldwide migration. The impact of chewing khat upon the oral mucosa is essentially unknown. Purpose The purpose of this study was to assess the occurrence of oral white changes in chronic khat chewers. Oral mucosal changes in a group of 47 Yemenite Israeli men over 30 years of age, who had chewed khat more than 3 years, were compared to those of 55 Yemenite men who did not chew. Results White lesions were significantly more prevalent in the khat chewers (83% compared to the non chewing individuals (16% (P Discussion This study demonstrated a relationship between khat chewing and oral white lesions, which we attribute to chronic local mechanical and chemical irritation of the mucosa. Our findings also suggest that mucosal changes associated with khat are benign, however, this initial study requires further studies including follow-up of khat users to confirm the current findings, including the likely benign changes associated with chronic use and histologic findings of clinical lesions.

  13. The Replication Mechanism in a Romanian ERP System Environment

    Directory of Open Access Journals (Sweden)

    Iuliana SCORTA


    Full Text Available Modern Relational Database Management Systems have Replication technology. Large enterprises are often spread around the country, and although WANs can be very fast and reliable these days, it is often better for each location to have a local copy of data rather than have a single database at a central location. This usually means that replication is a requirement in order for each location to have the most up-to-date data. This paper reveals a replication mechanism implemented in a Romanian ERP system environment.

  14. Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication

    Directory of Open Access Journals (Sweden)

    Olivier Reynard


    Full Text Available The current outbreak of Ebola virus (EBOV in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.

  15. Application of hepatitis B virus replication mouse model

    Institute of Scientific and Technical Information of China (English)


    AIM:To evaluate the value of the hepatitis B virus(HBV) replication mouse model with regard to several aspects of the study of HBV biology.METHODS:To evaluate the HBV replication mouse model in detecting the efficacy of anti-HBV agents,the interferon inducer polyinosinic-polytidylin acid(polyIC) and nucleotide analogues adefovir and entecavir were administered to mice injected with wild type pHBV4.1,and the inhibiting effect of these agents on HBV DNA replication was evaluated.To identify the model's value ...

  16. Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication



    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five...

  17. Mutation at Expanding Front of Self-Replicating Colloidal Clusters

    CERN Document Server

    Tanaka, Hidenori; Brenner, Michael P


    We construct a scheme for self-replicating square clusters of particles in two spatial dimensions, and validate it with computer simulations in a finite-temperature heat bath. We find that the self-replication reactions propagate through the bath in the form of Fisher waves. Our model reflects existing colloidal systems, but is simple enough to allow simulation of many generations and thereby the first study of evolutionary dynamics in an artificial system. By introducing spatially localized mutations in the replication rules, we show that the mutated cluster population can survive and spread with the expanding front in circular sectors of the colony.

  18. Culture in the cockpit: do Hofstede's dimensions replicate? (United States)

    Merritt, A.; Helmreich, R. L. (Principal Investigator)


    Survey data collected from 9,400 male commercial airline pilots in 19 countries were used in a replication study of Hofstede's indexes of national culture. The analysis that removed the constraint of item equivalence proved superior, both conceptually and empirically, to the analysis using Hofstede's items and formulae as prescribed, and rendered significant replication correlations for all indexes (Individualism-Collectivism .96, Power Distance .87, Masculinity-Femininity .75, and Uncertainty Avoidance .68). The successful replication confirms that national culture exerts an influence on cockpit behavior over and above the professional culture of pilots, and that "one size fits all" training is inappropriate.

  19. RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress

    DEFF Research Database (Denmark)

    Bhowmick, Rahul; Minocherhomji, Sheroy; Hickson, Ian D


    Homologous recombination (HR) is necessary to counteract DNA replication stress. Common fragile site (CFS) loci are particularly sensitive to replication stress and undergo pathological rearrangements in tumors. At these loci, replication stress frequently activates DNA repair synthesis in mitosis....... This mitotic DNA synthesis, termed MiDAS, requires the MUS81-EME1 endonuclease and a non-catalytic subunit of the Pol-delta complex, POLD3. Here, we examine the contribution of HR factors in promoting MiDAS in human cells. We report that RAD51 and BRCA2 are dispensable for MiDAS but are required to counteract...

  20. Replicating research in ecology and evolution: feasibility, incentives, and the cost-benefit conundrum. (United States)

    Nakagawa, Shinichi; Parker, Timothy H


    We believe that replicating studies in ecology and evolution is extremely valuable, but replication within species and systems is troublingly rare, and even 'quasi-replications' in different systems are often insufficient. We make a case for supporting multiple types of replications and point out that the current incentive structure needs to change if ecologists and evolutionary biologist are to value scientific replication sufficiently.

  1. Characterizing and Targeting Replication Stress Response Defects in Breast Cancer (United States)


    N/A 4 INTRODUCTION In both precancerous breast lesions and breast cancer, hyperproliferative activity due to...RSR defects distinguishes premalignant lesions and breast cancer from normal tissues, which makes these defects effective targets for both breast... oral gavage. i.p., intraperitoneal injection. N = 8. ! ! 8 ! ! ! ! ! !! ! Table 1. The summary of tumorigenesis assay in MDA-MB-231 xenograft model

  2. Spindle cell melanocytic lesions--part I: an approach to compound naevoidal pattern lesions with spindle cell morphology and Spitzoid pattern lesions. (United States)

    Sade, Shachar; Al Habeeb, Ayman; Ghazarian, Danny


    Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes reveal a dendritic cytomorphology and territorial isolation, lesional naevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may be either a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either because of its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion because of a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified. However, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions can reliably be resolved with this standard approach, problem areas do exist and cause no end of grief to the surgical pathologist or dermatopathologist. In this review, the authors present their algorithmic approach to spindle cell melanocytic lesions and discuss each entity in turn, in order to (1) model a systematic approach to such lesions, and (2) provide familiarity with those melanocytic lesions that either typically or occasionally display a spindled cytomorphology.

  3. Evaluating lesion segmentation on breast sonography as related to lesion type. (United States)

    Pons, Gerard; Martí, Joan; Martí, Robert; Ganau, Sergi; Vilanova, Joan Carles; Noble, J Alison


    Breast sonography currently provides a complementary diagnosis when other modalities are not conclusive. However, lesion segmentation on sonography is still a challenging problem due to the presence of artifacts. To solve these problems, Markov random fields and maximum a posteriori-based methods are used to estimate a distortion field while identifying regions of similar intensity inhomogeneity. In this study, different initialization approaches were exhaustively evaluated using a database of 212 B-mode breast sonograms and considering the lesion types. Finally, conclusions about the relationship between the segmentation results and lesions types are described.

  4. Photoacoustic characterization of radiofrequency ablation lesions (United States)

    Bouchard, Richard; Dana, Nicholas; Di Biase, Luigi; Natale, Andrea; Emelianov, Stanislav


    Radiofrequency ablation (RFA) procedures are used to destroy abnormal electrical pathways in the heart that can cause cardiac arrhythmias. Current methods relying on fluoroscopy, echocardiography and electrical conduction mapping are unable to accurately assess ablation lesion size. In an effort to better visualize RFA lesions, photoacoustic (PA) and ultrasonic (US) imaging were utilized to obtain co-registered images of ablated porcine cardiac tissue. The left ventricular free wall of fresh (i.e., never frozen) porcine hearts was harvested within 24 hours of the animals' sacrifice. A THERMOCOOLR Ablation System (Biosense Webster, Inc.) operating at 40 W for 30-60 s was used to induce lesions through the endocardial and epicardial walls of the cardiac samples. Following lesion creation, the ablated tissue samples were placed in 25 °C saline to allow for multi-wavelength PA imaging. Samples were imaged with a VevoR 2100 ultrasound system (VisualSonics, Inc.) using a modified 20-MHz array that could provide laser irradiation to the sample from a pulsed tunable laser (Newport Corp.) to allow for co-registered photoacoustic-ultrasound (PAUS) imaging. PA imaging was conducted from 750-1064 nm, with a surface fluence of approximately 15 mJ/cm2 maintained during imaging. In this preliminary study with PA imaging, the ablated region could be well visualized on the surface of the sample, with contrasts of 6-10 dB achieved at 750 nm. Although imaging penetration depth is a concern, PA imaging shows promise in being able to reliably visualize RF ablation lesions.


    Directory of Open Access Journals (Sweden)

    N. V. Pizova


    Full Text Available Objective: to determine the incidence of atherosclerotic lesions in the carotid and vertebral arteries of young patients from Doppler ultrasound data and to compare the quantitatively assessed traditional risk factors of coronary heart disease (CHD with severe extracranial artery atherosclerotic lesion.Subjects and methods. Doppler ultrasound was carried out evaluating structural changes in the aortic arch branches in 1563 railway transport workers less than 45 years of age. A separate sample consisted of 68 young people with carotid atherosclerotic changes, in whom traditional risk factors for CHD were studied, so were in a control group of individuals without atherosclerotic changes (n = 38.Results. Among the examinees, carotid atherosclerotic lesion was detected in 112 (7.1 % cases, the increase in the rate of atherosclerotic plaques in patients aged 35–45 years being 9.08 %; that in the rate of local intima-media thickness in those aged 31–40 years being 5.1 %. Smoking (particularly that along with hypercholesterolemia and a family history of cardiovascular diseases, obesity (along with low activity, and emotional overstrain were defined as important risk factors in the young patients. Moreover, factor analysis has shown that smoking,hypertension, and early cardiovascular pathology in the next of kin makes the greatest contribution to the development of carotid atherosclerotic lesion.Conclusion. Among the patients less than 45 years of age, carotid and vertebral artery atherosclerotic changes were found in 112 (7.1 % cases, which were more pronounced in male patients. Smoking, particularly along with hypercholesterolemia and genetic predisposition to cardiovascular diseases, was a risk factor that had the highest impact on the degree of atherosclerotic lesion in the aortic arch branches of the young patients.

  6. Vascular lesions secondary to osteotomy by corticotomy. (United States)

    Spinelli, Francesco; Spinelli, Renato; Stilo, Francesco; De Caridi, Giovanni; Mirenda, Francesco


    Management of vascular traumas is frequently delayed. Vascular injuries after elective operation for bone lengthening or correction of a deformity are very'rare situations. We describe 3 cases. Case 1: male, aged 22, undergoing corticotomy for bone lengthening; immediately presented acute limb ischaemia due to a partial lesion of the popliteal artery, documented by U.S. After 7 h, direct reconstruction of the artery and fasciotomies were performed. Case 2: male, aged 27, undergoing directional osteotomy for genu varus correction. For 30 days, constant increase in leg volume and decrease in function. US showed an important haematoma at the popliteal level; arteriography documented a partial lesion of the infra-genicular popliteal artery and a voluminous false aneurysm. Direct correction of the artery and fasciotomies were performed. Case 3: male, aged 22, undergoing corticotomy for leg lengthening; immediately presented leg pain with decreased distal pulses. After 4h, there was an increase in leg volume, and arteriography showed a total lesion of the infra-genicular popliteal artery and an arteriovenous fistula. Popliteo-tibial bypass with the contralateral greater saphenous vein and fasciotomies were performed. After 1 month endovascular closure of the fistula was obtained. All patients had recovered after two months with only minor leg insufficiency. Patency of the bypass and absence of infections or delayed false aneurysms were achieved. Vascular injuries after elective orthopaedic procedures are very rare situations. Such lesions are caused by an osteotomy via corticotomy performed percutaneously. The variety of clinical presentations accounts for the difficulty in diagnosing such lesions and for the delays in implementing treatment. It is very important to obtain an early diagnosis complete with an arteriography.

  7. Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients. (United States)

    Borgogna, Cinzia; Lanfredini, Simone; Peretti, Alberto; De Andrea, Marco; Zavattaro, Elisa; Colombo, Enrico; Quaglia, Marco; Boldorini, Renzo; Miglio, Umberto; Doorbar, John; Bavinck, Jan N Bouwes; Quint, Koen D; de Koning, Maurits N C; Landolfo, Santo; Gariglio, Marisa


    The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.

  8. A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein.

    Directory of Open Access Journals (Sweden)

    Ayman El-Guindy

    Full Text Available ZEBRA is a site-specific DNA binding protein that functions as a transcriptional activator and as an origin binding protein. Both activities require that ZEBRA recognizes DNA motifs that are scattered along the viral genome. The mechanism by which ZEBRA discriminates between the origin of lytic replication and promoters of EBV early genes is not well understood. We explored the hypothesis that activation of replication requires stronger association between ZEBRA and DNA than does transcription. A ZEBRA mutant, Z(S173A, at a phosphorylation site and three point mutants in the DNA recognition domain of ZEBRA, namely Z(Y180E, Z(R187K and Z(K188A, were similarly deficient at activating lytic DNA replication and expression of late gene expression but were competent to activate transcription of viral early lytic genes. These mutants all exhibited reduced capacity to interact with DNA as assessed by EMSA, ChIP and an in vivo biotinylated DNA pull-down assay. Over-expression of three virally encoded replication proteins, namely the primase (BSLF1, the single-stranded DNA-binding protein (BALF2 and the DNA polymerase processivity factor (BMRF1, partially rescued the replication defect in these mutants and enhanced ZEBRA's interaction with oriLyt. The findings demonstrate a functional role of replication proteins in stabilizing the association of ZEBRA with viral DNA. Enhanced binding of ZEBRA to oriLyt is crucial for lytic viral DNA replication.

  9. 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.

  10. Space Occupying Lesions in the Liver

    Directory of Open Access Journals (Sweden)

    Nasser Ebrahimi Daryani


    Full Text Available "nRadiology (imaging plays a pivotal role for the diagnosis, staging, treatment planning, and follow-up of focal liver lesions. The differential diagnosis in patients presenting with a focal liver lesion is broad. "nThe size of the liver mass is an important consideration in guiding the evaluation. Lesions smaller than approximately 1.0 cm are commonly benign incidental findings on imaging studies, and in most cases represent small cysts, hemangiomas, or biliary hamartomas. Furthermore, they are frequently difficult to definitively characterize by imaging methods, due to their small size, and difficult to biopsy percutaneously. Often clinical follow-up is the only recourse for these lesions. "nTo formulate a practical approach to these patients, several factors must be incorporated into a clinical decision-making algorithm (figure below, including: the particular clinical setting (e.g., known co-morbidities, underlying cirrhosis or a known primary neoplasm, the presence of clinical signs and symptoms, the results of laboratory tests, and the critical information provided by imaging studies. "nDue to a combination of high spatial resolution and inherent soft-tissue contrast, lack of ionizing radiation, low cost, and wide availability, ultrasonography (US is frequently the first-line imaging modality for the study of the liver. "nMulti-detector row CT (MDCT has become the most commonly used modality in the preoperative diagnosis, staging, treatment planning, and follow-up of patients with known or suspected hepatic tumors. "nTo maximize the detection and characterization of liver tumors, the CT protocol must be designed according to the diagnostic task. To increase the attenuation difference (i.e., conspicuity between the hepatic parenchyma and liver tumors,3 several injection factors need to be optimized, including the volume and iodine concentration of contrast media, the injection rate (4-5mL/s, and the scanning delay from the start of contrast

  11. Histological lesions, cell cycle arrest, apoptosis and T cell subsets changes of spleen in chicken fed aflatoxin-contaminated corn. (United States)

    Peng, Xi; Zhang, Keying; Bai, Shiping; Ding, Xuemei; Zeng, Qiufeng; Yang, Jun; Fang, Jing; Chen, Kejie


    The purpose of this study was to evaluate the effects of corn naturally contaminated with aflatoxin B1 and aflatoxin B2 on pathological lesions, apoptosis, cell cycle phases and T lymphocyte subsets of spleen, and to provide an experimental basis for understanding the mechanism of aflatoxin-induced immunosuppression. A total of 900 COBB500 male broilers were randomly allocated into five groups with six replicates per group and 30 birds per replicate. The experiment lasted for 6 weeks and the five dietary treatments consisted of control, 25% contaminated corn, 50% contaminated corn, 75% contaminated corn and 100% contaminated corn groups. The histopathological spleen lesions from the contaminated corn groups was characterized as congestion of red pulp, increased necrotic cells and vacuoles in the splenic corpuscle and periarterial lymphatic sheath. The contaminated corn intake significantly increased relative weight of spleen, percentages of apoptotic splenocytes, induced cell cycle arrest of splenocytes, increased the percentages of CD3+CD8+ T cells and decreased the ratios of CD3+CD4+ to CD3+CD8+. The results suggest that AFB-induced immunosuppression maybe closely related to the lesions of spleen.

  12. The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks. (United States)

    Machwe, Amrita; Karale, Rajashree; Xu, Xioahua; Liu, Yilun; Orren, David K


    Cells cope with blockage of replication fork progression in a manner that allows DNA synthesis to be completed and genomic instability minimized. Models for resolution of blocked replication involve fork regression to form Holliday junction structures. The human RecQ helicases WRN and BLM (deficient in Werner and Bloom syndromes, respectively) are critical for maintaining genomic stability and thought to function in accurate resolution of replication blockage. Consistent with this notion, WRN and BLM localize to sites of blocked replication after certain DNA-damaging treatments and exhibit enhanced activity on replication and recombination intermediates. Here we examine the actions of WRN and BLM on a special Holliday junction substrate reflective of a regressed replication fork. Our results demonstrate that, in reactions requiring ATP hydrolysis, both WRN and BLM convert this Holliday junction substrate primarily to a four-stranded replication fork structure, suggesting they target the Holliday junction to initiate branch migration. In agreement, the Holliday junction binding protein RuvA inhibits the WRN- and BLM-mediated conversion reactions. Importantly, this conversion product is suitable for replication with its leading daughter strand readily extended by DNA polymerases. Furthermore, binding to and conversion of this Holliday junction are optimal at low MgCl(2) concentrations, suggesting that WRN and BLM preferentially act on the square planar (open) conformation of Holliday junctions. Our findings suggest that, subsequent to fork regression events, WRN and/or BLM could re-establish functional replication forks to help overcome fork blockage. Such a function is highly consistent with phenotypes associated with WRN- and BLM-deficient cells.

  13. Penile lesion from gunshot wound: a 43-case experience

    Directory of Open Access Journals (Sweden)

    Cavalcanti Andre G.


    Full Text Available OBJECTIVE: To demonstrate the main aspects of diagnosis, treatment and follow-up of 43 patients with gunshot wounds to the penis. MATERIALS AND METHODS: The location of the lesion, the presence of associated lesions, the performance of complementary exams, surgical treatment, postoperative complications and long term follow-up of 43 patients with penile lesions from gunshot wounds were retrospectively analyzed. RESULTS: Of 43 cases assessed, 41 were submitted to surgical exploration (95.3% and 2 were submitted to conservative treatment (4.7%. We found penile lesions involving the corpus cavernosum in 37 cases; the remaining 4 patients presented no lesions involving the corpus cavernosum, urethra or testicles but did in the superficial structures. Ten cases presented an association with testicular lesions and 14 cases association with anterior urethral lesions. CONCLUSION: Penile lesions from gunshot wounds should be treated with immediate surgical intervention. In exceptional situations featuring superficial lesions only conservative treatment may be applied.

  14. Yellowish lesions of the oral cavity. Suggestion for a classification. (United States)

    Gómez, Iria; Varela, Pablo; Romero, Amparo; García, María José; Suárez, María Mercedes; Seoane, Juan


    The colour of a lesion is due to its nature and to its histological substratum. In order to ease diagnosis, oral cavity lesions have been classified according to their colour in: white, red, white and red, bluish and/or purple, brown, grey and/or black lesions. To the best of our knowledge, there is no such a classification for yellow lesions. So, a suggestion for a classification of yellowish lesions according to their semiology is made with the following headings: diffuse macular lesions, papular, hypertrophic, or pustular lesions, together with cysts and nodes. This interpretation of the lesions by its colour is the first step to diagnosis. It should be taken into account that, as happens with any other classification, the yellowish group of lesions includes items with different prognosis as well as possible markers of systemic disorders.

  15. 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;


    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...... as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications......., 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...

  16. A dimeric Rep protein initiates replication of a linear archaeal virus genome: implications for the Rep mechanism and viral replication

    DEFF Research Database (Denmark)

    Oke, Muse; Kerou, Melina; Liu, Huanting


    that a protein encoded in the 34-kbp genome of the rudivirus SIRV1 is a member of the replication initiator (Rep) superfamily of proteins, which initiate rolling-circle replication (RCR) of diverse viruses and plasmids. We show that SIRV Rep nicks the viral hairpin terminus, forming a covalent adduct between...... positioned active sites, each with a single tyrosine residue, work in tandem to catalyze DNA nicking and joining. We propose a novel mechanism for rudivirus DNA replication, incorporating the first known example of a Rep protein that is not linked to RCR. The implications for Rep protein function and viral...

  17. Submicron Composite Mirror Replication (PDRT08-027) Project (United States)

    National Aeronautics and Space Administration — This SBIR program will identify and address the primary technical issues that limit the current precision of replicated CFRP optics. These issues must be resolved to...

  18. Specificity and function of Archaeal DNA replication initiator proteins

    DEFF Research Database (Denmark)

    Samson, Rachel Y.; Xu, Yanqun; Gadelha, Catarina;


    Chromosomes with multiple DNA replication origins are a hallmark of Eukaryotes and some Archaea. All eukaryal nuclear replication origins are defined by the origin recognition complex (ORC) that recruits the replicative helicase MCM(2-7) via Cdc6 and Cdt1. We find that the three origins...... to investigate the role of ATP binding and hydrolysis in initiator function in vivo and in vitro. We find that the ATP-bound form of Orc1-1 is proficient for replication and implicates hydrolysis of ATP in downregulation of origin activity. Finally, we reveal that ATP and DNA binding by Orc1-1 remodels...... the protein's structure rather than that of the DNA template....

  19. Kinetic model of DNA replication in eukaryotic organisms

    CERN Document Server

    Herrick, J; Bensimon, A; Herrick, John; Bechhoefer, John; Bensimon, Aaron


    We formulate a kinetic model of DNA replication that quantitatively describes recent results on DNA replication in the in vitro system of Xenopus laevis prior to the mid-blastula transition. The model describes well a large amount of different data within a simple theoretical framework. This allows one, for the first time, to determine the parameters governing the DNA replication program in a eukaryote on a genome-wide basis. In particular, we have determined the frequency of origin activation in time and space during the cell cycle. Although we focus on a specific stage of development, this model can easily be adapted to describe replication in many other organisms, including budding yeast.

  20. Object Replication and CORBA Fault-Tolerant Object Service

    Institute of Scientific and Technical Information of China (English)


    CORBA (Common Object Request Broker Arc hitecture) provides 16Common Object Services for distributed application develo pment, but none of them are fault-tolerance related services. In this paper, we propose a replicated object based Fault-Tolerant Object Service (FTOS) for COR BA environment. Two fault-tolerant mechanisms are provided in FTOS including dy namic voting mechanism and object replication mechanism. The dynamic voting mech anism uses majority-voting strategy to ensure object state consistency in failu re situations. The object replication mechanism can help system administrators t o replicate and start-up objects easily. Our implementation provides a library according to the style of COSS. With this library, programmers can develop distr ibuted applications with fault-tolerance capability very easily.

  1. Advanced Optical Metrology for XRAY Replication Mandrels and Mirrors Project (United States)

    National Aeronautics and Space Administration — Advanced x-ray observatories such as IXO and GenX will require thousands of thin shell mirror segments produced by replication using convex mandrels. Quality and...

  2. FBH1 Catalyzes Regression of Stalled Replication Forks

    Directory of Open Access Journals (Sweden)

    Kasper Fugger


    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.

  3. Replicate periodic windows in the parameter space of driven oscillators

    Energy Technology Data Exchange (ETDEWEB)

    Medeiros, E.S., E-mail: [Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil); Souza, S.L.T. de [Universidade Federal de Sao Joao del-Rei, Campus Alto Paraopeba, Minas Gerais (Brazil); Medrano-T, R.O. [Departamento de Ciencias Exatas e da Terra, Universidade Federal de Sao Paulo, Diadema, Sao Paulo (Brazil); Caldas, I.L. [Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil)


    Highlights: > We apply a weak harmonic perturbation to control chaos in two driven oscillators. > We find replicate periodic windows in the driven oscillator parameter space. > We find that the periodic window replication is associated with the chaos control. - Abstract: In the bi-dimensional parameter space of driven oscillators, shrimp-shaped periodic windows are immersed in chaotic regions. For two of these oscillators, namely, Duffing and Josephson junction, we show that a weak harmonic perturbation replicates these periodic windows giving rise to parameter regions correspondent to periodic orbits. The new windows are composed of parameters whose periodic orbits have the same periodicity and pattern of stable and unstable periodic orbits already existent for the unperturbed oscillator. Moreover, these unstable periodic orbits are embedded in chaotic attractors in phase space regions where the new stable orbits are identified. Thus, the observed periodic window replication is an effective oscillator control process, once chaotic orbits are replaced by regular ones.

  4. A Transactional Asynchronous Replication Scheme for Mobile Database Systems

    Institute of Scientific and Technical Information of China (English)

    丁治明; 孟小峰; 王珊


    In mobile database systems, mobility of users has a significant impact on data replication. As a result, the various replica control protocols that exist today in traditional distributed and multidatabase environments are no longer suitable. To solve this problem, a new mobile database replication scheme, the Transaction-Level Result-Set Propagation (TLRSP)model, is put forward in this paper. The conflict detection and resolution strategy based on TLRSP is discussed in detail, and the implementation algorithm is proposed. In order to compare the performance of the TLRSP model with that of other mobile replication schemes, we have developed a detailed simulation model. Experimental results show that the TLRSP model provides an efficient support for replicated mobile database systems by reducing reprocessing overhead and maintaining database consistency.

  5. Process chain validation in micro and nano replication

    DEFF Research Database (Denmark)

    Calaon, Matteo

    to remove technology barrier between lab-scale proof-of-principle and high-volume low-cost production of nantechnology based products. The aim of the current study was to develop methods and approaches to process chain validation for final polymer micro and nano structures replication. Fidelity between...... nm and process reproducibility within a range of ±8 nm. Therefore test structures provide a process calibration tool enabling definition of tolerance limits within micro and nano replication...

  6. Lipids and Membrane Microdomains in HIV-1 Replication


    Waheed, Abdul A.; Freed, Eric O.


    Several critical steps in the replication cycle of human immunodeficiency virus type 1 (HIV-1) – entry, assembly and budding – are complex processes that take place at the plasma membrane of the host cell. A growing body of data indicates that these early and late steps in HIV-1 replication take place in specialized plasma membrane microdomains, and that many of the viral and cellular components required for entry, assembly, and budding are concentrated in these microdomains. In particular, a...

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

    DEFF Research Database (Denmark)

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


    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....

  8. Insights into the Initiation of Eukaryotic DNA Replication. (United States)

    Bruck, Irina; Perez-Arnaiz, Patricia; Colbert, Max K; Kaplan, Daniel L


    The initiation of DNA replication is a highly regulated event in eukaryotic cells to ensure that the entire genome is copied once and only once during S phase. The primary target of cellular regulation of eukaryotic DNA replication initiation is the assembly and activation of the replication fork helicase, the 11-subunit assembly that unwinds DNA at a replication fork. The replication fork helicase, called CMG for Cdc45-Mcm2-7, and GINS, assembles in S phase from the constituent Cdc45, Mcm2-7, and GINS proteins. The assembly and activation of the CMG replication fork helicase during S phase is governed by 2 S-phase specific kinases, CDK and DDK. CDK stimulates the interaction between Sld2, Sld3, and Dpb11, 3 initiation factors that are each required for the initiation of DNA replication. DDK, on the other hand, phosphorylates the Mcm2, Mcm4, and Mcm6 subunits of the Mcm2-7 complex. Sld3 recruits Cdc45 to Mcm2-7 in a manner that depends on DDK, and recent work suggests that Sld3 binds directly to Mcm2-7 and also to single-stranded DNA. Furthermore, recent work demonstrates that Sld3 and its human homolog Treslin substantially stimulate DDK phosphorylation of Mcm2. These data suggest that the initiation factor Sld3/Treslin coordinates the assembly and activation of the eukaryotic replication fork helicase by recruiting Cdc45 to Mcm2-7, stimulating DDK phosphorylation of Mcm2, and binding directly to single-stranded DNA as the origin is melted.

  9. Solving Replication Problems in Complete Market by Orthogonal Series Expansion


    Chaohua Dong; Jiti Gao


    We reconsider the replication problem for contingent claims in a complete market under a general framework. Since there are various limitations in the Black-Scholes pricing formula, we propose a new method to obtain an explicit self-financing trading strategy expression for replications of claims in a general model. The departure of our method from the literature is, using an orthogonal expansion of a process related to the proposed trading strategy, we can construct a complete orthonormal ba...

  10. Molecular architecture of the preinitiation complex in adenovirus DNA replication


    Mysiak, Monika Elzbieta


    After infection of a host cell, adenovirus (Ad) aims for generation of progeny viruses, and thus it rapidly replicates its genomic DNA. The replication process starts with the assembly of the preinitiation complex (PIC) on the origin DNA. The PIC consists of three viral proteins, DNA polymerase (pol), precursor terminal protein (pTP), DNA binding protein (DBP) and two transcription factors of the host cell, Nuclear Factor I (NFI) and Octamer binding protein (Oct-1). Both transcription factors...

  11. Verifying likelihoods for low template DNA profiles using multiple replicates (United States)

    Steele, Christopher D.; Greenhalgh, Matthew; Balding, David J.


    To date there is no generally accepted method to test the validity of algorithms used to compute likelihood ratios (LR) evaluating forensic DNA profiles from low-template and/or degraded samples. An upper bound on the LR is provided by the inverse of the match probability, which is the usual measure of weight of evidence for standard DNA profiles not subject to the stochastic effects that are the hallmark of low-template profiles. However, even for low-template profiles the LR in favour of a true prosecution hypothesis should approach this bound as the number of profiling replicates increases, provided that the queried contributor is the major contributor. Moreover, for sufficiently many replicates the standard LR for mixtures is often surpassed by the low-template LR. It follows that multiple LTDNA replicates can provide stronger evidence for a contributor to a mixture than a standard analysis of a good-quality profile. Here, we examine the performance of the likeLTD software for up to eight replicate profiling runs. We consider simulated and laboratory-generated replicates as well as resampling replicates from a real crime case. We show that LRs generated by likeLTD usually do exceed the mixture LR given sufficient replicates, are bounded above by the inverse match probability and do approach this bound closely when this is expected. We also show good performance of likeLTD even when a large majority of alleles are designated as uncertain, and suggest that there can be advantages to using different profiling sensitivities for different replicates. Overall, our results support both the validity of the underlying mathematical model and its correct implementation in the likeLTD software. PMID:25082140

  12. Increase in error threshold for quasispecies by heterogeneous replication accuracy (United States)

    Aoki, Kazuhiro; Furusawa, Mitsuru


    In this paper we investigate the error threshold for quasispecies with heterogeneous replication accuracy. We show that the coexistence of error-free and error-prone polymerases can greatly increase the error threshold without a catastrophic loss of genetic information. We also show that the error threshold is influenced by the number of replicores. Our research suggests that quasispecies with heterogeneous replication accuracy can reduce the genetic cost of selective evolution while still producing a variety of mutants.

  13. Limiting DNA replication to once and only once



    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...

  14. Preventing DNA over-replication: a Cdk perspective

    Directory of Open Access Journals (Sweden)

    Porter Andrew CG


    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.

  15. Insights into the Initiation of Eukaryotic DNA Replication (United States)

    Bruck, Irina; Perez-Arnaiz, Patricia; Colbert, Max K; Kaplan, Daniel L


    The initiation of DNA replication is a highly regulated event in eukaryotic cells to ensure that the entire genome is copied once and only once during S phase. The primary target of cellular regulation of eukaryotic DNA replication initiation is the assembly and activation of the replication fork helicase, the 11-subunit assembly that unwinds DNA at a replication fork. The replication fork helicase, called CMG for Cdc45-Mcm2–7, and GINS, assembles in S phase from the constituent Cdc45, Mcm2–7, and GINS proteins. The assembly and activation of the CMG replication fork helicase during S phase is governed by 2 S-phase specific kinases, CDK and DDK. CDK stimulates the interaction between Sld2, Sld3, and Dpb11, 3 initiation factors that are each required for the initiation of DNA replication. DDK, on the other hand, phosphorylates the Mcm2, Mcm4, and Mcm6 subunits of the Mcm2–7 complex. Sld3 recruits Cdc45 to Mcm2–7 in a manner that depends on DDK, and recent work suggests that Sld3 binds directly to Mcm2–7 and also to single-stranded DNA. Furthermore, recent work demonstrates that Sld3 and its human homolog Treslin substantially stimulate DDK phosphorylation of Mcm2. These data suggest that the initiation factor Sld3/Treslin coordinates the assembly and activation of the eukaryotic replication fork helicase by recruiting Cdc45 to Mcm2–7, stimulating DDK phosphorylation of Mcm2, and binding directly to single-stranded DNA as the origin is melted. PMID:26710261

  16. Differential roles of XRCC2 in S-phase RAD51 focus formation induced by DNA replication inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lim, C; Liu, N


    RAD51 proteins accumulate in discrete nuclear foci in response to DNA damage. Previous studies demonstrated that human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3) are essential for the assembly of RAD51 foci induced by ionizing radiation and cross-linking agents. Here we report that XRCC2 also plays important roles in RAD51 focus formation induced by replication arrest during S-phase of cell cycle. In wild-type hamster V79 cells treated with hydroxyurea (HU), RAD51 protein form punctuate nuclear foci, accompanied by increased RAD51 protein level in both cytoplasmic and nuclear fractions, and increased association of RAD51 with chromatin. In contrast, xrcc2 hamster mutant irs1 cells are deficient in the formation of RAD51 foci after HU treatment, suggesting that the function of XRCC2 is required for the assembly of RAD51 at HU-induced stalled replication forks. Interestingly, we found that irs1 cells are able to form intact RAD51 foci in S-phase cells treated with thymidine (TR) or aphidicolin, although irs1 cells are hypersensitive to both HU and TR. Our findings suggest that there may be two distinct pathways (XRCC2-dependent or XRCC2-independent) involved in loading of RAD51 onto stalled replication forks, probably depending upon the structure of DNA lesions.

  17. Roles of conserved residues within the pre-NH2-terminal domain of herpes simplex virus 1 DNA polymerase in replication and latency in mice. (United States)

    Terrell, Shariya L; Pesola, Jean M; Coen, Donald M


    The catalytic subunit of the herpes simplex virus 1 DNA polymerase (HSV-1 Pol) is essential for viral DNA synthesis and production of infectious virus in cell culture. While mutations that affect 5'-3' polymerase activity have been evaluated in animal models of HSV-1 infection, mutations that affect other functions of HSV-1 Pol have not. In a previous report, we utilized bacterial artificial chromosome technology to generate defined HSV-1 pol mutants with lesions in the previously uncharacterized pre-NH2-terminal domain. We found that the extreme N-terminal 42 residues (deletion mutant polΔN43) were dispensable for replication in cell culture, while residues 44-49 (alanine-substitution mutant polA6) were required for efficient viral DNA synthesis and production of infectious virus. In this study, we sought to address the importance of these conserved elements in viral replication in a mouse corneal infection model. Mutant virus polΔN43 exhibited no meaningful defect in acute or latent infection despite strong conservation of residues 1-42 with HSV-2 Pol. The polA6 mutation caused a modest defect in replication at the site of inoculation, and was severely impaired for ganglionic replication, even at high inocula that permitted efficient corneal replication. Additionally, the polA6 mutation resulted in reduced latency establishment and subsequent reactivation. Moreover, we found that the polA6 replication defect in cultured cells was exacerbated in resting cells as compared to dividing cells. These results reveal an important role for the conserved motif at residues 44-49 of HSV-1 Pol for ganglionic viral replication.

  18. [Color Doppler sonography of focal abdominal lesions]. (United States)

    Licanin, Zoran; Lincender, Lidija; Djurović, V; Salihefendić, Nizama; Smajlović, Fahrudin


    Color Doppler sonography (CDS--spectral, color and power), harmonic imaging techniques (THI, PHI), possibility of 3D analysis of picture, usage of contrast agents, have raised the values of ultrasound as a diagnostic method to a very high level. THI--non-linear gray scale modality, is based on the processing of higher reflected frequencies, that has improved a picture resolution, which is presented with less artifacts and limiting effects of obesity and gases. Ultrasound contrast agents improve analysis of micro and macro circulation of the examined area, and with the assessment of velocity of supply in ROI (wash in), distribution and time of signal weakening (wash out), are significantly increasing diagnostic value of ultrasound. Besides the anatomical and topographic presentation of examined region (color, power), Color Doppler sonography gives us haemodynamic-functional information on vascularisation of that region, as well as on pathologic vascularisation if present. Avascular aspect of a focal pathologic lesion corresponds to a cyst or haematoma, while coloration and positive spectral curve discover that anechogenic lesions actually represents aneurysms, pseudoaneurysms or AVF. In local inflammatory lesion, abscess in an acute phase, CDS shows first increased, and then decreased central perfusion, while in a chronic phase, a pericapsular vascularisation is present. Contribution of CDS in differentiation of hepatic tumors (hemangioma, HCC and metastasis) is very significant. Central color dots along the peripheral blood vessels and the blush phenomenon are characteristics of capillary hemangioma, peritumoral vascular ring "basket" of HCC, and "detour" sign of metastasis. The central artery, RI from 0.45 to 0.60 and radial spreading characterize FNH. Hepatic adenoma is characterized by an intratumoral vein, and rarely by a vascular hallo. Further on, blood velocity in tumor defined by Color Doppler, distinguishes malignant from benign lesion, where 40 cm/s is a

  19. Histochemical identification of malignant and premalignant lesions (United States)

    Liebow, Charles; Maloney, M. J.


    Malignant and transforming cells can be identified by biochemical parameters which can be used to localize lesions in situ for laser surgery. These cells express unique proteins, proteins in unusual quantities, or other biochemical alterations which can be utilized to image lesions of such cells. Several methods have been identified, both in vitro and in vivo, to identify such lesions. Several antibodies were examined for their properties of tissue identification, including CEA, F36/22, and AE1/AE3. F36/22, an antibody developed by M. T. Chu against human breast cancer cells, associated with two lines of oral cancer (KB and HCPC), and against two naturally occurring human oral squamous cell cancers. CEA, an antibody developed against human colon cancer, also reacted against both cell lines and both pathological samples. AE1/AE3, developed against normal fibrous components, also reacted against the samples, but in a much less regular manner. F36/22 associated with the histologically identifiably most dedifferentiated cells at the leading edge of the invading cancer. CEA, on the other hand, associated with more quiescent, older, established cancer cells. This demonstrates that antibodies developed against cancers of different organs can be used to identify a wide variety of cancers, and may have prognostic value. F36/22 coupled to fluorescein was used to identify oral cancer cells. Other properties of cancers and developing cancers can also be exploited to identify cancers, including their over-expression of tyrosine kinase and tyrosine kinase stimulating hormones such as Epidermal Growth Factor (EGF). A model of premalignant lesion produced in the hamster buccal cheek pouch with 6 week application of DMBA over-expresses constitutive tyrosine kinase which can be demonstrated biochemically. This initiated lesion can be promoted to frank cancer by growth factors released in response to laser surgery. Preliminary results suggest that these lesions can be identified by

  20. DNA is a co-factor for its own replication in Xenopus egg extracts

    NARCIS (Netherlands)

    Lebofsky, Ronald; van Oijen, Antoine M.; Walter, Johannes C.


    Soluble Xenopus egg extracts efficiently replicate added plasmids using a physiological mechanism, and thus represent a powerful system to understand vertebrate DNA replication. Surprisingly, DNA replication in this system is highly sensitive to plasmid concentration, being undetectable below simila