1,394 research outputs found

    DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

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    The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3β€²-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5β€²-terminated strand of the DNA break and to inhibit 3β€² to 5β€² degradation by Dna2, actions that generate and protect the 3β€²-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

    A new measurement of the structure functions PLLβˆ’PTT/epsilonP_{LL}-P_{TT}/epsilon and PLTP_{LT} in virtual Compton scattering at Q2=Q^2= 0.33 (GeV/c)2^2

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    The cross section of the epβ†’eβ€²pβ€²Ξ³ep \to e' p' \gamma reaction has been measured at Q2=0.33Q^2 = 0.33 (GeV/c)2^2. The experiment was performed using the electron beam of the MAMI accelerator and the standard detector setup of the A1 Collaboration. The cross section is analyzed using the low-energy theorem for virtual Compton scattering, yielding a new determination of the two structure functions P_LL}-P_{TT}/epsilon and PLTP_{LT} which are linear combinations of the generalized polarizabilities of the proton. We find somewhat larger values than in the previous investigation at the same Q2Q^2. This difference, however, is purely due to our more refined analysis of the data. The results tend to confirm the non-trivial Q2Q^2-evolution of the generalized polarizabilities and call for more measurements in the low-Q2Q^2 region (≀\le 1 (GeV/c)2^2).Comment: 9 pages, 10 figures. EPJA version. slight revisions in the text and figure

    Reconstructing phylogenies from noisy quartets in polynomial time with a high success probability

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    <p>Abstract</p> <p>Background</p> <p>In recent years, quartet-based phylogeny reconstruction methods have received considerable attentions in the computational biology community. Traditionally, the accuracy of a phylogeny reconstruction method is measured by simulations on synthetic datasets with known "true" phylogenies, while little theoretical analysis has been done. In this paper, we present a new model-based approach to measuring the accuracy of a quartet-based phylogeny reconstruction method. Under this model, we propose three efficient algorithms to reconstruct the "true" phylogeny with a high success probability.</p> <p>Results</p> <p>The first algorithm can reconstruct the "true" phylogeny from the input quartet topology set without quartet errors in <it>O</it>(<it>n</it><sup>2</sup>) time by querying at most (<it>n </it>- 4) log(<it>n </it>- 1) quartet topologies, where <it>n </it>is the number of the taxa. When the input quartet topology set contains errors, the second algorithm can reconstruct the "true" phylogeny with a probability approximately 1 - <it>p </it>in <it>O</it>(<it>n</it><sup>4 </sup>log <it>n</it>) time, where <it>p </it>is the probability for a quartet topology being an error. This probability is improved by the third algorithm to approximately <inline-formula><m:math name="1748-7188-3-1-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:mfrac><m:mn>1</m:mn><m:mrow><m:mn>1</m:mn><m:mo>+</m:mo><m:msup><m:mi>q</m:mi><m:mn>2</m:mn></m:msup><m:mo>+</m:mo><m:mfrac><m:mn>1</m:mn><m:mn>2</m:mn></m:mfrac><m:msup><m:mi>q</m:mi><m:mn>4</m:mn></m:msup><m:mo>+</m:mo><m:mfrac><m:mn>1</m:mn><m:mrow><m:mn>16</m:mn></m:mrow></m:mfrac><m:msup><m:mi>q</m:mi><m:mn>5</m:mn></m:msup></m:mrow></m:mfrac></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaqcfa4aaSaaaeaacqaIXaqmaeaacqaIXaqmcqGHRaWkcqWGXbqCdaahaaqabeaacqaIYaGmaaGaey4kaSYaaSaaaeaacqaIXaqmaeaacqaIYaGmaaGaemyCae3aaWbaaeqabaGaeGinaqdaaiabgUcaRmaalaaabaGaeGymaedabaGaeGymaeJaeGOnaydaaiabdghaXnaaCaaabeqaaiabiwda1aaaaaaaaa@3D5A@</m:annotation></m:semantics></m:math></inline-formula>, where <inline-formula><m:math name="1748-7188-3-1-i2" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:mi>q</m:mi><m:mo>=</m:mo><m:mfrac><m:mi>p</m:mi><m:mrow><m:mn>1</m:mn><m:mo>βˆ’</m:mo><m:mi>p</m:mi></m:mrow></m:mfrac></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaGaemyCaeNaeyypa0tcfa4aaSaaaeaacqWGWbaCaeaacqaIXaqmcqGHsislcqWGWbaCaaaaaa@3391@</m:annotation></m:semantics></m:math></inline-formula>, with running time of <it>O</it>(<it>n</it><sup>5</sup>), which is at least 0.984 when <it>p </it>< 0.05.</p> <p>Conclusion</p> <p>The three proposed algorithms are mathematically guaranteed to reconstruct the "true" phylogeny with a high success probability. The experimental results showed that the third algorithm produced phylogenies with a higher probability than its aforementioned theoretical lower bound and outperformed some existing phylogeny reconstruction methods in both speed and accuracy.</p

    A Resonant X-ray Scattering Study of Octahedral Tilt Ordering in LaMnO3_3 and Pr1βˆ’x_{1-x}Cax_xMnO3_3

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    We report an x-ray scattering study of octahedral tilt ordering in the manganite series Pr1βˆ’x_{1-x}Cax_xMnO3_3 with x=0.4 and 0.25 and in LaMnO3_3. The sensitivity to tilt ordering is achieved by tuning the incident x-ray energy to the LI_I, LII_{II} and LIII_{III} absorption edges of Pr and La, respectively. The resulting energy-dependent profiles are characterized by a dipole-resonant peak and higher energy fine structure. The polarization dependence is predominantly Οƒ\sigma-to-Ο€\pi and the azimuthal dependence follows a sin-squared behavior. These results are similar to those obtained in recent x-ray scattering studies of orbital ordering carried out in these same materials at the Mn K edge. They lead to a description of the cross-section in terms of Templeton scattering in which the tilt ordering breaks the symmetry at the rare earth site. The most interesting result of the present work is our observation that octahedral tilt ordering persists above the orbital ordering transition temperatures in all three samples. Indeed, we identify separate structural transitions which may be associated with the onset of orbital and tilt ordering, respectively, and characterize the loss of tilt ordering versus temperature in LaMnO3_3.Comment: 24 pages, 8 figure

    The pion photoproduction in the \Delta(1232) region

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    We investigate the pion photoproduction in the \Delta(1232) region in the framework of an effective Lagrangian including pions, nulceon and \Delta(1232). We work to third order in a small scale expansion with both mΟ€m_{\pi} and MΞ”βˆ’MNM_{\Delta}-M_N treated as light scales. We note that in the Ξ”\Delta region, straightward power counting breaks as the amplitudes become very large, to deal with this problem, we suggest that the appropriate way to compare theoretical calculations with experimental data is via weighted integrals of the amplitudes through the Ξ”\Delta region.Comment: 34 pages and 5 figures,new counterterms arr adde

    The Dog Mite, Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

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    Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3

    Double Field Theory for Double D-branes

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    We consider Hull's doubled formalism for open strings on D-branes in flat space and construct the corresponding effective double field theory. We show that the worldsheet boundary conditions of the doubled formalism describe in a unified way a T-dual pair of D-branes, which we call double D-branes. We evaluate the one-loop beta function for the boundary gauge coupling and then obtain the effective field theory for the double D-branes. The effective field theory is described by a DBI action of double fields. The T-duality covariant form of this DBI action is thus a kind of "master" action, which describes all the double D-brane configurations related by T-duality transformations. We discuss a number of aspects of this effective theory.Comment: Latex, 1+33 pages. v2 with minor corrections, a new reference added. v3 a typo correcte

    Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

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    Background: To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods: Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [ 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results: Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion: During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome
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