Involvement of Artemis in nonhomologous end-joining during immunoglobulin class switch recombination

DNA double-strand breaks (DSBs) introduced in the switch (S) regions are intermediates during immunoglobulin class switch recombination (CSR). These breaks are subsequently recognized, processed, and joined, leading to recombination of the two S regions. Nonhomologous end-joining (NHEJ) is believed to be the principle mechanism involved in DSB repair during CSR. One important component in NHEJ, Artemis, has however been considered to be dispensable for efficient CSR. In this study, we have characterized the S recombinational junctions from Artemis-deficient human B cells. Sμ–Sα junctions could be amplified from all patients tested and were characterized by a complete lack of “direct” end-joining and a remarkable shift in the use of an alternative, microhomology-based end-joining pathway. Sμ–Sγ junctions could only be amplified from one patient who carries “hypomorphic” mutations. Although these Sμ–Sγ junctions appear to be normal, a significant increase of an unusual type of sequential switching from immunoglobulin (Ig)M, through one IgG subclass, to a different IgG subclass was observed, and the Sγ–Sγ junctions showed long microhomologies. Thus, when the function of Artemis is impaired, varying modes of CSR junction resolution may be used for different S regions. Our findings strongly link Artemis to the predominant NHEJ pathway during CSR

Non-homologous end joining in class switch recombination: the beginning of the end

Immunoglobulin class switch recombination (CSR) is initiated by a B-cell-specific factor, activation-induced deaminase, probably through deamination of deoxycytidine residues within the switch (S) regions. The initial lesions in the S regions are subsequently processed, resulting in the production of DNA double-strand breaks (DSBs). These breaks will then be recognized, edited and repaired, finally leading to the recombination of the two S regions. Two major repair pathways have been implicated in CSR, the predominant non-homologous end joining (NHEJ) and the alternative end-joining (A-EJ) pathways. The former requires not only components of the ‘classical’ NHEJ machinery, i.e. Ku70/Ku80, DNA-dependent protein kinase catalytic subunit, DNA ligase IV and XRCC4, but also a number of DNA-damage sensors or adaptors, such as ataxia–telangiectasia mutated, γH2AX, 53BP1, MDC1, the Mre11–Rad50–NBS1 complex and the ataxia telangiectasia and Rad3-related protein (ATR). The latter pathway is not well characterized yet and probably requires microhomologies. In this review, we will focus on the current knowledge of the predominant NHEJ pathway in CSR and will also give a perspective on the A-EJ pathway

One Monopole with k Singularities

We present all charge one monopole solutions of the Bogomolny equation with k prescribed Dirac singularities for the gauge groups U(2), SO(3), or SU(2). We analyze these solutions comparing them to the previously known expressions for the cases of one or two singularities.Comment: 12 pages, LaTe

A Synoptical Classification of the Bivalvia (Mollusca)

The following classification summarizes the suprageneric taxono-my of the Bivalvia for the upcoming revision of the Bivalvia volumes of the Treatise on Invertebrate Paleontology, Part N. The development of this classification began with Carter (1990a), Campbell, Hoeks-tra, and Carter (1995, 1998), Campbell (2000, 2003), and Carter, Campbell, and Campbell (2000, 2006), who, with assistance from the United States National Science Foundation, conducted large-scale morphological phylogenetic analyses of mostly Paleozoic bivalves, as well as molecular phylogenetic analyses of living bivalves. Dur-ing the past several years, their initial phylogenetic framework has been revised and greatly expanded through collaboration with many students of bivalve biology and paleontology, many of whom are coauthors. During this process, all available sources of phylogenetic information, including molecular, anatomical, shell morphological, shell microstructural, bio- and paleobiogeographic as well as strati-graphic, have been integrated into the classification. The more recent sources of phylogenetic information include, but are not limited to, Carter (1990a), Malchus (1990), J. Schneider (1995, 1998a, 1998b, 2002), T. Waller (1998), Hautmann (1999, 2001a, 2001b), Giribet and Wheeler (2002), Giribet and Distel (2003), Dreyer, Steiner, and Harper (2003), Matsumoto (2003), Harper, Dreyer, and Steiner (2006), Kappner and Bieler (2006), Mikkelsen and others (2006), Neulinger and others (2006), Taylor and Glover (2006), Kříž (2007), B. Morton (2007), Taylor, Williams, and Glover (2007), Taylor and others (2007), Giribet (2008), and Kirkendale (2009). This work has also benefited from the nomenclator of bivalve families by Bouchet and Rocroi (2010) and its accompanying classification by Bieler, Carter, and Coan (2010).This classification strives to indicate the most likely phylogenetic position for each taxon. Uncertainty is indicated by a question mark before the name of the taxon. Many of the higher taxa continue to undergo major taxonomic revision. This is especially true for the superfamilies Sphaerioidea and Veneroidea, and the orders Pectinida and Unionida. Because of this state of flux, some parts of the clas-sification represent a compromise between opposing points of view. Placement of the Trigonioidoidea is especially problematic. This Mesozoic superfamily has traditionally been placed in the order Unionida, as a possible derivative of the superfamily Unionoidea (see Cox, 1952; Sha, 1992, 1993; Gu, 1998; Guo, 1998; Bieler, Carter, & Coan, 2010). However, Chen Jin-hua (2009) summarized evi-dence that Trigonioidoidea was derived instead from the superfamily Trigonioidea. Arguments for these alternatives appear equally strong, so we presently list the Trigonioidoidea, with question, under both the Trigoniida and Unionida, with the contents of the superfamily indicated under the Trigoniida.Fil: Carter, Joseph G.. University of North Carolina; Estados UnidosFil: Altaba, Cristian R.. Universidad de las Islas Baleares; EspañaFil: Anderson, Laurie C.. South Dakota School of Mines and Technology; Estados UnidosFil: Araujo, Rafael. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Ciencias Naturales; EspañaFil: Biakov, Alexander S.. Russian Academy of Sciences; RusiaFil: Bogan, Arthur E.. North Carolina State Museum of Natural Sciences; Estados UnidosFil: Campbell, David. Paleontological Research Institution; Estados UnidosFil: Campbell, Matthew. Charleston Southern University; Estados UnidosFil: Chen, Jin Hua. Chinese Academy of Sciences. Nanjing Institute of Geology and Palaeontology; República de ChinaFil: Cope, John C. W.. National Museum of Wales. Department of Geology; Reino UnidoFil: Delvene, Graciela. Instituto Geológico y Minero de España; EspañaFil: Dijkstra, Henk H.. Netherlands Centre for Biodiversity; Países BajosFil: Fang, Zong Jie. Chinese Academy of Sciences; República de ChinaFil: Gardner, Ronald N.. No especifica;Fil: Gavrilova, Vera A.. Russian Geological Research Institute; RusiaFil: Goncharova, Irina A.. Russian Academy of Sciences; RusiaFil: Harries, Peter J.. University of South Florida; Estados UnidosFil: Hartman, Joseph H.. University of North Dakota; Estados UnidosFil: Hautmann, Michael. Paläontologisches Institut und Museum; SuizaFil: Hoeh, Walter R.. Kent State University; Estados UnidosFil: Hylleberg, Jorgen. Institute of Biology; DinamarcaFil: Jiang, Bao Yu. Nanjing University; República de ChinaFil: Johnston, Paul. Mount Royal University; CanadáFil: Kirkendale, Lisa. University Of Wollongong; AustraliaFil: Kleemann, Karl. Universidad de Viena; AustriaFil: Koppka, Jens. Office de la Culture. Section d’Archéologie et Paléontologie; SuizaFil: Kříž, Jiří. Czech Geological Survey. Department of Sedimentary Formations. Lower Palaeozoic Section; República ChecaFil: Machado, Deusana. Universidade Federal do Rio de Janeiro; BrasilFil: Malchus, Nikolaus. Institut Català de Paleontologia; EspañaFil: Márquez Aliaga, Ana. Universidad de Valencia; EspañaFil: Masse, Jean Pierre. Universite de Provence; FranciaFil: McRoberts, Christopher A.. State University of New York at Cortland. Department of Geology; Estados UnidosFil: Middelfart, Peter U.. Australian Museum; AustraliaFil: Mitchell, Simon. The University of the West Indies at Mona; JamaicaFil: Nevesskaja, Lidiya A.. Russian Academy of Sciences; RusiaFil: Özer, Sacit. Dokuz Eylül University; TurquíaFil: Pojeta, John Jr.. National Museum of Natural History; Estados UnidosFil: Polubotko, Inga V.. Russian Geological Research Institute; RusiaFil: Pons, Jose Maria. Universitat Autònoma de Barcelona; EspañaFil: Popov, Sergey. Russian Academy of Sciences; RusiaFil: Sanchez, Teresa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Sartori, André F.. Field Museum of National History; Estados UnidosFil: Scott, Robert W.. Precision Stratigraphy Associates; Estados UnidosFil: Sey, Irina I.. Russian Geological Research Institute; RusiaFil: Signorelli, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Silantiev, Vladimir V.. Kazan Federal University; RusiaFil: Skelton, Peter W.. Open University. Department of Earth and Environmental Sciences; Reino UnidoFil: Steuber, Thomas. The Petroleum Institute; Emiratos Arabes UnidosFil: Waterhouse, J. Bruce. No especifica;Fil: Wingard, G. Lynn. United States Geological Survey; Estados UnidosFil: Yancey, Thomas. Texas A&M University; Estados Unido

Is Evolution of Blind Mole Rats Determined by Climate Oscillations?

The concept of climate variability facilitating adaptive radiation supported by the ‘‘Court Jester’’ hypothesis is disputed by the ‘‘Red Queen’’ one, but the prevalence of one or the other might be scale-dependent. We report on a detailed, comprehensive phylo-geographic study on the ,4 kb mtDNA sequence in underground blind mole rats of the family Spalacidae (or subfamily Spalacinae) from the East Mediterranean steppes. Our study aimed at testing the presence of periodicities in branching patterns on a constructed phylogenetic tree and at searching for congruence between branching events, tectonic history and paleoclimates. In contrast to the strong support for the majority of the branching events on the tree, the absence of support in a few instances indicates that network-like evolution could exist in spalacids. In our tree, robust support was given, in concordance with paleontological data, for the separation of spalacids from muroid rodents during the first half of the Miocene when open, grass-dominated habitats were established. Marine barriers formed between Anatolia and the Balkans could have facilitated the separation of the lineage ‘‘Spalax’’ from the lineage ‘‘Nannospalax’’ and of the clade ‘‘leucodon’’ from the clade ‘‘xanthodon’’. The separation of the clade ‘‘ehrenbergi’’ occurred during the late stages of the tectonically induced uplift of the Anatolian high plateaus and mountains, whereas the separation of the clade ‘‘vasvarii’’ took place when the rapidly uplifting Taurus mountain range prevented the Mediterranean rainfalls from reaching the Central Anatolian Plateau. The separation of Spalax antiquus and S. graecus occurred when the southeastern Carpathians were uplifted. Despite the role played by tectonic events, branching events that show periodicity corresponding to 400-kyr and 100-kyr eccentricity bands illuminate the important role of orbital fluctuations on adaptive radiation in spalacids. At the given scale, our results supports the ‘‘Court Jester’’ hypothesis over the ‘‘Red Queen’’ one

A Regulatory Role for NBS1 in Strand-Specific Mutagenesis during Somatic Hypermutation

Activation-induced cytidine deaminase (AID) is believed to initiate somatic hypermutation (SHM) by deamination of deoxycytidines to deoxyuridines within the immunoglobulin variable regions genes. The deaminated bases can subsequently be replicated over, processed by base excision repair or mismatch repair, leading to introduction of different types of point mutations (G/C transitions, G/C transversions and A/T mutations). It is evident that the base excision repair pathway is largely dependent on uracil-DNA glycosylase (UNG) through its uracil excision activity. It is not known, however, which endonuclease acts in the step immediately downstream of UNG, i.e. that cleaves at the abasic sites generated by the latter. Two candidates have been proposed, an apurinic/apyrimidinic endonuclease (APE) and the Mre11-Rad50-NBS1 complex. The latter is intriguing as this might explain how the mutagenic pathway is primed during SHM. We have investigated the latter possibility by studying the in vivo SHM pattern in B cells from ataxia-telangiectasia-like disorder (Mre11 deficient) and Nijmegen breakage syndrome (NBS1 deficient) patients. Our results show that, although the pattern of mutations in the variable heavy chain (VH) genes was altered in NBS1 deficient patients, with a significantly increased number of G (but not C) transversions occurring in the SHM and/or AID targeting hotspots, the general pattern of mutations in the VH genes in Mre11 deficient patients was only slightly altered, with an increased frequency of A to C transversions. The Mre11-Rad50-NBS1 complex is thus unlikely to be the major nuclease involved in cleavage of the abasic sites during SHM, whereas NBS1 might have a specific role in regulating the strand-biased repair during phase Ib mutagenesis

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio