AID Induces Double-Strand Breaks at Immunoglobulin Switch Regions and c-MYC Causing Chromosomal Translocations in Yeast THO Mutants

Transcription of the switch (S) regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID), triggering class switch recombination (CSR), as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs) which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ). AID–induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID–mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID–mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells

Iberian red deer: Paraphyletic nature at mtDNA but nuclear markers support its genetic identity

British Ecological Society Special Feature: Demography Beyond the Population.Red deer populations in the Iberian glacial refugium were the main source for postglacial recolonization and subspecific radiation in north-western Europe. However, the phylogenetic history of Iberian red deer (Cervus elaphus hispanicus) and its relationships with northern European populations remain uncertain. Here, we study DNA sequences at the mitochondrial control region along with STR markers for over 680 specimens from all the main red deer populations in Spain and other west European areas. Our results from mitochondrial and genomic DNA show contrasting patterns, likely related to the nature of these types of DNA markers and their specific processes of change over time. The results, taken together, bring support to two distinct, cryptic maternal lineages for Iberian red deer that predated the last glacial maximum and that have maintained geographically well differentiated until present. Haplotype relationships show that only one of them contributed to the northern postglacial recolonization. However, allele frequencies of nuclear markers evidenced one main differentiation between Iberian and northern European subspecies although also supported the structure of both matrilines within Iberia. Thus, our findings reveal a paraphyletic nature for Iberian red deer but also its genetic identity and differentiation with respect to northern subspecies. Finally, we suggest that maintaining the singularity of Iberian red deer requires preventing not only restocking practices with red deer specimens belonging to other European populations but also translocations between both Iberian lineages.This work was partly supported by project CGL2010-17163/BOS from the Spanish MInistry of Science and by Extremadura and Andalusian Regional Goverments.Peer Reviewe

Detection of the Saharan dust air layer in the North Atlantic free troposphere with AERONET, OMI and in-situ data at Izaña Atmospheric Observatory

Comunicación presentada en: Symposium on Atmospheric Chemistry and Physics at Mountain Sites celebrado del 8 al 10 de junio de 2010 en Interlaken, Suiza

Overexpression of FurA in Anabaena sp. PCC 7120 Reveals New Targets for This Regulator Involved in Photosynthesis, Iron Uptake and Cellular Morphology

Previous genomic analyses of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 have identified three ferric uptake regulator (Fur) homologs with low sequence identities and probably different functions in the cell. FurA is a constitutive protein that shares the highest homology with Fur from heterotrophic bacteria and appears to be essential for invitro growth. In this study, we have analysed the effects of FurA overexpression on the Anabaena sp. phenotype and investigated which of the observed alterations were directly operated by FurA. Overexpression of the regulator led to changes in cellular morphology, resulting in shorter filaments with rounded cells of different sizes. The furA-overexpressing strain showed a slower photoautotrophic growth and a marked decrease in the oxygen evolution rate. Overexpression of the regulator also decreased both catalase and superoxide dismutase activities, but did not lead to an increase in the levels of intracellular reactive oxygen species. By combining phenotypic studies, reverse transcription-PCR analyses and electrophoretic mobility shift assays, we identified three novel direct targets of FurA, including genes encoding a siderophore outer membrane transporter (schT), bacterial actins (mreBCD) and the PSII reaction center protein D1 (psbA). The affinity of FurA for these novel targets was markedly affected by the absence of divalent metal ions, confirming previous evidence of a critical role for the metal co-repressor in the function of the regulator invivo. The results unravel new cellular processes modulated by FurA, supporting its role as a global transcriptional regulator in Anabaena sp. PCC 712

First record of Leishmaniasis in wild Jaguars (Panthera onca) from Mexico

Leishmaniasis is a vector-borne disease and parasitic zoonosis that occurs worldwide (i.e., Latin America, Africa and Eurasian countries; Desjeux 2005, Dahroug et al. 2010, 2011, Otranto et al. 2013). It is caused by parasitic kinetoplastids of the Leishmania genus transmitted by arthropod vectors (i.e. sandflies such as Lutzomyia spp.) and presents a great diversity of clinical profiles, depending on the affected areas (Otranto et al. 2013). This disease mainly affects humans and wild carnivoran species, mostly canids, with dogs as major reservoir hosts (Deane & Deane 1954, Silva et al. 2000, Figueiredo et al. 2008, Dantas-Torres et al. 2012). Even though domestic and wild felids are unusual reservoirs, and rarely develop the disease, several studies suggest that these species may play an important role in the epidemiology of the disease (Poli et al. 2002, Maia et al. 2008, Nasereddin et al. 2008, Dantas-Torres et al. 2012). Here we report the first record of a clinical manifestation of Leishmaniasis disease in a wild Jaguar (Panthera onca) in Quintana Roo, Mexico.Leishmaniasis is a vector-borne disease and parasitic zoonosis that occurs worldwide (i.e., Latin America, Africa and Eurasian countries; Desjeux 2005, Dahroug et al. 2010, 2011, Otranto et al. 2013). It is caused by parasitic kinetoplastids of the Leishmania genus transmitted by arthropod vectors (i.e. sandflies such as Lutzomyia spp.) and presents a great diversity of clinical profiles, depending on the affected areas (Otranto et al. 2013). This disease mainly affects humans and wild carnivoran species, mostly canids, with dogs as major reservoir hosts (Deane & Deane 1954, Silva et al. 2000, Figueiredo et al. 2008, Dantas-Torres et al. 2012). Even though domestic and wild felids are unusual reservoirs, and rarely develop the disease, several studies suggest that these species may play an important role in the epidemiology of the disease (Poli et al. 2002, Maia et al. 2008, Nasereddin et al. 2008, Dantas-Torres et al. 2012). Here we report the first record of a clinical manifestation of Leishmaniasis disease in a wild Jaguar (Panthera onca) in Quintana Roo, Mexico

Características imaginológicas del paciente con anemia de Fanconi: informe de un caso

ResumenLa anemia de Fanconi (AF) es una enfermedad autosómica recesiva que se caracteriza por la presencia de aplasia de la medula ósea y que generalmente se acompaña de diversas malformaciones congénitas y la presencia de síndrome mielodisplásico o de leucemia mieloide aguda. Se presenta el caso de un paciente masculino deS años de edadI producío de un embarazo normalI que al eñamen físico presenta microcefalia y cuatro dedos en cada mano con ausencia de los dedos pulgares; las imágenes diagnósticas muestran la presencia de aplasia radial y ausencia de los huesos carpianos radiales del miembro superior izquierdo. Se hace impresióndiagnósíáca de anemáa de canconá por eñámenes de laboraíoráo. Al momento de sospechar el diagnóstico de AF, es importante tener en cuenta las distintas enfermedades que por sus características  clínicas y  las diferentes malformaciones congénitas que  las acompañan se consideran diagnósticos diferenciales, y así poderrealizar un adecuado manejo terapéutico.[Pérez AF, González JL Características imaginológicas del paciente con anemia de Fanconi: informe de un caso. MedUNAB 2006; 9:179-182].Palabras clave: Anemia de Fanconi, Anormalidades congénitas, Diagnósticos diferenciales

Magnetic-dipole spin effects in noncommutative quantum mechanics

A general three-dimensional noncommutative quantum mechanical system mixing spatial and spin degrees of freedom is proposed. The analogous of the harmonic oscillator in this description contains a magnetic dipole interaction and the ground state is explicitly computed and we show that it is infinitely degenerated and implying a spontaneous symmetry breaking. The model can be straightforwardly extended to many particles and the main above properties are retained. Possible applications to the Bose-Einstein condensation with dipole-dipole interactions are briefly discussed.Instituto de Física La Plat

The Challenge of Iron Stress in Cyanobacteria

Iron is an essential nutrient for most living organisms. Due to the low solubility of ferric iron at physiological pH, the transition from an anaerobic atmosphere to the actual oxidant environment caused a dramatical decrease of iron bioavailability. Therefore, most organisms had to adapt their lifestyle to survive under an iron-depleted environment. In cyanobacteria, the electron transport chains involved in photosynthesis and respiration, as well as the enzymes involved in nitrogen metabolism have a high content of iron. Hence, cyanobacterial iron requirements are much higher than those of heterotrophic organisms. In this chapter, we revise different strategies developed by this important group of microorganisms to cope with iron deficiency, as well as the regulatory networks involved in the homeostasis of this indispensable element