The enzymatic properties of Arabidopsis thaliana DNA polymerase λ suggest a role in base excision repair.

Base excision repair (BER) generates gapped DNA intermediates containing a 5'-terminal 2-deoxyribose-5-phosphate (5'-dRP) group. In mammalian cells, gap filling and dRP removal are catalyzed by Pol ß, which belongs to the X family of DNA polymerases. In higher plants, the only member of the X family of DNA polymerases is Pol λ. Although it is generally believed that plant Pol λ participates in BER, there is limited experimental evidence for this hypothesis. Here we have characterized the biochemical properties of Arabidopsis thaliana Pol λ (AtPol λ) in a BER context, using a variety of DNA repair intermediates. We have found that AtPol λ performs gap filling inserting the correct nucleotide, and that the rate of nucleotide incorporation is higher in substrates containing a C in the template strand. Gap filling catalyzed by AtPol λ is most efficient with a phosphate at the 5'-end of the gap and is not inhibited by the presence of a 5'-dRP mimic. We also show that AtPol λ possesses an intrinsic dRP lyase activity that is reduced by mutations at two lysine residues in its 8-kDa domain, one of which is present in Pol λ exclusively and not in any Pol ß homolog. Importantly, we also found that the dRP lyase activity of AtPol λ allows efficient completion of uracil repair in a reconstituted short-patch BER reaction. These results suggest that AtPol λ plays an important role in plant BER.

The C-terminal domain of Arabidopsis ROS1 DNA demethylase interacts with histone H3 and is required for DNA binding and catalytic activity.

Active DNA demethylation plays an important role in controlling methylation patterns in eukaryotes. In plants, the DEMETER-LIKE (DML) family of 5-methylcytosine DNA glycosylases initiates DNA demethylation through a base excision repair pathway. However, it is poorly understood how these DNA demethylases are recruited to their target loci and the role that histone marks play in this process. Arabidopsis REPRESSOR OF SILENCING 1 (ROS1) is a representative enzyme of the DML family, whose members are uniquely characterized by a basic amino-terminal domain mediating nonspecific binding to DNA, a discontinuous catalytic domain, and a conserved carboxy-terminal domain of unknown function. Here, we show that ROS1 interacts with the N-terminal tail of H3 through its C-terminal domain. Importantly, phosphorylation at H3 Ser28, but not Ser10, abrogates ROS1 interaction with H3. Conserved residues at the C-terminal domain are not only required for H3 interaction, but also for efficient DNA binding and catalytic activity. Our findings suggest that the C-terminal domain of ROS1 may function as a histone reader module involved in recruitment of the DNA demethylase activity to specific genomic regions.

[Baroreflex activation therapy: One more step in the treatment of resistant arterial hypertension and chronic heart failure]. / La terapia de activación de barorreceptores, un paso más en el tratamiento de la hipertensión arterial resistente y la insuficiencia cardiaca.

The number of patients who suffer refractory arterial hypertension and chronic heart failure in advanced stages is currently increasing. The case is presented of a patient with an implantable cardioverter defibrillator, and with the dual indication of chronic heart failure and refractory arterial hypertension, who required the implanting of a baroreceptors activation therapy device of the carotid sinus. As far as it is known, it is the first case reported in Spain?

The negative effect of nitrate on gametogenesis is independent of nitrate assimilation in Chlamydomonas reinhardtii.

The effect of nitrate on gamete differentiation as well as on the expression of genes involved in gametogenesis, nitrogen scavenging, and nitrate assimilation has been analyzed in wild-type and mutant strains of Chlamydomonas reinhardtii. Nitrate prevented gamete formation from wild-type strains and caused a strong reduction in the number of zygotes recovered in genetic crosses between nitrate-assimilation-deficient mutants, thus suggesting that nitrate by itself is providing a negative regulatory signal for the sexual differentiation of the alga. Addition of nitrate at low concentrations to wild-type cells, after an initial period of nitrogen starvation, resulted in a drastic decrease in transcript levels of both nitrate-assimilation genes (NIA1 and NRT2;1) and genes induced after N-starvation (NCG2 and NCG4). This strong effect of nitrate was due to its assimilation products since it was not evident in nitrate-assimilation mutants. A slight negative effect of nitrate on NCG4 expression was only observed in the mutant. Nitrate by itself was also found to provide a negative signal for the expression of gamete-specific genes (GAS3 and GAS18) in mutants incapable of assimilating nitrate.

Analgesia epidural y resultados obstétricos / Epidural analgesia and obstetric outcomes

Se realizó un estudio retrospectivo, descriptivo y comparativo acerca de los efectos de la analgesia epidural frente a no analgesia epidural en el parto, en una muestra de 1.928 partos acontecidos en un período de 3 años y se atendió a una serie de parámetros que se pueden ver influenciados de manera positiva o negativa, como son factores relacionados con las distintas fases del parto, distocias, instrumentación, índice de cesáreas, repercusiones neonatales e impacto sobre el suelo pélvico. Tras el tratamiento estadístico, se observaron diferencias significativas en la prolongación del parto, el mayor número de instrumentación, el aumento en la tasa de cesáreas y el incremento del índice de episiotomías en multíparas en los partos conducidos bajo analgesia epidural. Por el contrario, no se dieron diferencias significativas en las distocias en occipito posterior, fiebre intraparto, partos con cesárea anterior o episiotomías en primíparas. Hubo significación estadística a favor de los partos sin analgesia epidural en el número de infecciones neonatales, así como desgarros perineales de primer grado en multíparas e integridad perineal en multíparas. A tenor de estos resultados obtenidos en nuestro hospital, nos planteamos incorporar al documento de consentimiento informado sobre analgesia epidural todos los posibles efectos adversos derivados de ésta (AU)

We performed a descriptive retrospective study comparing the effects of the application versus non application of epidural analgesia during delivery in1928 women over a 3-year period. Several parameters that could be positively or negatively influenced by epidural analgesia administration, such as factors related to the different stages of delivery, dystocia, instrumentation, rate of cesarean sections, neonatal repercussion and impact on the pelvic floor, were evaluated. Statistical analysis revealed that epidural analgesia was associated with prolongation of delivery and increases in the number of instruments involved and the rates of cesarean section and episiotomy in multiparas. These differences were statistically significant. In contrast, no significant differences were found in the occurrence of dystocia in the occipito posterior position, intrapartum fever, deliveries with prior cesarian section or episiotomy in primiparas. Statistically significant differences were found in favor of deliveries without epidural analgesia in the number of neonatal infections, as well as in first degree lacerations and perineal integrity in multiparous women In view of the results obtained in our hospital, we are considering adding all the possible adverse effects associated with epidural analgesia to our informed consent document (AU)