The Molecular Basis and Biologic Significance of the ß-Dystroglycan-Emerin Interaction.

ß-dystroglycan (ß-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of ß-DG, we characterized the interaction between ß-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery-Dreifuss muscular dystrophy (EDMD). Using truncated variants of ß-DG and emerin, via a series of in vitro and in vivo binding experiments and a tailored computational analysis, we determined that the ß-DG-emerin interaction is mediated at least in part by their respective transmembrane domains (TM). Using surface plasmon resonance assays we showed that emerin binds to ß-DG with high affinity (KD in the nanomolar range). Remarkably, the analysis of cells in which DG was knocked out demonstrated that loss of ß-DG resulted in a decreased emerin stability and impairment of emerin-mediated processes. ß-DG and emerin are reciprocally required for their optimal targeting within the NE, as shown by immunofluorescence, western blotting and immunoprecipitation assays using emerin variants with mutations in the TM domain and B-lymphocytes of a patient with EDMD. In summary, we demonstrated that ß-DG plays a role as an emerin interacting partner modulating its stability and function.

The intracellular domain of ß-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity.

ß-dystroglycan (ß-DG) is a key component of multiprotein complexes in the plasma membrane and nuclear envelope. In addition, ß-DG undergoes two successive proteolytic cleavages that result in the liberation of its intracellular domain (ICD) into the cytosol and nucleus. However, stimuli-inducing ICD cleavage and the physiological relevance of this proteolytic fragment are largely unknown. In this study we show for the first time that ß-DG ICD is targeted to the nucleolus where it interacts with the nuclear proteins B23 and UBF (central factor of Pol I-mediated rRNA gene transcription) and binds to rDNA promoter regions. Interestingly DG silencing results in reduced B23 and UBF levels and aberrant nucleolar morphology. Furthermore, ß-DG ICD cleavage is induced by different nucleolar stressors, including oxidative stress, acidosis, and UV irradiation, which implies its participation in the response to nucleolar stress. Consistent with this idea, overexpression of ß-DG elicited mislocalization and decreased levels of UBF and suppression of rRNA expression, which in turn provoked altered ribosome profiling and decreased cell growth. Collectively our data reveal that ß-DG ICD acts as negative regulator of rDNA transcription by impeding the transcriptional activity of UBF, as a part of the protective mechanism activated in response to nucleolar stress.

Complicaciones hemodinámicas en una faco-vitrectomía: sospecha de una embolia aérea / Hemodynamic complications in a phaco-vitrectomy: suspicion of an air embolism

La embolia aérea es una complicación quirúrgica potencialmente fatal, que debe manejarse rápida y precozmente, por lo que su reconocimiento temprano es esencial. Al tener una amplia gama de posibles manifestaciones clínicas, la sospecha diagnóstica en base al procedimiento quirúrgico es fundamental. Presentamos el caso de una paciente de 69 años sometida a una faco-vitrectomía con anestesia general que sufrió un colapso hemodinámico brusco durante la fase de intercambio aire/fluido.(AU)

: Venous air embolism is a potentially fatal surgical complication which must be managed quickly, so early recognition is essential. Having a wide range of possible clinical manifestations, it requires a high index of suspicion based on the surgical procedure.We report a case of a 69-year-old woman undergoing general anesthesia for phaco-vitrectomy who suffered a sudden hemodynamic collapse during the air fluid exchange phase.(AU)

Toxicological features of maleilated polyflavonoids from Pinus radiata (D. Don.) as potential functional additives for biomaterials design.

Polyflavonoids from Pinus radiata (D. Don.) are an abundant natural oligomers highly desirable as renewable chemicals. However, structural modification of polyflavonoids is a viable strategy in order to use such polyphenols as macrobuilding-blocks for biomaterial design. Polyflavonoids were esterified with three five-member cyclic anhydrides (maleic, itaconic, and citraconic) at 20 °C during 24 h in order to diversify physicochemical-, and biological-properties for agricultural, and food-packaging applications. In addition, the influence of the chemical modification, as well as the chemical structure of the grafting on toxicological features was evaluated. Structural features of derivatives were analyzed by spectroscopy (FT-IR and 1H-NMR), and the degree of substitution was calculated. Toxicological profile was assessed by using three target species in a wide range of concentration (0.01-100 mgL-1). Effect of polyflavonoids on the growth rate (Selenastrum capricornutum), mortality (Daphnia magna), and germination and radicle length (Lactuca sativa) was determined. Chemical modification affects the toxicological profile on the derivatives in a high extent. Results described remarkable differences in function of the target specie. The bioassays indicate differences of the polyflavonoids toxicological profile associated to the chemical structure of the grafting. Results allowed conclude that polyflavonoids from pine bark show slight toxic properties.

Consideraciones perioperatorias en pacientes consumidores de drogas ilícitas de uso frecuente / Perioperative considerations in patients consumers of illicit drugs frequently used

Debido al importante aumento del consumo de drogas ilícitas o recreativas en nuestra sociedad, es cada vez más probable que nos encontremos con pacientes usuarios de ellas en el contexto quirúrgico. Es importante conocer los principales efectos de las sustancias ilícitas más frecuentemente usadas por los pacientes sometidos a cirugía, como cocaína, marihuana, pasta base de cocaína y psicoestimulantes, como también los efectos más significativos que pueden producirse al combinar estas sustancias recreativas con fármacos relacionados a la cirugía y anestesia. Asimismo, es relevante tener en cuenta las principales consideraciones perioperatorias en el proceso quirúrgico y anestésico de los pacientes consumidores de estas drogas ilícitas. La cocaína altera principalmente los sistemas cardiovascular, respiratorio, nervioso central, gastrointestinal y renal, teniendo los pacientes adictos mayor riesgo de infarto agudo al miocardio, arritmias y crisis hipertensivas arteriales. La marihuana inhibe los receptores muscarínicos de acetilcolina, afectando principalmente los sistemas cardiovascular, respiratorio y neuropsiquiátrico, teniendo un rol importante en el manejo analgésico intra y postoperatorio. La pasta base de cocaína provoca un aumento transitorio en la neurotransmisión dopaminérgica, siendo similar a la cocaína por lo que se recomienda un manejo perioperatorio parecido. Las drogas psicoestimulantes tienen efecto simpaticomimético, afectando esencialmente los sistemas cardiovascular y metabólico. Esta revisión resume la evidencia médica vigente sobre el tema, con el fin de unificar criterios y sugerir pautas de manejo de estos pacientes durante el período perioperatorio, donde los efectos de estas drogas ilícitas posiblemente sean más significativos, pudiendo generar complicaciones graves y poniendo en riesgo la vida del paciente.

Due to the significant increase of illicit or recreational drugs in our society, it is increasingly likely that we find patients using them in the surgical context. It is important to understand the main effects of illegal substances most commonly used by patients undergoing surgery, such as cocaine, marijuana, cocaine paste and psychostimulants, as the most significant effects that can be produced by combining these recreational drugs with related substances of surgery and anesthesia. It is also relevant to consider the major perioperative considerations (surgical and anesthetic) in consumer patients of these illicit drugs. Cocaine alters the cardiovascular, respiratory, central nervous, gastrointestinal and renal systems, addicted patients taking higher risk of acute myocardial infarction, arrhythmias and arterial hypertensive crisis. Marijuana inhibits muscarinic acetylcholine receptors, primarily affecting the cardiovascular, respiratory and neuropsychiatric systems, and has an important role in intra and postoperative analgesic management. The cocaine base paste causes transient increase in dopaminergic neurotransmission, being similar to cocaine so a similar perioperative management is recommended. The psychostimulant drugs are sympathomimetic effect, essentially affecting the cardiovascular and metabolic systems. This review summarizes the current medical evidence on the subject, in order to unify criteria and management guidelines suggest these patients during the perioperative period, where the effects of these illicit drugs are likely to be more significant, potentially leading to serious complications and endangering the patient's life.

Ecotoxicological sediment evaluations in marine aquaculture areas of Chile.

Given its geographic characteristics, the southern Chilean fjord area is subjected to growing environmental pressure from the development of diverse forms of aquaculture (i.e., fish, algae, shellfish). The sediments accumulate substances as a natural sink, and ecotoxicology assays offer a reliable and robust proxy for sediment quality analyses. This study's objective was to establish a mid-range toxicity base line for the sediments in the region by applying a battery of non-specific ecotoxicological assays. Sediment samples (28) were collected in the channels and fjords studied during the CIMAR-Fiordos 11 cruise (July 2005). The sediments were evaluated using different species endemic to the eastern Pacific as targets: Ampelisca araucana, Tisbe longicornis, Arbacia spatuligera, and Dunaliella tertiolecta. The conditions for each assay were reported previously. Of the four species used as ecotoxicological tools, only D. tertiolecta differed significantly from the control group (negative) in terms of its growth. This difference could be attributed to nutrient enrichment. In general, we concluded that, although local changes occurred in the sediments, the mesoscale magnitude of the ecotoxicological alterations was small. Nonetheless, a surveillance program should be implemented that would allow us to follow-up and analyze the changes that are taking place in the systems on broader scales of time and space.

Determination of toxicity levels in the San Pedro River Watershed, Aguascalientes, Mexico.

A quantitative study of toxicity levels of the San Pedro River and its main tributaries around the city of Aguascalientes, Mexico was conducted. Our study determined individual CL(50) values for each sampling point at 3 different times of the year corresponding to the main seasons of the year in terms of the hydrological cycle (dry, low rain and high rain season). Those LC(50) values were used to calculate the acute. Toxicity Units (aTU) that allowed us to compare levels of toxicity along the San Pedro River and two of its main tributaries. The sample that showed highest toxicity was IPIVA. This is due to the large quantity of industrial discharges that receives. Its effluent was responsible for the largest contribution of toxicity to the San Pedro River over the three rounds of sampling of this study. Our study classified an important portion of the San Pedro River and two of its main tributaries in toxic, moderately toxic and lightly toxic. No portion of the river studied was free of toxicity, either acute or sublethal. This study demonstrated that in spite of the operation of several water treatment plants along the San Pedro River, for the most part, the water quality of the river is still unacceptable.