Kv10.1 potassium channel: from the brain to the tumors.

The KCNH1 gene encodes the Kv10.1 (Eag1) ion channel, a member of the EAG (ether-à-go-go) family of voltage-gated potassium channels. Recent studies have demonstrated that KCHN1 mutations are implicated in Temple-Baraitser and Zimmermann-Laband syndromes and other forms of developmental deficits that all present with mental retardation and epilepsy, suggesting that Kv10.1 might be important for cognitive development in humans. Although the Kv10.1 channel is mainly expressed in the mammalian brain, its ectopic expression occurs in 70% of human cancers. Cancer cells and tumors expressing Kv10.1 acquire selective advantages that favor cancer progression through molecular mechanisms that involve several cellular pathways, indicating that protein-protein interactions may be important for Kv10.1 influence in cell proliferation and tumorigenesis. Several studies on transcriptional and post-transcriptional regulation of Kv10.1 expression have shown interesting mechanistic insights about Kv10.1 role in oncogenesis, increasing the importance of identifying the cellular factors that regulate Kv10.1 expression in tumors.

Ongoing expansion of the worldwide invader Didemnum vexillum (Ascidiacea) in the Mediterranean Sea: high plasticity of its biological cycle promotes establishment in warm waters.

Non-indigenous ascidians are of particular concern to aquaculture industry and, paradoxically, the activities associated with it represent an important way to translocate these species worldwide. In 2012 a non-indigenous ascidian was found covering the oyster crops in the Ebro Delta (Western Mediterranean). We have identified the ascidian genetically and morphologically as Didemnum vexillum Kott, 2002. This finding indicates that the species is currently expanding its distribution in the Mediterranean Sea, as it has recently been found in the eastern basin (Venice, Adriatic Sea). Introduced populations of D. vexillum are found in temperate and cold waters worldwide, and a successful establishment in the Mediterranean implies a remarkable capacity of adaptability to warm, subtropical conditions. We assessed the life cycle (growth and reproduction) of the ascidian at the studied site. The species has a marked seasonal cycle, with regression in the warmest months and reappearance during winter. In spring D. vexillum reaches its maximum abundance, followed by a peak in reproduction just before regression. This cycle is reversed with respect to the one observed in colder waters, highlighting a plastic biological cycle of this invader and an hitherto unknown ability to establish itself in warm waters. We also analysed the genetic structure of the population of the Ebro Delta and the one established in the Lagoon of Venice using COI sequence data. The low genetic diversity in our samples (three haplotypes) was consistent with what is observed in the introduced populations worldwide. It is likely that the ascidian was introduced with oyster stock from bivalve cultures in the Atlantic French coasts, where the same three haplotypes have been reported. The high boating activity in the Ebro Delta makes further human-mediated transport of the species highly likely, and nearby fishing grounds can be severely affected if invaded. It is urgent to implement measures to prevent the continuous expansion of this ascidian pest in the Mediterranean.

A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.

The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression.

Toxicity in semiarid sediments influenced by tailings of an abandoned gold mine.

The mining district of El Triunfo (ET-MD) has an estimated 800,000 t of mine wastes scattered in the environment, contaminating the sediment with potentially toxic elements such as As, Cd, Pb, and Zn. In order to estimate the toxicity of the sediment to the adjacent biota, the aims of our study are to calculate the mortality and inhibition through bioassays, using sediment, and test organisms such as Daphnia magna and Selenastrum capricornutum (Pseudokirchneriella subcapitata), respectively. The D. magna mortality was 31 ± 12% and the S. capricornutum growth inhibition was 53 ± 24%. The contamination of the sediment determines the high mortality of D. magna and the high inhibition of S. capricornutum in the system, indicating risk for the biota in the contaminated system.

Recombination and selection in the maintenance of the adaptive value of inversions.

A huge amount of data seem to confirm the adaptive value of inversions in Drosophila. The inhibition of recombination in heterokaryotypes mediated by inversions seems fundamental in maintaining their adaptive role. This study shows that recombination is highly suppressed in Drosophila subobscura because of chromosomal inversions, not only inside the inversions but also outside them. It seems that the region outside the inversion where recombination is inhibited is asymmetrical and independent of the inversion length. Despite the difficulty of crossovers taking place near inversion breakpoints, the only two recombination events detected inside inversions were located close to the breakpoint. Thus, selection could be largely responsible for the recombination reduction maintaining sets of adaptive alleles inside the inverted region. Heterokaryotype descendants were always in higher frequency than inbred or outbred homokaryotypes, regardless of the geographical origin of the chromosome, suggesting that chromosomes carrying the same arrangement, although with a different set of alleles for neutral markers, could be submitted to the same selection processes.

Sheep management and cryptosporidiosis in central Mexico.

To establish the association between sheep farm management practices and cryptosporidiosis in Central Mexico, 37 farms were invited and questionnaires answered by owners. Faeces samples were taken from lambs under 3 months old and ewes in the farms. Parasites were identified by modified Ziehl-Neelsen stain. Questionnaire included: general farm information, facilities characteristics, facilities cleaning measures, water use and farm and animal management practices. Farms were grouped in a low ( Pound 3,37%), medium (3.38-49.9%) and high basis ((3)50%) according to prevalence. Associations (OR) were calculated according to positivity, compared by chi-square test. A general prevalence of 34,33% was found. Five variables showed statistical significance (p<0.05). Associations found were: use of bed, grazing place, and bottle cleaning. The only association found between management practices and cryptosporidiosis that could represent a risk was the grazing place. This report is the first one in the country regarding predisposing conditions for cryptosporidiosis.

Liposarcoma lingual / Lingual liposarcoma

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[Survival of myeloma patients treated with dialysis]. / Supervivencia de pacientes con mieloma tratados con diálisis.

BACKGROUND: Renal failure is a common complication of myeloma. Renal replacement therapy in these patients is controversial due to poor survival outcomes and low tolerance to treatment. We reviewed our experience on patients with myeloma undergoing dialysis therapy at one centre. PATIENTS AND METHODS: Between 1980 and 2000, 28 patients (21 men and 7 women) with myeloma were admitted to chronic dialysis programme and the following variables were analysed: sex, age when starting dialysis, lapse of time between diagnosis of myeloma and admission to dialysis (TD), disease stage, comorbity, mode of presentation, calcium, creatinine at diagnostic, albumin and Hb at the beginning of dialysis, and cause of death. We studied survival among these patients (Kaplan-Meier), identified predictors of survival outcome (Cox's regression) and compared survival between the two decades studied. RESULTS: Mean age was 65 years, median TD was 0.4 months, and modes of presentation were: end-stage renal failure (18 patients), acute renal failure (8), amyloldosis (2). Eleven patients (39%) had myeloma IgG, four (14%) IgA and thirteen (46%) had light chains. Kappa light chain was the most frequent one. In 75% of patients myeloma was at IIIb stage. Cause of death were: Cardiovascular disease (5 patients), infections (4), suspension of treatment (4), tumours (4), and others causes (2). Median survival for all patients was 16.8 months (range 0.4-78) and 25% survived over 39 months. Hb level was the only significant predictor in the multivariant analysis (p = 0.02). In the 80's median survival was 6.17 months versus 17 months in the 90's but this difference was not significant with long-rank test. CONCLUSION: Although survival of patients with myeloma treated with dialysis is still short, 25 percent survive over 3 years, being Hb level the only predictive factor. Moreover, we observed an improvement of survival in recent years.

Supervivencia de pacientes con mieloma tratados con diálisis / Survival in patients with myeloma treated with dialysis

Introducción: La insuficiencia renal es una complicación frecuente del mieloma (MM). La indicación de tratamiento sustitutivo de la función renal en estos pacientes es controvertida, debido a mala supervivencia y tolerancia. Se revisa la experiencia de nuestro centro con todos los pacientes diagnosticados de MM durante los últimos 20 años y admitidos a programa de diálisis crónica. Pacientes y métodos: Se estudian 28 pacientes (21 hombres y 7 mujeres) con MM y que iniciaron tratamiento con diálisis entre los años 1980 y 2000 en los que se evaluaron variables clínicas y analíticas: sexo, edad al inicio de diálisis, tiempo entre el diagnóstico y la entrada en diálisis (TD), estadio de la enfermedad, presencia de comorbilidad, forma de presentación, calcio sérico, creatinina en el momento del diagnóstico, albúmina, hemoglobina al inicio de la diálisis (Hb) y causa de muerte. Se estudia también la supervivencia (método de Kaplan-Meier) y se trató de identificar variables predictoras con el análisis de regresión de Cox. Para valorar la respuesta al tratamiento se dividieron los casos aparecidos en dos períodos de diez años. Resultados: Con una edad media de 65 años, la mediana para el intervalo diagnóstico inicio diálisis (TD) fue de 0,4 meses. En 18 casos la afectación renal se presentó como insuficiencia renal crónica, fracaso renal agudo en 8 y amiloidosis en 2. Once pacientes (39%) fueron MM IgG, 4 (14%) IgA, y 13 (46%) con cadenas ligeras. El 75% presentaban un estadio IIIb. Las causas de muerte fueron: cardiovasculares en 5 casos, infecciones en 4, cese del tratamiento en 4, tumoral en 4 y otras en 2. La mediana de la supervivencia fue de 16,8 meses para todo el grupo (rango 0,4-78), y en el análisis multivariante sólo las concentraciones de hemoglobina resultaron predictivas (p = 0,02). El 25% de los pacientes sobrevivió 39 meses. En la década de los ochenta la mediana fue de 6,17 meses y para los noventa de 17 meses. Esta diferencia no alcanzó significación estadística con el log-rank test (p = 0,12). Conclusión: Aunque la supervivencia de los pacientes con MM en diálisis sigue siendo baja, una proporción estimable sobrevive más de tres años y además se evidencia una tendencia hacia una mayor supervivencia en la última década. La Hb fue la única variable predictora encontrada

Background: Renal failure is a common complication of myeloma. Renal replacement therapy in these patients is controversial due to poor survival outcomes and low tolerance to treatment. We reviewed our experience on patients with myeloma undergoing dialysis therapy at one centre. Patients and methods: Between 1980 and 2000, 28 patients (21 men and 7 women) with myeloma were admitted to chronic dialysis programme and the following variables were analysed: sex, age when starting dialysis, lapse of time between diagnosis of myeloma and admission to dialysis (TD), disease stage, comorbidity, mode of presentation, calcium, creatinine at diagnostic, albumin and Hb at the beginning of dialysis, and cause of death. We studied survival among these patients (Kaplan-Meier), identified predictors of survival outcome (Cox’s regression) and compared survival between the two decades studied. Results: Mean age was 65 years, median TD was 0.4 months, and modes of presentation were: end-stage renal failure (18 patients), acute renal failure (8), amyloldosis (2). Eleven patients (39%) had myeloma IgG, four (14%) lgA and thirteen (46%) had light chains. Kappa light chain was the most frequent one. In 75% of patients myeloma was at Illb stage. Cause of death were: Cardiovascular disease (5 patients), infections (4), suspension of treatment (4), tumours (4), and others causes (2). Median survival for all patients was 16.8 months (range 0.4-78) and 25% survived over 39 months. Hb level was the only significant predictor in the multivariant analysis (p = 0.02). In the 80’s median survival was 6.17 months versus 17 months in the 90's but this difference was not significant with long- rank test. Conclusion: Although survival of patients with myeloma treated with dialysis is still short, 25 percent survives over 3 years, being Hb level the only predictive factor. Moreover, we observed an improvement of survival in recent years