Late-onset thymidine kinase 2 deficiency: a review of 18 cases

BACKGROUND: TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the 'myopathic form' of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity. METHODS: We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12. RESULTS: The mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients. CONCLUSIONS: The late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency.Instituto de Salud Carlos III PI16-01843 PI16/00579 CP09/00011Subdirección General de Evaluación y Fomento de la Investigación Sanitaria PI16-01843 PI16/00579 CP09/00011 PI 15/00431 PMP15/0002

Extension of geographical distribution of three common species of diurnal butterflies (Lepidoptera: Papilionoidea) from the Colombian Caribbean

En este documento se registran tres especies comunes de mariposas diurnas de la región Caribe colombiana (Aides dysoni, Calpodes ethlius y Anteos clorinde). Los especímenes fueron capturados con red entomológica en muestreos realizados en el municipio de Arjona (departamento de Bolívar) en el año de 2015 entre las 8:00 y 16:00 horas. Para cada una de ellas se proporcionan caracteres morfológicos útiles para su reconocimiento y se complementa su distribución en el Neotrópico.In this document we extend the geographical distribution for three common species of diurnal butterflies from the Colombian Caribbean region (Aides dysoni, Calpodes ethlius, and Anteos clorinde). The specimens were captured with an insect net in samplings conducted in the Arjona jurisdiction (Bolivar, Deparment) in 2015, between 8:00 and 16:00 hours. For each of them we provide important morphological characters for their recognition, and complement their distribution in the Neotropic

Adsorción competitiva de Ni (II) y Pb (II) sobre materiales residuales lignocelulósicos

Introduction: a batch study was carried out for the adsorption of Pb (II) and Ni (II) in binary solution using biomasses from corncob and orange peel.Methods: the initial concentrations of each metal were varied in 25, 50, 75 and 100 ppm. The adsorption was conducted at pH 6.0 and biomass size of 0.5 mm. Measurements of residual metal concentrations were determined by atomic absorption.Results: it was found that the initial metal concentration and binary solutions not interfere with the removal percentage of the contaminants, and the Freundlich and Langmuir models provided a good fit of the experimental data.Conclusion: it was also established that the metal antagonistic action changes according to the biomass used, being the capacity of Ni (II)>Pb (II) for the corncob biomass, and Pb (II)> Ni (II) for the orange peels.Introducción: un estudio batch fue realizado para la adsorción de Pb (II) y Ni (II) en solución binaria, utilizando biomasas de tusa de maíz y cáscara de naranja.Métodos: las concentraciones iniciales de cada metal variaron en 25, 50, 75 y 100 ppm. La adsorción se llevó a cabo a pH 6,0 y tamaño de biomasas de 0,5 mm. Las mediciones de concentración residual de los metales se determinaron por absorción atómica.Resultados: se encontró que la concentración inicial del metal y las soluciones binarias no interfieren en el porcentaje de remoción de los contaminantes, y que los modelos Freundlich y Langmuir ofrecen un buen ajuste de los datos experimentales.Conclusión: se estableció que la acción antagonista de los metales cambia de acuerdo a la biomasa utilizada, siendo la capacidad del Ni (II) > Pb (II) para la tusa de maíz, y Pb (II) > Ni (II) para las cáscaras de naranj

Longevity of Cleruchoides noackae (Hymenoptera: Mymaridae), an egg parasitoid of Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae), with various honey concentrations and at several temperatures.

Thaumastocoris peregrinus Carpintero and Dellapé (Hemiptera: Thaumastocoridae), damages eucalyptus plants by sucking their sap. This pest can be controlled by releases of the egg parasitoid Cleruchoides noackae Lin and Huber (Hymenoptera: Mymaridae). Increasing the survival of this parasitoid is critically important for its mass rearing in order to release large numbers in integrated programs to manage T. peregrinus. The aim of this study was to evaluate the longevity of C. noackae adults fed various honey concentrations at 6 constant temperatures. The longevity of C. noackae was studied by keeping adults in a 1st experiment with 100, 50, or 10% honey solution, with distilled water, or without water and food in climate-controlled chambers at 25 ± 2 °C, 70 ± 10% RH, and a 12:12 h L:D photoperiod and?in a 2nd experiment?with 100% honey at constant temperatures of 15, 18, 21, 25, 28, or 31 °C in a climatic chamber at 70 ± 10% RH and a 12:12 h L:D photoperiod. Each adult parasitoid was held individually in a glass tube capped with plastic wrap under the conditions described, and the survival of adults was recorded daily. The longevity of C. noackae varied with food and temperature such that longevity was enhanced by all honey concentrations and temperatures of 25 °C and below. When fed honey, this parasitoid lived 2 to 3 fold longer when kept at 15, 18, 21, and 25 °C than at 28 and 31 °C. Thus, the parasitoid C. noackae should be mass reared with honey at temperatures from 15 to 25 °C for subsequent distribution of parasitoid adults in eucalyptus plantations for suppressing T. peregrinus

Ocorrência de Megastigmus sp. (Hymenoptera: Torymidae) parasitoide da vespa da galha Leptocybe invasa (Hymenoptera: Eulophidae) no Brasil.

Resumo

Desempenho do parasitoide Trichospilus diatreae (Hymenoptera: Eulophidae) utilizando como hospedeiro Spodoptera frugiperda (Lepdoptera: Noctuidae), sob diferentes tempos de exposição.

Resumo

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

Background: The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease. Methods: This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped. Results: A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97–2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00–6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16–3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16–1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants. Conclusion: The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE

Aplicación de Fotocatalizadores Obtenidos a partir de Ácido Tungstofosfórico sobre NH4ZSM5 en Remediación de Aguas Contaminadas

Se prepararon materiales a partir de la inmovilización de ácido tungstofosfórico sobre zeolita NH4ZSM5 mediante impregnación húmeda para ser aplicados en la degradación de moléculas representativas de contaminantes presentes en efluentes empleando fotocatálisis heterogénea. La concentración de ácido tunstofosfórico incorporada fue de 10 y 30% p/p en el sólido obtenido. Los materiales se caracterizaron mediante diferentes técnicas fisicoquímicas. El área superficial disminuyó respecto de la matriz sin modificar como resultado de bloqueo de los poros de la zeolita. Los patrones de difracción de rayos X de las muestras modificadas presentaron los picos característicos de zeolita NH4ZSM5 y un conjunto de picos adicionales asignados a la presencia de la sal (NH4)3[PW12O40]. Además, las muestras exhibieron valores de band gap similares a los reportados para los semiconductores más estudiados. Se obtuvieron catalizadores con elevada actividad fotocatalítica en las moléculas de estudio

DNA Methylation-Independent Reversion of Gemcitabine Resistance by Hydralazine in Cervical Cancer Cells

BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase