Unnexin is a protein subunit of a large-pore channel expressed by unicellular organisms.

Cells of vertebrate and invertebrate organisms express proteins specialized in membrane channel-based cell-cell communication that are absent in unicellular organisms. We recently described the prediction of some members of the large-pore channel family in kinetoplastids, consisting of proteins called unnexins, which share several structural features with innexin and pannexin proteins. Here, we demonstrated that the unnexin1 protein (Unx1) is delivered to the cell membrane, displaying a topology consisting of four transmembrane domains with C and N termini on the cytoplasmic side and form large-pore channels that are permeable to small molecules. Low extracellular Ca2+/Mg2+ levels or extracellular alkalinization, but not mechanical stretching, increases channel activity. The Unx1 channel mediates the influx of Ca2+ and does not form intercellular dye coupling between HeLa Unx1 transfected cells. Unx1 channel function was further evidenced by its ability to mediate ionic currents when expressed in Xenopus oocytes. Downregulation of Unx1 mRNA with morpholine contains Trypanosoma cruzi invasion. Phylogenetic analysis revealed the presence of Unx1 homologs in other protozoan parasites, suggesting a conserved function for these channel parasites in other protists. Our data demonstrate that Unx1 forms large-pore membrane channels, which may serve as a diffusional pathway for ions and small molecules that are likely to be metabolic substrates or waste products, and signaling autocrine and paracrine molecules that could be involved in cell invasion. As morpholinos-induced downregulation of Unx1 reduces the infectivity of trypomastigotes, the Unx1 channels might be an attractive target for developing trypanocide drugs.

Direct inhibition of CaV2.3 by Gem is dynamin dependent and does not require a direct alfa/beta interaction.

The Rad, Rem, Rem2, and Gem/Kir (RGK) sub-family of small GTP-binding proteins are crucial in regulating high voltage-activated (HVA) calcium channels. RGK proteins inhibit calcium current by either promoting endocytosis or reducing channel activity. They all can associate directly with Ca2+ channel ß subunit (CaVß), and the binding between CaVα1/CaVß appears essential for the endocytic promotion of CaV1.X, CaV2.1, and CaV2.2 channels. In this study, we investigated the inhibition of CaV2.3 channels by RGK proteins in the absence of CaVß. To this end, Xenopus laevis oocytes expressing CaV2.3 channels devoid of auxiliary subunit were injected with purified Gem and Rem and found that only Gem had an effect. Ca currents and charge movements were reduced by injection of Gem, pointing to a reduction in the number of channels in the plasma membrane. Since this reduction was ablated by co-expression of the dominant-negative mutant of dynamin K44A, enhanced endocytosis appears to mediate this reduction in the number of channels. Thus, Gem inhibition of CaV2.3 channels would be the only example of a CaVß independent promotion of dynamin-dependent endocytosis.

Incidental discovery of desmoid-type fibromatosis encapsulating granular cell tumor in a neck mass.

Multiple primary cancers are defined as primary malignant tumors of different histological origins in one person. Desmoid-type fibromatosis (DF) is an extremely rare, locally aggressive, connective tissue malignancy that can be rooted anywhere in the body with the most common sites being thoracic wall and extremities. In contrast, granular cell tumors are rare neoplasms derived from Schwann cells commonly found in the oral cavity, skin and gastrointestinal tract. Moreover, diagnosing a patient with two primary cell tumors has become more common and the challenge of treatment becomes the focus in clinical situations. However, findings of a mass containing DF encapsulated by a granular cell tumor. Currently, there are no established guidelines for this rare condition. This case report serves to raise awareness of these two uncommon primary tumors emerging in an idiosyncratic nature.

Clinical Outcomes after Surgical Resection Combined with Brachytherapy for Uveal Melanomas.

Currently, brachytherapy is the most commonly used therapeutic approach for uveal melanomas. Surgical resection by means of endoresection or exoresection is an alternative approach. The present report recounts our experience over 15 years in the treatment of uveal melanoma using a combined approach of resection surgery with brachytherapy. This is a single-center observational retrospective cohort study in which we describe clinical outcomes, complications and survival in 35 cases of melanoma of the iris or the ciliary body after a combination of surgery and brachytherapy or brachytherapy alone. Local treatment of the tumor was successful in all cases with surgery and brachytherapy. The most frequent complications were scleromalacia, bullous keratopathy, retinal toxicity, cataracts, hypotonia, and photophobia. There were three cases of recurrence, all of which were found in the group of patients who had received brachytherapy alone, and in one case we had to perform a secondary enucleation due to tumor growth after brachytherapy. At present, only one patient has died during follow-up due to liver metastases six years after the start of treatment. In carefully selected patients, this approach can be effective and safe, as long as a close follow-up is carried out after surgery.

Experimental induction and mathematical modeling of Ca2+ dynamics in rat round spermatids.

Cytosolic Ca2+ concentration ([Ca2+ ]) has an important role in spermatozoa and hence it regulates fertilization. In male germinal cells, there are indirect evidences that this ion could regulate physiological processes in spermatogenesis. Since little is known about Ca2+ homeostasis in spermatogenic cells, in this work we propose a mathematical model that accounts for experimental [Ca2+ ] dynamics triggered by blockade of the SERCA transport ATPase with thapsigargin in round rat spermatids, without external Ca2+ and with different extracellular lactate concentrations. The model included three homogeneous calcium compartments and Ca2+-ATPase activities sensitive and insensitive to thapsigargin, and it adjusted satisfactorily the experimental calcium dynamic data. Moreover, an extended version of the model satisfactorily adjusted the stationary states of calcium modulated by extracellular lactate, which is consistent with the participation of a low affinity lactate transporter and further lactate metabolism in these cells. Further studies and modeling would be necessary to shed some light into the relation between Ca2+-lactate-ATP homeostasis and cell-cell interactions in the seminiferous tubules that are expected to modulate Ca2+ dynamics by hormonal factors or energetic substrates in meiotic and postmeiotic spermatogenic cells.

Patología tiroidea en niños con diabetes mellitus tipo 1 en el Instituto Nacional de Salud del Niño / Thyroid pathology in children with diabetes mellitus type 1 in the National Institute of Health of the Child

El presente estudio se realizó en el Servicio Endocrinología del Instituto Nacional de Salud del Niño en el periodo comprendido del 27 de Octubre al 4 de Noviembre del presente año. El estudio fue de tipo descriptivo, retrospectivo, transversal. Objetivo: Determinar la prevalencia de patología tiroidea en pacientes con diagnóstico de DM1. Material y métodos: La muestra estuvo constituida por 235 casos de pacientes pediátricos con el diagnostico de Diabetes Mellitus tipo I que fueron atendidos en el Servicio de Endocrinología del Instituto Nacional de Salud del Niño, de estas se excluyeron 34 historias clínicas ya que no contenían datos de las variables planteadas para nuestro estudio, se tomaron al final 201 historias clínicas del archivo del servicio. Los datos obtenidos durante la investigación durante la investigación, por medio de la ficha de recolección de datos, elaborada para los fines de la investigación se ordenaron y procesaron en una computadora personal, valiéndonos del programa SPSS 17.0 para Windows 2007. Resultados. La media de la edad de la población estudiada de 9.2±4.2 años...

This study was performed at the National Institute of Endocrinology, Child Health in the period from October 27 to November 4 this year. The study was descriptive, retrospective, and transversal. Objective: To determinate the prevalence of thyroid disease in patients with a diagnosis of DM1. Methods: the sample consisted of 235 cases (all stories clinics) of pediatric patients with the diagnosis of type I diabetes mellitus who were trated in the endocrinology service at the National Institute of Child Health, of these 34stories were excluded and clinical data did not contain the variables proposed in our study, 201 were taken at the end of the file histories of service. The data obtained during the investigation, though data collection sheet, developed for search purposes were ordered and processed in a personal computer, availing the SPSS 17.0 for Windows 2007. Results: The mean age of the study population of 9.2+ /-4.2 years...