Single-channel Properties of Human NaV1.1 and Mechanism of Channel Dysfunction in SCN1A-associated Epilepsy

Mutations in genes encoding neuronal voltage-gated sodium channel subunits have been linked to inherited forms of epilepsy. The majority of mutations (>100) associated with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) occur in SCN1A encoding the NaV1.1 neuronal sodium channel α-subunit. Previous studies demonstrated functional heterogeneity among mutant SCN1A channels, revealing a complex relationship between clinical and biophysical phenotypes. To further understand the mechanisms responsible for mutant SCN1A behavior, we performed a comprehensive analysis of the single-channel properties of heterologously expressed recombinant WT-SCN1A channels. Based on these data, we then determined the mechanisms for dysfunction of two GEFS+-associated mutations (R1648H, R1657C) both affecting the S4 segment of domain 4. WT-SCN1A has a slope conductance (17 pS) similar to channels found in native mammalian neurons. The mean open time is ∼0.3 ms in the −30 to −10 mV range. The R1648H mutant, previously shown to display persistent sodium current in whole-cell recordings, exhibited similar slope conductance but had an increased probability of late reopening and a subfraction of channels with prolonged open times. We did not observe bursting behavior and found no evidence for a gating mode shift to explain the increased persistent current caused by R1648H. Cells expressing R1657C exhibited conductance, open probability, mean open time, and latency to first opening similar to WT channels but reduced whole-cell current density, suggesting decreased number of functional channels at the plasma membrane. In summary, our findings define single-channel properties for WT-SCN1A, detail the functional phenotypes for two human epilepsy-associated sodium channel mutants, and clarify the mechanism for increased persistent sodium current induced by the R1648H allele

Estudio Comparativo en la Calidad Nutricional y Empatique de Galletas de Pulido de Arroz

El pulido de arroz se define como un subproducto de aspecto harinoso, suave y fibroso al tacto, constituido por el pericarpio, el tegumento, la aleurona, parte del grano, en polvo o en fragmentos y germen entero y triturado, así como cascarilla. Es rico en proteínas, grasas, y contiene una cantidad apreciable de vitaminas y minerales; sin embargo el uso al que se ha destinado este subproducto es únicamente para el consumo animal. En base a lo anterior, el objetivo de este trabajo de investigación es contribuir en la trasformación del pulido de arroz para consumo humano, mediante la elaboración de galletas utilizando el subproducto de arroz pulido. Para el logro del trabajo de investigación, la materia prima se obtuvo de la empresa arrocera Agrocampo Arisanta S.P.R de R.L de C.V. una vez obtenida la materia prima, esta llevo a laboratorio para la preparación de las galletas, realizar los distintos análisis físico-químicos e identificar la vida en anaquel, la cual se valoró cada 15 días durante un periode de cinco meses. Los resultados indican que la porción por galleta debe de ser de 40 gramos, teniendo cada galleta un contenido de fibra de 3.2% y 12.5% de proteína. En relación a la vida en anaquel, se observó que las galletas conservan sus características organolépticas hasta por un tiempo de cinco meses. Estos resultados contribuyen de forma directa a los beneficios a la salud, por lo que sus características permite que se desarrollen alimentos funcionales, tal es el caso de la elaboración de galletas a base de pulido, de consistencia y  sabor agradable al paladar de aquellas personas que gustan de cuidar su dieta   Rice polishing is defined as a by-product with a floury appearance, soft and fibrous to the touch, consisting of the pericarp, the integument, the aleurone, part of the grain, in powder or fragments and whole and ground germ, as well as a husk. It is rich in proteins, and fats, and contains an appreciable amount of vitamins and minerals; however, the use to which this by-product has been destined is solely for animal consumption. Based on the above, the objective of this research work is to contribute to the transformation of polished rice for human consumption, by making biscuits using the polished rice by-product. For the achievement of the research work, the raw material was obtained from the rice company Agrocampo Arisanta S.P.R de R.L de C.V. Once the raw material was obtained, it was taken to the laboratory for the preparation of the cookies, to carry out the different physical-chemical analyzes and to identify the shelf life, which was valued every 15 days during a period of five months. The results indicate that the serving per cookie should be 40 grams, with each cookie having a fiber content of 3.2% and 12.5% ​​protein. In relation to shelf life, it was observed that cookies retain their organoleptic characteristics for up to five months. These results contribute directly to health benefits, so its characteristics allow functional foods to be developed, such is the case of the production of polishing-based biscuits, with a consistency and a palatable taste for those who like to take care of your diet

Analisis Exploratorio En La Industria De Quesos Artesanales En Escárcega, Campeche De Acuerdo A Los Prerrequisitos De Haccp

This article presents a diagnosis of hygiene management based on the fulfillment of the prerequisites of a HACCP system, in three companies of the agrifood sector that operate in the municipality of Escárcega, Campeche, especially in the elaboration of artisanal cheeses. The evaluation methodology corresponded to the verification of compliance with the checklist of the instrument GHYCAL (Hygiene and Quality Management). The results allowed to find levels of hygiene management in a percentage scale and to classify the three companies in low level of compliance for all, due mainly to the little knowledge and technological development that is presented in the region

Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome

The cardiac action potential is critical to the production of a synchronized heartbeat. This electrical impulse is governed by the intricate activity of cardiac ion channels, among them the cardiac voltage-gated potassium (Kv) channels KCNQ1 and hERG as well as the voltage-gated sodium (Nav) channel encoded by SCN5A. Each channel performs a highly distinct function, despite sharing a common topology and structural components. These three channels are also the primary proteins mutated in congenital long QT syndrome (LQTS), a genetic condition that predisposes to cardiac arrhythmia and sudden cardiac death due to impaired repolarization of the action potential and has a particular proclivity for reentrant ventricular arrhythmias. Recent cryo-electron microscopy structures of human KCNQ1 and hERG, along with the rat homolog of SCN5A and other mammalian sodium channels, provide atomic-level insight into the structure and function of these proteins that advance our understanding of their distinct functions in the cardiac action potential, as well as the molecular basis of LQTS. In this review, the gating, regulation, LQTS mechanisms, and pharmacological properties of KCNQ1, hERG, and SCN5A are discussed in light of these recent structural findings

Problema de planeamento do projeto para biblioteca de desenvolvimento de software - PSPSWDLIB

Um Problema de Gestão de Projetos de Desenvolvimento de Software é uma variante do Problemas Gestão de Projetos onde o modelo de desenvolvimento de software pode ser apresentado como um conjunto de actividades de software a realizar, um conjunto de recursos humanos, um conjunto de recursos financeiros e o variável tempo dividida por actividade. Este artigo apresenta um exemplo do Problema de Gestão de Projetos de Desenvolvimento de Software para projectos de desenvolvimento de software.A Project Scheduling Problem for Software Development is a variant of Project Scheduling Problem where the software development model can be presented as a set of software activities, a set of developer skills and a set of resources specified on money and the total time divided on time per activity. This paper presents an instance set of Project Scheduling Problem for Software Development for projects of software development

Caracterización Físico-Química Y Organoléptica De Un Licor A Base De Piñuela

La piñuela es una baya agridulce y jugosa, su pulpa es de color blanco. En la península de Yucatán, la población maya la conoce con distintos nombres, sin embargo, también ha sido registrado para al menos 13 estados del país. Esta especie crece en las regiones tropicales de ambos litorales en México, así como en Centroamérica y las islas del Caribe, presentando mayor abundancia en la zona costera y en la selva baja caducifolia. Los usos que se le da a la piñuela son diversos (ornamental, medicinal, fines alimenticios, decorativos y ceremonial). Por lo anterior, el objetivo de la presente investigación fue elaboración y caracterización de un licor del fruto de la piñuela (Bromelia pinguin L) de forma artesanal en el municipio de Escárcega, Campeche. Para el logro de la investigación se hizo la recolección del fruto en localidades rurales del municipio de Candelaria, las cuales fueron trasladas a las instalaciones del Instituto Tecnológico Superior de Escárcega para la elaboración del licor, en donde después de tres meses se procedió a la evaluación de aceptabilidad ante un panel semientrenado. Los resultados indican que presenta una alta concentración de alcohol (31). Los panelistas valoraron el licor de piñuela satisfactoriamente (más del 80%). Como conclusión del estudio es importante considerar a este fruto como parte de un crecimiento en la industria alimentaria de la región, ya que por sus características naturales se le considera como un fuerte producto potencial para ser aprovechado por la comunidad local. The piñuela is a bittersweet and juicy berry, its pulp is white in color. In the Yucatan Peninsula, the Mayan population knows it by different names, however, it has also been recorded for at least 13 states in the country. This species grows in the tropical regions of both coasts in Mexico, as well as in Central America and the Caribbean islands, presenting greater abundance in the coastal zone and in the low deciduous forest. Piñuelas are used for a variety of purposes (ornamental, medicinal, food, decorative, and ceremonial). Therefore, the objective of this research was to elaborate and characterize a liqueur made from the fruit of the piñuela (Bromelia pinguin L) in an artisanal way in the municipality of Escárcega, Campeche. For the achievement of the research, the fruit was collected in rural localities of the municipality of Candelaria, which were transferred to the facilities of the Instituto Tecnológico Superior de Escárcega for the elaboration of the liquor, where after three months the evaluation of acceptability was made before a semi-trained panel. The results indicate that it has a high alcohol concentration (31). The panelists rated the piñuela liqueur satisfactorily (more than 80%). As a conclusion of the study, it is important to consider this fruit as part of a growing food industry in the region, since its natural characteristics make it a strong potential product to be exploited by the local community

Complexity of Instances for Combinatorial Optimization Problems

Non

Nuevos registros de especies del género Anastrepha (Diptera: Tephritidae) en Tamaulipas, México

New records of two Anastrepha species for the state of Tamaulipas, Mexico are informed, A. bicolor (Stone) and A. distincta Greene collected by McPhail traps in neighboring areas to commercial orchards of citrus fruits and mangoes