Bioinformatics Insights on the Physicochemical Properties of SCN5A Mutant Proteins Associated with the Brugada Syndrome.

BACKGROUND: The Brugada syndrome (BrS) is a heart rhythm condition that is commonly associated with a strong predisposition for sudden cardiac death. Malignant ventricular arrhythmias could occur secondary to the dysfunction of the cardiac sodium voltage-gated Na(v)1.5 channel (SCN5A). OBJECTIVE: This study aimed to perform a multiparametric computational analysis of the physicochemical properties of SCN5A mutants associated with BrS using a set of bioinformatics tools. METHODS: In-house algorithms were calibrated to calculate, in a double-blind test, the Polarity Index Method (PIM) profile and protein intrinsic disorder predisposition (PIDP) profile of each sequence, and computer programs specialized in the genomic analysis were used. RESULTS: Specific regularities in the charge/polarity and PIDP profile of the SCN5A mutant proteins enabled the re-creation of the taxonomy, allowing us to propose a bioinformatics method that takes advantage of the PIM profile to identify this group of proteins from their sequence. CONCLUSION: Bioinformatics programs could reproduce characteristic PIM and PIDP profiles of the BrS-related SCN5A mutant proteins. This information can contribute to a better understanding of these altered proteins.

Bioinformatics-based Characterization of the Sequence Variability of Zika Virus Polyprotein and Envelope Protein (E).

Background: Zika virus, which is widely spread and infects humans through the bites of Aedes albopictus and Aedes aegypti female mosquitoes, represents a serious global health issue. Objective: The objective of the present study is to computationally characterize Zika virus polyproteins (UniProt Name: PRO_0000443018 [residues 1-3423], PRO_0000445659 [residues 1-3423] and PRO_0000435828 [residues 1-3419]) and their envelope proteins using their physico-chemical properties. Methods: To achieve this, the Polarity Index Method (PIM) profile and the Protein Intrinsic Disorder Predisposition (PIDP) profile of 3 main groups of proteins were evaluated: structural proteins extracted from specific Databases, Zika virus polyproteins, and their envelope proteins (E) extracted from UniProt Database. Once the PIM profile of the Zika virus envelope proteins (E) was obtained and since the Zika virus polyproteins were also identified with this profile, the proteins defined as "reviewed proteins" extracted from the UniProt Database were searched for the similar PIM profile. Finally, the difference between the PIM profiles of the Zika virus polyproteins and their envelope proteins (E) was tested using 2 non-parametric statistical tests. Results: It was found and tested that the PIM profile is an efficient discriminant that allows obtaining a "computational fingerprint" of each Zika virus polyprotein from its envelope protein (E). Conclusion: PIM profile represents a computational tool, which can be used to effectively discover Zika virus polyproteins from Databases, from their envelope proteins (E) sequences.

Bioinformatics characterisation of the (mutated) proteins related to Andersen-Tawil syndrome.

In the last two decades, a group of proteins whose mutations are associated with a disease manifested by episodes of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and developmental abnormalities has been under constant study. This malady is known as Andersen-Tawil syndrome, with ~60% of cases of this syndrome being caused by 16 mutations in the KCNJ2 gene [UniProt ID: P63252-01-P63252-17]. In this work, we present a computational study designed to obtain a fingerprint of Andersen-Tawil mutated proteins and differentiate them from mutated proteins associated with Brugada syndrome and from functional groups of proteins belonging to APD3, UniProt, and CPPsite databases. We show here that Andersen-Tawil mutated proteins are characterized by specific features that can be used to differentiate, with a high level of certainty (90%), proteins carrying these mutations from similar functional groups, such as mutated proteins associated with Brugada syndrome, and from different functional protein and peptide groups, such as antimicrobial peptides, Cell-Penetrating Peptides, and intrinsically disorder proteins. Therefore, our main results allow us to conjecture that it is possible to identify the group of the Andersen-Tawil mutated proteins by their "PIM profile". Furthermore, when we applied this "fingerprint PIM profile" on the UniProt database, we observed that one protein found in humans [UniProt ID: Q9NZV8], and six of all "reviewed" proteins found in living organisms, possess a very similar PIM profile as the Andersen-Tawil mutated protein group. The bioinformatics "fingerprint" of the Andersen-Tawil mutated proteins was retrieved using the in-house bioinformatics system named Polarity Index Method® and supported-at residues level- by the algorithms for the prediction of intrinsic disorder predisposition, such as PONDR® FIT, PONDR® VLXT, PONDR® VSL2, PONDR® VL3, FoldIndex, IUPred, and TopIDP.

Molecular cloning and characterization of the crustacean hyperglycemic hormone cDNA from Litopenaeus schmitti. Functional analysis by double-stranded RNA interference technique.

The crustacean hyperglycemic hormone (CHH) plays an important role in the regulation of hemolymph glucose levels, but it is also involved in other functions such as growth, molting and reproduction. In the present study we describe the first CHH family gene isolated from the Atlantic Ocean shrimp Litopenaeus schmitti. Sequence analysis of the amplified cDNA fragment revealed a high nucleotide sequence identity with other CHHs. Northern blot analysis showed that the isolated CHH mRNA from L. schmitti is present in the eyestalk but not in muscle or stomach. We also investigated the ability of dsRNA to inhibit the CHH function in shrimps in vivo. Injection of CHH dsRNA into the abdominal hemolymph sinuses resulted in undetectable CHH mRNA levels within 24 h and a corresponding decrease in hemolymph glucose levels, suggesting that functional gene silencing had occurred. These findings are the first evidence that dsRNA technique is operative in adult shrimps in vivo.

Induction of brain glucose uptake by a factor secreted into cerebrospinal fluid.

It is well established that the carotid body receptors (CBR), at the bifurcation of the carotid artery, inform the brain of changes in the concentration of CO(2) and O(2) in arterial blood. More recent work suggests that these receptors are also extremely sensitive to blood glucose levels suggesting that they may play an important role as sensors of blood components important for brain energy metabolism. Much less is known about changes in brain glucose metabolism in response to CBR activation. Here we show that 2-8 min after local injection of sodium cyanide (NaCN) into the CBR or after electrical stimulation of the carotid sinus nerve in dogs and rats, brain glucose uptake increased fourfold. Cerebrospinal fluids (CSF) transferred from dogs, 2-8 min after CBR stimulation, into the cisterna magna of non-stimulated dogs or rats induced a similar increase in brain glucose uptake. CSF from stimulated dogs was also active when injected intravenously in anesthetized or awake rats. The activity was destroyed when the stimulated CSF was heated to 100 degrees C or treated with trypsin. We conclude that a peptide important for brain glucose regulation appears in the CSF shortly after CBR stimulation.

La presión coloidosmótica sérica en población mexicana adulta / Seric colloidosmotic pressure in the Mexican population

La presión coloidosmótica (PCO) del suero es un parámetro útil para controlar la reposición del fluidos en la clínica y en la cirugía que en México ha sido poco utilizado. Con el objeto de establecer la distribución normal de la PCO, ésta se midió en el suero de 160 individuos hospitalizados, seleccionados por no presentar alteraciones en los análisis de proteína total, albúmina globulina y relación A/G. Fueron excluidos los pacientes que según su historia clínica presentaron daño hepático o renal. Se utilizó un coloidosmómetro electrónico marca Wescor, modelo 4100. A cada suero problema se le hicieron tres determinaciones de la PCO no consecutivas y el promedio de las tres fue utilizado para el estudio estadístico, que consistió en la prueba t de Student y el cálculo de la desviación estándar. Se encontró un valor de 26.21 ñ 7.35 mm Hg (promedio ñ 1.96 DE) para la PCO de las 160 muestras de suero, entre los valores límites de 18.86 y 33.56 mm Hg. No se encontró diferencia significativa alguna entre los valores correspondientes a 99 mujeres y 61 hombres (26.45 ñ 5.93 y 26.20 + 6.37 mm Hg, respectivamente, p = 0.20). Este valor de PCO puede servir de base para controlar el tratamiento de pacientes cirróticos, nefróticos y quemados, entre otros

Pigmentation of the rainbow trout (Oncorhynchus mykiss) with oil-extrated astaxanthin from the langostilla (Pleuroncodes planipes) / Astaxantina de la langostilla, pleuroncodes planipes, extraída con aceite y su uso en la pigmentación de la trucha arcoiris oncorhynchus mykiss

The effect of oil-extracted astaxanthin from the red crab or langostilla (Pleuroncodes planipes) on the growth and pigmentation of forty five rainbow trouts (Oncorhynchus mykiss) was investigated by feeding a test diet supplemented with 75 mg/kg of astanthin during six weeks and compared with a control diet. The oil-extraction process of the pigment is described. Weight, flesh astaxanthin concentration, and color (A*a*,b*) of the flesh were measured at 0,3, and 6 weeks. No apparent effect of astaxanthin supplementation was observed on fish development. In spite of the low free astaxanthin amount in the diet (8 por ciento), an acceptable carotenoid concentration in the flesh (3,60 ñ 0,78 mg/kg, w/w), and a red hue (Hº ab = 44,13 ñ 2,36) were obtained at the end of the study. The red hue was strongly correlated with thecarotenoid concentration (r=0,98)

Cronología de hipertensión portal, disminución de excreción de sodio y activación del sistema renina-angiotensina en cirrosis biliar experimental / Time relationships between portal hypertension, decrease in sodium excretion, and activation of the renin angiotensin system in rats with experimental biliary cirrhosis

Objetivos. 1) Evaluar las alteraciones bioquímicas, renales, histológicas y hemodinámicas esplácnicas y sistémicas que ocurren en la cirrosis biliar inducida por ligadura del conducto colédoco en ratas; y 2) conocer la relación cronológica entre el inicio de hipertensión portal, disminución de excreción urinaria de sodio y activación del sistema renina-angiotensina. Metodología. Se estudiaron 127 ratas macho de la cepa Wistar con ligadura del conducto colédoco a diferentes periodos de tiempo (una, dos, tres y cuatro semanas de obstrucción) y se compararon con 30 ratas controles. Resultados. La presión portal aumentó significativamante a partir de la primera semana de obstrucción (11.7 ñ 1.5 vs 7.8 ñ 1.5 mmHg, p < 0.05) mientras que la presión arterial media se mantuvo estable hasta la cuarta semana en que presentó una ligera disminución no significativa (91.3 ñ 6.6 vs 96.1 ñ 8.6 mmHg) en ratas controles. Se observó una disminución significativa en la excreción urinaria de sodio a partir de la primera semana de obstrucción (1.1 ñ 0.5 mEq/24 h) comparado con el grupo de las ratas controles (2.3 ñ 0.6). También se observó hiperreninemia desde la primera semana (5.1 ñ 2 vs 2.4 ñ 1.3 ng Ang I/mL/h, p < 0.05) e hiperaldosteronismo desde la segunda semana (103 ñ 46 vs 25 ñ 8.8 ng/24 h, p < 0.05) comparados con el grupo control. Conclusión. El inicio de la hipertensión portal a la primera semana de obstrucción biliar se relaciona cronológicamente con el inicio de la disminución de la excreción urinaria de sodio y con la hiperreninemia y el hiperaldosteronismo. Este modelo experimental de cirrosis podría ser útil para evaluar el efecto de diversas maniobras terapéuticas que tengan como objetivo detener o prevenir el proceso cirrógeno, incluyendo las alteraciones en la excreción urinaria de sodio