Scorpions belonging to the Buthidae family have traditionally drawn much of the biochemist’s attention due to the strong toxicity of their venoms. Scorpions not toxic to mammals, however, also have complex venoms. They have been shown to be an important source of bioactive peptides, some of them identified as potential drug candidates for the treatment of several emerging diseases and conditions. It is therefore important to characterize the large diversity of components found in the non-Buthidae venoms. As a contribution to this goal, this manuscript reports the construction and characterization of cDNA libraries from four scorpion species belonging to the Vaejovis genus of the Vaejovidae family: Vaejovis mexicanus, V. intrepidus, V. subcristatus and V. punctatus. Some sequences coding for channel-acting toxins were found, as expected, but the main transcribed genes in the glands actively producing venom were those coding for non disulfide-bridged peptides. The ESTs coding for putative channel-acting toxins, corresponded to sodium channel β toxins, to members of the potassium channel-acting α or κ families, and to calcium channel-acting toxins of the calcin family. Transcripts for scorpine-like peptides of two different lengths were found, with some of the species coding for the two kinds. One sequence coding for La1-like peptides, of yet unknown function, was found for each species. Finally, the most abundant transcripts corresponded to peptides belonging to the long chain multifunctional NDBP-2 family and to the short antimicrobials of the NDBP-4 family. This apparent venom composition is in correspondence with the data obtained to date for other non-Buthidae species. Our study constitutes the first approach to the characterization of the venom gland transcriptome for scorpion species belonging to the Vaejovidae family.
Centruroides tecomanus is a Mexican scorpion endemic of the State of Colima, that causes human fatalities. This communication describes a proteome analysis obtained from milked venom and a transcriptome analysis from a cDNA library constructed from two pairs of venom glands of this scorpion. High perfomance liquid chromatography separation of soluble venom produced 80 fractions, from which at least 104 individual components were identified by mass spectrometry analysis, showing to contain molecular masses from 259 to 44,392 Da. Most of these components are within the expected molecular masses for Na+- and K+-channel specific toxic peptides, supporting the clinical findings of intoxication, when humans are stung by this scorpion. From the cDNA library 162 clones were randomly chosen, from which 130 sequences of good quality were identified and were clustered in 28 contigs containing, each, two or more expressed sequence tags (EST) and 49 singlets with only one EST. Deduced amino acid sequence analysis from 53% of the total ESTs showed that 81% (24 sequences) are similar to known toxic peptides that affect Na+-channel activity, and 19% (7 unique sequences) are similar to K+-channel especific toxins. Out of the 31 sequences, at least 8 peptides were confirmed by direct Edman degradation, using components isolated directly from the venom. The remaining 19%, 4%, 4%, 15% and 5% of the ESTs correspond respectively to proteins involved in cellular processes, antimicrobial peptides, venom components, proteins without defined function and sequences without similarity in databases. Among the cloned genes are those similar to metalloproteinases.
Meclofenamic acid was shown to be a potential antineoplastic agent for both androgen-dependent and androgen-independent prostate cancer.
Introduction. Premature rupture of membranes (PRM) is a late pregnancy complication commonly associated with preterm delivery (PD).Although several markers related to the renin-angiotensin system (RAS) have been evaluated in certain pregnancy complications, only the angiotensin-converting enzyme (ACE) I/D variant has been studied in PD-PRM.The aim of this survey was to investigate the association of the polymorphisms (angiotensin II type 1 [AT1] receptor T174M and M235T, renin G2805A,ACE I/D and AT1-receptor A1166C) of the genes of RAS in women with PD-PRM. Design. Deoxyribonucleic acid samples from 89 Mexican Mestizo women with PD and PRM and 224—288 controls were studied. Polymorphisms were analysed by polymerase chain reaction-sequence specific primer assays. restricted fragment length polymorphism or sequence specific prim assays. Results. For all loci , genotype distribution was in agreement with Hardy—Weinberg expectations in the control group. Significant intergroup difference (case vs. control) was seen for angiotensinogen (AGT) M235T polymorphism, with an increased allele M235 in affected cases (50% vs. 40% in controls).Analysis of two- locus haplotype agrees with an independent segregation of physically unlinked genes. Haplotype AGT 174T-235M was also increased (50 % vs. 40% in controls). Conclusions. Physically unlinked genes involved in RAS segregate independently. The AGT 174—235 region is associated with PD-PRM in this population.
Recebido em 21/6/11; aceito em 5/9/11; publicado na web em 8/11/11 A USABILITY STUDY OF EDUCATIONAL MOLECULAR VISUALIZATION ON SMART PHONES. Chemistry students have difficulty understanding molecular structures and their functions. To aide their comprehension, molecular visualization software has been developed to run on smart phones, but in order to positively influence learning it must have a high degree of usability (usability measures how software is used in terms of efficiency, efficacy and satisfaction). This paper describes a usability study of molecular visualization software running on a smart phone, where chemistry students analyzed molecular models. Results showed very good usability and 95% of students wanted to use it in further classes.Keywords: molecular visualization; mobile computing; usability. INTRODUCCIÓNLos estudiantes de química generalmente tienen dificultad para comprender ciertos conceptos científicos de bioquímica y áreas afines, por ejemplo, las estructuras moleculares.1 Estudios empíricos llevados a cabo anteriormente 2 han mostrado que muchos estudiantes no comprenden fácilmente las representaciones microscópicas de moléculas debido a su escala y sus características físico-químicas abstractas. La dificultad en el aprendizaje se debe principalmente a que suceden los procesos a una escala muy diferente y diminuta y con una estructura tridimensional demasiado intrincada, por lo que su comprensión resulta difícil. Esto sucede a menudo con la comprensión de los enlaces moleculares.3 A pesar de que los alumnos de química, en los primeros años de estudio de licenciatura, aprenden a cómo representar en diferentes formatos las geometrías moleculares (proyecciones de Fisher, taquigráfica, etc.) aún se requiere que el alumno muestre ciertas facultades espaciales para construir y entender la disposición tridimensional de las estructuras moleculares. 4 Las herramientas didácticas tradicionales (por ejemplo, el pizarrón o los modelos moleculares de plástico) pueden servir para aprender ciertos conceptos generales sobre la estructura de las moléculas, pero tienen ciertas limitaciones para analizar y entender conceptos muy puntuales y precisos en la estructura y dinámica de las moléculas. Es por esto que para ayudar a su comprensión, los estudiantes deben apoyarse en información multisensorial, principalmente visual y táctil y dicha información debe mostrarse al estudiante de manera práctica y accesible. 5Una aplicación importante de la visualización molecular por computadora es en la enseñanza de las estructuras moleculares, de los elementos de simetría inherentes a las moléculas y algunas propiedades electrónicas que puedan visualizarse de acuerdo a algún código de colores, por ejemplo, densidad electrónica, el potencial electrostático, disposición de las fuerzas de van der Waals.6 Desde que se creó la WWW, los estudiantes de química pueden obtener de Internet infinidad de modelos moleculares en 3D, almacenados en formatos tales como VRML (Virtual Reality Modeling Language), el cual es un lenguaje...
Abstract. Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10-40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50-90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug.
The polymorphisms in the genes related to angiogenesis -675 4G/5G PAI-1 and G-800A TGF-β1, segregated solely or combined, might contribute to the increased susceptibility to UCC in a Mexican population.
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