The polar profile of ancient proteins: a computational extrapolation from prebiotics to paleobiochemistry.

This paper addresses the polar profile of ancient proteins using a comparative study of amino acids found in 25 000 000-year-old shells described in Abelson's work. We simulated the polar profile with a computer platform that represented an evolutionary computational toy model that mimicked the generation of small proteins starting from a pool of monomeric amino acids and that included several dynamic properties, such as self-replication and fragmentation-recombination of the proteins. The simulations were taken up to 15 generations and produced a considerable number of proteins of 25 amino acids in length. The computational model included the amino acids found in the ancient shells, the thermal degradation factor, and the relative abundance of the amino acids observed in the Miller-Urey experimental simulation of the prebiotic amino acid formation. We found that the amino acid polar profiles of the ancient shells and those simulated and extrapolated from the Miller-Urey abundances are coincident.

Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer.

Angiotensin II (ANGII) has been associated with vascular proliferation in tumor and non-tumor models through its receptors AT1 and AT2. Our objective was to determine AT1 and AT2 receptor expression in operable breast cancer and its association with tumor grade, vascular density, and cellular proliferation. Seventy-seven surgically malignant breast tumors with no distant metastasis were included, and 7 benign lesions were used as controls. AT1 and AT2 receptor expression was determined by RT-PCR and immunohistochemistry (IHC) in 68 out of the 77 malignant lesions and in the 7 benign lesions. AT1 and AT2 receptor expression was detected in 35.3 and 25 % of cases, in both RT-PCR and IHC. Tumors that express AT1 showed an increase in T3 stage (92.3 vs. 7.7 % p < 0.001), mitotic index (4 ± 1 vs 2 ± 1, p = 0.05), vascular density (15 ± 3 vs 8 ± 5, p = 0.05), and cellular proliferation (85 ± 18 vs 55 ± 10, p = 0.01) versus AT1-negative lesions. Non-differences between clinical-pathologic variables and AT2 expression were found. AT1 receptor expression was associated to enhance angiogenesis and cellular proliferation rate, but no relationship with AT2 was found. ANGII and its peptides might play a role in the development and pathophysiology of breast cancer, and this could be valuable in the in the development of targeted therapies.

Single nucleotide polymorphisms in the promoter region of the E-cadherin gene in gastric cancer: case-control study in a young Mexican population.

BACKGROUND: Gastric cancer has a tendency to present at early age in the Mexican population, and it is frequently associated with a family history. A polymorphism at position -160 at the CDH1 promoter region has been reported to lead to transcriptional downregulation of the gene in vitro, with possible increase in the risk of gastric cancer. We evaluated the role of the -160A allele in the risk of gastric cancer in a young Mexican population. METHODS: Peripheral blood sample of Mexican patients younger than 45 years old with diagnosis of diffuse gastric cancer were obtained. We performed DNA extraction and analyzed the frequencies of -160 promoter polymorphism of E-cadherin gene by polymerase chain reaction-single strand conformational polymorphism. These frequencies were compared with those of healthy controls. The chi2 test for association was used to test differences of the genotype frequencies between normal controls and patients with gastric cancer. Findings were considered significant at P < .05. RESULTS: The frequency of the -160 A allele was significantly higher (P = .002) in 39 patients with diffuse gastric cancer compared with 78 matched controls. The odds ratio associated with the A-allele was 1.98 for C/A heterozygotes (95% CI 1.01-3.98) and 6.5 for A/A homozygotes (95% CI 2.1-19.6). We found an increased risk of diffuse gastric cancer according to family history, independent of the expression of the polymorphism. CONCLUSIONS: The -160 C/A polymorphism of the E-cadherin has a direct effect on the risk of diffuse gastric cancer at young age in Mexican population.

Influencia genética sobre los requerimientos de energía: I desarrollo de un modelo experimental / Genetic variation of energy requirements: I development of an experimental model

Se presentan los resultados obtenidos en el desarrollo de un modelo animal para estudiar la variación individual en requerimientos de energía, partiendo del postulado de que los requerimientos nutricios son determinados genéticamente pero su expresión, como fenotipos distintos, está condicionada por factores ambientales. Se partió del cruzamiento sucesivo de ratas Wistar machos y hembras "buenos" y "malos" convertidores de energía. La primera generación dió tres machos y cinco hembras cuya mediana de índice de conversión (IC) fue de 2.90 y extremos de 2.54 y 3.25. Al observar los valores individuales se hizo aparente que la proporción de machos con IC abajo de la mediana era 3/3 y para las hembras 2/5; esta distribución llevó a considerar si los machos fueran mejores utilizadores de energía que las hembras, al necesitar ingerir menos alimentos para aumentar su peso. Esta hipótesis se exploró cuantificando el IC en 91 ratas.La proporción de machos por arriba de la mediana (33/38) contrastó significativamente (p menor que 0.0001) con la proporción 13/53 encontrada en las hembras. La prueba de ratas (Z = 5.47, p = 0.00003) rechaza la probabilidad de sesgo de entrada por series. La diferencia de utilización en función del sexo hizo que se buscaran si el fenómeno es general para la rata o únicamente para la cepa Wistar. Experimentos con cepas Brown-Norway y Lewis mostraron resultados iguales: los machos eran mejores convertidores de energía. Los datos de Campbell y Taverner en cerdos machos castrados apoyan los del presente informe y la sugerencia de que el modelo de liga al sexo pudiera ser adecuado para estudiar mecanismos de variación de los requerimientos energéticos.