Can colour vision re-evolve? Variation in the X-linked opsin locus of cathemeral Azara's owl monkeys (Aotus azarae azarae).

BACKGROUND: Do evolutionary specializations lead to evolutionary constraint? This appears plausible, particularly when specialization leads to loss of complex adaptations. In the owl monkey lineage, nocturnality clearly arose from a diurnal ancestor. This behavioural shift was accompanied by morphological changes in the eye and orbit and complete loss of colour vision via missense mutations in the gene encoding the short-wave sensitive visual pigment (SWS opsin). Interestingly, at least one subspecies of owl monkey, Azara's owl monkey (Aotus azarae azarae), has regained activity in daylight. Given that all primate species that are active in daylight, including primarily diurnal species and species that are active during both day and night, have at least dichromatic colour vision, it seems reasonable to propose that dichromacy would be adaptive in A. a. azarae. With a disabled SWS opsin, the main avenue available for Azara's owl monkeys to re-evolve colour vision is via a polymorphism in the intact X-linked opsin locus, which commonly occurs in other New World monkeys. To examine this possibility we assayed variation in the X-linked opsin of A. a. azarae, focusing on the three exons (3, 4 and 5) that control spectral sensitivity. RESULTS: We found low opsin genetic variation on a population level, and no differences at the three main sites that lead to variation in spectral sensitivity in the opsins of other New World monkeys. Two rare alleles with single amino acid variants are segregating in the population, but previous functional studies indicate that these are unlikely to affect spectral sensitivity. CONCLUSIONS: Genetic constraint on the re-evolution of colour vision is likely operating in Azara's owl monkey, which may affect the niche that this subspecies is able to occupy.

Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis.

Epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transitions occur in the development of human tumorigenesis and are part of the natural history of the process to adapt to the changing microenvironment. In this setting, the miR-200 family is recognized as a master regulator of the epithelial phenotype by targeting ZEB1 and ZEB2, two important transcriptional repressors of the cell adherence (E-cadherin) and polarity (CRB3 and LGL2) genes. Recently, the putative DNA methylation associated inactivation of various miR-200 members has been described in cancer. Herein, we show that the miR-200ba429 and miR-200c141 transcripts undergo a dynamic epigenetic regulation linked to EMT or MET phenotypes in tumor progression. The 5'-CpG islands of both miR-200 loci were found unmethylated and coupled to the expression of the corresponding miRNAs in human cancer cell lines with epithelial features, such as low levels of ZEB1/ZEB2 and high expression of E-cadherin, CRB3 and LGL2, while CpG island hypermethylation-associated silencing was observed in transformed cells with mesenchymal characteristics. The recovery of miR-200ba429 and miR-200c141 expression by stable transfection in the hypermethylated cells restored the epithelial markers and inhibited migration in cell culture and tumoral growth and metastasis formation in nude mice. We also discovered, using both cell culture and animal models, that the miR-200 epigenetic silencing is not an static and fixed process but it can be shifted to hypermethylated or unmethylated 5'-CpG island status corresponding to the EMT and MET phenotypes, respectively. In fact, careful laser microdissection in human primary colorectal tumorigenesis unveiled that in normal colon mucosa crypts (epithelia) and stroma (mesenchyma) already are unmethylated and methylated at these loci, respectively; and that the colorectal tumors undergo selective miR-200 hypermethylation of their epithelial component. These findings indicate that the epigenetic silencing plasticity of the miR-200 family contributes to the evolving and adapting phenotypes of human tumors.

High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability.

The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.

Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.

Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression profiling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by expression profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

[Outbreak of bubonic plague in Jacocha, Huancabamba, Perú ]. / Surto de peste bubônica na localidade de Jacocha, Huancabamba, Perú

Climatic alterations arising in the north of Perú as a result of the El Niño phenomenon (ENSO) have caused variations in the crop volume, changes in the direction of rivers and probably an increase in the rodent population. In February 1999, in a native community in Jacocha, Huancabamba, Piura's mountains, Perú, an outbreak of bubonic plague appeared with five human cases, one of which lead to death. The diagnosis was confirmed by serology (passive hemaglutination). The presence of antibodies in dogs of localities close to Jacocha has confirmed the circulation of Yersinia pestis in the region. The outbreak was controlled by the local sanitary authorities' prompt action. This episode, after an epidemiological silence for more than four years, showed the necessity of intensifying the plague epidemiological surveillance system in this area.

Surto de peste bubônica na localidade de Jacocha, Huancabamba, Perú / Outbreak of bubonic plague in Jacocha, Huancabamba, Perú

Climatic alterations arising in the north of Perú as a result of the El Niño phenomenon (ENSO) have caused variations in the crop volume, changes in the direction of rivers and probably an increase in the rodent population. In February 1999, in a native community in Jacocha, Huancabamba, Piura's mountains, Perú, an outbreak of bubonic plague appeared with five human cases, one of which lead to death. The diagnosis was confirmed by serology (passive hemaglutination). The presence of antibodies in dogs of localities close to Jacocha has confirmed the circulation of Yersinia pestis in the region. The outbreak was controlled by the local sanitary authorities' prompt action. This episode, after an epidemiological silence for more than four years, showed the necessity of intensifying the plague epidemiological surveillance system in this area.

As alterações climáticas produzidas no norte do Perú devidas ao Fenômeno El Niño (ENSO), ocasionaram variações no volume das safras, redistribuição do curso dos rios e provavelmente aumento da população de roedores. Em fevereiro de 1999, em uma comunidade indígena em Jacocha, Huancabamba, na serra de Piura, Perú, surgiu um surto de peste com cinco casos humanos, um dos quais faleceu. O diagnóstico foi confirmado pela sorologia (hemaglutinação passiva). A presença de anticorpos em cães de localidades próximas de Jacocha confirmaram a circulação da Yersinia pestis na área. O surto foi debelado pela rápida atuação das autoridades sanitárias locais. O episódio após silêncio epidemiológico por mais de quatro anos, mostrou a necessidade de reforçar o sistema de vigilância epidemiológica de peste nesta área.

Telomeric associations in cigarette smokers exposed to low levels of X-rays.

Telomeric association (TA), i.e. fusion of chromosomes by their telomeres, predisposes a cell to genetic instability. Because of this we investigated the effect of X-rays exposure and cigarette smoking on the frequency of TA in peripheral blood lymphocytes of exposed individuals, in order to determine if TA can be a chromosomal marker in populations exposed to these carcinogens and if there is an synergistic effect between both agents. We found that the exposed groups show a greater percentage of TA when compared with the control group (P<0.001). However, although the percentage of metaphases with TA in the group with combined exposure (12.6%) was greater than in the others exposed groups (P<0.05), this value was less than the sum of the two individual effects (15.1%). Our results suggest that probably there is not an additive or synergistic effect between X-rays and smoking, and that TA may be a useful cytogenetic marker for evaluating populations exposed to mutagens.

Long-term control of Chagas disease in Venezuela: effects on serologic findings, electrocardiographic abnormalities, and clinical outcome.

To evaluate the long-term effects (20 years) of a Chagas control program (CCP) in Venezuela, a prospective serologic evaluation was carried out from 1981 to 1984 on 5771 inhabitants (8%) of Roscio county. This region was selected as a representative area where the national CCP was implemented effectively. Comparison with a serologic survey performed in the same region before the CCP disclosed a reduction in seropositive subjects from 47.8% to 17.1% (p less than .001), most marked amongst children and teenagers from 29.9% to 1.9%, suggesting that transmission of the disease had diminished. Similar seropositivity changes after the CCP were observed nationwide. Because decreased superinfection would also be expected to occur, we tried to ascertain whether the clinical outcome of seropositive individuals living in Roscio county had improved. The mean age of seropositive subjects between both surveys increased significantly from 34.9 +/- 17.3 to 46.7 +/- 15.1 years (p less than .001). Additionally, we examined clinically and obtained electrocardiograms from 775 seropositive subjects. They were classified as asymptomatic (group A, n = 614) or as symptomatic, having mild-to-moderate heart symptoms (group B, n = 99) or having advanced congestive heart failure (group C, n = 62). Their electrocardiograms were compared with those of 923 seronegative subjects collected simultaneously and with published data obtained before the CCP. Comparison of the age-related rates of electrocardiographic abnormalities of seropositive individuals before and after the CCP showed that they did not differ significantly by linear regression analysis, by the Kruskal-Wallis test, or by the normal approximation to the binomial distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Propuesta social: Guanay-segunda sección, Provincia Larecaja, La Paz

Resumen del proyecto 1. Introducción 2. Aspectos generales 3. Diseño de la propuesta 4. Metas 5. Implementación de la propuesta 6. Sustentabilidad 7. Modalidad de ejecución de la propuesta social 8. Recursos humanos 9. Sistema de información 10. Monitoreo y evaluación 11. Coordinación técnica 12. Cronograma de actividades 13. Presupuesto global de la propuesta 14. Anexos