Regulación de expresión de genes de la familia de ß-globina humana, útil en la búsqueda de nuevos blancos terapéuticos para tratamiento de hemoglobinopatías / Regulation of the ß-globin gene family expression, useful in the search for new therapeutic targets for hemoglobinopathies

Durante la etapa embrionaria, el desarrollo fetal y la vida posnatal se expresan isoformas funcionalmente distintas de hemoglobina, producto de la combinación de cadenas polipeptídicas sintetizadas a partir de los distintos genes que componen las familias de α- y β-globina. En función de que la presencia de altos niveles de hemoglobina fetal (Hb F) es beneficiosa en síndromes falciformes y talasémicos graves, se plantea revisar las bases de la regulación de la expresión de los genes de la familia de β-globina, en particular los genes que codifican las cadenas de γ-globina (HBG1 y HBG2). En este trabajo se revisan los conocimientos sobre factores de transcripción y reguladores epigenéticos que gobiernan los eventos de encendido y apagado de los genes de la familia de β-globina. Se espera que la consolidación de estos conocimientos permita hallar nuevos blancos terapéuticos para el tratamiento de hemoglobinopatías.

Different hemoglobin isoforms are expressed during the embryonic, fetal and postnatal stages. They are formed by combination of polypeptide chains synthesized from the α- and β- globin gene clusters. Based on the fact that the presence of high hemoglobin F levels is beneficial in both sickle cell disease and severe thalassemic syndromes, a revision of the regulation of the β-globin cluster expression is proposed, especially regarding the genes encoding the γ-globin chains (HBG1 and HBG2). In this review we describe the current knowledge about transcription factors and epigenetic regulators involved in the switches of the β-globin cluster. It is expected that the consolidation of knowledge in this field will allow finding new therapeutic targets for the treatment of hemoglobinopathies.

Roadkill hotspots in a protected area of Cerrado in Brazil: planning actions to conservation

Objective. Here we aimed to identify the main points of animal death by roadkill in the view of helping mitigation plans and reducing the impact over the local fauna of a protected area. Materials and methods. We surveyed the roads around a protected area of Cerrado (São Paulo, Brazil) from May 2012 to August 2013. We recorded the local of roadkills, biometric and morphologic data of the animals, and collected samples of tissue for molecular species confirmation. Results. Thirty-one roadkilled animals were registered, including threatened species: Leopardus pardalis; Cuniculus paca and Chrysocyon brachyurus. Most roadkills were represented by mammals (54.8%) and reptiles (38.7%), and the mortality rate was 1.46 animals/km/year. Three roadkill hotspots were detected, suggesting that they were important points of animal crossing, probably because of the existence of natural remnant vegetation and intersection of roads by riparian vegetation. Conclusions. This work provided strong evidence of the most critical points where mitigation strategies should be immediately implemented and highlighted the importance of detecting roadkill hotspots and the species or taxonomic groups more affected, helping to elaborate effective actions that can improve fauna conservation.

Objetivo. Identificar los principales puntos donde mueren animales para proponer planes de mitigación. Materiales y métodos. Se recorrieron las vías alrededor de una área protegida de Cerrado (São Paulo, Brasil) entre Mayo de 2012 y Agosto de 2013. Se registró el lugar del atropellamiento, datos biométricos y morfológicos de los animales y se colectaron muestras de tejido para la confirmación molecular de la especie. Resultados. Se registraron 31 animales atropellados (muertos), incluyendo especies amenazadas: Leopardus pardalis; Cuniculus paca y Chrysocyon brachyurus. La mayoría de los atropellamientos fueron representados por mamíferos (54.8%) y reptiles (38.7%) y la tasa de mortalidad fue de 1.46 animales/km/año. Fueron detectados tres hotspots de atropellamiento, sugiriendo que son puntos importantes en la probabilidad de cruce de animales, debido a un remanente de vegetación natural y la intercepción de la carretera con bosques de galería. Conclusiones. Este trabajo proporciona fuerte evidencia de los puntos más críticos donde las estrategias de mitigación deben ser implementadas inmediatamente y resalta la importancia de detectar hotspots de atropellamiento, las especies y los grupos taxonómicos más afectados ayudando a elaborar acciones efectivas que pueden mejorar la conservación de la fauna.

Bases moleculares de alfa-talasemia en la Argentina

La α-talasemia, es uno de los desórdenes hereditarios más frecuentes mundialmente. Al presente, el diagnóstico molecular es la única herramienta que permite el diagnóstico certero. El propósito de este trabajo fue caracterizar las bases moleculares de estos síndromes en nuestro medio, y establecer relaciones genotipo-fenotipo. Mediante la complementación de distintas técnicas de biología molecular e hibridación fluorescente in situ (FISH), se logró poner en evidencia la presencia de mutaciones α-talasémicas en 145 de 184 (78.8%) pacientes estudiados con perfil hematológico compatible con α-talasemia. Dentro de este grupo, las deleciones correspondieron al defecto genético más frecuente, prevaleciendo la mutación -α3.7 en genotipos heterocigotas y homocigotas. Asimismo, en pacientes con fenotipo α0 las deleciones prevalentes fueron -MED y -CAL/CAMP. Este estudio permitió también describir una deleción de la región sub-telomérica en un paciente con α-talasemia y retraso mental. En el 7.6% de los pacientes caracterizados clínicamente como posibles α-talasémicos (microcitosis con valores de Hb A2 inferiores al 3.5%), se hallaron mutaciones β-talasémicas en estado heterocigota. Se lograron establecer perfiles hematológicos asociados a los genotipos α+ y α0 para pacientes adultos y niños. Esperamos que este trabajo pueda servir como guía para reconocer posibles portadores α-talasémicos. También permite destacar el trabajo en conjunto de médicos hematólogos, el laboratorio (bioquímico y de biología molecular) y de los médicos genetistas, con el fin de proporcionar adecuado consejo genético.

The α-thalassemia is one of the most common hereditary disorders worldwide. Currently, molecular diagnostics is the only available tool to achieve an accurate diagnosis. The purpose of this study was to characterize the molecular bases of these syndromes in our environment and to establish genotype-phenotype associations. Through a combination of different molecular techniques and fluorescent in situ hybridization (FISH),we were able to find α-thalassemic mutations in 145 of the 184 patients (78.8%) studied with hematological parameters compatible with α-thalassemia. Deletions of the a-globin genes resulted the major molecular cause of the disease, and the most frequent mutation was -α3.7, found in homozygous and heterozygous genotypes. In patients with α0 phenotypes, other prevalent mutations were -MED and -CAL/CAMP. The description of a sub-telomeric deletion in a patient with α-thalassemia and mental retardation was also achieved. β-thalassemic mutations in heterozygous state were found in 7.6% of the patients, who presented α-thalassemic clinical features (microcytosis and Hb A2 levels below 3.5%). Hematologic profiles for the α+ and α0 genotypes were established for adult and pediatric patients. Hopefully, this work will provide guidelines for the detection of possible α-thalassemic carriers. It also highlights the collaborative work of hematologists, the biochemical and molecular biology laboratory and genetists, in order to provide appropriate genetic counseling.

Construct validation of the language independent functional evaluation versus the barthel index in a Mongolian community / Монголын Анагаах Ухаан

Purpose. Differences in language and literacy impede our understanding of the impact of disability around the world. Since function is primarily action, the computer-animated Language Independent Functional Evaluation (L.I.F.E.) might bypass the use of written or verbal scales. This study validates L.I.F.E. in a developing world population. Methods. Families were randomly chosen from the city centre, suburban ‘ger’ districts and countryside of Arvaikheer, Mongolia. The L.I.F.E. and cross-translated Mongolian Barthel Index were administered in random order. Demographics including subjective observation of disability were gathered. L.I.F.E. scores were converted to Barthel equivalents. Results. One hundred sixty eight persons completed the test. Persons with observed disability had lower L.I.F.E. scores (64.55 vs. 94.53, p<0.001). L.I.F.E. and Barthel scores related well. (Spearman’s rho=0.757, p<0.001; for persons with observed disability Pearson r=0.820, p<0.001). Individual functions all had high interclass correlations (40.75), except bowel and bladder, which had moderate correlations. Qualitative inquiry found the L.I.F.E. was preferred over the Barthel. Conclusions. Using L.I.F.E., function can be measured without language or literacy. L.I.F.E. expands our ability to measure and compare the prevalence of disability and the impact of rehabilitation across regions perhaps leading to more rational allocation of resources.

Predictors of Suicidal Ideation for Adolescents by Gender / 간호학회지

PURPOSE: The purposes of this study were 1) to examine the differences in suicidal ideation and psychological variables by gender, 2) compare the contribution of demographic-behavioral variables and psychosocial variables in explaining the variance in suicidal ideation, and 3) identify the most important predictors of suicidal ideation for male adolescents and female adolescents. METHODS: The subjects consisted of 271 male adolescents and 230 female adolescents. Data were collected through self-report questionnaires, which were constructed to include SSI-C, DEP subscale of the SCL-90-R, PACI, and SWLS. The data were analyzed by the SPSS/WIN program. RESULTS: Suicidal ideation differed by gender. Depression and family communication differed by gender. The unique contribution of demographic-behavioral variables and psychosocial variables in explaining the variance in suicidal ideation differed between male adolescents and female adolescents. The significant predictors of suicidal ideation for male adolescents were life satisfaction, depression, and family communication, explaining 28% of the variance in suicidal ideation. The significant predictors of suicidal ideation for female adolescents were depression, smoking, and life satisfaction, explaining 38% of the variance in suicidal ideation. CONCLUSION: The findings of this study suggest that the approach to effective suicide prevention program for adolescents should consider gender differences.