RESUMEN
Approaches to rapidly collecting global biodiversity data are increasingly important, but biodiversity blind spots persist. We organized a three-day Datathon event to improve the openness of local biodiversity data and facilitate data reuse by local researchers. The first Datathon, organized among microbial ecologists in Uruguay and Argentina assembled the largest microbiome dataset in the region to date and formed collaborative consortia for microbiome data synthesis.
Asunto(s)
Biodiversidad , Ecología , Microbiota , Argentina , UruguayRESUMEN
A proposta deste trabalho é fomentar a discussão acerca dos fatores e parafatoresde proteção e de risco ao uso de drogas, visando contribuir para a evolução da consciência,por meio da compreensão de mecanismos de prevenção ao uso de substânciaspsicoativas, que podem favorecer a interrupção de um ciclo de patologias conscienciaisautomiméticas. Para elaboração desse artigo, foi realizada uma síntese, no tocanteao tema proposto, do conhecimento adquirido no decorrer dos anos de estudo, atua-ção profissional e pesquisa nessa área, cuja intenção é colaborar, por meio da escrita,com a autopesquisa intraconsciencial e o aperfeiçoamento da assistencialidade(AU)
The purpose of this paper is to stimulate a discussion about drug use preventivefactors and parafactors in order to contribute to the evolution of consciousnesses byunderstanding the psychoactive substance prevention mechanisms, which may lead tothe interruption of a pathological cycle of consciential mimicry. To write this article,there was a synthesis of the subject proposed, some knowledge acquired along theyears of study, professional experience and a survey in the area, aimed at collaborating,through writing, on intraconsciential self-research and assistance developmen(AU)
La propuesta de este trabajo es fomentar la discusión sobre los factores y parafactoresde protección y del riesgo en el uso de drogas, con vistas a contribuir para laevolución de la conciencia, mediante la comprensión de mecanismos de prevenciónen el uso de sustancias psicoactivas, pudiendo favorecer la interrupción del ciclo depatologías concienciales automiméticas. Para la elaboración del artículo fue realizadala síntesis en relación a la pesquisa en el área, con la intención de colaborar, a travésdel escrito, en la autoinvestigación intraconciencial y el perfeccionamiento de la asistencialidad(AU)
RESUMEN
BACKGROUND: The human hemoglobin switch (HbF-->HbA) takes place in the peri/post-natal period. In adult life, however, the residual HbF (<1%) may be partially reactivated by chemical inducers and/or cytokines such as the kit ligand (KL). MicroRNAs (miRs) play a pivotal role in normal hematopoiesis: downmodulation of miR-221/222 stimulates human erythropoietic proliferation through upmodulation of the kit receptor. DESIGN AND METHODS: We have explored the possible role of kit/KL in perinatal Hb switching by evaluating: i) the expression levels of both kit and kit ligand on CD34(+) cells and in plasma isolated from pre-, mid- and full-term cord blood samples; ii) the reactivation of HbF synthesis in KL-treated unilineage erythroid cell cultures; iii) the functional role of miR-221/222 in HbF production. RESULTS: In perinatal life, kit expression showed a gradual decline directly correlated to the decrease of HbF (from 80-90% to <30%). Moreover, in full-term cord blood erythroid cultures, kit ligand induced a marked increase of HbF (up to 80%) specifically abrogated by addition of the kit inhibitor imatinib, thus reversing the Hb switch. MiR-221/222 expression exhibited rising levels during peri/post-natal development. In functional studies, overexpression of these miRs in cord blood progenitors caused a remarkable decrease in kit expression, erythroblast proliferation and HbF content, whereas their suppression induced opposite effects. CONCLUSIONS: Our studies indicate that human perinatal Hb switching is under control of the kit receptor/miR 221-222 complex. We do not exclude, however, that other mechanisms (i.e. glucocorticoids and the HbF inhibitor BCL11A) may also contribute to the peri/post-natal Hb switch.
Asunto(s)
Hemoglobina Fetal/metabolismo , Hemoglobina A/metabolismo , MicroARNs/fisiología , Factor de Células Madre/fisiología , Adulto , Antígenos CD34/sangre , Benzamidas , Ciclo Celular , Células Cultivadas , Células Eritroides/citología , Células Eritroides/efectos de los fármacos , Células Eritroides/metabolismo , Eritropoyesis/efectos de los fármacos , Eritropoyesis/genética , Sangre Fetal/citología , Sangre Fetal/metabolismo , Citometría de Flujo , Expresión Génica , Humanos , Mesilato de Imatinib , Recién Nacido , MicroARNs/genética , Piperazinas/farmacología , Proteínas Proto-Oncogénicas c-kit/sangre , Proteínas Proto-Oncogénicas c-kit/genética , Pirimidinas/farmacología , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Células Madre/sangre , Factor de Células Madre/genética , Factores de TiempoRESUMEN
In human beta-thalassemia, the imbalance between alpha- and non-alpha-globin chains causes ineffective erythropoiesis, hemolysis, and anemia: this condition is effectively treated by an enhanced level of fetal hemoglobin (HbF). In spite of extensive studies on pharmacologic induction of HbF synthesis, clinical trials based on HbF reactivation in beta-thalassemia produced inconsistent results. Here, we investigated the in vitro response of beta-thalassemic erythroid progenitors to kit ligand (KL) in terms of HbF reactivation, stimulation of effective erythropoiesis, and inhibition of apoptosis. In unilineage erythroid cultures of 20 patients with intermedia or major beta-thalassemia, addition of KL, alone or combined with dexamethasone (Dex), remarkably stimulated cell proliferation (3-4 logs more than control cultures), while decreasing the percentage of apoptotic and dyserythropoietic cells (<5%). More important, in both thalassemic groups, addition of KL or KL plus Dex induced a marked increase of gamma-globin synthesis, thus reaching HbF levels 3-fold higher than in con-trol cultures (eg, from 27% to 75% or 81%, respectively, in beta-thalassemia major). These studies indicate that in beta-thalassemia, KL, alone or combined with Dex, induces an expansion of effective erythropoiesis and the reactivation of gamma-globin genes up to fetal levels and may hence be considered as a potential therapeutic agent for this disease.
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Eritropoyesis/efectos de los fármacos , Hemoglobina Fetal/fisiología , Factor de Células Madre/farmacología , Talasemia beta/sangre , Talasemia beta/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Dexametasona/farmacología , Quimioterapia Combinada , Eritrocitos/citología , Eritrocitos/fisiología , Glucocorticoides/farmacología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , HumanosRESUMEN
In sheep carrying simultaneously extra alpha-globin genes (triplications and quadruplications) and two alpha-chain allelic variants, a gradient of decreasing expression of the downstream genes was previously reported. We show here that in these sheep the proportions of the normal and variant Hbs reflect not only the position effect, but also the differential affinity of one of the alpha variants for the betaA and betaB allelic chains.
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Dosificación de Gen , Globinas/genética , Fenotipo , Ovinos/genética , Animales , Regulación de la Expresión Génica , Globinas/metabolismo , Unión Proteica , Ovinos/metabolismo , Especificidad por Sustrato/genéticaRESUMEN
Mechanisms underlying fetal hemoglobin (HbF) reactivation in stress erythropoiesis have not been fully elucidated. We suggested that a key role is played by kit ligand (KL). Because glucocorticoids (GCs) mediate stress erythropoiesis, we explored their capacity to potentiate the stimulatory effect of KL on HbF reactivation, as evaluated in unilineage erythropoietic culture of purified adult progenitors (erythroid burst-forming units [BFU-Es]). The GC derivative dexamethasone (Dex) was tested in minibulk cultures at graded dosages within the therapeutical range (10(-6) to 10(-9) M). Dex did not exert significant effects alone, but synergistically it potentiated the action of KL in a dose-dependent fashion. Specifically, Dex induced delayed erythroid maturation coupled with a 2-log increased number of generated erythroblasts and enhanced HbF synthesis up to 85% F cells and 55% gamma-globin content at terminal maturation (ie, in more than 80%-90% mature erythroblasts). Equivalent results were obtained in unicellular erythroid cultures of sibling BFU-Es treated with KL alone or combined with graded amounts of Dex. These results indicate that the stimulatory effect of KL + Dex is related to the modulation of gamma-globin expression rather than to recruitment of BFU-Es with elevated HbF synthetic potential. At the molecular level, Id2 expression is totally suppressed in control erythroid culture but is sustained in KL + Dex culture. Hypothetically, Id2 may mediate the expansion of early erythroid cells, which correlates with HbF reactivation. These studies indicate that GCs play an important role in HbF reactivation. Because Dex acts at dosages used in immunologic disease therapy, KL + Dex administration may be considered to develop preclinical models for beta-hemoglobinopathy treatment.