AKT-1 Regulates DNA-Damage-Induced Germline Apoptosis in C. elegans

SummaryThe cellular response to genotoxic stress involves the integration of multiple prosurvival and proapoptotic signals that dictate whether a cell lives or dies. In mammals, AKT/PKB regulates cell survival by modulating the activity of several apoptotic proteins, including p53 [1]. In Caenorhabditis elegans, akt-1 and akt-2 regulate development in response to environmental cues by controlling the FOXO transcription factor daf-16[2], but the role of these genes in regulating p53-dependent apoptosis is not known. In this study, we show that akt-1 and akt-2 negatively regulate DNA-damage-induced apoptosis in the C. elegans germline. The antiapoptotic activity of akt-1 is independent of its target gene daf-16 but dependent on cep-1/p53. Although only akt-1 regulates the apoptotic activity of cep-1, both akt-1 and akt-2 modulate the intensity of the apoptotic response independently of the transcriptional activity of CEP-1. Finally, we show that AKT-1 regulates apoptosis but not cell-cycle progression downstream of the HUS-1/MRT-2 branch of the DNA damage checkpoint

Automated morphological feature assessment for zebrafish embryo developmental toxicity screens

Detection of developmental phenotypes in zebrafish embryos typically involves a visual assessment and scoring of morphological features by an individual researcher. Subjective scoring could impact results and be of particular concern when phenotypic effect patterns are also used as a diagnostic tool to classify compounds. Here we introduce a quantitative morphometric approach based on image analysis of zebrafish embryos. A software called FishInspector was developed to detect morphological features from images collected using an automated system to position zebrafish embryos. The analysis was verified and compared with visual assessments of 3 participating laboratories using 3 known developmental toxicants (methotrexate, dexamethasone, and topiramate) and 2 negative compounds (loratadine and glibenclamide). The quantitative approach exhibited higher sensitivity and made it possible to compare patterns of effects with the potential to establish a grouping and classification of developmental toxicants. Our approach improves the robustness of phenotype scoring and reliability of assay performance and, hence, is anticipated to improve the predictivity of developmental toxicity screening using the zebrafish embryo

SHP-1 negatively regulates neuronal survival by functioning as a TrkA phosphatase

Nerve growth factor (NGF) mediates the survival and differentiation of neurons by stimulating the tyrosine kinase activity of the TrkA/NGF receptor. Here, we identify SHP-1 as a phosphotyrosine phosphatase that negatively regulates TrkA. SHP-1 formed complexes with TrkA at Y490, and dephosphorylated it at Y674/675. Expression of SHP-1 in sympathetic neurons induced apoptosis and TrkA dephosphorylation. Conversely, inhibition of endogenous SHP-1 with a dominant-inhibitory mutant stimulated basal tyrosine phosphorylation of TrkA, thereby promoting NGF-independent survival and causing sustained and elevated TrkA activation in the presence of NGF. Mice lacking SHP-1 had increased numbers of sympathetic neurons during the period of naturally occurring neuronal cell death, and when cultured, these neurons survived better than wild-type neurons in the absence of NGF. These data indicate that SHP-1 can function as a TrkA phosphatase, controlling both the basal and NGF-regulated level of TrkA activity in neurons, and suggest that SHP-1 regulates neuron number during the developmental cell death period by directly regulating TrkA activity

Educación para la salud de la embarazada y el bebé en contexto de pandemia viral

El proyecto de extensión se denomina “Mil días para educar” Los primeros mil días de la vida de un niño, el período que transcurre desde la concepción hasta cumplir los dos años de edad; se consideran una” ventana de oportunidades” para el desarrollo futuro del niño y es el momento ideal para promover sus potencialidades y prevenir enfermedades en la vida adulta. En esta etapa, el buen uso de los recursos preventivos permite optimizar su crecimiento y mejorar el desarrollo en general, inteligencia, talla, fuerza muscular y a nivel odontológico disminuir la susceptibidad a caries y malos hábitos.. Educar a la gestante sobre lactancia materna es de suma relevancia y es nuestro deber como asesorarla sobre los numerosos beneficios que le otorga tanto a ella como a su bebé. Desde el punto de vista odontológico, favorece el crecimiento y avance de la mandíbula del niño, estabiliza la relación de sus bases maxilares, ayuda en el proceso de la erupción dentaria, estimula el movimiento de su articulación temporomandibular, previene la respiración bucal entre otros.Trabajo publicado en Herrero, D.; Sosa, B.; Brutti, F.; Prado, M. (comps.). Reflexiones y desafíos de la extensión universitaria en América Latina. Tandil: UNICEN, 2021.Facultad de Odontologí

Integrando sonrisas. Parte II : Los selladores de hoy… una alternativa de tratamiento preventivo o terapéutico

Hoy en día, la prevención y el tratamiento de la caries dental deben estar basados en la detección apropiada de la misma en sus etapas más tempranas, no sólo detectar cavidades sino también signos tempranos de desmineralización. La caries dental continúa siendo un problema de salud pública que afecta considerablemente a la población infantil. Es un compromiso social implementar medidas preventivas que disminuyan el riesgo para la enfermedad. Los selladores de fosas y fisuras en los últimos años han ganado popularidad como procedimiento de prevención de la caries, siempre y cuando se apliquen en el caso adecuado.Facultad de Odontologí

Much more than a harmful habit… Report of a clinical case

Introducción: La persistencia del uso del biberón más allá de aproximadamente los 18 meses de edad causa deformación en dientes y maxilares. Si a ese hábito le sumamos la ingesta de un líquido azucarado nocturno en ausencia del cepillado, no sólo causará deformación en la mordida sino también destrucción masiva de los tejidos dentarios del sector anterosuperior del niño/a llamada caries temprana de la infancia.Introduction: The persistence of the use of the bottle beyond approximately 18 months of age causes deformation in teeth and jaws. If we add to this habit the ingestion of a sugary liquid at night in the absence of brushing, it will not only cause deformation in the bite but also massive destruction of the dental tissues of the child's front and top sector called early childhood caries.Facultad de Odontologí

Comprehensive description of clinical characteristics of a large systemic Lupus Erythematosus Cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) with emphasis on complete versus incomplete lupus differences

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries. RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions. A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis-adjusted by gender, age at diagnosis, and disease duration-revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08-1.20 (P < 0.001); 1.29; 95% CI: 1.15-1.44 (P < 0.001); and 2.10; 95% CI: 1.83-2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0-4)], damage [median SLICC/ACR/DI: 1 (IQ: 0-2)], and severity [median KATZ index: 2 (IQ: 1-3)] scores were low, 1 of every 4 deaths was due to SLE activity. RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population

Development and Validation of an Automated High-Throughput System for Zebrafish In Vivo Screenings

The zebrafish is a vertebrate model compatible with the paradigms of drug discovery. The small size and transparency of zebrafish embryos make them amenable for the automation necessary in high-throughput screenings. We have developed an automated high-throughput platform for in vivo chemical screenings on zebrafish embryos that includes automated methods for embryo dispensation, compound delivery, incubation, imaging and analysis of the results. At present, two different assays to detect cardiotoxic compounds and angiogenesis inhibitors can be automatically run in the platform, showing the versatility of the system. A validation of these two assays with known positive and negative compounds, as well as a screening for the detection of unknown anti-angiogenic compounds, have been successfully carried out in the system developed. We present a totally automated platform that allows for high-throughput screenings in a vertebrate organism

De lo diverso hacia lo singular

Contenido del resumen de trabajos de investigación: Introducción: En un primer momento fue la socióloga Judy Singer quien acuño el término “neurodiversidad” en 1998. Su libro autoeditado y su tesis formaron parte del recorrido en relación a la neurodiversidad. Se establecen algunas diferencias en base a si es una cuestión de identidad o una discapacidad. En un primer tiempo: el diagnóstico, puede permitir cierto alivio al nombrar algo y desde allí puede que al compartirlos con otros permita comprender, entender, identificarse, pero puede que eso no alcance, o no lo explique todo, puede que el diagnostico no nombre todo lo que a alguien en su particularidad le pase. Objetivos: -Encontrar diversas maneras de pensar la diversidad -Ubicar a lo diverso como lo que hace comunidad. -Situar las implicancias del diagnósticoFacultad de Odontologí