We're in This Together: Intergenerational Health Policies as an Emerging Public Health Necessity

The global handling of the COVID-19 pandemic has highlighted the lack of intergenerational public health solutions. Discontinuity of educational and health care services and environmental threats increase various pathologies and may provoke long-term health damage among the youngest. Unbalanced generational approaches within health policies have been evident before the pandemic and will continue to be a global challenge as both acute and chronic threats due to environmental hazards and social disparities are increasing. We therefore aim to bring with the present article the concept of intergenerational health to the center of socio-political attention as it must become beyond the COVID-19 crisis a core concept in the development and implementation of health policies

Cumes. Recherches archéologiques dans la nécropole de la Porte médiane.

Données scientifiques produites :https://centrejeanberard.cnrs.fr/spip.php?article34&lang=fr Chroniques de l’EFR : https://journals.openedition.org/cefr/990 Introduction En 2001, le Centre Jean Bérard a lancé un programme de recherche pour étudier la nécropole de Cumes qui s’étend à l’extérieur des fortifications septentrionales (fig. 1‑2). Fig. 1. Le site de Cumes et au premier plan la nécropole de la Porte médiane. E. Botte, CNRS, CCJ / © CC BY‑NC‑ND. Fig. 2. Plan la nécropole de la Port..

Molecular and functional characterization of the newly identified interaction between the Rett syndrome-associated factor MeCP2 and the pro-apoptotic factor HIPK2.

RTT Syndrome is an X-linked neuronal progressive disorder causing mental retardation mostly in females. MeCP2, a methyl-DNA-binding protein that represses transcription by modulating chromatin structure, is mutated in about 80% of classical RTT-patients. The rather large number of patients with a normal MeCP2 gene and the lack of an apparent genotype-phenotype correlation, suggests that other genes may be involved in the onset of this neurological disorder. Based on these considerations, we reasoned that the identification of novel MeCP2 interacting factors might help to refine the comprehension of the molecular mechanism(s) involved in RTT syndrome. Thus, we performed a yeast two hybrid screening using MeCP2 as a bait. We identified the homeodomaininteracting kinase 2 (HIPK2) as a new MeCP2 interactor. HIPK2 belongs to a family of nuclear serine/threonine kinases originally cloned due to their ability to interact with homeodomain transcription factors. HIPK2, the most studied of this family, binds also to a series of proteins involved in the regulation of cell survival and proliferation, including the oncosoppressor p53. In the present study, we have confirmed the physical interaction between MeCP2 and HIPK2 and, by in vitro phosphorylation assays, we have demonstrated that HIPK2 is able to phosphorylate MeCP2. Furthermore, we have mapped the specific MeCP2 site targeted by HIPK2. At the functional level, we have demonstrated that the ectopic expression of MeCP2 leads to apoptosis in different cell lines and that this effect is increased by the presence of HIPK2. Importantly, the serine residue on MeCP2 which is phosphorylated by HIPK2 in vitro, is required for the cooperation between the two proteins in inducing apoptosis, strongly suggesting that this residue is also an in vivo target of HIPK2. In conclusion our findings indicate that MeCP2 belongs to the HIPK2 apoptotic pathway and clearly suggest a novel role for MeCP2 in programmed cell death that might provide novel valuable insights into Rett syndrome

Molecular and functional characterization of the newly identified interaction between the Rett syndrome-associated factor MeCP2 and the pro-apoptotic factor HIPK2.

RTT Syndrome is an X-linked neuronal progressive disorder causing mental retardation mostly in females. MeCP2, a methyl-DNA-binding protein that represses transcription by modulating chromatin structure, is mutated in about 80% of classical RTT-patients. The rather large number of patients with a normal MeCP2 gene and the lack of an apparent genotype-phenotype correlation, suggests that other genes may be involved in the onset of this neurological disorder. Based on these considerations, we reasoned that the identification of novel MeCP2 interacting factors might help to refine the comprehension of the molecular mechanism(s) involved in RTT syndrome. Thus, we performed a yeast two hybrid screening using MeCP2 as a bait. We identified the homeodomaininteracting kinase 2 (HIPK2) as a new MeCP2 interactor. HIPK2 belongs to a family of nuclear serine/threonine kinases originally cloned due to their ability to interact with homeodomain transcription factors. HIPK2, the most studied of this family, binds also to a series of proteins involved in the regulation of cell survival and proliferation, including the oncosoppressor p53. In the present study, we have confirmed the physical interaction between MeCP2 and HIPK2 and, by in vitro phosphorylation assays, we have demonstrated that HIPK2 is able to phosphorylate MeCP2. Furthermore, we have mapped the specific MeCP2 site targeted by HIPK2. At the functional level, we have demonstrated that the ectopic expression of MeCP2 leads to apoptosis in different cell lines and that this effect is increased by the presence of HIPK2. Importantly, the serine residue on MeCP2 which is phosphorylated by HIPK2 in vitro, is required for the cooperation between the two proteins in inducing apoptosis, strongly suggesting that this residue is also an in vivo target of HIPK2. In conclusion our findings indicate that MeCP2 belongs to the HIPK2 apoptotic pathway and clearly suggest a novel role for MeCP2 in programmed cell death that might provide novel valuable insights into Rett syndrome

Molecular and functional characterization of the newly identified interaction between the Rett syndrome-associated factor MeCP2 and the pro-apoptotic factor HIPK2.

RTT Syndrome is an X-linked neuronal progressive disorder causing mental retardation mostly in females. MeCP2, a methyl-DNA-binding protein that represses transcription by modulating chromatin structure, is mutated in about 80% of classical RTT-patients. The rather large number of patients with a normal MeCP2 gene and the lack of an apparent genotype-phenotype correlation, suggests that other genes may be involved in the onset of this neurological disorder. Based on these considerations, we reasoned that the identification of novel MeCP2 interacting factors might help to refine the comprehension of the molecular mechanism(s) involved in RTT syndrome. Thus, we performed a yeast two hybrid screening using MeCP2 as a bait. We identified the homeodomaininteracting kinase 2 (HIPK2) as a new MeCP2 interactor. HIPK2 belongs to a family of nuclear serine/threonine kinases originally cloned due to their ability to interact with homeodomain transcription factors. HIPK2, the most studied of this family, binds also to a series of proteins involved in the regulation of cell survival and proliferation, including the oncosoppressor p53. In the present study, we have confirmed the physical interaction between MeCP2 and HIPK2 and, by in vitro phosphorylation assays, we have demonstrated that HIPK2 is able to phosphorylate MeCP2. Furthermore, we have mapped the specific MeCP2 site targeted by HIPK2. At the functional level, we have demonstrated that the ectopic expression of MeCP2 leads to apoptosis in different cell lines and that this effect is increased by the presence of HIPK2. Importantly, the serine residue on MeCP2 which is phosphorylated by HIPK2 in vitro, is required for the cooperation between the two proteins in inducing apoptosis, strongly suggesting that this residue is also an in vivo target of HIPK2. In conclusion our findings indicate that MeCP2 belongs to the HIPK2 apoptotic pathway and clearly suggest a novel role for MeCP2 in programmed cell death that might provide novel valuable insights into Rett syndrome

Análisis de índices financieros y su influencia en la toma de decisiones de la Corporación Aceros Arequipa SA de los periodos 2017-2019

El trabajo de investigación titulado “Análisis de índices financieros y su influencia en la toma de decisiones de la Corporación Aceros Arequipa SA de los periodos 2017-2019” tuvo como objetivo: Determinar cómo el análisis de índices financieros influye en la toma de decisiones de la Corporación Aceros Arequipa SA de los periodos 2017-2019. Desde el aspecto metodológico, el estudio se trabajó bajo un enfoque cuantitativo, de tipo básica, de nivel correlacional-causal, con un diseño no experimental, de corte longitudinal. La población estuvo conformada por la empresa Corporación Aceros Arequipa, la cual cotiza en la BVL. Se utilizó como técnica el análisis documental, donde se analizó el estado de situación financiera y estado de resultados mediante las ratios de liquidez, solvencia y rentabilidad con el objeto de saber si en los periodos se tomaron buenas decisiones. Los instrumentos fueron validados mediante el juicio de expertos donde se dictamino la razonabilidad y suficiencia de los mismos. De acuerdo al objetivo general, se determinó que, el análisis de índices financieros influye en la toma de decisiones de la Corporación Aceros Arequipa SA de los periodos 2017-2019. Esto debido a que, los índices financieros para la toma decisoria en la gerencia de la compañía le han permitido evaluar a los gerentes el estado situacional financiero, siendo estas herramientas necesarias y determinantes en la gestión financiera en materia de liquidez, solvencia y rentabilidad para competir en el sector

Characterization of HIPK2 that, by Associating with MeCP2, Might Function as a Modifier Gene in Rett Syndrome.

Mutations in the methyl CpG-binding protein 2 (MECP2) gene, located on Xq28, are responsible for almost all cases of classic RTT. Conversely, less than half of the patients with one of the variant forms of RTT carry mutations in MECP2. It seems, thus, that other genes are involved in causing RTT; moreover the fact that there are patients with milder phenotypes in spite of severe mutations argues that modifier genes might restrict the clinical outcome by regulating MeCP2 functions. To search for MeCP2 interacting proteins possibly involved in RTT we performed a yeast two-hybrid screening and identified among the positive clones HIPK2 (homeodomain interacting protein kinase 2) that belongs to a family of Ser/Thr kinases originally identified as corepressors for homeodomain transcription factors. HIPK2 has a clear role in regulating cell growth and genotoxic stress-induced apoptosis. Furthermore, its involvement in the nervous system is indicated by the neuronal defects of null mice that partially overlap those observed in Mecp2 ko mice. Since important MeCP2 functions in the nervous system are regulated by its phosphorylation we found it interesting to analyze the functional role of its interaction with HIPK2. We have thus confirmed that the two proteins associate in vitro and in vivo and phosphorylation assays have shown that MeCP2 is significantly phosphorylated by HIPK2 in vitro. Importantly, these assays have also allowed us to establish that Ser80 within the MBD of MeCP2 is a specific target of HIPK2. Functional assays have shown that ectopic MeCP2 causes an increase in cell death and an additive effect of the two proteins in inducing apoptosis in cultured cells was observed. Importantly, the role of MeCP2 in inducing apoptosis together with HIPK2 is lost when Ser80 is mutated or a kinase dead derivative of HIPK2 is used. Presently we are analyzing whether MeCP2 is a target of the kinase also in vivo and the role of the interaction for the nervous system. In favor of the hypothesis that the two proteins work in a common molecular pathway we have shown by immunohistochemistry experiments that the expression pattern of MeCP2 and HIPK2 in the brain of adult mice is highly similar. We therefore believe that these studies are relevant for understanding whether this novel MeCP2 interactor acts as a modifier gene influencing disease severity in RTT patients with mutations in MeCP2

Characterization of HIPK2 that, by Associating with MeCP2, Might Function as a Modifier Gene in Rett Syndrome

Mutations in the methyl CpG-binding protein 2 (MECP2) gene, located on Xq28, are responsible for almost all cases of classic RTT. Conversely, less than half of the patients with one of the variant forms of RTT carry mutations in MECP2. It seems, thus, that other genes are involved in causing RTT; moreover the fact that there are patients with milder phenotypes in spite of severe mutations argues that modifier genes might restrict the clinical outcome by regulating MeCP2 functions. To search for MeCP2 interacting proteins possibly involved in RTT we performed a yeast two-hybrid screening and identified among the positive clones HIPK2 (homeodomain interacting protein kinase 2) that belongs to a family of Ser/Thr kinases originally identified as corepressors for homeodomain transcription factors. HIPK2 has a clear role in regulating cell growth and genotoxic stress-induced apoptosis. Furthermore, its involvement in the nervous system is indicated by the neuronal defects of null mice that partially overlap those observed in Mecp2 ko mice. Since important MeCP2 functions in the nervous system are regulated by its phosphorylation we found it interesting to analyze the functional role of its interaction with HIPK2. We have thus confirmed that the two proteins associate in vitro and in vivo and phosphorylation assays have shown that MeCP2 is significantly phosphorylated by HIPK2 in vitro. Importantly, these assays have also allowed us to establish that Ser80 within the MBD of MeCP2 is a specific target of HIPK2. Functional assays have shown that ectopic MeCP2 causes an increase in cell death and an additive effect of the two proteins in inducing apoptosis in cultured cells was observed. Importantly, the role of MeCP2 in inducing apoptosis together with HIPK2 is lost when Ser80 is mutated or a kinase dead derivative of HIPK2 is used. Presently we are analyzing whether MeCP2 is a target of the kinase also in vivo and the role of the interaction for the nervous system. In favor of the hypothesis that the two proteins work in a common molecular pathway we have shown by immunohistochemistry experiments that the expression pattern of MeCP2 and HIPK2 in the brain of adult mice is highly similar. We therefore believe that these studies are relevant for understanding whether this novel MeCP2 interactor acts as a modifier gene influencing disease severity in RTT patients with mutations in MeCP2

Bei Eintritt den Austritt bereits im Blick : der PACD am Kantonsspital Aarau

Die Erfassung und Bewertung des «biopsychosozialen Risikos» ermöglicht es, bereits frühzeitigerkennen und entscheiden zu können, ob ein Patient nach einem stationären Aufenthalt aufUnterstützung in einer post-akuten Institution zu Hause angewiesen sein wird. Das KantonsspitalAarau setzt dafür das Einschätzungsinstrument «Post-acute-care-discharge» (PACD) ein

Intense Foxp3+CD25+regulatory T cell infiltration is associated with high-grade cutaneous squamous cell carcinoma and counterbalanced by CD8+/Foxp3+CD25+ratio

Recent reports revealed the therapeutic potential of cell-mediated immunity in neoplasms like cutaneous squamous cell carcinomas (SCC).We evaluated the content and distribution of Foxp3+CD25+ regulatory T and CD123+ plasmacytoid dendritic cells infiltration and assessed CD8+/Foxp3+CD25+ cell ratio at peritumoral and intratumoral levels in 40 SCC (20 well-differentiated G1, and 20 moderately to poorly-differentiated G2-G3) to evidence a correlation with their aggressiveness. We determined the profiles of Tregs and CD123+ cells and also run an immunostaining for CD4, CD8, CD123, IL-10, TGF-beta 1 and an unequivocal double staining for Foxp3CD25. Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123+ cells were fewer in the G2-G3 (p= 0.0005) while Foxp3+CD25+ cells were more numerous (p=0.0005). The Foxp3+CD25+/Foxp3+ ratio was higher in G2-G3 cases (p=0.0005), confirming the prevalence in this group of activated T lymphocytes towards total regulatory T Foxp3+ cells, while the CD8+/Foxp3+CD25+ ratio was higher in G1 specimens (p=0.0005). Intratumorally, CD4+ and CD8+ cells infiltrated G2-G3 (p=0.048) more than G1 (p=0.004), whereas almost all cells were CD123 negative. Regarding Foxp3+CD25+, TGF-beta 1+ and IL-10+ , they were less expressed in G1, whereas G2-G3 were positive (p<0.05). The result of CD8+/Foxp3+CD25+ ratio was similar to that observed in the peritumoral infiltration. Our data suggest that an intratumoral recruitment of Tregs, a high expression of TGF-beta 1 and IL-10, an almost negative CD123+ cells finding, and a low CD8+/Foxp3+CD25+ T cell ratio may contribute to the aggressiveness of cutaneous SCC as already evidenced for other solid tumors