Control of cccDNA function in hepatitis B virus infection

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EZH2, JMJD3 and UTX epigenetically regulate hepatic plasticity inducing retro-differentiation and proliferation of liver cells

Modification of histones by lysine methylation plays a role in many biological processes, and it is dynamically regulated by several histone methyltransferases and demethylases. The polycomb repressive complex contains the H3K27 methyltransferase EZH2 and controls dimethylation and trimethylation of H3K27 (H3K27me2/3), which trigger gene suppression. JMJD3 and UTX have been identified as H3K27 demethylases that catalyze the demethylation of H3K27me2/3, which in turns lead to gene transcriptional activation. EZH2, JMJD3 and UTX have been extensively studied for their involvement in development, immune system, neurodegenerative disease, and cancer. However, their role in molecular mechanisms underlying the differentiation process of hepatic cells is yet to be elucidated. Here, we show that EZH2 methyltransferase and JMJD3/UTX demethylases were deregulated during hepatic differentiation of human HepaRG cells resulting in a strong reduction of H3K27 methylation levels. Inhibition of JMJD3 and UTX H3K27 demethylase activity by GSK-J4 epi-drug reverted phenotype of HepaRG DMSO-differentiated cells and human primary hepatocytes, drastically decreasing expression of hepatic markers and inducing cell proliferation. In parallel, inhibition of EZH2 H3K27me3 activity by GSK-126 epi-drug induced upregulation of hepatic markers and downregulated the expression of cell cycle inhibitor genes. To conclude, we demonstrated that modulation of H3K27 methylation by inhibiting methyl-transferase and dimethyl-transferase activity influences the differentiation status of hepatic cells, identifying a possible new role of EZH2, JMJD3 and UTX epi-drugs to modulate hepatic cell plasticity

La importancia de la metodología de la investigación en la carrera de Medicina en la Universidad Nacional de Rosario

Kerlinger and Lee (2002) mention that research is and must be so orderly that the researcher can have full confidence in its results, for this reason, methodology is used as a pillar of all research because it does not give room for error, it is responsible for classifying and filtering the information in such a way that knowledge is obtained in the most accurate way possible to the historical, social and cultural context of the researcher (p. 13). All knowledge must be questioned and tested, a fact that refers us to the analysis carried out by this discipline to evaluate the quality of the information collected and cannot be separated from the process of obtaining - renewing knowledge, since it has been postponed from the beginning in the background to better understand the function of methodology.Kerlinger y Lee (2002) menciona que la investigación es y debe ser tan ordenada que el investigador pueda tener plena confianza en sus resultados, por esta razón, se utiliza a la metodología como pilar de toda investigación pues no dar lugar al error, se encarga de clasificar y filtrar la información de manera tal, que se obtenga el conocimiento de la forma más acertada posible al contexto histórico, social y cultural del investigador (p. 13). Todo conocimiento debe ser cuestionado y puesto a prueba, hecho que nos remite al análisis que realiza esta disciplina para evaluar la calidad de la información recabada, y no puede ser desligada del proceso obtención – renovación de conocimiento, pues se ha pospuesto desde los inicios en un segundo plano para comprender mejor la función de la metodología.

Exploring Cluster Ellipticals as Cosmological Standard Rods

We explore the possibility to calibrate massive cluster ellipticals as cosmological standard rods using the Fundamental Plane relation combined with a correction for luminosity evolution. Though cluster ellipticals certainly formed in a complex way, their passive evolution out to redshifts of about 1 indicates that basically all major merging and accretion events took place at higher redshifts. Therefore, a calibration of their luminosity evolution can be attempted. We propose to use the Mg$-\sigma$ relation for that purpose because it is independent of distance and cosmology. We discuss a variety of possible caveats, ranging from dynamical evolution to uncertainties in stellar population models and evolution corrections to the presence of age spread. Sources of major random and systematic errors are analysed as well. We apply the described procedure to nine elliptical galaxies in two clusters at $z=0.375$ and derive constraints on the cosmological model. For the best fitting $\Lambda$-free cosmological model we obtain: $q_o \approx 0.1$, with 90% confidence limits being $0 < q_o < 0.7$ (the lower limit being due to the presence of matter in the Universe). If the inflationary scenario applies (i.e. the Universe has flat geometry), then, for the best fitting model, matter and $\Lambda$ contribute about equally to the critical cosmic density (i.e. $\Omega_m \approx \Omega_\Lambda \approx 0.5$). With 90% confidence $\Omega_\Lambda$ should be smaller than 0.9.Comment: 21 pages, including 5 eps-figures, Latex, uses aasms4.sty, accepted by ApJ main journa

Especificación formal de escenarios a partir de ontologías temporales

Los escenarios son artefactos de gran relevancia en la Ingeniería de Requerimientos ya que permiten documentar y analizar la dimensión dinámica de los sistemas de información describiendo tanto situaciones actuales como futuras. En el marco de un desarrollo guiado por modelos basados en ontologías, se propone aquí una ontología para Escenarios y para ello se señala la importancia de utilizar relaciones temporales cualitativas a partir de la extensión y reutilización de definiciones de ontologías de “alto nivel” (upper level ontologies).Sociedad Argentina de Informática e Investigación Operativa (SADIO

The Importance of Reading the Skin: Cutaneous Metastases of Pancreatic Cancer, a Systematic Review

Background: Pancreatic cancer is notorious for its aggressive nature and low survival rate, with less than 10% of patients surviving beyond five years. Early detection is difficult, but skin metastases can be a rare but significant indicator. This systematic review focuses on the epidemiology, clinical features, and histology of skin metastases from pancreatic cancer to determine their importance in early diagnosis and overall management of the disease. Materials and methods: Following PRISMA guidelines, we conducted an exhaustive search of MEDLINE/PubMed, EMBASE, and SCOPUS databases up to June 2023, using specific keywords. Four independent investigators screened the studies using predefined criteria, and two investigators checked the accuracy and consistency of the data extraction. We assessed the quality of the trials using adapted criteria from the Joanna Briggs Institute. A narrative synthesis rather than a meta-analysis was chosen because of the different study designs. Results: The final analysis included 57 patients with skin metastases from pancreatic cancer. Cutaneous metastases, although rare, presented with approximately equal gender distribution and a mean age of 63.4 years. Predominantly non-umbilical (77%), these metastases showed clinical diversity, ranging from asymptomatic nodules to painful or ulcerated lesions. Notably, skin metastases often preceded the diagnosis of primary pancreatic cancer (58%). Primary tumor characteristics revealed different localizations, with adenocarcinoma being the most prevalent histological type (77%). A significant association (p = 0.008) was observed between pancreatic tumor location and the timing of presentation of skin metastases. Tumors located in the body and tail of the pancreas were more likely to manifest skin metastases as an initial clinical manifestation (62.2%) than those in the head of the pancreas (20.8%). Conclusions: In conclusion, although skin metastases are rare, they are important indicators of pancreatic cancer, highlighting the need for multidisciplinary healthcare collaboration and thorough skin examination. Recognizing them could lead to earlier diagnosis, which is crucial in a cancer with limited treatment options

Especificación formal de escenarios a partir de ontologías temporales

Los escenarios son artefactos de gran relevancia en la Ingeniería de Requerimientos ya que permiten documentar y analizar la dimensión dinámica de los sistemas de información describiendo tanto situaciones actuales como futuras. En el marco de un desarrollo guiado por modelos basados en ontologías, se propone aquí una ontología para Escenarios y para ello se señala la importancia de utilizar relaciones temporales cualitativas a partir de la extensión y reutilización de definiciones de ontologías de “alto nivel” (upper level ontologies).Sociedad Argentina de Informática e Investigación Operativa (SADIO

Especificación formal de escenarios a partir de ontologías temporales

Los escenarios son artefactos de gran relevancia en la Ingeniería de Requerimientos ya que permiten documentar y analizar la dimensión dinámica de los sistemas de información describiendo tanto situaciones actuales como futuras. En el marco de un desarrollo guiado por modelos basados en ontologías, se propone aquí una ontología para Escenarios y para ello se señala la importancia de utilizar relaciones temporales cualitativas a partir de la extensión y reutilización de definiciones de ontologías de “alto nivel” (upper level ontologies).Sociedad Argentina de Informática e Investigación Operativa (SADIO

Lesiones papulosas en rodillas. ¿Cuál es su diagnóstico?

Giant Juvenile Xanthogranuloma presents as papular lesions with well-defined borders, a yellowish color, and is asymptomatic. These lesions, which began to appear at the age of two, have increased in size and number on the knees. Diagnosis is based on clinical characteristics and is confirmed histologically. Histologically, dermal lesions display a dense linfohistiocytic infiltrate and multinucleated Touton-type giant cells. An interdisciplinary approach is required for study and treatment, with periodic follow-ups. The prognosis is benign, as the lesions tend to disappear over time, but extracutaneous manifestations or associations with systemic diseases should be considered.El Xantogranuloma Juvenil Gigante se manifiesta con lesiones papulosas de límites netos, color amarillento, y es asintomático. Estas lesiones, que comenzaron a aparecer a los dos años, han aumentado en tamaño y número en las rodillas. El diagnóstico se basa en características clínicas y se confirma histológicamente. Histológicamente, las lesiones dérmicas muestran un denso infiltrado linfohistiocitario y células gigantes multinucleadas de tipo Touton. Se requiere un enfoque interdisciplinario para el estudio y tratamiento, con seguimientos periódicos. El pronóstico es benigno, ya que las lesiones tienden a desaparecer con el tiempo, pero se deben considerar manifestaciones extracutáneas o asociaciones con enfermedades sistémicas

Lesiones papulosas en rodillas. ¿Cuál es su diagnóstico?

El Xantogranuloma Juvenil Gigante se manifiesta con lesiones papulosas de límites netos, color amarillento, y es asintomático. Estas lesiones, que comenzaron a aparecer a los dos años, han aumentado en tamaño y número en las rodillas. El diagnóstico se basa en características clínicas y se confirma histológicamente. Histológicamente, las lesiones dérmicas muestran un denso infiltrado linfohistiocitario y células gigantes multinucleadas de tipo Touton. Se requiere un enfoque interdisciplinario para el estudio y tratamiento, con seguimientos periódicos. El pronóstico es benigno, ya que las lesiones tienden a desaparecer con el tiempo, pero se deben considerar manifestaciones extracutáneas o asociaciones con enfermedades sistémicas