The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate

<p>Abstract</p> <p>Background</p> <p>Secreted frizzled related proteins (SFRPs) are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein) signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold in two independent domains: the cysteine rich domain (Sfrp_CRD) related to the extracellular portion of Frizzled (Fz, Wnt receptors) and the Netrin module (Sfrp_NTR) defined by homologies with molecules such as Netrin-1, inhibitors of metalloproteinases and complement proteins. Due to its structural relationship with Fz, it is believed that Sfrp_CRDinterferes with Wnt signalling by binding and sequestering the ligand. In contrast, the functional relevance of the Sfrp_NTRhas been barely addressed.</p> <p>Results</p> <p>Here, we combine biochemical studies, mutational analysis and functional assays in cell culture and medaka-fish embryos to show that the Sfrp1_NTRmimics the function of the entire molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity requires intact tertiary structure and is shared by the distantly related Netrin-1_NTR. In contrast, the Sfrp1_CRDcannot mirror the function of the entire molecule <it>in vivo </it>but interacts with Fz receptors and antagonizes Wnt8-mediated β-catenin transcriptional activity.</p> <p>Conclusion</p> <p>On the basis of these results, we propose that SFRP modulation of Wnt signalling may involve multiple and differential interactions among Wnt, Fz and SFRPs.</p

Multidisciplinary approach to treatment with immune checkpoint inhibitors in patients with HIV, tuberculosis, or underlying autoimmune diseases

Autoimmune diseases; Checkpoint inhibition therapy; Human immunodeficiency virusEnfermedades autoinmunes; Terapia de inhibición de puntos de control; Virus de inmunodeficiencia humanaMalalties autoimmunes; Teràpia d'inhibició del punt de control; Virus de la immunodeficiència humanaWe reviewed the available information on the use of immune checkpoint inhibitors (ICIs) in populations with special conditions, namely, patients with HIV, tuberculosis, or underlying autoimmune disease. Available data show that treatment with ICIs is safe in patients with HIV; it is advisable, however, that these patients receive adequate antiretroviral therapy and have an undetectable viral load before ICIs are initiated. Tuberculosis reactivation has been reported with the use of ICIs, possibly due to immune dysregulation. Tuberculosis has also been associated with the use of immunosuppressors to treat immune-related adverse events (irAEs). Active tuberculosis must be ruled out in patients with symptoms or signs, and selected patients may benefit from screening for latent tuberculosis infection, although more data are required. Limited data exist regarding the safety of ICIs in patients with cancer and autoimmune disease. Data from observational studies suggest that up to 29% of patients with a preexisting autoimmune disease treated with an ICI present with an autoimmune disease flare, and 30% present with a de novo irAE of any type. The frequency of flares appears to differ according to the type of ICI received, with higher rates associated with PD-1/PD-L1 inhibitors. The most common autoimmune diseases for which patients reported flares with ICI therapy are rheumatoid arthritis, other inflammatory arthritis, and psoriasis. Most studies have reported flares or de novo irAEs associated with ICIs that were mild to moderate, with low rates of discontinuation and no deaths due to flares. Therefore, the use of ICIs in these patients is possible, but careful monitoring is required.ML-O's work is supported by the National Cancer Institute (#CA237619)

An Analysis Of The Temporal Evolution Of Agrarian Prices

At the end of 2007 and principles of 2008 took place the greater nourishing crisis of the last decades. This crisis was caused by a spectacular increase in the prices of some agricultural raw materials and in the costs of the agrarian production. Since the end of 2008 the prices of the agricultural raw materials have decreased with similar intensity as when they raised. In the upward period, the increases of prices quickly were moved to the final consumer prices without great impact in the farmer’s income but when the prices decreased they do not allow seeing so fast in the final consumers prices. In this paper, we analyse the evolution of the agricultural activity results over the last years. In order to do so, we consider the prices of agricultural raw materials and products made with these, without forgetting the production costs. This study analyses the evolution of: the differential between the producer (farmer and stockman) prices and the prices charged for agrarian products to the final consumers and the differential between the producer price and the production cost

Estrategias de inbound marketing para incrementar la captación de clientes en el centro psicodesarrollo personal, Sullana 2022

La presente investigación se sustenta con el objetivo principal de proponer estrategias de Inbound marketing para incrementar la captación de clientes en el Centro Psicodesarrollo Personal, Sullana 2022. La metodología que se aplicó en esta investigación es de tipo de investigación aplicada, de diseño no experimental y transeccional, con enfoque cuantitativo a nivel descriptivo. Se desarrolló un cuestionario a 161 clientes del centro Psicodesarrollo Personal. Entre los resultados obtenidos se pudo resaltar que el centro Psicodesarrollo Personal no logra cautivar a los clientes por las redes sociales por la poca participación y creatividad en sus publicaciones, además de no mostrar la información necesaria, ni se adapta a las nuevas tecnologías que lo exigen sus clientes hoy en día, en este contexto, se llegó a la conclusión que el centro psicológico Psicodesarrollo Personal, captura a un lead, a través de recomendaciones de otros pacientes que fueron dados de alta y solucionaron sus problemas por el profesionalismo de este centro, despertando el interés y la confianza de los recomendados, pero no es lo suficiente, debido a las nuevas búsquedas y formas de contactar a una empresa que es a través de los medios sociales, es por ello que captar clientes le resulta difícil para este centro muy aparte que la provincia donde se encuentra ubicada esta empresa no cuentan con cultura de salud mental, por lo que el centro Psicodesarrollo Personal, tiene la ardua tarea de informar acerca de la importancia de las enfermedades psicológicas y los beneficios que este centro ofrece

Antimicrobial Activity and Physicochemical Characterization of Oregano, Thyme and Clove Leave Essential Oils, Nonencapsulated and Nanoencapsulated, Using Emulsification

Background and objective: Functional properties of essential oils are attributed to their components, many of which exhibit antimicrobial activity against pathogenic and spoilage microorganisms in a wide variety of foods. However, essential oils are unstable compounds; therefore, they can be encapsulated for a better protection and increase of functionality. In this work, antimicrobial activities of oregano, thyme and clove leave essential oils (non-encapsulated and nanoencapsulated) were assessed against Escherichia coli ATCC 29922, Salmonella typhimurium ATCC 14028 and Staphylococcus aureus ATCC 25923 using emulsification.Material and methods: The essential oils were characterized based on their physicochemical properties. Nanoemulsions were prepared, using 5% (w w-1) of essential oils, and then characterized based on their physical properties, stability and encapsulation efficiency. The microdilution antimicrobial assay was carried out to assess minimum inhibitory concentration and minimum bactericidal concentration of the essential oils and their nanoemulsions. Data from physical properties of the essential oils and physical properties, stability and encapsulation efficiency of the nanoemulsions were statistically analyzed.Results and conclusion: Antimicrobial activity of the essential oils showed decreases in minimum inhibitory concentration by 27-60% for the nanoencapsulated oils, compared to nonencapsulated oils. Nanoencapsulated and nonencapsulated oregano essential oils exhibited the lowest minimum inhibitory concentration and minimum bactericidal concentration values. Based on the results, nanoencapslulated essential oils may further be used in various foods to avoid microbial contaminations.Conflict of interest: The authors declare no conflict of interest

A Systematic Review of Clinical Practice Guidelines for Cancer Screening in Patients with Autoimmune Diseases

https://openworks.mdanderson.org/sumexp23/1110/thumbnail.jp

Health inequity in workers of Latin America and the Caribbean

Latin America and the Caribbean (LAC) is the world’s most inequitable region in terms of wealth distribution. The full scale of social inequalities in health has been hidden by the lack of reliable data. This study aimed to measure and compare health inequalities in the working population within and between 15 countries of LAC

Monitoring Self-Perceived Occupational Health inequities in Central america, 2011 and 2018

Objectives. to analyze changes in occupational health inequity between 2011 and 2018 among workers in Central America. Methods. Data were collected by face-to-face interviews at the workers\u27 homes for the 2 Central America Working Conditions Surveys (n = 12 024 in 2011 and n = 9030 in 2018). We estimated health inequity gaps by means of absolute and relative population attributable risks and the weighted Keppel index. We stratified all analyses by gender. Results. Between 2011 and 2018, the proportion of workers reporting poor self-perceived health decreased both in women (from 32% to 29%) and men (from 33% to 30%). However, the health inequity gaps remained wide in the 4 stratifiers. Measured by the Keppel index, health inequity gaps between countries increased from 22% to 39% in women and from 20% to 29% in men. Conclusions. While health improved between 2011 and 2018, health inequity gaps remained wide. Wider health inequity gaps were observed between countries than by gender, age, occupation, or education. Public Health Implications. This first benchmark of occupational health inequities in Central America could be useful when developing and evaluating the impact of public policies on work

Aplicación de una nariz electrónica tipo QCM para la medida de aromas emitidos por manzanas cv. Fuji conservadas con diferentes tecnologías

La nariz electrónica (NE) “Libra Nose” se basa en una matriz de 8 sensores del tipo Microbalanzas de Cristal de Cuarzo. Estudios previos muestran que es posible utilizar una NE para hacer un seguimiento de la evolución de la calidad de fruta sometida a diferentes periodos de almacenamiento. En este trabajo se muestra que al analizar la emisión aromática de frutos de manzana cv.Fuji, con NE y cromatografía de gases, es posible por una lado detectar con la NE diferencias significativas en el espacio de cabeza generado por manzanas sometidas a diferentes tiempos de almacenamiento y periodos de vida en estantería, y por otro lado establecer para los frutos almacenados en condiciones de frío normal y atmósfera controlada estándar, una correlación positiva entre la respuesta de los sensores de la NE y la emisión de uno de los compuestos predominantes en el aroma de la variedad Fuji, el acetato de hexilo