Effect of water models on transmembrane self-assembled cyclic peptide nanotubes

Self-assembling cyclic peptide nanotubes can form nanopores when they are inserted in lipid bilayers, acting as ion and/or water permeable channels. In order to improve the versatility of these systems, it is possible to specifically design cyclic peptides with a combination of natural and non-natural amino acids, enabling the control of the nature of the inner cavity of the channels. Here, the behavior of two types of self-assembling peptide motifs, alternating α-amino acids with γ- or δ-aminocycloalkanecarboxylic acids, is studied via molecular dynamics (MD) simulations. The behavior of water molecules in nanopores is expected to affect the properties of these channels and therefore merits detailed examination. A number of water models commonly used in MD simulations have been validated by how well they reproduce bulk water properties. However, it is less clear how these water models behave in the nanoconfined condition inside a channel. The behavior of four different water models—TIP3P, TIP4P, TIP4P/2005, and OPC—are evaluated in MD simulations of self-assembled cyclic peptide nanotubes of distinct composition and diameter. The dynamic behavior of the water molecules and ions in these designed artificial channels depends subtly on the water model used. TIP3P water molecules move faster than those of TIP4P, TIP4P/2005, and OPC. This demeanor is clearly observed in the filling of the nanotube, in water diffusion within the pore, and in the number and stability of hydrogen bonds of the peptides with water. It was also shown that the water model influences the simulated ion flux through the nanotubes, with TIP3P producing the greatest ion flux. Additionally, the two more recent models, TIP4P/2005 and OPC, which are known to reproduce the experimental self-diffusion coefficient of bulk water quite well, exhibit very similar results under the nanoconfined conditions studied here. Because none of these models have been parametrized specifically for waters confined in peptide nanotubes, this study provides a point of reference for further validationThis work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (CTQ2016-78423-R, PID2019-111126RB-100, and RTI2018-098795-A-I00) and by the Xunta de Galicia and the ERDF (ED431F 2020/05, ED431C 2017/25, and Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09). M.C. thanks Xunta de Galicia for a predoctoral fellowship (ED481A-2017/068). R.G.-F. thanks Ministerio de Ciencia, Innovación y Universidades for a Ramón y Cajal contract (RYC-2016- 20335). Research in MSPS’s group is supported by EPSRC (EP/R004722/1; EP/V010948/1) BBSRC (BB/R00126X/1) and Wellcome Trust (208361/Z/17/Z)S

Las políticas públicas nacionales de Colombia para la formación de educadores infantiles

El presente trabajo tiene como objetivo delinear el estado del arte de las políticas públicas para la formación del profesorado en los últimos quince años en Colombia, en especial la formación del educador infantil. Para tal fin se realizó una extensa revisión bibliográfica de normativas, artículos y trabajos investigativos en el área. Se apuntan algunos puntos relevantes: el aumento de la importancia de la educación infantil en las últimas décadas, principalmente en el marco de nuevas políticas para la infancia. Aunque la normativa apunta a nuevos e innovadores parámetros educativos, el asistencialismo está en primer orden. Esto se refleja en la visión social de la infancia como momento restringido al cuidado, que disminuye la importancia de las intervenciones educativas planeadas y los aspectos educativos en general, agravado por la falta de profesionales de la educación infantil que fomenten y concreten el área de la educación infantil, y que construyan conocimiento práctico. Se recomienda invertir en la formación de docentes, valorizar la realización de investigación en el área, así como promover mayor profesionalización del personal, tomando medidas para la valorización del profesional de educación infanti

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Empremtes : espais d’interacció entre el patrimoni històric i natural de la muntanya de Can Palomeres i els seus cohabitants

Empremtes neix de la creença que Malgrat de Mar forma part d’una xarxa extensa de coneixement, història i interès patrimonial que el vincula amb el seu entorn. Part d’aquest valor rau en la muntanya de Can Palomeres, escenari d’activitats molt diverses al llarg de la història i on destaca l’activitat minera que es va dur a terme al segle XX, i que posteriorment ha permès que s’hi hagi desenvolupat un gran ecosistema de biodiversitat a les seves galeries. La intervenció busca donar resposta a l’abandonament del patrimoni històric i natural de la muntanya de Can Palomeres a través d’una mirada que permeti la seva divulgació, protecció i investigació. Es generen espais d’interacció amb els seus cohabitants per tal de reconsiderar el valor històric i protegir la riquesa natural.Empremtes nace de la creencia que Malgrat de Mar forma parte de una red extensa de conocimiento, historia e interés patrimonial que lo vincula con su entorno. Parte de este valor rae en la montaña de Can Palomeres, escenario de actividades muy diversas a lo largo de la historia y dónde destaca la actividad minera que se llevó a cabo en el siglo XX, y que posteriormente ha permitido que se haya desarrollado un gran ecosistema de biodiversidad a sus galerías. La intervención busca dar respuesta al abandono del patrimonio histórico y natural de la montaña de Can Palomeres a través de una mirada que permita su divulgación, protección e investigación. Se generan espacios de interacción con sus cohabitantes para reconsiderar el valor histórico y proteger la riqueza natural.Empremtes is a result of the belief that Malgrat de Mar is part of an extensive network of knowledge, history and patrimonial interest that connects it with its surroundings. Part of this value lies in the mountain of Can Palomeres, the scene of very diverse activities throughout history. The mining activity that took place in the twentieth century has subsequently allowed the development of a large ecosystem of biodiversity in its galleries. The intervention seeks to respond to the abandonment of the historical and natural heritage of the mountain of Can Palomeres through a look that allows its dissemination, protection and research. The project generates spaces for interaction with its co-inhabitants to reconsider the historical value and protect the natural wealth

Effect of the high-pressure-release phase on the protein composition of the soluble milk fraction

This paper describes a study on the influence of the high-pressure-release rate on the protein distribution between the soluble and colloidal fractions of milk. Skim milk, without or with sulfhydryl-blocking agents, was pressure treated at 250 and 350. MPa for 5 to 15. min at 25°C, applying different pressure-release rates (pressure-release times between 0.07 to 10. min). The liberation of caseins to the soluble phase and the denaturation of whey proteins were assessed. A significantly higher increase in the content of soluble casein took place during the pressure-release phase as compared with a pressure-holding phase. Denaturation of β-lactoglobulin mainly took place by -SH-S-S exchange reactions during the holding phase. The present results, thus, show a negligible influence of whey proteins on the increase in the content of nonsedimentable casein in pressure-treated milk and provide evidence for the importance of the pressure-release rate in this process, so that the slower the pressure release rate, the higher the level of soluble casein. © 2012 American Dairy Science Association.This work received financial support from the project Consorcios Estratégicos Nacionales de Investigación Técnica (CENIT)-2007-2016 Futural, Ingenio Program. F. I. Bravo acknowledges the Autonomous Community of Madrid (Spain) for the contract of researching supporting personnel through the project ALIBIRD-CM-S-505/AGR-0153.S0505/AGR-0153/ALIBIRDPeer Reviewe