Effects of sphingolipid extracts on the morphological structure and lipid profile in an in vitro model of canine skin

Ceramides (CER) are essential sphingolipids of the stratum corneum (SC) that play an important role in maintaining cutaneous barrier function. Skin barrier defects occur in both human beings and dogs affected with atopic dermatitis, and have been associated with decreased CER concentrations and morphological alterations in the SC. The aim of the present study was to investigate the changes induced by three different sphingolipid extracts (SPE-1, SPE-2 and SPE-3) on the morphological structure and lipid composition of canine skin, using an in vitro model, whereby keratinocytes were seeded onto fibroblast-embedded collagen type I matrix at the air-liquid interface. Cell cultures were supplemented with SPE-1, SPE-2, SPE-3 or vehicle (control) for 14 days. The relative concentrations of lipids were determined by ultra-performance liquid chromatography coupled to mass spectrometry. The ultrastructural morphology of samples was examined by transmission electron microscopy. SPE-1 induced significant elevation in total CERs, CER[NS], CER[NDS], CER[NP], CER[AS], CER[AP], CER[EOS] and CER[EOP] subclasses, whereas SPE-2 induced a significant elevation in total CER, CER[AP] and CER[EOS] compared with control conditions. Ultrastructural analysis revealed an increase in lamellar-lipid structures in the SC of SPE-1-treated samples. The findings demonstrated that SPE-1 stimulates production of CERs, as shown by changes in lipid composition and ultrastructural morphology. Thus, SPE-1 contributes to the formation of a well-organised SC and represents a potential therapeutic target for improving skin barrier function in atopic dermatitis

Comprehensive identification of native medium-sized and short bioactive peptides in sea bass muscle

Native peptides from sea bass muscle were analyzed by two different approaches: medium-sized peptides by peptidomics analysis, whereas short peptides by suspect screening analysis employing an inclusion list of exact m/z values of all possible amino acid combinations (from 2 up to 4). The method was also extended to common post-translational modifications potentially interesting in food analysis, as well as non-proteolytic aminoacyl derivatives, which are well-known taste-active building blocks in pseudo-peptides. The medium-sized peptides were identified by de novo and combination of de novo and spectra matching to a protein sequence database, with up to 4077 peptides (2725 modified) identified by database search and 2665 peptides (223 modified) identified by de novo only; 102 short peptide sequences were identified (with 12 modified ones), and most of them had multiple reported bioactivities. The method can be extended to any peptide mixture, either endogenous or by protein hydrolysis, from other food matrices. © 2020 Elsevier Lt

Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents

Prodigiosin is one of the most potent anion transporters in lipid bilayer membranes reported to date. Inspired by the structure of this natural product, we have recently designed and synthesised a new class of H+/Cl− cotransporters named 'perenosins'. Here we report a new library of indole-based perenosins and their anion transport properties. The new transporters demonstrated superior transmembrane transport efciency when compared to other indole-based transporters, due to favourable encapsulating efects from the substituents on the perenosin backbone. Anion transport assays were used to determine the mechanism of chloride transport revealing that the compounds function as 'strict' HCl cotransporters. Cell viability studies showed that some compounds specifcally trigger lateonset cell death after 72h with a unique correlation to the position of alkyl chains on the perenosins. Further investigations of cell death mechanism showed a mixture of cell cycle arrest and apoptosis was responsible for the observed decrease in cell viability

Minecraft Programable: una herramienta para aprender programación en nivel medio

The rise of smart devices which in one way or another have an internal software development (mobile phones, home appliances, cars, among others), has increased the need for programmers. Since formal education has not been successful in meeting this need, several projects with tools that enable to learn programming in a simple and entertaining way have arisen, such as The Hour of Code (http://code.org), which bases its tutorials in different games. Following this trend, a variant of Minecraft, which allows creating and modifying the behavior of its objects in real-time using Smalltalk as a language, was created.La aparición de dispositivos inteligentes que de una forma u otra tienen un desarrollo de software interno (celulares, electrodomésticos, automóviles, entre otros), ha incrementado la necesidad de programadores. Dado que la educación formal no ha logrado cubrir esta necesidad, han surgido diversos proyectos con herramientas que permiten aprender a programar en forma sencilla y entretenida, como por ejemplo, La Hora del Código (http://code.org), que basa sus tutoriales en diferentes juegos. Dentro de esta línea se construyó una variante de Minecraft que permite en tiempo real crear y modificar el comportamiento de sus objetos utilizando Smalltalk como lenguaje

Programmable Minecraft: a tool to learn programming in high school

La aparición de dispositivos inteligentes que de una forma u otra tienen un desarrollo de software interno (celulares, electrodomésticos, automóviles, entre otros), ha incrementado la necesidad de programadores. Dado que la educación formal no ha logrado cubrir esta necesidad, han surgido diversos proyectos con herramientas que permiten aprender a programar en forma sencilla y entretenida, como por ejemplo, La Hora del Código (http://code.org), que basa sus tutoriales en diferentes juegos. Dentro de esta línea se construyó una variante de Minecraft que permite en tiempo real crear y modificar el comportamiento de sus objetos utilizando Smalltalk como lenguaje.The rise of smart devices which in one way or another have an internal software development (mobile phones, home appliances, cars, among others), has increased the need for programmers. Since formal education has not been successful in meeting this need, several projects with tools that enable to learn programming in a simple and entertaining way have arisen, such as The Hour of Code (http://code. org), which bases its tutorials in different games. Following this trend, a variant of Minecraft, which allows creating and modifying the behavior of its objects in real-time using Smalltalk as a language, was created.Fil: Zabala, Gonzalo Esteban. Universidad Abierta Interamericana. Facultad de Tecnología Informatica. Departamento de Sistemas de Computación. Cent.de Altos Estudios En Tecnología Informatica; ArgentinaFil: Pérez Cerrato, Laura. Universidad Abierta Interamericana. Facultad de Tecnología Informatica. Departamento de Sistemas de Computación. Cent.de Altos Estudios En Tecnología Informatica; ArgentinaFil: Blanco, Sebastian. Universidad Abierta Interamericana. Facultad de Tecnología Informatica. Departamento de Sistemas de Computación. Cent.de Altos Estudios En Tecnología Informatica; ArgentinaFil: Moran, Jorge Ricardo. Universidad Abierta Interamericana. Facultad de Tecnología Informatica. Departamento de Sistemas de Computación. Cent.de Altos Estudios En Tecnología Informatica; ArgentinaFil: Teragni, Matias Ivan. Universidad Abierta Interamericana. Facultad de Tecnología Informatica. Departamento de Sistemas de Computación. Cent.de Altos Estudios En Tecnología Informatica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Opsonin-deficient nucleoproteic corona endows unPEGylated liposomes with stealth properties in vivo

For several decades, surface grafted polyethylene glycol (PEG) has been a go-to strategy for preserving the synthetic identity of liposomes in physiological milieu and preventing clearance by immune cells. However, the limited clinical translation of PEGylated liposomes is mainly due to the protein corona formation and the subsequent modification of liposomes’ synthetic identity, which affects their interactions with immune cells and blood residency. Here we exploit the electric charge of DNA to generate unPEGylated liposome/DNA complexes that, upon exposure to human plasma, gets covered with an opsonin-deficient protein corona. The final product of the synthetic process is a biomimetic nanoparticle type covered by a proteonucleotidic corona, or “proteoDNAsome”, which maintains its synthetic identity in vivo and is able to slip past the immune system more efficiently than PEGylated liposomes. Accumulation of proteoDNAsomes in the spleen and the liver was lower than that of PEGylated systems. Our work highlights the importance of generating stable biomolecular coronas in the development of stealth unPEGylated particles, thus providing a connection between the biological behavior of particles in vivo and their synthetic identity

Crosstalk between Neospora caninum and the bovine host at the maternal-foetal interface determines the outcome of infection

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.[EN]Neospora caninum is an apicomplexan cyst-forming parasite that is considered one of the main causes of abortion. The pathogenic mechanisms associated with parasite virulence at the maternal-foetal interface that are responsible for the outcome of infection are largely unknown. Here, utilizing placentomes from cattle experimentally infected with high-virulence (Nc-Spain7) and low-virulence (Nc-Spain1H) isolates, we studied key elements of the innate and adaptive immune responses, as well as components of the extracellular matrix (ECM), at 10 and 20 days post-infection (dpi). The low-virulence isolate elicited a robust immune response characterized by upregulation of genes involved in pathogen recognition, chemokines and pro-inflammatory cytokines, crucial for its adequate control. In addition, Nc-Spain1H triggered the expression of anti-inflammatory cytokines and other mechanisms implicated in the maintenance of ECM integrity to ensure foetal survival. In contrast, local immune responses were initially (10 dpi) impaired by Nc-Spain7, allowing parasite multiplication. Subsequently (20 dpi), a predominantly pro-inflammatory Th1-based response and an increase in leucocyte infiltration were observed. Moreover, Nc-Spain7-infected placentomes from animals carrying non-viable foetuses exhibited higher expression of the IL-8, TNF-α, iNOS and SERP-1 genes and lower expression of the metalloproteases and their inhibitors than Nc-Spain7-infected placentomes from animals carrying viable foetuses. In addition, profound placental damage characterized by an alteration in the ECM organization in necrotic foci, which could contribute to foetal death, was found. Two different host-parasite interaction patterns were observed at the bovine placenta as representative examples of different evolutionary strategies used by this parasite for transmission to offspring.SIThis work was supported by the Spanish Ministry of Economy and Competitiveness (AGL2013-44694-R and AGL2016-75935-C2-1-R) and the Community of Madrid (PLATESA2-CM P2018/BAA-4370). Laura Jiménez-Pelayo was financially supported by a fellowship from the University Complutense of Madrid (including two research stays in 2017 and 2018) and Marta García-Sánchez was financially supported through a grant from the Spanish Ministry of Economy and Competitiveness (BES-2014-070723). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Clinical and molecular characterization of patients affected by Beckwith-Wiedemann spectrum conceived through assisted reproduction techniques

The prevalence of Beckwith-Wiedemann spectrum (BWSp) is tenfold increased in children conceived through assisted reproductive techniques (ART). More than 90% of ART-BWSp patients reported so far display imprinting center 2 loss-of-methylations (IC2-LoM), versus 50% of naturally conceived BWSp patients. We describe a cohort of 74 ART-BWSp patients comparing their features with a cohort of naturally conceived BWSp patients, with the ART-BWSp patients previously described in literature, and with the general population of children born from ART. We found that the distribution of UPD(11)pat was not significantly different in ART and naturally conceived patients. We observed 68.9% of IC2-LoM and 16.2% of mosaic UPD(11)pat in our ART cohort, that strongly differ from the figure reported in other cohorts so far. Since UPD(11)pat likely results from post-fertilization recombination events, our findings allows to hypothesize that more complex molecular mechanisms, besides methylation disturbances, may underlie BWSp increased risk in ART pregnancies. Moreover, comparing the clinical features of ART and non-ART BWSp patients, we found that ART-BWSp patients might have a milder phenotype. Finally, our data show a progressive increase in the prevalence of BWSp over time, paralleling that of ART usage in the last decades