Increased Protein Stability and Interleukin-2 Production of a LAT(G131D)Variant With Possible Implications for T Cell Anergy

The adaptor LAT plays a crucial role in the transduction of signals coming from the TCR/CD3 complex. Phosphorylation of some of its tyrosines generates recruitment sites for other cytosolic signaling molecules. Tyrosine 132 in human LAT is essential for PLC-gamma activation and calcium influx generation. It has been recently reported that a conserved glycine residue preceding tyrosine 132 decreases its phosphorylation kinetics, which constitutes a mechanism for ligand discrimination. Here we confirm that a LAT mutant in which glycine 131 has been substituted by an aspartate (LAT(G131D)) increases phosphorylation of Tyr132, PLC-gamma activation and calcium influx generation. Interestingly, the LAT(G131D)mutant has a slower protein turnover while being equally sensitive to Fas-mediated protein cleavage by caspases. Moreover, J.CaM2 cells expressing LAT(G131D)secrete greater amounts of interleukin-2 (IL-2) in response to CD3/CD28 engagement. However, despite this increased IL-2 secretion, J.CaM2 cells expressing the LAT(G131D)mutant are more sensitive to inhibition of IL-2 production by pre-treatment with anti-CD3, which points to a possible role of this residue in the generation of anergy. Our results suggest that the increased kinetics of LAT Tyr132 phosphorylation could contribute to the establishment of T cell anergy, and thus constitutes an earliest known intracellular event responsible for the induction of peripheral tolerance

Apertium: a free/open-source platform for rule-based machine translation

Apertium is a free/open-source platform for rule-based machine translation. It is being widely used to build machine translation systems for a variety of language pairs, especially in those cases (mainly with related-language pairs) where shallow transfer suffices to produce good quality translations, although it has also proven useful in assimilation scenarios with more distant pairs involved. This article summarises the Apertium platform: the translation engine, the encoding of linguistic data, and the tools developed around the platform. The present limitations of the platform and the challenges posed for the coming years are also discussed. Finally, evaluation results for some of the most active language pairs are presented. An appendix describes Apertium as a free/open-source project.We thank the support of the Spanish Ministry of Science and Innovation through project TIN2009-14009-C02-01. Apertium has been mainly funded by the Ministries of Industry, Tourism and Commerce, of Education and Science, and of Science and Technology of Spain, the Government of Catalonia, the Ministry of Foreign Affairs of Romania, the Universitat d’Alacant, the Universidade de Vigo, Ofis ar Brezhoneg and Google Summer of Code (2009, 2010 and 2011 editions). Many companies have also invested in it: Prompsit Language Engineering, ABC Enciklopedioj, Eleka Ingeniaritza Linguistikoa, imaxin|software, etc

A Review on Sustainable Inks for Printed Electronics: Materials for Conductive, Dielectric and Piezoelectric Sustainable Inks

In the last decades, the demand for electronics and, therefore, electronic waste, has increased. To reduce this electronic waste and the impact of this sector on the environment, it is necessary to develop biodegradable systems using naturally produced materials with low impact on the environment or systems that can degrade in a certain period. One way to manufacture these types of systems is by using printed electronics because the inks and the substrates used are sustainable. Printed electronics involve different methods of deposition, such as screen printing or inkjet printing. Depending on the method of deposition selected, the developed inks should have different properties, such as viscosity or solid content. To produce sustainable inks, it is necessary to ensure that most of the materials used in the formulation are biobased, biodegradable, or not considered critical raw materials. In this review, different inks for inkjet printing or screen printing that are considered sustainable, and the materials that can be used to formulate them, are collected. Printed electronics need inks with different functionalities, which can be mainly classified into three groups: conductive, dielectric, or piezoelectric inks. Materials need to be selected depending on the ink’s final purpose. For example, functional materials such as carbon or biobased silver should be used to secure the conductivity of an ink, a material with dielectric properties could be used to develop a dielectric ink, or materials that present piezoelectric properties could be mixed with different binders to develop a piezoelectric ink. A good combination of all the components selected must be achieved to ensure the proper features of each ink.This publication is supported by the SUINK project funded by the European Union’s Horizon Europe research and innovation programme under Grant Agreement No. 101070112. Funded by the Basque Government ELKARTEK2021 (KK-2021/00040) and ELKARTEK2023 KK-2023/0005

A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling

Intracellular signaling through the T cell receptor (TCR) is essential for T cell development and function. Proper TCR signaling requires the sequential activities of Lck and ZAP-70 kinases, which result in the phosphorylation of tyrosine residues located in the CD3 ITAMs and the LAT adaptor, respectively. LAT, linker for the activation of T cells, is a transmembrane adaptor protein that acts as a scaffold coupling the early signals coming from the TCR with downstream signaling pathways leading to cellular responses. The leukemic T cell line Jurkat and its derivative mutants J.CaM1.6 (Lck deficient) and J.CaM2 (LAT deficient) have been widely used to study the first signaling events upon TCR triggering. In this work, we describe the loss of LAT adaptor expression found in a subline of J.CaM1.6 cells and analyze cis-elements responsible for the LAT expression defect. This new cell subline, which we have called J.CaM1.7, can re-express LAT adaptor after Protein Kinase C (PKC) activation, which suggests that activation-induced LAT expression is not affected in this new cell subline. Contrary to J.CaM1.6 cells, re-expression of Lck in J.CaM1.7 cells was not sufficient to recover TCR-associated signals, and both LAT and Lck had to be introduced to recover activatory intracellular signals triggered after CD3 crosslinking. Overall, our work shows that the new LAT negative J.CaM1.7 cell subline could represent a new model to study the functions of the tyrosine kinase Lck and the LAT adaptor in TCR signaling, and their mutual interaction, which seems to constitute an essential early signaling event associated with the TCR/CD3 complex.This research was funded by Consejeria de Salud de Andalucia, Junta de Andalucia (grant PI-0055-2017 to E.A.), and Fundacion Biomedica Cadiz Proyectos INIBICA 2019 (grant LI19/I14NCO15 to E.A. and M.M.A.-E.)

Adquisición automática de recursos para traducción automática en el proyecto Abu-MaTran

This paper provides an overview of the research and development activities carried out to alleviate the language resources' bottleneck in machine translation within the Abu-MaTran project. We have developed a range of tools for the acquisition of the main resources required by the two most popular approaches to machine translation, i.e. statistical (corpora) and rule-based models (dictionaries and rules). All these tools have been released under open-source licenses and have been developed with the aim of being useful for industrial exploitation.Este artículo presenta una panorámica de las actividades de investigación y desarrollo destinadas a aliviar el cuello de botella que supone la falta de recursos lingüísticos en el campo de la traducción automática que se han llevado a cabo en el ámbito del proyecto Abu-MaTran. Hemos desarrollado un conjunto de herramientas para la adquisición de los principales recursos requeridos por las dos aproximaciones m as comunes a la traducción automática, modelos estadísticos (corpus) y basados en reglas (diccionarios y reglas). Todas estas herramientas han sido publicadas con licencias libres y han sido desarrolladas con el objetivo de ser útiles para ser explotadas en el ámbito comercial.The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement PIAP-GA-2012-324414 (Abu-MaTran)

Assisting non-expert speakers of under-resourced languages in assigning stems and inflectional paradigms to new word entries of morphological dictionaries

This paper presents a new method with which to assist individuals with no background in linguistics to create monolingual dictionaries such as those used by the morphological analysers of many natural language processing applications. The involvement of non-expert users is especially critical for under-resourced languages which either lack or cannot afford the recruitment of a skilled workforce. Adding a word to a morphological dictionary usually requires identifying its stem along with the inflection paradigm that can be used in order to generate all the word forms of the new entry. Our method works under the assumption that the average speakers of a language can successfully answer the polar question “is x a valid form of the word w to be inserted?”, where x represents tentative alternative (inflected) forms of the new word w. The experiments show that with a small number of polar questions the correct stem and paradigm can be obtained from non-experts with high success rates. We study the impact of different heuristic and probabilistic approaches on the actual number of questions.This work has been partially funded by the Spanish Ministry of Science & Innovation through project TIN2009-14009-C02-01, by the Spanish Ministry of Economy & Competitiveness through Project TIN2012-32615, by the Generalitat Valenciana through grant ACIF/2010/174 from VALi+d programme, and by the European Commission through Project PIAP-GA-2012-324414 (Abu-MaTran)

Feeding habits of young international elite motorcyclists

La alimentación es fundamental para rendir en el deporte, ya que una dieta inadecuada puede limitar el resultado. Por ello, el objetivo de este estudio ha sido conocer los hábitos nutricionales de 27 jóvenes pilotos de motociclismo de élite internacional a través de un cuestionario. Los resultados muestran cómo un 96.2% de los pilotos se alejan de las recomendaciones nutricionales de cinco comidas al día, así como de la recomendación de 3 raciones diarias de cereales y pan, que son cumplidas por 15,4% y 30,8% respectivamente. No existen diferencias estadísticamente significativas para ninguno de los macronutrientes entre los momentos de entrenamiento y justo antes de una competición. Respecto a la hidratación, existen diferencias significativas entre un día de entrenamiento y un día de competición (p= 0,008). Los resultados sugieren que los hábitos alimentarios de los jóvenes pilotos de motociclismo deberían ser mejorados, estableciéndose pautas de actuación e implicando a los deportistas, familias y entrenadores.Feeding is crutial to perform at the highest level in elite sport. So, to offer feeding patterns to the next Moto GP pilots, we have analyzed the feeding patterns of 27 elite young worldwide motorcycling pilots coming from the 5 continents, selected after a rigorous process developed by the organizers of the word motorcycling championship (Moto GP). It has been found that although pilots give a big importance to their weigth and feeding, their feeding habits are not adapted to the standards and recommendations for athletes. They are no big or meaningful differences for any of the macronutrients in the training sessions and the period before a competition. Regarding hidratation, there are significant differences between a training day and a competition one (p=0,008). Results suggest that feeding habits of the elite young motorcyclists should be clearly improved, stablishing patterns that involve athletes, parents, and coaches, all of them taking care about the nutrition

N7-methylguanosine methylation of tRNAs regulates survival to stress in cancer

Tumour progression and therapy tolerance are highly regulated and complex processes largely dependent on the plasticity of cancer cells and their capacity to respond to stress. The higher plasticity of cancer cells highlights the need for identifying targetable molecular pathways that challenge cancer cell survival. Here, we show that

Toward an Improvement of the Analysis of Neural Coding

Machine learning and artificial intelligence have strong roots on principles of neural computation. Some examples are the structure of the first perceptron, inspired in the retina, neuroprosthetics based on ganglion cell recordings or Hopfield networks. In addition, machine learning provides a powerful set of tools to analyze neural data, which has already proved its efficacy in so distant fields of research as speech recognition, behavioral states classification, or LFP recordings. However, despite the huge technological advances in neural data reduction of dimensionality, pattern selection, and clustering during the last years, there has not been a proportional development of the analytical tools used for Time–Frequency (T–F) analysis in neuroscience. Bearing this in mind, we introduce the convenience of using non-linear, non-stationary tools, EMD algorithms in particular, for the transformation of the oscillatory neural data (EEG, EMG, spike oscillations…) into the T–F domain prior to its analysis with machine learning tools. We support that to achieve meaningful conclusions, the transformed data we analyze has to be as faithful as possible to the original recording, so that the transformations forced into the data due to restrictions in the T–F computation are not extended to the results of the machine learning analysis. Moreover, bioinspired computation such as brain–machine interface may be enriched from a more precise definition of neuronal coding where non-linearities of the neuronal dynamics are considered.This work has been supported in part by the Spanish national research program (MAT2015-69967-C3-1), by Research Chair Bidons Egara and by a research grant of the Spanish Blind Organization (ONCE)