Bleomycin-induced trans lipid formation in cell membranes and in liposome models

Cell cultures of NTera-2 cells incubated with bleomycin and liposomes as biomimetic models of cell membranes were used for examining some novel aspects of drug-metal induced reactivity with unsaturated lipids under oxidative conditions. In cell cultures, bleomycin was found for the first time to cause the formation of trans fatty acids. The chemical basis of this transformation was ascertained by liposome experiments, using bleomycin-iron complexes in the presence of thiol as a reducing agent that by incubation at 37 °C gave rise to the thiyl radical-catalysed double bond isomerisation of membrane phospholipids. The effect of oxygen and reagent concentrations on the reaction outcome was studied. An interesting scenario of free radical reactivity is proposed, which can be relevant for understanding the role of membrane lipids in antitumoral treatments and drug carrier interaction.Fil: Cort, Aysegul. Akdeniz University. Faculty of Medicine; Turquía. Consiglio Nazionale delle Ricerche; ItaliaFil: Ozben, Tomris. Akdeniz University. Faculty of Medicine; TurquíaFil: Sansone, Anna. Consiglio Nazionale delle Ricerche; ItaliaFil: Barata Vallejo, Sebastian. Consiglio Nazionale delle Ricerche; Italia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chatgilialoglu, Chryssostomos. Demokritos National Centre For Scientific Research; GreciaFil: Ferreri, Carla. Consiglio Nazionale delle Ricerche; Itali

Total electron content PCA-NN model for middle latitudes

A regression-based model was previously developed to forecast the total electron content (TEC) at middle latitudes. We present a more sophisticated model using neural networks (NN) instead of linear regression. This regional model prototype simulates and forecasts TEC variations in relation to space weather conditions. The development of a prototype consisted of the selection of the best set of predictors, NN architecture and the length of the input series. Tests made using the data from December 2014 to June 2018 show that the PCA-NN model based on a simple feed-forward NN with a very limited number (up to 6) of space weather predictors performs better than the PCA-MRM model that uses up to 27 space weather predictors. The prototype is developed on a TEC series obtained from a GNSS receiver at Lisbon airport and tested on TEC series from three other locations at middle altitudes of the Eastern North Atlantic. Conclusions on the dependence of the forecast quality on longitude and latitude are made.Comment: arXiv admin note: text overlap with arXiv:2201.0347

LOS CLUBES DEPORTIVOS CHILENOS Y SU RELACIÓN CON SU ENTORNO. EL CASO DE LA REGIÓN DEL BIOBÍO

Objetivo: Verificar y analizar la relación de los clubes deportivos chilenos con las organizaciones públicas y privadas con y sin fines de lucro. Problemática: Las organizaciones deportivas son un objeto carente de análisis en Latinoamérica y también en Chile. En este país, las exiguas investigaciones no se han enfocado exclusivamente en la figura del club, por lo tanto no existen mayores evidencias respecto a sus relaciones con el entorno, lo cual ha generado un desconocimiento de información que podría emplearse en el diseño de estrategias que permitieran abordarlos. Referentes teóricos: La comprensión de la relación de los clubes con otras organizaciones de la sociedad se enfoca a partir de la teoría del tercer sector (Levitt, 1973; Salamon et al., 1999). Junto a ello, se observan las características de los clubes (Heinemann, 1999) que permiten distinguirlos de otras organizaciones del deporte. Los anteriores onstructos teóricos se sitúan desde el deporte como un sistema abierto (Puig y Heinemann, 1991). Metodología: Se trata de un estudio descriptivo, experimental y de corte transversal, con enfoque cuantitativo. Se aplicó un cuestionario a ciento cincuenta dirigentes deportivos provenientes de clubes de la región del Biobío. La muestra fue probabilística y estratificada, y el análisis de los datos se realizó a través de estadística descriptiva. Conclusiones: Se observó que los clubes presentaban una importante cercanía con las instituciones públicas. Llamó la atención también que tuvieran más vínculos con otras organizaciones de la sociedad que no están relacionadas directamente con el deporte

Quality of life in hematopoietic cell transplantation /

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2016-2017El trasplantament al·logènic de progenitors hematopoètics (TPH) és la principal opció curativa per diverses neoplàsies hematològiques tot i que comporta una morbiditat física i psicològica significativa. L'objectiu de la tesi és avaluar la qualitat de vida, la depressió, les estratègies d'afrontament de problemes i les necessitats psicosocials en receptors de TPH al·logènic i els seus cuidadors. Els participants són receptors adults de TPH al·logènic que havien rebut un TPH en el Moffitt Cancer Center (Tampa, Estats Units) i els seus cuidadors. Els resultats s'han analitzat mitjançant metodologia qualitativa i quantitativa. La tesi es basa en cinc articles. En el primer estudi vam observar que els pacients diagnosticats d'hemopatia maligna, i especialment els supervivents de TPH al·logènic, tenen necessitats psicosocials significatives. Els resultats del segon estudi mostren que la fatiga i les nàusees associades a la profilaxis de la malaltia de l'empelt contra l'hoste amb sirolimus contribueixen a disminuir la qualitat de vida durant el primer any post- TPH. En el tercer estudi vam observar que les estratègies d'afrontament adaptatives mitiguen la relació entre els símptomes associats al TPH i la depressió. En el quart treball, que avalua l'educació sobre la qualitat de vida post-TPH, vàrem trobar que els receptors de TPH al·logènic estan ben preparats per afrontar la fase aguda del TPH, però no els efectes tardans o la malaltia del l'empelt contra l'hoste crònica. De manera similar, el cinquè estudi mostra que els cuidadors dels receptors de TPH necessiten més informació sobre els efectes tardans del TPH al·logènic, així com suport emocional. En conclusió, els resultats d'aquesta tesi destaquen la càrrega física i emocional associada al TPH al·logènic i les significatives necessitats psicosocials d'aquesta població. Futurs estudis han d'avaluar i desenvolupar intervencions dirigides a millorar l'educació del pacient, la comunicació metge pacient, el maneig dels símptomes relacionats amb el TPH, i l'afrontament dels efectes secundaris del TPH.Allogeneic hematopoietic cell transplantation (HCT) is the primary curative option for some hematological cancers but is associated with significant physical and psychological morbidity. The aim of this thesis is to assess quality of life (QoL), depression, coping strategies, and unmet needs for psychosocial care among allogeneic recipients and their caregivers. Participants were adult allogeneic recipients who received an HCT at the Moffitt Cancer Center (Tampa, United States) and their caregivers. Qualitative and quantitative methodology were used. Five papers contribute to the current thesis. In the first study, we found significant unmet needs for psychosocial care among patients diagnosed with hematological malignancies, particularly allogeneic survivors. In the second paper, results showed that fatigue and nausea were associated with receipt of sirolimus (SIR) for graft-versus-host disease (GvHD) prophylaxis and contributed to diminished QoL during the first year post-HCT. In the third study, we found that adaptive coping mitigated the relationship between HCT symptoms and depression. In the fourth work focused on patient education about post-HCT QoL, we observed that HCT patients reported feeling well prepared to deal with the acute transplant phase, but unprepared to deal with the late onset of late effects and chronic GvHD. Similarly, the fifth study showed that caregivers also reported significant unmet needs for information on late effects as well as unmet needs for emotional support. In conclusion, results of this thesis highlight the emotional and physical burden associated with allogeneic HCT and the significant unmet needs for psychosocial care among this population. Future studies should assess and develop interventions aimed at improving patient education, patient and physician communication, symptom management, and coping with the side effects of HCT

Cytosolic Sequestration of Prep1 Influences Early Stages of T Cell Development

Objective: Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the N-terminal fragment of Pbx1 (Pbx1NT) under the control of the Lck proximal promoter. Principal Findings: Pbx1NT causes Prep1 cytosolic sequestration, abolishes Prep1-dependent DNA-binding activity and results in reduced Pbx2 expression in developing thymocytes. Transgenic thymi reveal increased numbers of CD4 2 CD8 2 CD44 2 (DN3 and DN4) thymocytes, due to a higher frequency of DN2 and DN4 Pbx1NT thymocytes in the S phase. Transgenic thymocytes however do not accumulate at later stages, as revealed by a normal representation of CD4/CD8 double positive and single positive thymocytes, due to a higher rate of apoptotic cell death of DN4 Pbx1NT thymocytes. Conclusion: The results obtained by genetic (Prep1 hypomorphic) and functional (Pbx1NT transgenic) inactivation of Prep

Infancia, violencia y televisión. Los espacios informativos y los imaginarios de la violencia en los niños y niñas. Avance de resultados

Desde hace tiempo se escuchan voces que manifiestan una grave preocupación por la calidad y el escaso valor educativo de algunos programas audiovisuales que aunque estén pensados para la población adulta en muchas ocasiones también son consumidos por los más pequeños. En este contexto nace el proyecto de investigación del que ahora presentamos las conclusiones. El proyecto Infancia, Violencia y Televisión. Los espacios informativos y los imaginarios de la violencia en los niños y adolescentes, financiado por el Ministerio de Educación y Ciencia (Plan Nacional I+D+I, 2004-2007) ha pretendido, desde sus inicios, conocer mejor los usos televisivos y ahondar en la percepción de los niños y niñas acerca de las diferentes formas de violencia y de su presencia en los espacios informativos audiovisuales.It has long been heard voices expressing serious concern about the low quality and educational value of audio-visual programs. This programs are designed for adults, are often consumed by the youngest. In this context arises and grows, the research project we are now presenting: Children and Television Violence. Information spaces and imaginaries of violence on children and adolescents, funded by the Ministry of Education and Science (Plan Nacional I + D + I, 2004-2007). It deals with an approximation to children’s uses of television and their perception about the different ways of violence and its presence in the audio-visual information spaces

Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina

© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs-sprouting angiogenesis and vascular remodeling-is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.Funding: European Research Council: C.A.F. (679368); X.T. (883739). European Commission: C.A.F. and M.O.B. (801423); X.T. and P.R.-C. (731957). H2020-MSCA-PF grants to M.G.-G. (797621) and M.O. (842498). Fondation LeDucq: C.A.F., A.E., and M.O.B. (17CVD03). EPSRC: M.O.B. (EP/T008806/1; EP/R029598/1). Fundação para a Ciência e Tecnologia: C.A.F. (PTDC/MED-PAT/31639/2017; PTDC/BIA-CEL/32180/2017; CEECIND/04251/2017). Spanish Ministry of Science and Innovation: P.R.-C. (PID2019-110298GB-I00); X.T. (PGC2018-099645-B-I00). Generalitat de Catalunya: X.T. and P.R.-C. (2017-SGR-1602). La Caixa Foundation: X.T. and P.R.-C. (LCF/PR/HR20/52400004). Fundació la Marató de TV3: X.T. (201903-30-31-32). EMBO: L.M.F. (ALTF 2-2018)info:eu-repo/semantics/publishedVersio

Conducting robust ecological analyses with climate data

Although the number of studies discerning the impact of climate change on ecological systems continues to increase, there has been relatively little sharing of the lessons learnt when accumulating this evidence. At a recent workshop entitled ‘Using climate data in ecological research’ held at the UK Met Office, ecologists and climate scientists came together to discuss the robust analysis of climate data in ecology. The discussions identified three common pitfalls encountered by ecologists: 1) selection of inappropriate spatial resolutions for analysis; 2) improper use of publically available data or code; and 3) insufficient representation of the uncertainties behind the adopted approach. Here, we discuss how these pitfalls can be avoided, before suggesting ways that both ecology and climate science can move forward. Our main recommendation is that ecologists and climate scientists collaborate more closely, on grant proposals and scientific publications, and informally through online media and workshops. More sharing of data and code (e.g. via online repositories), lessons and guidance would help to reconcile differing approaches to the robust handling of data. We call on ecologists to think critically about which aspects of the climate are relevant to their study system, and to acknowledge and actively explore uncertainty in all types of climate data. And we call on climate scientists to make simple estimates of uncertainty available to the wider research community. Through steps such as these, we will improve our ability to robustly attribute observed ecological changes to climate or other factors, while providing the sort of influential, comprehensive analyses that efforts to mitigate and adapt to climate change so urgently require

An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia

© The Author(s) 2022. Open Access 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in poor-prognosis "ph-like" BCP-ALL. Here we show that expression of activated mutant IL7RA in human CD34+ hematopoietic stem and progenitor cells induces a preleukemic state in transplanted immunodeficient NOD/LtSz-scid IL2Rγnull mice, characterized by persistence of self-renewing Pro-B cells with non-productive V(D)J gene rearrangements. Preleukemic CD34+CD10highCD19+ cells evolve into BCP-ALL with spontaneously acquired Cyclin Dependent Kinase Inhibitor 2 A (CDKN2A) deletions, as commonly observed in primary human BCP-ALL. CRISPR mediated gene silencing of CDKN2A in primary human CD34+ cells transduced with activated IL7RA results in robust development of BCP-ALLs in-vivo. Thus, we demonstrate that constitutive activation of IL7RA can initiate preleukemia in primary human hematopoietic progenitors and cooperates with CDKN2A silencing in progression into BCP-ALL.This work was supported by the Israel Science Foundation (# 1178/12 to S.I.), Children with Cancer (UK) (S.I. and T.E.), Swiss Bridge Foundation (S.I.), WLBH Foundation (S.I.), Waxman Cancer Research Foundation (S.I.), US–Israel Binational Science Foundation, Israeli health ministry ERA-NET program (#CANCER11-FP-127 to S.I.), Hans Neufeld Stiftung, the International Collaboration Grant from the Jacki and Bruce Barron Cancer Research Scholars’ Program, a partnership of the Israel Cancer Research Fund and City of Hope (S.I. grants # 00161), the Nevzlin Genomic Center for Precision Medicine in Schneider Children’s Medical Center of Israel, The European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813091 (S.I.) and the Israel Childhood Cancer Foundation (S.I.). I.G. was partially supported by Israeli ministry of Immigrant Absorption.info:eu-repo/semantics/publishedVersio