Color Engineering of Silicon Nitride Surfaces to Characterize the Polydopamine Refractive Index

A simple methodology to generate polydopamine (PDA) surfaces featured with color due to thin-film interference phenomena is presented. It is based on depositing ultra-thin films of polydopamine on a Si/Si 3 N 4 wafer that exhibits an interferential reflectance maximum right at the visible/UV boundary (∼400 nm). Therefore, a small deposit of PDA modifies the optical path, in such manner that the wavelength of the maximum of reflectance red shifts. Because the human eye is very sensitive to any change of the light spectral distribution at the visible region, very small film thickness changes (∼30 nm) are enough to notably modify the perceived color. Consequently, a controlled deposit of PDA, tune the color along the whole visible spectrum. Additionally, good quality of PDA deposits allowed us to determine the refractive index of polydopamine by ellipsometry spectroscopy. This data can be crucial in confocal skin microscopic techniques, presently used in diagnosis of skin tumors.Fil: Vega Moreno, Milena Amparo. Universidad de Salamanca; EspañaFil: Martín del Valle, Eva M.. Universidad de Salamanca; EspañaFil: Perez, Maximiliano Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Haedo; ArgentinaFil: Pecharromán, Carlos. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia de los Materiales de Barcelona; EspañaFil: Marcelo, Gema. Universidad de Salamanca; Españ

Friendship conceptions: an exploratory study with spanish and immigrant children established in the Madrid Community

El objetivo de nuestro estudio es conocer la concepción que tienen los niños acerca de la amistad, viendo si ésta varía en función del género y las características culturales de los participantes. Para ello, se elaboró una entrevista semiestructurada de respuesta abierta, que se aplicó –siguiendo el método clínico propuesto por Piaget–, a una muestra de 30 estudiantes (16 niñas y 14 niños) de 5º y 6º de Educación Primaria, con un rango de edad que oscilaba entre los 11;1 y 12;3 años, y donde el 50% eran inmigrantes y la parte restante españoles (autóctonos). Los resultados de este trabajo indican que no hay diferencias significativas en la concepción que tienen los niños de la amistad según su origen nacional, entendiéndola como un vínculo que se basa en la ayuda, la confianza, la compañía y la fidelidad. Sin embargo, se encontraron diferencias significativas en cuanto a la facilidad a la hora de entablar relaciones con los iguales, y el origen étnico de las amistades, asegurando los españoles, en mayor medida que los inmigrantes, que les costaba hacer amigos, y que éstos eran en su mayoría de origen español. Igualmente, se hallaron diferencias significativas en función del género, destacando las niñas en mayor medida que los niños, la confianza como el rasgo que diferencia a los amigos, del resto de iguales que no lo son.The aim of our study is to know the childrens’ conceptions of friendship and looking at if it changes according to gender and the cultural characteristics of the participants. To this end, a semistructured interview of open answerered questions was developed, and applied –following the piagetian method– to a sample of 30 students (16 girls and 14 boys) of the 5th and 6th grades of primary school. The ages of the children varied between 11;1 and 12;3 years, and the 50% were immigrants, with the remaining part being natives Spaniards. The results of this work show that there aren’t significant differences in the childrens’ conceptions of friendship based on their national origin, understanding it as a link based on help, confidence, company and faithfulness. However, significant differences were found in relation to the ease of starting relationships with the peers, and the ethnical origin of their friends, confirming a higher number of Spanish natives that had the most problems making friends, as opposed to the immigrants, and whose friends were mostly Spanish natives. Likewise, significant differences were found according to gender, pointing out that the girls, rather than boys, found confidence as a trait that differentiated their friends from the rest of their peers.peerReviewe

Antineoplastic behavior of polydopamine nanoparticles prepared in different water/alcohol media

[EN] Polydopamine nanoparticles (PD NPs) have been synthesized in the present work through the oxidative polymerization of dopamine in aqueous media containing five different types of alcohol in a constant solvent volume ratio. We have shown that the type of alcohol, along with the ammonium hydroxide concentration used in the synthesis process, conditions particle size. Additionally, it has been found that the type of alcohol employed influences the well-known capacity of polydopamine nanoparticles to adsorb iron. As a consequence, since a ferroptosis-like mechanism may account for the cytotoxicity of these nanoparticles, the type of alcohol could also have a determining role in their antineoplastic activity. Here, the existence of a correlation between the ability of polydopamine nanoparticles to load Fe3+ and their toxic effect on breast cancer cells has been proven. For instance, nanoparticles synthesized using 2-propanol adsorbed more Fe3+ and had the greatest capacity to reduce breast tumor cell viability. Moreover, none of the nanoparticle synthesized with the different alcohols significantly decreased normal cell survival. Cancer cells present greater iron-dependence than healthy cells and this fact may explain why polydopamine nanoparticles toxicity, in which Fenton chemistry could be implicated, seems tumor-specific

“Desayuna con la ciencia”: como acercar la ciencia a niños de forma amena

En la actualidad es primordial que los centros del conocimiento como las universidades divulguen y promuevan el acercamiento de todas las disciplinas científicas (entendiendo estas como arte y humanidades, ciencias, ciencias de la salud, ciencias sociales y jurídicas e ingeniería y arquitectura) a la ciudadanía a través de distintas metodologías. Este acercamiento es fundamental en el contexto escolar, mediante la aplicación de nuevas metodologías didácticas y prácticas que fomenten el interés de los estudiantes por el ámbito científico, de esta forma se conseguirá una mayor apertura de la sociedad hacia la ciencia. En la Universidad de Extremadura este acercamiento se realiza a través de las jornadas “Desayuna con la ciencia”, una actividad abierta a alumnos de 5º y 6º de primaria de los colegios de la comunidad autónoma de Extremadura y cuyos objetivos fundamentales son acercar y promover actividades de divulgación científica que motiven la ciencia y la tecnología como herramientas en el desarrollo intelectual, promover una cultura científica a niños y niñas de zonas rurales de la región, hacer visible la relación entre la ciencia y las actividades de la vida diaria permitiendo la aplicación del conocimiento científico a los problemas cotidianos, incorporar nuevas formas innovadoras de trabajo mediante demostraciones práctica de los contenidos y fijar capital humano a nuestra región. Además la importancia del programa está en consonancia con lo recogido en la Declaración sobre la Ciencia y el Uso del saber Científico aprobada por la UNESCO en 1999, y en la que se aboga por, “El fortalecimiento del papel de la ciencia en pro de un mundo más equitativo, próspero y sostenible requiere un compromiso a largo plazo de todas las partes interesadas, sean del sector público o privado, que incluya un aumento de las inversiones y el análisis correspondiente de las prioridades en materia de inversión, y el aprovechamiento compartido del saber científico”. Desayuna con la ciencia se desarrolla mediante Talleres didáctico- científicos, estos pueden ser desde un experimento, una demostración, o una exhibición que muestre los pasos del método científico que hay que seguir para estudiar un fenómeno. Estos talleres son eminentemente prácticos, de esta forma se introduce al alumnado en grandes conceptos científicos, valorando así sus propias observaciones. A través de esta comunicación, analizamos la relación entre ciencia y divulgación científica a niños de primaria a través de una actividad que aúna práctica y diversión, pero sin perder el rigor educativo y científico aprovechando de esta forma la curiosidad natural de los niños

Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation.

Sox2 is a pluripotency transcription factor that as an oncogene can also regulate cell proliferation. Therefore, genes implicated in several different aspects of cell proliferation, such as the VRK1 chromatin-kinase, are candidates to be targets of Sox2. Sox 2 and VRK1 colocalize in nuclei of proliferating cells forming a stable complex. Sox2 knockdown abrogates VRK1 gene expression. Depletion of either Sox2 or VRK1 caused a reduction of cell proliferation. Sox2 up-regulates VRK1 expression and both proteins cooperate in the activation of CCND1. The accumulation of VRK1 protein downregulates SOX2 expression and both proteins are lost in terminally differentiated cells. Induction of neural differentiation with retinoic acid resulted in downregulation of Sox2 and VRK1 that inversely correlated with the expression of differentiation markers such as N-cadherin, Pax6, mH2A1.2 and mH2A2. Differentiation-associated macro histones mH2A1.2and mH2A2 inhibit CCND1 and VRK1 expression and also block the activation of the VRK1 promoter by Sox2. VRK1 is a downstream target of Sox2 and both form an autoregulatory loop in epithelial cell differentiation.Ministerio de Economía y Competitividad [SAF2013-44810R, SAF2014-57791-REDC].Consejería de Educación de la Junta de Castilla y León [CSI002U14 and UIC-017] to P.A.L

Serum HER-2 concentration is associated with insulin resistance and decreases after weight loss

<p>Abstract</p> <p>Background</p> <p>HER2/<it>neu </it>is a member of the epidermal growth factor receptor family easily detectable in the serum of cancer patients. We aimed to evaluate circulating HER-2 concentrations in association with insulin resistance in healthy and obese subjects.</p> <p>Methods</p> <p>Insulin sensitivity (minimal model) and serum HER-2 concentrations were evaluated in a cross sectional study in men (cohort 1, n = 167) and longitudinally after weight loss in obese subjects (cohort 2, n = 30).</p> <p>Results</p> <p>Serum HER-2 concentrations were positively associated with BMI and waist circumference (both r = 0.18, p = 0.02), post-load glucose (r = 0.28, p = 0.001) and fasting triglycerides (r = 0.26, p = 0.001); and negatively associated with insulin sensitivity (r = -0.29, p = 0.002, n = 109). Subjects with type 2 diabetes showed significantly increased soluble serum HER-2 concentrations. In different multivariate regression models, fasting triglycerides emerged as the factor that independently contributed to 10-11% of serum HER-2 variance.</p> <p>Serum HER-2 concentrations correlated significantly with fasting triglycerides and insulin sensitivity index in subjects from cohort 2. Weight loss led to a significant decrease of serum HER-2 concentrations. The change in serum HER-2 concentrations were significantly associated with the change in percent body fat and fasting triglycerides in young (below the median age of the cohort) subjects.</p> <p>Conclusions</p> <p>Serum HER-2 concentrations might be implicated in the pathophysiology of insulin resistance and associated comorbidities.</p

Intra-tumor heterogeneity in TP53 null high grade serous ovarian carcinoma progression

[Background]: High grade serous ovarian cancer is characterised by high initial response to chemotherapy but poor outcome in the long term due to acquired resistance. One of the main genetic features of this disease is TP53 mutation. The majority of TP53 mutated tumors harbor missense mutations in this gene, correlated with p53 accumulation. TP53 null tumors constitute a specific subgroup characterised by nonsense, frameshift or splice-site mutations associated to complete absence of p53 expression. Different studies show that this kind of tumors may have a worse prognosis than other TP53 mutated HGSC. [Methods]: In this study, we sought to characterise the intra-tumor heterogeneity of a TP53 null HGSC consisting of six primary tumor samples, two intra-pelvic and four extra-pelvic recurrences using exome sequencing and comparative genome hybridisation. [Results]: Significant heterogeneity was found among the different tumor samples, both at the mutational and copy number levels. Exome sequencing identified 102 variants, of which only 42 were common to all three samples; whereas 7 of the 18 copy number changes found by CGH analysis were presented in all samples. Sanger validation of 20 variants found by exome sequencing in additional regions of the primary tumor and the recurrence allowed us to establish a sequence of the tumor clonal evolution, identifying those populations that most likely gave rise to recurrences and genes potentially involved in this process, like GPNMB and TFDP1. Using functional annotation and network analysis, we identified those biological functions most significantly altered in this tumor. Remarkably, unexpected functions such as microtubule-based movement and lipid metabolism emerged as important for tumor development and progression, suggesting its potential interest as therapeutic targets. [Conclusions]: Altogether, our results shed light on the clonal evolution of the distinct tumor regions identifying the most aggressive subpopulations and at least some of the genes that may be implicated in its progression and recurrence, and highlights the importance of considering intra-tumor heterogeneity when carrying out genetic and genomic studies, especially when these are aimed to diagnostic procedures or to uncover possible therapeutic strategies.This work has been supported by grants from the AECC network-2012, Telemarató 2013, Instituto de Salud Carlos III (ISCIII) (PI13/00132 and RETIC-RD12/0036/0007), GEIS award 2013, and by the Community of Madrid (S2010/BMD-2303). AM is a predoctoral student supported by FPU fellowship (Spanish Education Ministry). PGS is founded by postdoc contracts from the AECC Scientific Foundation.Peer Reviewe

Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study.

Objectives Reverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers’ reincorporation. Materials and methods This is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables. Results 159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20–35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48–096) for dyspnoea and 0.61 (0.42–0.88) for dry cough. Conclusions RT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.pre-print396 K

Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas

Basal-like breast carcinoma is characterized by the expression of basal/ myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR , PR , Her2neu ). We have previously shown that epithelial–mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtypeThis work was supported by grants from the Spanish Ministry of Science and Innovation, MICINN, (SAF2007-53061; SAF2010-21143; Consolider Ingenio CSD2007/00017, to AC; SAF2007-63075; SAF2010-20175 to GM-B); Fundacion Mutua Madrileña (2007, 2009 to AC and GM-B); Instituto de Salud Carlos III (ISCIII) (PI 080971 to JP), and Junta de Andalucıa (PI-0384/2007; PI 080971, P07-CVI- 03100 to JP). FS and A Martı´n are recipients of JAE-pre and JAE-postdoc contracts from the Spanish Research Council (CSIC), respectively; MAC is founded by the RETICS (ISCIII)