Ultrafast excited state dynamics of silver ion-mediated cytosine–cytosine base pairs in metallo-DNA

The following article appeared in The Journal of Chemical Physics 153.10 (2020): 105104 and may be found at ttps://doi.org/10.1063/5.0020463To better understand the nexus between structure and photophysics in metallo-DNA assemblies, the parallel-stranded duplex formed by the all-cytosine oligonucleotide, dC20, and silver nitrate was studied by circular dichroism (CD), femtosecond transient absorption spectroscopy, and time-dependent-density functional theory calculations. Silver(I) ions mediate Cytosine–Cytosine (CC) base pairs by coordinating to the N3 atoms of two cytosines. Although these silver(I) mediated CC base pairs resemble the proton-mediated CC base pairs found in i-motif DNA at first glance, a comparison of experimental and calculated CD spectra reveals that silver ion-mediated i-motif structures do not form. Instead, the parallel-stranded duplex formed between dC20 and silver ions is proposed to contain consecutive silver-mediated base pairs with high propeller twist-like ones seen in a recent crystal structure of an emissive, DNA-templated silver cluster. Femtosecond transient absorption measurements with broadband probing from the near UV to the near IR reveal an unusually long-lived (>10 ns) excited state in the dC20 silver ion complex that is not seen in dC20 in single-stranded or i-motif forms. This state is also absent in a concentrated solution of cytosine–silver ion complexes that are thought to assemble into planar ribbons or sheets that lack stacked silver(I) mediated CC base pairs. The large propeller twist angle present in metal-mediated base pairs may promote the formation of long-lived charged separated or triplet states in this metallo-DNAThe work at The Ohio State University was supported by a grant from the U.S. National Science Foundation (Grant No. CHE1800471). L.M.-F. thanks the MINECO project (No. CTQ2016- 76061-P) for financial support and the Centro de Computación Científica, CCC-UAM, for generous allocation of computational time. The authors declare no competing financial interes

Circular Sponge against miR-21 Enhances the Antitumor Activity of Doxorubicin against Breast Cancer Cells

Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.CTS-107 GroupInstituto de Salud Carlos IIIEuropean Commission PI19/0147

Aprendendo a e-empreender: valorização da iniciativa empreendedora em futuros professores em e.s.o., bachillerato, f.p. e ensinamentos de línguas

Resumen: Introducción: El presente estudio analiza las diferencias en la intención emprendedora del alumnado de la rama de Educación Física en la primera y última semana de clases del MAES. Objetivos: El objetivo general de este trabajo es analizar la intención de emprendimiento en estudiantes universitarios del Máster Universitario de Profesorado de Educación Secundaria de la Universidad de Sevilla. Métodos: En el estudio participaron 24 alumnos, 5 mujeres y 19 hombres, de entre 22 y 28 años (M= 24,17; DT= 1,97). La intención emprendedora se evaluó a través del Cuestionario de Intención Emprendedora de Jaén y Liñán (2013). Resultados y discusión: Los resultados indicaron que no existen diferencias estadísticamente significativas antes y después de cursar el Máster Universitario en Profesorado en Enseñanza Secundaria Obligatoria y Bachillerato Formación Profesional y Enseñanzas de Idiomas, por lo que parece que este Máster no incide sobre el aspecto emprendedor expuesto en la Competencia General 12 “Fomentar el espíritu crítico, reflexivo y emprendedor”. Conclusiones: El estudio y análisis de las variables socio-demográficas indica que los hombres son algo más emprendedores que las mujeres, aunque no de forma significativa.Abstract: Introduction: The present study analyzes the differences in the entrepreneurial intention of the students of the Physical Education branch in the first and last week of MAES classes Aim: The general objective of this work is to analyze the intention of entrepreneurship in university students of the University Master's Degree in Secondary Education at the University of Seville. Methods: 24 students, 5 women and 19 men, aged between 22 and 28 years (M = 24.17; DT = 1.97) participated in the study. Entrepreneurial intention was evaluated through the Entrepreneurial Intention Questionnaire of Jaén and Liñán (2013). Results & discussion: The results indicated that there are no statistically significant differences before and after completing the University Master's Degree in Teaching in Compulsory Secondary Education and Baccalaureate Vocational Training and Language Teaching, so it seems that this Master does not affect the entrepreneurial aspect exposed in the General Competence 12 "Promote a critical, reflective and entrepreneurial spirit". Conclusions: The study and analysis of socio-demographic variables indicates that men are somewhat more entrepreneurial than women, although not significantly.Resumo: Introdução: Este estudo analisa as diferenças de intenção empreendedora dos alunos do ramo de Educação Física na primeira e na última semana de aulas do MAES. Objectivos: O objetivo geral deste trabalho é analisar a intenção do empreendedorismo em estudantes universitários do Mestrado Universitário em Ensino Secundário da Universidade de Sevilha. Métodos: Participaram do estudo 24 estudantes, 5 mulheres e 19 homens, com idades entre 22 e 28 anos (M = 24,17; TD = 1,97). A intenção empreendedora foi avaliada através do Questionário de Intenção Empreendedora de Jaén e Liñán (2013). Resultados e discussão: Os resultados indicaram que não existem diferenças estatisticamente significantes antes e após a conclusão do Mestrado Universitário em Ensino no Ensino Secundário Obrigatório e Bacharelado em Formação Profissional e Ensino de Idiomas, pelo que parece que este Mestrado não afeta o aspecto empreendedor exposto na Competência Geral 12 "Promover um espírito crítico, reflexivo e empreendedor". Conclusões: O estudo e a análise de variáveis sociodemográficas indicam que os homens são um pouco mais empreendedores do que as mulheres, embora não sejam significativamente

Fractional-order operators: Boundary problems, heat equations

The first half of this work gives a survey of the fractional Laplacian (and related operators), its restricted Dirichlet realization on a bounded domain, and its nonhomogeneous local boundary conditions, as treated by pseudodifferential methods. The second half takes up the associated heat equation with homogeneous Dirichlet condition. Here we recall recently shown sharp results on interior regularity and on $L_p$-estimates up to the boundary, as well as recent H\"older estimates. This is supplied with new higher regularity estimates in $L_2$-spaces using a technique of Lions and Magenes, and higher $L_p$-regularity estimates (with arbitrarily high H\"older estimates in the time-parameter) based on a general result of Amann. Moreover, it is shown that an improvement to spatial $C^\infty$-regularity at the boundary is not in general possible.Comment: 29 pages, updated version, to appear in a Springer Proceedings in Mathematics and Statistics: "New Perspectives in Mathematical Analysis - Plenary Lectures, ISAAC 2017, Vaxjo Sweden

Postharvest insect resistance in maize

One of the main challenges for the 21st century is ensuring global food security. Today, maize is the largest staple crop produced worldwide. Postharvest primary insect pests, especially the maize weevil (Sitophilus zeamais) and the large grain borer (Prostephanus truncatus) cause food-grain losses during storage up to 40% of total production, mainly in developing countries. Alternatives for pest management have been explored, including the implementation of hermetic storage structures and the application of chemical insecticides. Nevertheless, in low-income regions, both strategies are rarely accessible to smallholders. Modern breeding programs have endeavored to develop insect-resistant varieties, which diminish postharvest pest losses. In this review, we report the current status and advances in maize kernel-pest interactions, the bases and mechanisms of kernel resistance and their biotechnological perspectives. We demonstrate that the comprehension of resistance mechanisms has been fundamental for the development of new productive and resistant varieties, representing a sustainable alternative for developing countries. Finally, we analyse the biotechnological perspectives of natural kernel resistance in global food security

An upper limit for the water outgassing rate of the main-belt comet 176P/LINEAR observed with Herschel/HIFI

176P/LINEAR is a member of the new cometary class known as main-belt comets (MBCs). It displayed cometary activity shortly during its 2005 perihelion passage that may be driven by the sublimation of sub-surface ices. We have therefore searched for emission of the H2O 110-101 ground state rotational line at 557 GHz toward 176P/LINEAR with the Heterodyne Instrument for the Far Infrared (HIFI) on board the Herschel Space Observatory on UT 8.78 August 2011, about 40 days after its most recent perihelion passage, when the object was at a heliocentric distance of 2.58 AU. No H2O line emission was detected in our observations, from which we derive sensitive 3-sigma upper limits for the water production rate and column density of < 4e25 molec/s and of < 3e10 cm^{-2}, respectively. From the peak brightness measured during the object's active period in 2005, this upper limit is lower than predicted by the relation between production rates and visual magnitudes observed for a sample of comets by Jorda et al. (2008) at this heliocentric distance. Thus, 176P/LINEAR was likely less active at the time of our observation than during its previous perihelion passage. The retrieved upper limit is lower than most values derived for the H2O production rate from the spectroscopic search for CN emission in MBCs.Comment: 5 pages, 2 figures. Minor changes to match published versio

Peptide bond formation in the protonated serine dimer following vacuum UV photon-induced excitation

Possible routes for intra-cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision-induced dissociation (in correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the 4.6–14 eV range. Moreover, the comparison of photon-induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by ab initio molecular dynamics and exploration of several excited state potential energy surfaces, unraveling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitatio

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Bacteria-instructed B cells cross-prime naïve CD8+ T cells triggering effective cytotoxic responses.

In addition to triggering humoral responses, conventional B cells have been described in vitro to cross-present exogenous antigens activating naïve CD8+ T cells. Nevertheless, the way B cells capture these exogenous antigens and the physiological roles of B cell-mediated cross-presentation remain poorly explored. Here, we show that B cells capture bacteria by trans-phagocytosis from previously infected dendritic cells (DC) when they are in close contact. Bacterial encounter "instructs" the B cells to acquire antigen cross-presentation abilities, in a process that involves autophagy. Bacteria-instructed B cells, henceforth referred to as BacB cells, rapidly degrade phagocytosed bacteria, process bacterial antigens and cross-prime naïve CD8+ T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Moreover, a proof-of-concept experiment shows that BacB cells that have captured bacteria expressing tumor antigens could be useful as novel cellular immunotherapies against cancer.We are grateful to advanced light microscopy and cytometry facilities of CNB for technical supporting. The research is supported by grants: SAF2017-84091- R, and PID2020-116393RB-I00/AEI/10.13039/501100011033, financed by MCIN, BFERO2020.04, financed by FERO foundation and PI20/0036 from ISCIII. RGF is supported by BES-2016-076526 from the Spanish Ministry of Economy Industry and Competitiveness, JOP is supported by fellowship LCF/BQ/SO16/ 52270012 from La Caixa, BHF is supported by FPU18/00895 and AMP by FPU18/03199 from Ministry of Science, Innovation and Universities. LdC has been supported by Juan de la Cierva grant IJC2018-035386-I and a contract associated to SEV-2017-0712. EVC, AMP, AMAM, and NMM belong to the Spanish National Research Council (CSIC)’s Cancer Hub. Synopsis image made with biorender.com by Eduardo Roman Camacho and Esteban Veiga. We thanks Prof. Dan Portnoy who kindly provided bacterial strains.S

Evaluation of Current Methods to Detect Cellular Leucine-Rich Repeat Kinase 2 (LRRK2) Kinase Activity

Background: Coding variation in the Leucine rich repeat kinase 2 gene linked to Parkinson’s disease (PD) promotes enhanced activity of the encoded LRRK2 kinase, particularly with respect to autophosphorylation at S1292 and/or phosphorylation of the heterologous substrate RAB10. Objective: To determine the inter-laboratory reliability of measurements of cellular LRRK2 kinase activity in the context of wildtype or mutant LRRK2 expression using published protocols. Methods: Benchmark western blot assessments of phospho-LRRK2 and phospho-RAB10 were performed in parallel with in situ immunological approaches in HEK293T, mouse embryonic fibroblasts, and lymphoblastoid cell lines. Rat brain tissue, with or without adenovirus-mediated LRRK2 expression, and human brain tissues from subjects with or without PD, were also evaluated for LRRK2 kinase activity markers. Results: Western blots were able to detect extracted LRRK2 activity in cells and tissue with pS1292-LRRK2 or pT73-RAB10 antibodies. However, while LRRK2 kinase signal could be detected at the cellular level with over-expressed mutant LRRK2 in cell lines, we were unable to demonstrate specific detection of endogenous cellular LRRK2 activity in cell culture models or tissues that we evaluated. Conclusion: Further development of reliable methods that can be deployed in multiple laboratories to measure endogenous LRRK2 activities are likely required, especially at cellular resolution