Optical binding-driven micropatterning and photosculpting with silver nanorods

Controlling the nano- and micropatterning of metal structures is an important requirement for various technological applications in photonics and biosensing. This work presents a method for controllably creating silver micropatterns by laser-induced photosculpting. Photosculpting is driven by plasmonic interactions between pulsed laser radiation and silver nanorods (AgNRs) in aqueous suspension; this process leads to optical binding forces transporting the AgNRs in the surroundings, while electronic thermalization results in photooxidation, melting, and ripening of the AgNRs into well-defined 3D structures. This work call these structures Airy castles due to their structural similarity with a diffraction-limited Airy disk. The photosculpted Airy castles contain emissive Ag nanoclusters, allowing for the visualization and examination of the aggregation process using luminescence microscopy. This work comprehensively examines the factors that define the photosculpting process, namely, the concentration and shape of the AgNRs, as well as the energy, power, and repetition rate of the laser. Finally, this work investigates the potential applications by measuring the metal-enhanced luminescence of a europium-based luminophore using Airy castles

Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells

AbstractBH3-only proteins are required for execution of apoptotic cell death. We have found that one of these proteins, Bik, is strongly induced in cancer cells treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy-induced expression of bik is independent of p53. Consistent with its pro-apoptotic activity, blockade of bik expression reduces the adriamycin-mediated apoptotic cell death. We also found that the bik gene is transcriptionally activated by E2F proteins. Consistently, adriamycin induces the E2F-bik pathway. In addition, E2Fs transactivate bik by a p53-independent mechanism. Thus, our data indicate that transcriptional regulation of bik contributes to the efficient apoptotic response to chemotherapeutic agents

Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

BACKGROUND: We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. RESULTS: Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1) highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. CONCLUSION: Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer

Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

BACKGROUND: We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. RESULTS: Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1) highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. CONCLUSION: Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer

Modelling the Inorganic Bromine Partitioning in the Tropical Tropopause over the Pacific Ocean

The stratospheric inorganic bromine burden (Bry) arising from the degradation of brominated very short-lived organic substances (VSL org ), and its partitioning between reactive and reservoir species, is needed for a comprehensive assessment of the ozone depletion potential of brominated trace gases. Here we present modelled inorganic bromine abundances over the Pacific tropical tropopause based on aircraft observations of VSL org of two campaigns of the Airborne Tropical TRopopause EXperiment (ATTREX 2013 carried out over eastern Pacific and ATTREX 2014 carried out over the western Pacific) and chemistry-climate simulations (along ATTREX flight tracks) using the specific meteorology prevailing. Using the Community Atmosphere Model with Chemistry (CAM-Chem), we model that BrO and Br are the daytime dominant species. Integrated across all ATTREX flights BrO represents ~ 43 % and 48 % of daytime Bry abundance at 17 km over the Western and Eastern Pacific, respectively. The results also show zones where Br/BrO >1 depending on the solar zenith angle (SZA), ozone concentration and temperature. On the other hand, BrCl and BrONO 2 were found to be the dominant night-time species with ~ 61% and 56 % of abundance at 17 km over the Western and Eastern Pacific, respectively. The western-to-eastern differences in the partitioning of inorganic bromine are explained by different abundances of ozone (O3), nitrogen dioxide (NO2) , and total inorganic chlorine (Cly).Fil: Navarro, María A.. University of Miami; Estados UnidosFil: Saiz-lopez, Alfonso. Consejo Superior de Investigaciones Científicas. Instituto de Química Física; EspañaFil: Cuevas, Carlos Alberto. Consejo Superior de Investigaciones Científicas. Instituto de Química Física; EspañaFil: Fernandez, Rafael Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Tecnologica Nacional. Facultad Regional Mendoza. Secretaría de Ciencia, Tecnología y Postgrado; ArgentinaFil: Atlas, Elliot. University of Miami; Estados UnidosFil: Rodriguez Lloeveras, Xavier. Consejo Superior de Investigaciones Científicas. Instituto de Química Física; EspañaFil: Kinnison, Douglas E.. National Center For Atmospheric Research. Amospheric Chemistry División; Estados UnidosFil: Lamarque, Jean Francois. National Center For Atmospheric Research. Amospheric Chemistry División; Estados UnidosFil: Tilmes, Simone. National Center For Atmospheric Research. Amospheric Chemistry División; Estados UnidosFil: Thornberry, Troy. State University of Colorado at Boulder; Estados Unidos. Earth System Research Laboratory; Estados UnidosFil: Rollins, Andrew. State University of Colorado at Boulder; Estados Unidos. Earth System Research Laboratory; Estados UnidosFil: Elkins, James W.. Earth System Research Laboratory; Estados UnidosFil: Hintsa, Eric J.. State University of Colorado at Boulder; Estados Unidos. Earth System Research Laboratory; Estados UnidosFil: Moore, Fred L.. State University of Colorado at Boulder; Estados Unidos. Earth System Research Laboratory; Estados Unido

GENYOi004-A: An induced pluripotent stem cells (iPSCs) line generated from a patient with autism-related ADNP syndrome carrying a pTyr719* mutation

ADNP syndrome is an intellectual disability associated with Autism spectrum disorder caused by mutations in ADNP. We generated an iPSC line from an ADNP syndrome pediatric patient harboring the mutation p.Trp719* (GENYOi004-A). Peripheral blood mononuclear cells were reprogrammed using a non-transmissible form of Sendai viruses expressing the four Yamanaka factors (Oct3/4, SOX2, KLF4 and c-MYC). Characterization of GENYOi004-A included mutation analysis of ADNP by allele-specific PCR, genetic identity by Short Tandem Repeats polymorphism profiling, alkaline phosphatase enzymatic activity, expression of pluripotency-associated factors and pluripotency studies in vivo. GENYOi004-A will be useful to evaluate ADNP syndrome alterations at early developmental stages.This work was supported by the Postdoctoral Subprogramme Juan de la Cierva (JCI_2012_12666) to RM and Ramon y Cajal (RYC-2015-18382) to PJR founded by the Ministry of Economy and Competitiveness; the Instituto de Salud Carlos III-FEDER (CP12/03175 and CPII17/00032) to V.R-M. and (PI12/1598, CPII15/00018 and PI16/01340) to PJR; the Instituto de Investigación Valdecilla (IDIVAL) 2014.041 to JLF-L and DG-L and APG/03 to JLF-L

Cellular and animal models of skin alterations in the autism-related ADNP syndrome

Mutations in ADNP have been recently associated with intellectual disability and autism spectrum disorder. However, the clinical features of patients with this syndrome are not fully identified, and no treatment currently exists for these patients. Here, we extended the ADNP syndrome phenotype describing skin abnormalities in both a patient with ADNP syndrome and an Adnp haploinsufficient mice. The patient displayed thin dermis, hyperkeratotic lesions in periarticular areas and delayed wound healing. Patient-derived skin keratinocytes showed reduced proliferation and increased differentiation. Additionally, detection of cell cycle markers indicated that mutant cells exhibited impaired cell cycle progression. Treatment of ADNP-deficient keratinocytes with the ADNP-derived NAP peptide significantly reduced the expression of differentiation markers. Sonography and immunofluorescence staining of epidermal layers revealed that the dermis was thinner in the patient than in a healthy control. Adnp haploinsufficient mice (Adnp+/-) mimicked the human condition showing reduced dermal thickness. Intranasal administration of NAP significantly increased dermal thickness and normalized the levels of cell cycle and differentiation markers. Our observations provide a novel activity of the autism-linked ADNP in the skin that may serve to define the clinical phenotype of patients with ADNP syndrome and provide an attractive therapeutic option for skin alterations in these patients.This work was supported by grant CI14/09 from Fundacion Instituto de Investigacion Valdecilla to J.L.F.-L., PI14/00900 from Instituto de Salud Carlos III (ISCIII) to A.G., and AMN Foundation and ERA-NET Neuron to I.G. We are grateful to Ana Freije and Laura Ceballos for technical assistance at isolating skin cells, and to Profs. Carmit Levi and Chen Luxenburg and the student Chen Slonimsky for their help in the in vivo experiments. We thank Prof. Joseph Levine for his help with the analysis of the Facebook answers regarding the skin conditions in ADNP children. We also thank Isabel Garcia for her constant support and help to obtain phenotypic information of the skin of patients with ADNP syndrome

Characterization of Conserved and Promiscuous Human Rhinovirus CD4 T Cell Epitopes

This research was supported by UCM research special funds to P.A.R. and by the CAM research agency through grant IND2020/BMD-17364 to P.A.R.Human rhinovirus (RV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from RV A and 8 from RV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in RV A and C serotypes and predicted to bind to multiple human leukocyte antigen class II (HLA II) molecules. We found positive T cell recall responses by interferon gamma (IFNγ)-ELISPOT assays to eight peptides, validating seven of them (three from RV A and four from RV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these seven epitopes could be recognized by >95% of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor RV infections and to develop peptide-based vaccines against most RV A and C serotypes.Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEComunidad de MadridUniversidad Complutense de Madridpu

Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes

Lipoic acid (LA) is an antioxidant with therapeutic potential on several diseases such as diabetes and obesity. Hyperleptinemia and oxidative stress play a major role in the development of obesity-linked diseases. The aim of this study was to examine in vivo and in vitro the effects of LA on leptin production, as well as to elucidate the mechanisms and signalling pathways involved in LA actions. Methods and results: Dietary supplementation with LA decreased both circulating leptin, and adipose tissue leptin mRNA in rats. Treatment of 3T3-L1 adipocytes with LA caused a concentration-dependent inhibition of leptin secretion and gene expression. Moreover, LA stimulated the anaerobic utilization of glucose to lactate, which negatively correlated with leptin secretion. Furthermore, LA enhanced phosphorylation of Sp1 and inhibited Sp1 transcriptional activity in 3T3-L1 adipocytes. Moreover, LA inhibited Akt phosphorylation, a downstream target of phosphatidylinositol 3-kinase (PI3K). Treatment with the PI3K inhibitor LY294002 mimicked LA actions, dramatically inhibiting both leptin secretion and gene expression and stimulating Sp1 phosphorylation. Conclusion: All of these data suggest that the phosphorylation of Sp1 and the accompanying reduced DNA-binding activity are likely to be involved in the inhibition of leptin induced by LA, which could be mediated in part by the abrogation of the PI3K/Akt pathway