Baby Boomers: The Use of Technology to Support Learning

Baby Boomers are lifelong learners. Mobile devices and shared information over the Internet have made technology a significant platform for learning. It is a popular misconception, however, that Baby Boomers are alien to technology. This paper explores existing literature on the use of technology to support learning in Baby Boomers

Comprehensive transcriptomic analysis of heat shock proteins in the molecular subtypes of human breast cancer

Background: Heat Shock Proteins (HSPs), a family of genes with key roles in proteostasis, have been extensively associated with cancer behaviour. However, the HSP family is quite large and many of its members have not been investigated in breast cancer (BRCA), particularly in relation with the current molecular BRCA classification. In this work, we performed a comprehensive transcriptomic study of the HSP gene family in BRCA patients from both The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts discriminating the BRCA intrinsic molecular subtypes. Methods: We examined gene expression levels of 1097 BRCA tissue samples retrieved from TCGA and 1981 samples of METABRIC, focusing mainly on the HSP family (95 genes). Data were stratified according to the PAM50 gene expression (Luminal A, Luminal B, HER2, Basal, and Normal-like). Transcriptomic analyses include several statistical approaches: differential gene expression, hierarchical clustering and survival analysis. Results: Of the 20,531 analysed genes we found that in BRCA almost 30% presented deregulated expression (19% upregulated and 10% downregulated), while of the HSP family 25% appeared deregulated (14% upregulated and 11% downregulated) (|fold change| > 2 comparing BRCA with normal breast tissues). The study revealed the existence of shared HSP genes deregulated in all subtypes of BRCA while other HSPs were deregulated in specific subtypes. Many members of the Chaperonin subfamily were found upregulated while three members (BBS10, BBS12 and CCTB6) were found downregulated. HSPC subfamily had moderate increments of transcripts levels. Various genes of the HSP70 subfamily were upregulated; meanwhile, HSPA12A and HSPA12B appeared strongly downregulated. The strongest downregulation was observed in several HSPB members except for HSPB1. DNAJ members showed heterogeneous expression pattern. We found that 23 HSP genes correlated with overall survival and three HSP-based transcriptional profiles with impact on disease outcome were recognized. Conclusions: We identified shared and specific HSP genes deregulated in BRCA subtypes. This study allowed the recognition of HSP genes not previously associated with BRCA and/or any cancer type, and the identification of three clinically relevant clusters based on HSPs expression patterns with influence on overall survival.Fil: Zoppino, Felipe Carlos Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Guerrero Gimenez, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Castro, Gisela Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Resistencia a drogas en pacientes con cáncer de mama

El cáncer de mama sigue siendo una de las principales causas de muerte en la mujer. Uno de los tratamientos que se utiliza en la actualidad para combatir esta enfermedad es la quimioterapia. Lamentablemente en muchos casos esta terapia fracasa porque las células tumorales desarrollan múltiples mecanismos de resistencia a las drogas antitumorales. Existen diversos genes/proteínas que cuando se expresan anormalmente en los tumores impiden que las drogas antitumorales cumplan su función. Entre las proteínas relacionadas con resistencia a drogas antineoplásicas figuran la proteína P170, la proteína HER-2/neu y las proteínas de golpe de calor. Nuestro grupo de trabajo estudia diversas moléculas que se expresan en los tumores de mama y que podrían predecir la sensibilidad/resistencia a la quimioterapia. El objetivo es poder orientar a los oncólogos en la selección de las terapias más efectivas para cada paciente.Breast cancer is one of the principal causes of death in women. Chemotherapy is one of the effective treatments used in breast cancer patients. However, in several cases chemotherapy fails because tumor cells may develop several mechanisms of antitumor drug resistance. There are different genes/proteins that, when abnormally expressed in the tumors, prevent the function of the antitumor drugs. Among the proteins related with chemotherapy resistance is the proteins P170, HER-2/neu, and heat shock. Our research group is studying molecules expressed in breast tumors that can be associated with sensitivity/resistance to chemotherapy.Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

The involvement of heat shock proteins and related molecules in the resistance to therapies in breast and gynecologic cancer

The HSP response is implicated in conferring to breast and gynecologic malignancies different sensitivities to anticancer therapies including chemotherapy, endocrine therapy and immunotherapy (weare in the need of more studies about radiotherapy). The heat shock proteins are mainly implicated in cell death mechanisms, in cell differentiation including epithelial-mesenchymal transition, in tumordormancy, in angiogenesis, metastasis formation, and in the escape of immunosurveillance. Considering the ample functions where the HSPs are implicated and that the HSP response is quite complex it is not surprising that the HSP response affects the anticancer therapies. Several of the HSPs have different predominant roles according to the molecular partners with which they interact, thus it is difficult to dissect the molecular mechanisms to find the sensitivity to the therapies. In this review we present the implications of some the major HSPs (HSP27, HSP70 and HSP90) with drug resistance and present some of the main partners that are also implicated in drug resistance like p53, PTEN and MDR. We have given priority to the incorporation of clinical data where the HSPs have been studied using standard chemotherapies and new therapeutic strategies. It is clear that in order to have a significant understanding of the degree of drug resistance/sensitivity presented by a particular patient we need to examine the molecular status of several key molecular markers involved in the drug resistance pathways and that in this context the study of the HSP response should be incorporated. One of the other major problems in this field is that an inhibitor of one particular HSP will not be enough to achieve a significant anticancer response. Now that we know the complexity of this field we need to design strategies aiming to inhibit several molecular HSP pathways simultaneously without significantly affecting the normal cells, this is the principal challenge for the near future.Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fanelli, Mariel Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Castro, Gisela Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cayado Gutiérrez, Niubys de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

In MMTV-Her-2/neu transgenic mammary tumors the absence of caveolin-1−/− alters PTEN and NHERF1 but not β-catenin expression

In a recent study, we have shown that in mammary tumors from mice lacking the Cav-1 gene, there are alterations in specific heat shock proteins as well as in tumor development. With this in mind, we have now investigated other proteins in the same mammary mouse tumor model (Her-2/neu expressing mammary tumors from Cav-1 wild type and Cav-1 null mice), to further comprehend the complex tumor-stroma mechanisms involved in regulating stress responses during tumor development. In this tumor model the cancer cells always lacked of Cav-1, so the KO influenced the Cav-1 in the stroma. By immunohistochemistry, we have found a striking co-expression of β-catenin and Her-2/neu in the tumor cells. The absence of Cav-1 in the tumor stroma had no effect on expression or localization of β-catenin and Her-2/neu. Both proteins appeared co-localized at the cell surface during tumor development and progression. Since Her-2/neu activation induces MTA1, we next evaluated MTA1 in the mouse tumors. Although this protein was found in numerous nuclei, the absence of Cav-1 did not alter its expression level. In contrast, significantly more PTEN protein was noted in the tumors lacking Cav-1 in the stroma, with the protein localized mainly in the nuclei. P-Akt levels were relatively low in tumors from both Cav-1 WT and Cav-1 KO mice. There was also an increase in nuclear NHERF1 expression levels in the tumors arising from Cav-1 KO mice. The data obtained in the MMTV-neu model are consistent with a role for Cav-1 in adjacent breast cancer stromal cells in modulating the expression and localization of important proteins implicated in tumor cell behavior.Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cayado Gutiérrez, Niubys de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Natoli, Anthony L. . Peter MacCallum Cancer Centre. Metastasis Research Laboratory; AustraliaFil: Restall, Christina. Peter MacCallum Cancer Centre. Metastasis Research Laboratory; AustraliaFil: Anderson, Robin L.. Peter MacCallum Cancer Centre. Metastasis Research Laboratory; AustraliaFil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Alvarez Olmedo, Daiana Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Castro, Gisela N.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gago, Francisco E.. Facultad de Ciencias Médicas. Universidad Nacional de Cuyo; ArgentinaFil: Fanelli, Mariel Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina

Fil: Munné, María Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Vladimirsky, Sara. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Otegui, Lucio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Brajterman, Leonardo. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Castro, Raúl. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Soto, Sonia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Moreiro, Rita. Hospital Nacional de Pediatría J. P. Garrahan. Laboratorio; Argentina.Fil: Ciocca, Mirta. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Cuarterolo, Miriam. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Buamscha, Daniel. Hospital Nacional de Pediatría J. P. Garrahan. Terapia Intensiva de Transplante Hepático; Argentina.Fil: Giannivelli, Silvina. Hospital Nacional de Pediatría J. P. Garrahan. Terapia Intensiva de Transplante Hepático; Argentina.Fil: Sasbón, Jorge. Hospital Nacional de Pediatría J. P. Garrahan. Terapia Intensiva de Transplante Hepático; Argentina.Fil: Schlauder, George. Abbott Laboratories; Estados Unidos.Fil: González, Jorge E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Las cepas de virus de hepatitis E (HEV) encontradas en casos esporádicos humanos y en cerdos en Argentina corresponden al genotipo 3. Se han descripto variantes de este genotipo asociadas a fallas hepáticas fulminantes (FHF) en adultos de Japón e Inglaterra. En Argentina el 30% de las FHF en adultos y en niños es de etiología desconocida. Para estudiar si el HEV podría ser el agente etiológico asociado a FHF en niños se analizaron el suero y/o la materia fecal de 35 niños (edad media 6 años, 20 mujeres, 15 varones) durante 2003 y 2004. El HEV RNA fue detectado por RT-nested PCR con cebadores dirigidos a las regiones ORF 1 y ORF 2. El HEV RNA pudo detectarse en 3 casos. Dos eran varones de 12 años residentes en la provincia de Buenos Aires y el tercero, una niña de 3 años de la provincia de Corrientes. El análisis de las secuencias muestra que las 3 variantes son distintas, pero pertenecen todas al genotipo 3 y están muy relacionadas a las cepas encontradas previamente en casos esporádicos en humanos y en cerdos de Argentina. Estos datos sugieren una posible relación entre FHF y HEV en niños de Argentina e indican la necesidad de considerar la infección con HEV en el diagnóstico diferencial de las FHF. Se necesitan más estudios que demuestren el verdadero impacto de esta infección y el beneficio potencial de una vacuna para HEV, actualmente en fase III

Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina

Fil: Munné, María Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Vladimirsky, Sara. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Otegui, Lucio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Brajterman, Leonardo. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Castro, Raúl. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Soto, Sonia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Fil: Moreiro, Rita. Hospital Nacional de Pediatría J. P. Garrahan. Laboratorio; Argentina.Fil: Ciocca, Mirta. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Cuarterolo, Miriam. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Buamscha, Daniel. Hospital Nacional de Pediatría J. P. Garrahan. Terapia Intensiva de Transplante Hepático; Argentina.Fil: Giannivelli, Silvina. Hospital Nacional de Pediatría J. P. Garrahan. Terapia Intensiva de Transplante Hepático; Argentina.Fil: Sasbón, Jorge. Hospital Nacional de Pediatría J. P. Garrahan. Terapia Intensiva de Transplante Hepático; Argentina.Fil: Schlauder, George. Abbott Laboratories; Estados Unidos.Fil: González, Jorge E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia para Hepatitis Virales; Argentina.Las cepas de virus de hepatitis E (HEV) encontradas en casos esporádicos humanos y en cerdos en Argentina corresponden al genotipo 3. Se han descripto variantes de este genotipo asociadas a fallas hepáticas fulminantes (FHF) en adultos de Japón e Inglaterra. En Argentina el 30% de las FHF en adultos y en niños es de etiología desconocida. Para estudiar si el HEV podría ser el agente etiológico asociado a FHF en niños se analizaron el suero y/o la materia fecal de 35 niños (edad media 6 años, 20 mujeres, 15 varones) durante 2003 y 2004. El HEV RNA fue detectado por RT-nested PCR con cebadores dirigidos a las regiones ORF 1 y ORF 2. El HEV RNA pudo detectarse en 3 casos. Dos eran varones de 12 años residentes en la provincia de Buenos Aires y el tercero, una niña de 3 años de la provincia de Corrientes. El análisis de las secuencias muestra que las 3 variantes son distintas, pero pertenecen todas al genotipo 3 y están muy relacionadas a las cepas encontradas previamente en casos esporádicos en humanos y en cerdos de Argentina. Estos datos sugieren una posible relación entre FHF y HEV en niños de Argentina e indican la necesidad de considerar la infección con HEV en el diagnóstico diferencial de las FHF. Se necesitan más estudios que demuestren el verdadero impacto de esta infección y el beneficio potencial de una vacuna para HEV, actualmente en fase III

Bose-Einstein Correlations of Three Charged Pions in Hadronic Z^0 Decays

Bose-Einstein Correlations (BEC) of three identical charged pions were studied in 4 x 10^6 hadronic Z^0 decays recorded with the OPAL detector at LEP. The genuine three-pion correlations, corrected for the Coulomb effect, were separated from the known two-pion correlations by a new subtraction procedure. A significant genuine three-pion BEC enhancement near threshold was observed having an emitter source radius of r_3 = 0.580 +/- 0.004 (stat.) +/- 0.029 (syst.) fm and a strength of \lambda_3 = 0.504 +/- 0.010 (stat.) +/- 0.041 (syst.). The Coulomb correction was found to increase the \lambda_3 value by \~9% and to reduce r_3 by ~6%. The measured \lambda_3 corresponds to a value of 0.707 +/- 0.014 (stat.) +/- 0.078 (syst.) when one takes into account the three-pion sample purity. A relation between the two-pion and the three-pion source parameters is discussed.Comment: 19 pages, LaTeX, 5 eps figures included, accepted by Eur. Phys. J.

Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer

International audienceIntroduction: Breast cancers are traditionally divided into hormone-receptor positive and negative cases. This classification helps to guide patient management. However, a subgroup of hormone-receptor positive patients relapse irrespective of hormonal therapy. Gene expression profiling has classified breast tumours into five major subtypes with significant different outcome. The two luminal subtypes, A and B, show high expression of ESR1, GATA3 and FOXA1 genes. Prognostic biomarkers for oestrogen receptor (ER)-positive cases include progesterone receptor (PR) and androgen receptor (AR), and proteins related to proliferation or apoptotic resistance. The aim of this study was to identify the best predictors of success of hormonal therapy.Methods: By immunohistochemistry we studied 10 markers in a consecutive series of 832 cases of breast carcinoma treated at the Paoli-Calmettes Institute from 1990 to 2002 and deposited onto tissue microarrays (TMA). These markers were luminal-related markers ER, PR, AR, FOXA1 and GATA3 transcription factors, proliferation-related Ki67 and CCND1, ERBB2, anti-apoptotic BCL2 and P53. We also measured vascular peritumoural invasion (VPI), size, grade and lymph node involvement. For 143 cases, gene expression profiles were available. Adjuvant chemotherapy and hormonal therapy were given to high- and low-risk patients, respectively. The 162 events observed and taken into account were metastases.Results: Molecular expression of the 10 parameters and subtype with ER status were strongly correlated. Of the 67 luminal A cases of this series, 63 were ER-positive. Multivariate analyses showed the highly significant prognostic value of VPI (hazard ratio (HR) = 2.47), Ki67 (HR = 2.9), P53 (HR = 2.9) and GATA3 (HR = 0.5) for the 240 patients who received hormonal therapy.Conclusions: A panel of three antibodies (Ki67, P53 and GATA3) associated with VPI can significantly improve the traditional prognosticators in predicting outcome for ER-positive breast cancer patients receiving hormonal therapy

Manipulating the alpha level cannot cure significance testing

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable