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

Standard addition method based on four-way PARAFAC decomposition to solve the matrix interferences in the determination of carbamate pesticides in lettuce using excitation–emission fluorescence data

The simultaneous determination of two carbamate pesticides (carbaryl and carbendazim) and of the degradation product of carbaryl (1-naphthol) in iceberg lettuce was achieved by means of PARAFAC decomposition and excitation–emission fluorescence matrices. A standard addition method for a calibration based on four-way data was applied using different dilutions of the extract from iceberg lettuce as a fourth way that provided the enough variation of the matrix to carry out the four-way analysis. A high fluorescent overlapping existed between the three analytes and the fluorophores of the matrix. The identification of two fluorescent matrix constituents through the four-way model enabled to know the matrix contribution in each dilution of the extract. This contribution was subtracted from the previous signals and a subsequent three-way analysis was carried out with the tensors corresponding to each dilution. The PARAFAC decomposition of these resulting tensors showed a CORCONDIA index equal to 99%. For the identification of the analytes, the correlation between the PARAFAC spectral loadings and the reference spectra has been used. The trueness of the method, in the concentration range studied, was guaranteed because there was neither constant nor proportional bias according to the appropriate hypothesis tests. The best recovery percentages were obtained with the data from the most diluted extract, being the results: 127.6% for carbaryl, 125.55% for carbendazim and 87.6% for 1-naphthol. When the solvent calibration was performed, the decision limit (CCα) and the capability of detection (CCβ) values, in x0=0, were 2.21 and 4.38 μg L−1 for carbaryl, 4.87 and 9.64 μg L−1 for carbendazim; and 3.22 and 6.38 μg L−1 for 1-naphthol, respectively, for probabilities of false positive and false negative fixed at 0.05. However, these values were 5.30 and 10.49 μg L−1 for carbaryl, 18.05 and 35.73 μg L−1 for carbendazim; and 1.92 and 3.79 μg L−1 for 1-naphthol, respectively, when the matrix-matched calibration using the most diluted extract was carried out in the recovery study.Ministerio de Economía y Competitividad(CTQ2011-26022) and JuntadeCastillayLeón(BU108A11-2)

Red de Seguimiento e indicadores en el Máster Universitario en Ingeniería de Telecomunicación

El profesorado de la red docente, que forma parte de la comisión académica del Máster, realizó durante el curso 2011/12 un proyecto para el estudio de los indicadores de calidad del Máster, en función de los indicadores de calidad de las Agencias acreditadoras y dependiendo de las tasas de éxito y eficacias durante el primer curso de implantación del Máster

Estudio experimental sobre la influencia de la temperatura ambiental en la resistencia del hormigón preparado. Bases teóricas

The present article discusses the effects of temperature on the performance of both fresh and hardened concrete and on the properties of its constituent materials, from an industrial perspective. The primary aim of the study was to optimize concrete in very warm environments. Certain industrial procedures are proposed to minimize the adverse effects of climate on ready-mixed concrete performance. A number of experiments were conducted to determine the effect of extreme temperatures on the thermal behaviour, workability and mechanical properties of concrete, cement mortars, cement pastes, and aggregates. The results showed that aggregates, the predominant component of concrete, are especially temperature-labile. Basic measures for optimizing concrete performance in very warm weather were also developed. This procedure was successfully applied on an industrial scale in readymixed concrete production plants, where it yielded significant savings in summertime cement consumption.En este artículo se presenta un estudio sobre los efectos de la temperatura ambiental sobre las prestaciones del hormigón, en estado fresco y endurecido, y sobre las propiedades de los materiales constituyentes del mismo, desde una perspectiva industrial. El objetivo principal es el de optimizar la dosificación del hormigón en climas cálidos y al mismo tiempo, establecer medidas de actuación a nivel industrial para minimizar los efectos adversos en plantas de producción de hormigón preparado. En la primera parte del artículo, se muestran los resultados de varias campañas experimentales cuyo propósito ha sido determinar la influencia de las temperaturas ambientales extremas sobre las propiedades térmicas, de trabajabilidad y mecánicas del hormigón, así como de morteros, pastas de cemento y áridos. Las conclusiones apuntan al árido como un factor de gran importancia, no sólo por las características específicas de su comportamiento con la temperatura, sino también, porque es el componente presente en mayor contenido en el hormigón. En la segunda parte del artículo, se presentan las bases de una formulación metodológica para llevar a cabo la optimización del hormigón en climas cálidos

Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials

Background: Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often have functional dependency, multimorbidity, and polypharmacy, is inconclusive. We aimed to establish the effects of exercise interventions on the physical function of this population. Methods: For this systematic review and network meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Rehabilitation & Sports Medicine Source, and SPORTDiscus to identify randomised controlled trials assessing the effects of exercise interventions (vs usual care) on physical function (ie, functional independence, physical performance, and other related measures, such as muscle strength, balance, or flexibility) in adults aged 60 years or older living in residential care. Relevant studies published in English or Spanish up to Jan 12, 2023, were included in the systematic review. The quality of studies was assessed using the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) score. A network meta-analysis was performed for physical function-related outcomes reported in at least ten studies, with subanalyses for specific intervention (ie, exercise type, training volume, and study duration) and participant (eg, having cognitive impairment or dementia, pre-frail or frail status, and being functionally dependent) characteristics. The study protocol was registered on PROSPERO (CRD42021247809). Findings: 147 studies (11 609 participants, with mean ages ranging from 67 years [SD 9] to 92 years [2]) were included in the systematic review, and were rated as having overall good quality (median TESTEX score 9 [range 3–14]). In the meta-analysis (including 105 studies, n=7759 participants), exercise interventions were associated with significantly improved overall physical function, with a standardised mean difference [SMD] of 0·13 (95% credible interval [CrI] 0·04–0·21), which was confirmed in all analysed subpopulations. The strongest association was observed with 110–225 min per week of exercise, and the greatest improvements were observed with 170 min per week (SMD 0·36 [95% CrI 0·20–0·52]). No significant differences were found between exercise types. Subanalyses showed significant improvements for almost all analysed physical function-related outcomes (Barthel index, five-times sit-to-stand test, 30-s sit-to-stand test, knee extension, hand grip strength, bicep curl strength, Short Physical Performance Battery, 6-min walking test, walking speed, Berg balance scale, and sit-and-reach test). Large heterogeneity was found between and within studies in terms of population and intervention characteristics. Interpretation: Exercise interventions are associated with improved physical function in older adults in residential care, and should, therefore, be routinely promoted in long-term care facilities. Funding: None. Translation: For the Spanish translation of the abstract see Supplementary Materials section.10 página

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Physical Exercise and Alzheimer's Disease: Effects on Pathophysiological Molecular Pathways of the Disease

Alzheimer's disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD