623 research outputs found
Recommended from our members
Cancer gene mutation discovery and detection using array-based resequencing
Nationalistic collective rituals, intergroup relations, and legitimation of national social systems
Indexación: Scopus.In this article, we test if international football matches in Latin America can be understood as nationalistic collective rituals and if participating in them leads to prejudicial attitudes toward immigrants and to legitimize the national social systems. Based on social identity theory and literature on collective rituals, we propose that participating in collective rituals makes cognitively salient social identity over self-identity through collective emotions. Therefore, individuals are more motivated to perceive the social systems as fair and legitimate and to show outgroup derogation. In Study 1 (N = 414), interest in football was associated with national identification a week before an international tournament in Brazil, Chile, and Spain. This association was mediated by fusion of identity with the national ingroup but not by experiencing collective positive emotions. In Study 2 (N = 118), we used an experimental design and showed that nationalism moderated the effect of participating in nationalistic collective rituals on measures related to behavioral intentions. Specifically, these rituals decreased outgroup prejudice among high nationalistic participants. Collective rituals are discussed as a form of collective self-affirmation that may have reduced defensiveness and led nationalistic individuals to behave according to the predominant values within a society.https://www.rips-irsp.com/articles/10.5334/irsp.291
P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments
Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes
Morbilidad percibida por pobladores del Bañado Sur previa a la implementación de la Vigilancia Comunitaria del SÃndrome Febril Agudo, utilizando las TecnologÃas de la Información y Comunicación (TICs)
El Ministerio de Salud Pública y Bienestar Social conjuntamente con la UniversidadNacional de Asunción, con el apoyo técnico de la Universidad del PaÃs Vasco de España,han desarrollado un sistema de vigilancia comunitaria para SÃndrome Febril Agudollamado BONIS, implementado en forma piloto en el área del Bañado Sur de Asunción-Paraguay en la Unidad de Salud Familiar (USF) de Centro de Ayuda Mutua y Salud paraTodos (CAMSAT). Previa a la implementación del sistema se realizó una encuestatelefónica del 18 al 28 de Febrero de 2010 para establecer una lÃnea de base sobreaspectos de la salud de la población. Trescientos sesenta y seis jefes de hogares fueronencuestados, de los cuales el 76,2% era del sexo femenino. En 246 hogares (70%) sereportó por lo menos una persona con alguna enfermedad. De las 438 personas enfermasreportadas, el 36,3% declaró tener hipertensión arterial, 13,5% alergias, 12,8% sÃndromemetabólico, 10% enfermedad del corazón, 7,8% asma, 6,8% diabetes y 5,9% sÃndromerespiratorio agudo. Un bajo número de personas reportó sÃntomas compatibles consÃndromes febriles como el dengue. Las patologÃas que afectan a esta comunidad sonsimilares al resto del paÃs. Se puso en evidencia la necesidad de fortalecer los programasde promoción dirigidas a identificar y notificar los casos sospechosos de dengue. AsÃmismo, se pudo percibir la buena predisposición de los pobladores para colaborar en lasolución de problemas relacionados a su salud, lo que propicia la implementación de lavigilancia comunitaria basada en las TICs
ProSAAS-Derived Peptides are Colocalized with Neuropeptide Y and Function as Neuropeptides in the Regulation of Food Intake
ProSAAS is the precursor of a number of peptides that have been proposed to function as neuropeptides. Because proSAAS mRNA is highly expressed in the arcuate nucleus of the hypothalamus, we examined the cellular localization of several proSAAS-derived peptides in the mouse hypothalamus and found that they generally colocalized with neuropeptide Y (NPY), but not α-melanocyte stimulating hormone. However, unlike proNPY mRNA, which is upregulated by food deprivation in the mediobasal hypothalamus, neither proSAAS mRNA nor proSAAS-derived peptides were significantly altered by 1–2 days of food deprivation in wild-type mice. Furthermore, while proSAAS mRNA levels in the mediobasal hypothalamus were significantly lower in Cpefat/fat mice as compared to wild-type littermates, proNPY mRNA levels in the mediobasal hypothalamus and in other subregions of the hypothalamus were not significantly different between wild-type and Cpefat/fat mice. Intracerebroventricular injections of antibodies to two proSAAS-derived peptides (big LEN and PEN) significantly reduced food intake in fasted mice, while injections of antibodies to two other proSAAS-derived peptides (little LEN and little SAAS) did not. Whole-cell patch clamp recordings of parvocellular neurons in the hypothalamic paraventricular nucleus, a target of arcuate NPY projections, showed that big LEN produced a rapid and reversible inhibition of synaptic glutamate release that was spike independent and abolished by blocking postsynaptic G protein activity, suggesting the involvement of a postsynaptic G protein-coupled receptor and the release of a retrograde synaptic messenger. Taken together with previous studies, these findings support a role for proSAAS-derived peptides such as big LEN as neuropeptides regulating food intake
The multiple roles of myelin protein genes during the development of the oligodendrocyte
It has become clear that the products of several of the earliest identified myelin protein genes perform functions that extend beyond the myelin sheath. Interestingly, these myelin proteins, which comprise proteolipid protein, 2′,3′-cyclic nucleotide 3′-phosphodiesterase and the classic and golli MBPs (myelin basic proteins), play important roles during different stages of oligodendroglial development. These non-myelin-related functions are varied and include roles in the regulation of process outgrowth, migration, RNA transport, oligodendrocyte survival and ion channel modulation. However, despite the wide variety of cellular functions performed by the different myelin genes, the route by which they achieve these many functions seems to converge upon a common mechanism involving Ca2+ regulation, cytoskeletal rearrangements and signal transduction. In the present review, the newly emerging functions of these myelin proteins will be described, and these will then be discussed in the context of their contribution to oligodendroglial development
Local spatial regression models : a comparative analysis on soil contamination
Spatial data analysis focuses on both attribute and locational information. Local analyses deal with differences across space whereas global analyses deal with similarities across space. This paper addresses an experimental comparative study to analyse the spatial data by some weighted local regression models. Five local regression models have been developed and their estimation capacities have been evaluated. The experimental studies showed that integration of objective function based fuzzy clustering to geostatistics provides some accurate and general models structures. In particular, the estimation performance of the model established by combining the extended fuzzy clustering algorithm and standard regional dependence function is higher than that of the other regression models. Finally, it could be suggested that the hybrid regression models developed by combining soft computing and geostatistics could be used in spatial data analysis
A comparison of ARMS and direct sequencing for EGFR mutation analysis and Tyrosine Kinase Inhibitors treatment prediction in body fluid samples of Non-Small-Cell Lung Cancer patients
<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (<it>EGFR</it>) mutation is strongly associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable. Body fluid was considered to be a feasible substitute for the analysis, but arising problems in clinical practice such as relatively lower mutation rate and poor clinical correlation are not yet fully resolved.</p> <p>Method</p> <p>In this study, 50 patients (32 pleural fluids and 18 plasmas) with TKIs therapy experience and with direct sequencing results were selected from 220 patients for further analysis. The <it>EGFR </it>mutation status was re-evaluated by Amplification Refractory Mutation System (ARMS), and the clinical outcomes of TKIs were analyzed retrospectively.</p> <p>Results</p> <p>As compared with direct sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The objective response rate (ORR) of positive patients was significant, 81.3% (direct sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma. Notably, even reclassified by ARMS, the ORR for negative patients was still relatively high, 60% for pleural fluids and 46.2% for plasma.</p> <p>Conclusions</p> <p>When using body fluids for <it>EGFR </it>mutation analysis, positive result is consistently a good indicator for TKIs therapy, and the predictive effect was no less than that of tumor tissue, no matter what method was employed. However, even reclassified by ARMS, the correlation between negative results and clinical outcome of TKIs was still unsatisfied. The results indicated that false negative mutation still existed, which may be settled by using method with sensitivity to single DNA molecule or by optimizing the extraction procedure with RNA or CTC to ensure adequate amount of tumor-derived nucleic acid for the test.</p
Oxidative Phosphorylation Is a Metabolic Vulnerability in Chemotherapy-Resistant Triple-Negative Breast Cance
Oxidative phosphorylation (OXPHOS) is an active metabolic pathway in many cancers. RNA from pretreatment biopsies from patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy demonstrated that the top canonical pathway associated with worse outcome was higher expression of OXPHOS signature. IACS-10759, a novel inhibitor of OXPHOS, stabilized growth in multiple TNBC patient-derived xenografts (PDX). On gene expression profiling, all of the sensitive models displayed a basal-like 1 TNBC subtype. Expression of mitochondrial genes was significantly higher in sensitive PDXs. An in vivo functional genomics screen to identify synthetic lethal targets in tumors treated with IACS-10759 found several potential targets, including CDK4. We validated the antitumor efficacy of the combination of palbociclib, a CDK4/6 inhibitor, and IACS-10759 in vitro and in vivo. In addition, the combination of IACS-10759 and multikinase inhibitor cabozantinib had improved antitumor efficacy. Taken together, our data suggest that OXPHOS is a metabolic vulnerability in TNBC that may be leveraged with novel therapeutics in combination regimens. SIGNIFICANCE: These findings suggest that triple-negative breast cancer is highly reliant on OXPHOS and that inhibiting OXPHOS may be a novel approach to enhance efficacy of several targeted therapies
Validation of a locked nucleic acid based wild-type blocking PCR for the detection of EGFR exon 18/19 mutations
- …