Pilot study: prognostic biomarkers for interstitial lung disease in systemic sclerosis

Interstitial lung disease is one of the main causes of mortality in Systemic Sclerosis. The course of the disease is clinically variable where patients can suffer from a range of stable disease to rapid progressive clinical deterioration. Therefore, it is important to identify biomarkers that can predict the clinical course of patients in order to provide early treatment. We evaluated 1129 proteins utilizing novel high-throughput SOMAlogic proteomic technology from the serum of 13 LSSc, 13 progressive ILD and 11 stable ILD patients. Calpain-1 was significantly elevated in progressive ILD patients (median 15129 RFU, 11091-24561) compared to LSSc patients (12759, 9904-15498, p=0.0015) and stable ILD patients (11876, 10271-14249, p=0.0005). Coagulation Factor V was significantly lower in the progressive ILD patients (7161 RFU, 2140-8296) compared to LSSc patients (10311 RFU, 6396-12260, p=0.001) and stable ILD patients (9646 RFU, 6510-11941, p=0.0016). The combination of Coagulation Factor V and Calpain-1 produced an area under the curve of 0.97 (95% CI, 0.921-0.99), sensitivity of 99% and specificity of 91% for the identification of progressive ILD. We have identified a combination of proteins that show potential to be prognostic biomarkers for ILD in SSc.2016-12-31T00:00:00

The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients

Introduction\ud HLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characterized by activation of ER stress/UPR and inflammation, the goal of this study was to assess whether the presence of HLA-B*35 contributes to those characteristics.\ud \ud Methods\ud PBMCs were purified from healthy controls (n = 49 HC) and lcSSc patients, (n = 44 with PAH, n = 53 without PAH). PBMCs from each group were stratified for the presence of HLA-B*35. Global changes in gene expression in response to HLA-B*35, HLA-B*8 or empty lentivirus were investigated by microarray analysis in HC PBMCs. Total RNA was extracted and qPCR was performed to measure gene expression.\ud \ud Results\ud ER stress markers, in particular the chaperones BiP and DNAJB1 were significantly elevated in PBMC samples carrying the HLA-B*35 allele. IL-6 expression was also significantly increased in HLA-B*35 lcSSc PBMCs and positively correlated with ER stress markers. Likewise, HMGB1 was increased in HLA-B*35-positive lcSSc PBMCs. Global gene expression analysis was used to further probe the role of HLA-B*35. Among genes downregulated by HLA-B*35 lentivirus were genes related to complement (C1QB, C1QC), cell cycle (CDNK1A) and apoptosis (Bax, Gadd45). Interestingly, complement genes (C1QC and C1QB) showed elevated expression in lcSSc without PAH, but were expressed at the low levels in lcSSc-PAH. The presence of HLA-B*35 correlated with the decreased expression of the complement genes. Furthermore, HLA-B*35 correlated with decreased expression of cyclin inhibitors (p21, p57) and pro-apoptotic genes (Bax, Gadd45) in lcSSc B35 subjects. FYN, a tyrosine kinase involved in proliferation of immune cells, was among the genes that were positively regulated by HLA-B*35. HLA-B*35 correlated with increased levels of FYN in lcSSc PBMCs.\ud \ud Conclusions\ud Our study demonstrates that HLA-B*35 contributes to the dysregulated expression of selected ER stress, inflammation and proliferation related genes in lcSSc patient PBMCs, as well as healthy individuals, thus supporting a pathogenic role of HLA-B*35 in the development of PAH in SSc patients

Aplicación de la metodología input-output al análisis económico de un área de montaña

[ES] Aplicación de la metodología input-output al análisis económico de un área de montañ

La «justicia» en el reparto: las misivas matemáticas mantenidas entre Fermat y Pascal

La probabilidad puede llegar a ser un concepto complejo de introducir dado su carácter abstracto. Fueron las preguntas que se hacían los jugadores de azar en el siglo XVII las que motivaron el estudio de la probabilidad que conocemos en la actualidad. En este trabajo se presenta una idea de aula en la que se emplea una metodología activa de Aprendizaje Basado en Juegos caracterizada por su estilo manipulativo, significativo y constructivista que, enfocado desde un punto de vista solidario, puede llegar a ser muy enriquecedor para los alumnos de educación secundaria, así como eficaz para la comprensión de los conceptos relacionados con la probabilidad

Epsilon

Título, resumen y palabras clave en español e inglésResumen basado en el de la publicaciónLa probabilidad puede llegar a ser un concepto complejo de introducir dado su carácter abstracto. Fueron las preguntas que se hacían los jugadores de azar en el siglo XVII las que motivaron el estudio de la probabilidad que conocemos en la actualidad. Se presenta una idea de aula en la que se emplea una metodología activa de Aprendizaje Basado en Juegos caracterizada por su estilo manipulativo, significativo y constructivista que, enfocado desde un punto de vista solidario, puede llegar a ser muy enriquecedor para los alumnos de educación secundaria.ES

Transcriptional vulnerabilities of striatal neurons in human and rodent models of Huntington’s disease

In human and mouse models of Huntington’s disease, Matsushima, Pineda et al. show, using snRNAsequencing, the two axes defining identities of striatal projection neurons are multiplexed and differentially compromised, calling for distinct therapies

Cocaethylene: A Unique Cocaine Metabolite Displays High Affinity for the Dopamine Transporter

: Concurrent cocaine and alcohol use is common practice in the general population, as indicated by recent prevalence studies. In the presence of ethyl alcohol, cocaine is metabolized to its ethyl homolog, cocaethylene. The transesterification of cocaine and ethanol to cocaethylene takes place in the liver and represents a novel metabolic reaction. Cocaethylene was detected in postmortem blood, liver, and neurological tissues in concentrations equal to and sometimes exceeding those of cocaine. In vitro binding studies demonstrate that cocaethylene has a pharmacological profile similar but not identical to that of cocaine at monoamine transport sites assayed in the human brain. Cocaethylene was equipotent to cocaine at inhibiting [3H]mazindol binding to the dopamine transporter. The blockade of dopamine reuptake in the synaptic cleft by cocaethylene may account for the enhanced euphoria associated with combined alcohol and cocaine abuse

The development of writing skills in master's level english as a foreign language teacher education programs: insight into the process and perceptions from stakeholders in Colombian universities

This study explored the perception of students, graduates and supervisors on students' development of general writing skills and academic writing skills through the completion of the master's thesis in teacher education programs in Colombia. In-depth interviews were conducted and online surveys were completed by participants from seven teacher education programs in this mixed methods study. Also, this study examined the process of writing the thesis through the analyses of drafts from three graduates. The findings of this study show how students' development of academic writing skills is grounded on their initial general writing skills and is realized through the appropriation of the thesis genre. This development follows different paths according to students' writing ability. This study argues that there are factors at the personal, supervision, and program levels that contribute to this development. Similarly, the development of these writing skills has an impact on the individual, their teaching, and their academic communities. (Published By University of Alabama Libraries

Serum biomarker for diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis

Abstract Background Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is one of the leading causes of death in SSc. Identification of a serum-based proteomic diagnostic biomarker for SSc-PAH would allow for rapid non-invasive screening and could positively impact patient survival. Identification and validation of novel proteins could potentially facilitate the identification of SSc-PAH, and might also point to important protein mediators in pathogenesis. Methods Thirteen treatment-naïve SSc-PAH patients had serum collected at time of diagnosis and were used as the discovery cohort for the protein-expression biomarker. Two proteins, Midkine and Follistatin-like 3 (FSTL3) were then validated by enzyme-linked immunosorbent assays. Midkine and FSTL3 were tested in combination to identify SSc-PAH and were validated in two independent cohorts of SSc-PAH (n = 23, n = 11). Results Eighty-two proteins were found to be differentially regulated in SSc-PAH sera. Two proteins (Midkine and FSTL3) were also shown to be elevated in publicly available data and their expression was evaluated in independent cohorts. In the validation cohorts, the combination of Midkine and FSTL3 had an area under the receiver operating characteristic curve (AUC) of 0.85 and 0.92 with respective corresponding measures of sensitivity of 76% and 91%, and specificity measures of 76% and 80%. Conclusions These findings indicate that there is a clear delineation between overall protein expression in sera from SSc patients and those with SSc-PAH. The combination of Midkine and FSTL3 can serve as an SSc-PAH biomarker and are potential drug targets for this rare disease population

Otro título: [Tertulia Literaria Hispanoamericana]. Sesión 355, 18 de abril de 1961

Rafael Montesinos. Manuel Mantero. Julio Alfredo EgeaMadrid, Instituto de Cultura Hispánica. Martes, 18 de abril a las ocho menos cuarto de la tardeRafael Montesinos anuncia el acto de la tertulia y comenta que Manuel Mantero leerá la presentación de Arturo Medina por no poder acudir al acto. 00.45: Presentación de Manuel Mantero – Min. 04.02: Toma la palabra Julio Alfredo Egea, quien lee algunos de sus poemas como: “Poema del niño mudo que murió en otoño”, “Esperando al hijo”, “La llegada”, “Tiempo”, “Equipaje”… -- Min. 26.04: Incompleto