Caracterización por Proteómica del tejido muscular esquelético como órgano endocrino

Comunicaciones a congreso

Nutrición y secreción gástrica: un nuevo enfoque proteómico

Comunicación a congreso

El complejo volcánico cerros Bravos, región de Maricunga, Chile: Geología, alteración hidrotermal y mineralización

El Complejo Volcánico Cerros Bravos (Oligoceno-Mioceno) es un conjunto de lavas y domos dacítico-andesíticos calcoalcalinos de gran extensión (450 km2) ubicado a unos 140 km al este de Copiapó, Chile, que integra la Franja de Maricunga, cadena volcánica neógena que representa un arco pluto-volcánico de margen continental. Los análisis radiométricos K-Ar señalan que el complejo volcánico Cerros Bravos estuvo activo entre los 26-18 Ma (Oligoceno-Mioceno inferior) en tanto que el complejo La Coipa registra actividad hasta el Mioceno medio (15 Ma), y desde allí hacia el sur los centros volcánicos presentan edades entre 16 y 6 Ma. El complejo hospeda la zona de alteración hidrotermal del Prospecto Esperanza, sistema epitermal del tipo sulfato-ácido con mineralización de oro y plata controlada estructuralmente y asociada a una intensa silicificación y argilización con calcolinita, alunita y jarosita, con edades radiométricas K-Ar entre 20-18 Ma. Los estudios isotópicos de Pb realizados en rocas y sulfuros de los depósitos de la Franja de Maricunga indican que las rocas ígneas del Oligoceno-Mioceno son una mezcla de manto subcortical máfico o material cortical y material cortical radiogénico. El Pb en los depósitos de metales preciosos de la franja es dominado por una fuente como las rocas ígneas huéspedes y, localmente, otras rocas huéspedes (sedimentarias triásicas) pueden haber contribuido con Pb durante la circulación hidrotermal en ambiente cercano a la superficie. La aplicación de las metodologías de la teledetección en imágenes Landsat TM en la zona de Maricunga demostró ser una herramienta eficaz para la exploración ya que permitió destacar perfectamente las zonas de alteración hidrotermal presentes en el área y la elaboración de mapas de alta confiabilidad a escala regional

Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma

Response kinetics is not well-established as a prognostic marker in multiple myeloma (MM). We developed a mathematical model to assess the prognostic value of serum monoclonal component (MC) response kinetics during 6 induction cycles in 373 newly diagnosed MM patients. The model calculated a resistance parameter that reflects the stagnation in the response after an initial descent, dividing the patients into two kinetics categories with significantly different progression-free survival (PFS). Introduction: Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). Materials and Methods: We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a resistance parameter that reflects the stagnation in the response after an initial descent. Results: Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P =.02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P =.02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P <.002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. Conclusion: This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies. (C) 2022 The Authors. Published by Elsevier Inc

BCR-ABL1-induced expression of HSPA8 promotes cell survival in chronic myeloid leukaemia

In order to determine new signal transduction pathways implicated in chronic myeloid leukaemia (CML), we performed a gene expression profile comparison between CD34+ cells from CML patients and healthy donors. Functional studies were performed using the Mo7e and Mo7e-p210 cell lines. Expression of CCND1 (Cyclin D1), as well as the chaperone HSPA8, which is important for regulation of CCND1, were significantly upregulated in CD34+ CML cells. Upregulation of HSPA8 was dependent, at least in part, on STAT5 (signal transducer and activator of transcrition 5)-dependent transcriptional activation, as demonstrated by chromatin immunoprecipitation. The presence of HSPA8 in the nuclear protein fraction as well as its binding to CCND1 suggests that it may contribute to stabilization of the CCND1/CDK4 complex, which, in turn, may participate in proliferation of CML cells. Treatment of CML cells with the specific HSPA8 inhibitor 15-deoxyspergualin induced inhibition of CML cell viability but did not induce apoptosis. In conclusion, our studies suggest that STAT5-mediated activation of HSPA8 induces nuclear translocation and activation of the CCND1/CDK4 complex leading to increased proliferation of CML cells, deciphering a new pathway implicated in CML and supporting a potential role of chaperone inhibitors in the treatment of CML

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.Tis project was funded in part by CRIS CANCER FOUNDATION

Multilateral benefit-sharing from digital sequence information will support both science and biodiversity conservation

Open access to sequence data is a cornerstone of biology and biodiversity research, but has created tension under the United Nations Convention on Biological Diversity (CBD). Policy decisions could compromise research and development, unless a practical multilateral solution is implemented.This workwas funded by the German Federal Ministry of Education and Research (BMBF) WiLDSI 031B0862 (A.H.S., J.O., and J.F.) and Horizon Europe EVA-GLOBAL 871029 (A.H.S.). I.K.M. was supported by the National Center for Biotechnology Information of the National Library of Medicine, National Institutes of Health

Summary of Pb isotopic compositions in epitermal precios metal deposits, Orcopampa área of Southern Peru, Berenguela area of Western Bolivia, and the Maricunga belt in north-central Chile

The Mesozoic and Cenozoic Central Andes are divided into three Pb isotopic provinces, based upon the Pb isotopic compositions of ore minerals (MacFarlane et al., 1990). Macfarlane et al., 0990), furthermore, argue that the Pb isotopic compositions of the ore minerals reílect those of the igneous rocks associated with the deposits. Province I lies along the coast of Perú, Chile, and westernmost Bolivia. Mcsozoic and early Cenozoic volcapic and plutonic ares built upon a rifted and thinned continental margin dominate this province. Three subprovinces are distinguished based upon slight differences in Pb isotopic compositions. Province la includes northern and central Chile south of 19°S; province lb includes central Perú north of 13°S; whereas province le includes central and southern Perú between the two other subprovinces. Province II lies in the high Andes of central Perú and, perhaps, in northern Chile and Argentina, where miogeoclinal sedimentary rocks crop out and the crust underwent a lower magnitude of extension in the early Mesozoic. This region generally represents a back-arc position relative to the Mesozoic and early Cenozoic magmatic ares, and extensive magmatism related to the Andean cycle has only occurred since the Oligocene. Paleozoic ares are the dominant basement in this province. Province III lies in the Cordillera Oriental and Altiplano of Perú and Bolivia where Paleozoic, Mesozoic, and Cenozoic sedimentary rocks are multiply dcformed by thrust faults. Magma ti-e episodes of Triassic to Jurassic and Oligocene to Miocene age are documented. Proterozoic rocks of the Brazilian shicld are underthrust beneath the Cordillera Oriental, with the youngest shortcning episode beginning in the Oligocene. Province III is subdivided into two subprovinces: ma lies in southeastern Perú where both episodes of magmatism occurred, whereas IIIb lies in Bolivia where magmatism is primarily of Oligocene and Miocene age. Pb isotopic compositions for Province I are slightly less radiogenic than those from province II, whereas province III isotopic compositions are much more varied with consistently higher 207Pb/ 204pb and 208pb/204pb at a given 206pb/ 204pb_Province I Pb isotopic compositions (206pb/ 204pb =18.21-18.82; 207Pb/2<YíPb = 15.55-15.69; 2º8Pb/2º4Pb = 38.11-38.95) overlap with and extend below the average crustal growth curve of Staccy and Kramers (1975) on the uranogenic diagram (207pb/204pb versus 206pb/204Pb). Province lT Pb isotopic compositions (206pb/2<Yípb = 18.76-18.90; 207pb/204pb 15.62-15.73; 208pb/204pb 38.63-39.16) and Province III Pb isotopic compositions (206pb/204Pb 17.97-25.18; 207pb/204pb 15.51-16.00; 208pb/20/4pb 37.71-40.07) lie above the average crustal growth curve on the same diagram. The Pb isotopic compositions from these last two provinces require contribution from a high mu (238U/204pb) Proterozoic or Archean source. On the thorogcnic Pb isotopic variation diagram (208Pb/ 204Pb versus 206pb/204pb), isotopic compositions for province I, 11, and IIIa scatter along the average crustal growth curve of Stacey and Kramers (1975-) indicating that a time averaged Th/U ratio - 4 (the average cristal value) characterizes the Central Andes. Pb isotopic compositions for province IIIb are the most radiogenic and also the most heterogeneous. The variable radiogenic Pb isotopic compositions of province III suggcst heterogeneous upper cristal sources, whereas the isotopic compositions of province I probably reflect a mafic cristal lithospheric source, probably modified by subduction processcs. Province II isotopic compositions conceivably represent a mix betwecn the two model reservoirs

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services

Background: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist’s perception of its quality has not been evaluated. Methods: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of cen‑ tral tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. Results: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfed in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores>70/100 from the frst procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies : a multicenter study in 21 Spanish pulmonology services

Background: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. Methods: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. Results: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. Conclusions: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images