The Rotational Spectrum of Tyrosine

Producción CientíficaIn this work neutral tyrosine has been generated in the gas phase by laser ablation of solid samples, and its most abundant conformers characterized through their rotational spectra. Their identification has been made by comparison between the experimental and ab initio values of the rotational and quadrupole coupling constants. Both conformers are stabilized by an O–H•••N hydrogen bond established within the amino acid skeleton chain and an additional weak N–H•••π hydrogen bond. The observed conformers differ in the orientation of the phenolic −OH group.Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA175U13

Ensayos de validación de la técnica de quimioluminiscencia SPIN-CLIA™ para su uso en la detección de marcadores tumorales serológicos

Contexto: Los biomarcadores de cáncer tienen una especificidad y sensibilidad muy limitadas como para ser utilizados en el diagnóstico clínico. Estos biomarcadores requieren un sistema preciso para evaluar sus concentraciones en muestras de suero (2). Hoy en día, las técnicas que emplean los ensayos quimioluminiscentes (CLIA) representan un modo importante de detectar y cuantificar estos biomarcadores (3,5). Nuevos métodos como la técnica SPIN-CLIA™ pueden mejorar los sistemas actuales.El objetivo de este trabajo fue validar la viabilidad de la nueva técnica SPIN-CLIA™ para detectar biomarcadores de cáncer y observar sus ventajas sobre otros métodos de detección de biomarcadores tumorales convencionales. El marcador tumoral CA 15-3 es un candidato perfecto para ser utilizado como un biomarcador habitual para el cáncer de mama una vez que la nueva metodología haya sido optimizada (1). Metodología: En primer lugar, se realizó un análisis cromogénico inicial a diferentes concentraciones de anticuerpos para conocer la concentración óptima necesaria para detectar el marcador tumoral CA 15-3. En segundo lugar, para demostrar el correcto funcionamiento del ensayo de quimioluminiscencia SPIN-CLIA™ se realizó una curva de calibración utilizando un intervalo de concentraciones del marcador CA 15-3 comprendido entre 0 y 60U/mL.Resultados: El ensayo cromogénico demostró que una concentración del anticuerpo de detección de 0,05µg/mL era la mejor para detectar el marcador tumoral CA 15-3. El ensayo de quimioluminiscencia SPIN-CLIA™ demostró una relación entre las diferentes concentraciones del marcador tumoral CA 15-3 y la cantidad de luz medida, con una correlación en la curva de calibración de dicho marcador del 98,61%. El intervalo de detección empleado para este marcador tumoral fue el adecuado, ya que el valor normal de este marcador en pacientes sin cáncer es inferior a 30U/mL. Por encima de este valor, se considera una anomalía y el paciente corre el riesgo de padecer cáncer de mama (4).Conclusiones: Realizar un ensayo cromogénico es importante cuando se está detectando la concentración mínima de anticuerpos durante un proceso de detección por inmunoensayo de quimioluminiscencia. La técnica SPIN-CLIA™ puede representar un método prometedor para la futura detección y cuantificación de biomarcadores tumorales

4,4′-Dicyano- versus 4,4′-Difluoro-BODIPYs in Chemoselective Postfunctionalization Reactions: Synthetic Advantages and Applications

The presence of F or CN substituents at boron in BODIPYs causes a dramatic effect on their reactivity, which allows their chemoselective postfunctionalization. Thus, whereas 1,3,5,7-tetramethyl B(CN)2-BODIPYs displayed enhanced reactivity in Knoevenagel condensations with aldehydes, the corresponding BF2-BODIPYs can experience selective aromatic electrophilic substitution (SEAr) reactions in the presence of the former. These (selective) reactions have been employed in the preparation of BODIPY dimers and tetramers, with balanced fluorescence and singlet oxygen formation, and all-BODIPY trimers and heptamers, with potential application as light-harvesting systems.The authors gratefully acknowledge Spanish Ministerio de Ciencia e Innovación (MCIN)/Agencia Estatal de Investigación (AEI) Grant PID2021-122504NB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe and Grants PID2020-114755GB-C31 and -C33 funded by MCIN/AEI. The authors thank the Gobierno Vasco (Project IT1639-22) for financial support. The authors are indebted to Ms. Marina Rodríguez (IQOG-CSIC) for skillful technical support

Evaluación del uso de microorganismos de montaña activados en el cultivo de rosas, Zinacantán, Chiapas, México

The research was carried out in the municipality of Zinacantán, Chiapas, Mexico, in an area of rose’s production in plastic greenhouses, located at 16° 45′ 35″ N latitude, 92° 43′ 20″ W and at an altitude of 2162 masl. The climate is dub-humid temperate with rains in summer, the temperature reaches an average of 21 °C and the accumulated annual average precipitation is 599 mm. The objective of this study was to evaluate the effect on plant growth of Activated Mountain Microorganisms (MMA) sprayed under two doses (10 % and 20 %) and two spraying frequencies (every 8 and every 15 days). The four treatments were evaluated under the conventional rose crop management, and one control of conventional crop management and another control of ecological crop management were included. The six treatments were set up in a completely randomized design, each treatment consisting of a seedbed, where two rows of rose plants were planted under a three-point planting system, each bed containing a total of 530 plants. The results indicate that the bio-fertilizer MMA at doses of 20 % sprayed every 15 days, and the MMA at doses of 20 % sprayed every 8 days were statistically superior, for stem length, stem diameter, number of leaves, length of leaves, width of leaves, flower size, and shelf life. Therefore, it is concluded that MMA at 20 % dose improves rose production indicators under greenhouse conditions.La investigación se desarrolló en el municipio de Zinacantán, Chiapas, México, en invernaderos de producción de rosas, localizado a 16° 45′ 35″ latitud norte, 92° 43′ 20″, longitud oeste y a una altitud de 2.162 msnm.  El clima de esta región es templado, subhúmedo, con lluvias en verano, con una temperatura media de 21 °C y una precipitación media anual acumulada de 599 mm. El objetivo de este estudio fue evaluar el efecto en el crecimiento de la planta de la utilización de microorganismos de montaña activados (MMA), asperjados bajo dos dosis (10% y 20 %) y dos frecuencias de aplicación (cada 8 y cada 25 días). Los tratamientos se evaluaron bajo el manejo convencional de rosas de la región, y se incluyéron un testigo de manejo convencional y un testigo de manejo ecológico, Los seis tratamientos se expusieron en un diseño completamente al azar, cada uno constituido por una cama de siembra, donde se sembraron dos filas de plantas de rosas bajo un sistema de plantación de tres bolillos; y cada cama presentó un total de 530 plantas. Los resultados indican que los tratamientos de uso del biofertilizante MMA en manejo convencional al 20 % cada 15 días y el tratamiento de MMA al 20% cada 8 días manejado de forma orgánica, fueron estadísticamente mejores para las variables: longitud del tallo, diámetro del tallo, número de hojas, largo de hojas, ancho de hojas, tamaño de la flor y mayor vida de anaquel. Se concluye que la dosis de 20 % de MMA favorece los indicadores de producción de rosas bajo condiciones de invernadero

Gas6, una proteína dependiente de la vitamina k implicada en la respuesta a la infección por sars-cov-2

Trabajo presentado en el LXIII Congreso Nacional SEHH/ XXXVII Congreso Nacional SETH, celebrado en Pamplona (Navarra) del 14 al 16 de octubre de 2021

Molecular genetic heterogeneity in undifferentiated endometrial carcinomas

Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value

Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome

Producción CientíficaBackground: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.Ministerio de Ciencia, Innovación y Universidades (project RTI2018-095672-B-I00)Instituto de Salud Carlos III - Fondo de Investigación Sanitaria (grants PI15/00531 and PI19/01410)Fundació La Marató TV3 (grants 20153030 and 20153031)Consejo Superior de Investigaciones Científicas (project CSIC-COV19-016/202020E155)Junta de Castilla y León (project 07.04.467B04.74011.0

Mesothelial-to-mesenchymal transition as a possible therapeutic target in peritoneal metastasis of ovarian cancer.

Peritoneal dissemination is the primary metastatic route of ovarian cancer (OvCa), and is often accompanied by the accumulation of ascitic fluid. The peritoneal cavity is lined by mesothelial cells (MCs), which can be converted into carcinoma-associated fibroblasts (CAFs) through mesothelial-to-mesenchymal transition (MMT). Here, we demonstrate that MCs isolated from ascitic fluid (AFMCs) of OvCa patients with peritoneal implants also undergo MMT and promote subcutaneous tumour growth in mice. RNA sequencing of AFMCs revealed that MMT-related pathways – including transforming growth factor (TGF)- signalling – are differentially regulated, and a gene signature was verified in peritoneal implants from OvCa patients. In a mouse model, pre-induction of MMT resulted in increased peritoneal tumour growth, whereas interfering with the TGF- receptor reduced metastasis. MC-derived CAFs showed activation of Smad-dependent TGF- signalling, which was disrupted in OvCa cells, despite their elevated TGF- production. Accordingly, targeting Smad-dependent signalling in the peritoneal pre-metastatic niche in mice reduced tumour colonization, suggesting that Smad-dependent MMT could be crucial in peritoneal carcinomatosis. Together, these results indicate that bidirectional communication between OvCa cells and MC-derived CAFs, via TGF--mediated MMT, seems to be crucial to form a suitable metastatic niche. We suggest MMT as a possible target for therapeutic intervention and a potential source of biomarkers for improving OvCa diagnosis and/or prognosis.post-print2310 K

The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)

Early stages are under-represented in studies on the molecular and immune features of high-grade serous ovarian carcinoma (HGSOC), and specific studies focused on early-stage HGSOC are required for a better prognostic stratification and to personalize chemotherapy. The aim of this study was to determine the prognostic significance of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs), tumoral cell PD-L1 expression, BRCA mutational status and tumor mutation burden (TMB) in early-stage HGSOC. A retrospective study was performed on stage I and II HGSOC from the Molecular Reclassification of Early Stages of Ovarian Cancer (RECLAMO) cohort from the Spanish Group of Ovarian Cancer Research (GEICO). Centralized histological typing was performed based on morphological and immunohistochemical features. Intraepithelial (i) and stromal (s) CD8+ and CD4+ T cells and PD-L1 were evaluated on tissue microarrays by immunohistochemistry. BRCA1 and BRCA2 mutation status and TMB were analyzed in tumor DNA using next-generation sequencing. The study included 124 tumors. High iCD8+ (>20 TILs/core), low/intermediate CD4+ (35/core) were associated with favorable outcomes. Tumor cell PD-L1 expression (TPS ≥ 1) was present in only 8% of tumors. In total, 11 (16%) and 6 (9%) out of 69 HGSOC tested carried pathogenic or likely pathogenic BRCA1 or BRCA2 mutations, respectively. Median TMB of 40 tumors analyzed was 5.04 mutations/Mb and only 6 tumors had 10 or more mutations/Mb. BRCA status and TMB were not associated with TILs or prognosis. When compared with studies on advanced HGSOC, our results suggested that prognostic variables differed according to stage and that more studies focused on early stages of HGSOC are needed to better stratify these tumors: This work was supported by Instituto de Salud Carlos III (ISCIII) (grants PI19/01331, PI22/01892 and PMP22/00054); CIBERONC (grant CB16/12/00316); European Development Re gional Fund ‘A way to achieve Europe’ (FEDER), Spanish Group of Research in Ovarian Cancer (GEICO group); and by the Spanish Association Against Cancer Scientific Foundation (AECC)