Copper-Catalyzed Oxidation of Alkenes and Heterocycles

A variety of copper species catalyze the allylic oxidation of olefins and the introduction of an ester group at the α-position of a heterocycle. Both transformations are closely related in terms of reaction conditions and radical species involved. This short review highlights the progress made in these two types of oxidations, emphasizing work that has occurred within the last fifteen years

Copper-iron mixed oxide supported onto cordierite honeycomb as a heterogeneous catalyst in the Kharasch-Sosnovsky oxidation of cyclohexene

A copper-iron mixed oxide was deposited by the washcoating procedure over cordierite honeycomb monoliths for its use as a heterogeneous catalyst in organic synthesis processes. In particular, the prepared catalyst, characterized by techniques such as X-ray fluorescence, X-ray diffraction, SEM-EDS, laser granulometry, adherence tests, Temperature-Programmed Oxidation and Temperature-Programmed Reduction, showed an excellent yield and stability in the selective production of the allylic ester derived from the Kharasch-Sosnovsky oxidation of cyclohexene with benzoic acid. The use of a structured catalyst here proposed opens up an interesting alternative to homogeneous catalysis in the field of synthetic chemistry. © 2021 The AuthorsThe authors thank the Ministry of Economy and Competitiveness of Spain (Projects MAT2017-85-719-R , and AGL2017-88083-R ), the Junta de Andalucía ( FQM-110 and FQM-169 groups), and the Institute of Electron Microscopy and Materials (IMEYMAT) of Cadiz University (UCA) (Projects HOMOGREEN and NUPRECAT) for their financial support. They also acknowledge the SC-ICYT of the UCA for using its XRD NMR, and electron microscopy division facilities

Carbon integral honeycomb monoliths as support of copper catalysts in the Kharasch–Sosnovsky oxidation of cyclohexene

Carbon integral honeycomb monoliths prepared from a natural coal were employed as support of copper catalysts for organic synthetic purposes. In particular good to excellent yields (60–100% as function of the carboxylic acid employed) were obtained in the preparation of allylic esters by the Kharasch–Sosnovsky oxidation of cyclohexene. Different characterization techniques such as chemical analysis by Inductively Coupled Plasma Spectroscopy, nitrogen physisorption, X-ray Diffraction with Rietveld analysis, X-ray Photoelectron and Raman Spectroscopies, Temperature-Programmed Reduction and Scanning Electron Microscopy allowed finding that key parameters such as textural properties, degree of copper precursor decomposition and active phase homogeneity and dispersion can be modulated as function of a simple synthetic variable: the method used to dry the monoliths after impregnation with the metal precursor, either conventional or using microwaves. The results obtained allow understanding the key role of the nature and chemical surrounding (O2 anions or OH groups) of Cu2+ ions in the catalytic activity in the reaction investigated as well as the operating deactivation mechanisms. The use of the structured catalysts here proposed also opens up an interesting alternative to homogeneous catalysis in the field of organic synthesis

Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress

AIMS: Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vascular damage associated with hypertension is unknown. METHODS AND RESULTS: Bioinformatics identified ISG15 as a mediator of hypertension-associated vascular damage. ISG15 expression positively correlated with systolic and diastolic blood pressure and carotid intima-media thickness in human peripheral blood mononuclear cells. Consistently, Isg15 expression was enhanced in aorta from hypertension models and in angiotensin II (AngII)-treated vascular cells and macrophages. Proteomics revealed differential expression of proteins implicated in cardiovascular function, extracellular matrix and remodelling, and vascular redox state in aorta from AngII-infused ISG15-/- mice. Moreover, ISG15-/- mice were protected against AngII-induced hypertension, vascular stiffness, elastin remodelling, endothelial dysfunction, and expression of inflammatory and oxidative stress markers. Conversely, mice with excessive ISGylation (USP18C61A) show enhanced AngII-induced hypertension, vascular fibrosis, inflammation and reactive oxygen species (ROS) generation along with elastin breaks, aortic dilation, and rupture. Accordingly, human and murine abdominal aortic aneurysms showed augmented ISG15 expression. Mechanistically, ISG15 induces vascular ROS production, while antioxidant treatment prevented ISG15-induced endothelial dysfunction and vascular remodelling. CONCLUSION: ISG15 is a novel mediator of vascular damage in hypertension through oxidative stress and inflammation.This work was supported by the Ministerio de Ciencia e Innovación and Fondo Europeo de Desarrollo Regional (FEDER)/FSE (SAF2016-80305P; SAF2017-88089-R; SAF2016-79151-R; RTI2018-099246-B-I00), Ministerio de Innovación, Cultura y Deportes (PGC2018-097019-B-I00), Instituto de Salud Carlos III (ISCIII; FIS PI18/0919); Comunidad de Madrid (CM) (AORTASANA B2017/BMD-3676) FEDER-a way to build Europe, Bayer AG (2019-09-2433), CM-Universidad Autónoma de Madrid (SI1-PJI-2019-00321), and British Heart Foundation (CH/12/4/29762; RE//18/6/34217). M.G.-A. was supported by an FPI-UAM fellowship, R.R.-D. by a Juan de la Cierva contract (IJCI-2017-31399), and A.C.M. by a Walton Fellowship, University of Glasgow. The CNIC is supported by ISCIII, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer

Background: Preclinical data support a key role for the human epidermal growth factor receptor 3 (HER3) pathway in hormone receptor (HR)-positive breast cancer. Recently, new HER3 directed antibody drug conjugates have shown activity in breast cancer. Given the need to better understand the molecular biology, tumor microenvironment, and mechanisms of drug resistance in breast cancer, we designed this window-of-opportunity study with the HER3 directed antibody drug conjugate patritumab deruxtecan (HER3-DXd; U3-1402). Trial Design: Based on these data, a prospective, multicenter, single-arm, window-of-opportunity study was designed to evaluate the biological effect of patritumab deruxtecan in the treatment of naïve patients with HR-positive/HER2-negative early breast cancer whose primary tumors are ≥1 cm by ultrasound evaluation. Patients will be enrolled in four cohorts according to the mRNA-based ERBB3 expression by central assessment. The primary endpoint is a CelTIL score after one single dose. A translational research plan is also included to provide biological information and to evaluate secondary and exploratory objectives of the study

Salidas profesionales y desarrollo de carreras relacionadas con la titulación estudiada

El objetivo de este proyecto es la mejora de la empleabilidad de los alumnos del grado de Comercio. El proyecto consiste en un ciclo de conferencias con directivos que tienen responsabilidades en áreas comerciales de empresas, con el objetivo de que conozcan las posibilidades de trabajo y las competencias y habilidades que se exigen.Depto. de Organización de EmpresasFac. de Ciencias Económicas y EmpresarialesFALSEsubmitte

Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved

Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn''s disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and ß-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology. © 2021 The Author

Revisitando el cine documental: de Flaherty al webdoc

En los últimos tiempos, y propiciado por el auge de la imagen digital, el género documental ha liderado una importante renovación en sus formas cinematográficas indagando en nuevos lenguajes para la imagen contemporánea. Desdibujando por completo los límites entre la ficción y la no ficción, el documental contemporáneo ha fraccionado algunas de las convenciones asociadas al género, encontrando fácil acomodo entre lo narrativo, lo observacional, lo etnográfico, lo ensayístico, la videocreación, lo autobiográfico y, obviamente, lo experimental. Tras décadas de constante mutación, el cine documental se nos presenta como un fascinante territorio de exploración fílmica, aportando una reflexión sobre las fronteras actuales del lenguaje cinematográfico y que requiere a su vez un nuevo tipo de mirada desde el ámbito académico. Dispuestas así las cosas, el presente libro se propone revisitar el género documental y recoger experiencias e investigaciones que, desde diferentes planteamientos, buscan reflexionar sobre la evolución del propio género desde un enfoque multidisciplinar. De este modo, se pretende establecer un estado de la cuestión con textos vinculados a los disímiles modos de abordar el documental a lo largo de su dilatada historia: estudios historiográficos, análisis fílmicos sustentados en ejemplos concretos de películas o directores de especial interés, investigaciones que ponen en relieve la influencia y consecuencia de la evolución de la tecnología digital e Internet, así como la evolución e innovación en los modos de producción, exhibición y/o distribución por los que el documental ha transitado.Este Libro se ha realizado dentro del Grupo de Investigación GIU 13/21 (2013-2016), MAC (Mutaciones del Audiovisual Contemporáneo) de la Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU).La redacción del capítulo "Un lugar ético para las imágenes documentales (en el contexto de las ciencias sociales) / Josetxo Cerdán Los Arcos" fue posible gracias al proyecto de investigación CSO2010/15798 (TRANSCINE), financiado por el Ministerio de Ciencia e Innovación del Gobierno de España. -- La redacción del capítulo "Documentalidad. Cine sin autoría, pedagogías visuales colectivas y valor afectivo / Virginia Villaplana Ruiz" fue posible gracias al proyecto de investigación eDCINEMA: "Hacia el Espacio Digital Europeo", financiado por el Plan Nacional de I+D+i del Ministerio de Economía y Competitividad. Ref. CSO2012-35784. -- La redacción del capítulo "Cosas que hacen crack. Emociones y cinefilia en Color perro que huye (Andrés Duque, 2011) / Miguel Fernández Labayen y Elena Oroz" se ha realizado en el marco del proyecto de investigación CSO2010-15798 (TRANSCINE), "El audiovisual español contemporáneo en el contexto transnacional: aproximaciones cualitativas a sus relaciones transfronterizas", financiado por el Ministerio de Economía y Competitividad del Gobierno de España. -- El capítulo "Aproximación a la no ficción interactiva: panorámica del webdocumental español en la era digital / Robert Arnau Roselló" ha sido financiado con la ayuda del Proyecto de Investigación de la convocatoria Universitat Jaume I-Bancaja, con el título "Análisis de los flujos de transferencia de conocimiento entre los sistemas educativos superiores y la industria del videojuego", código 11I301.01/1, bajo la dirección del Dr. Javier Marzal Felici.Prólogo / J.M. Català Domènech (pp. 9-14). -- Un lugar ético para las imágenes documentales (en el contexto de las ciencias sociales) / Josetxo Cerdán Los Arcos (pp. 17-32). -- Documentalidad. Cine sin autoría, pedagogías visuales colectivas y valor afectivo / Virginia Villaplana Ruiz (pp. 33-54). -- Diseño de títulos en documental: cuestión de etiqueta / Koldo Atxaga Arnedo (pp. 55-65). -- La creación del documental: archivo, recreaciones y entrevistas / Mónica del Sagrario Medina Cuevas y Alejandro Jiménez Arrazquito (pp. 67-76). -- Desterritorialización, modulación y puntos de inflexión en el documental contemporáneo español / Vanesa Fernández Guerra y Estibaliz Alonso Ruiz de Erentzun (pp. 79-103). -- La propuesta de vertebración del Novo Cine Galego: lo procesual y la marca documental / Fernando Redondo Neira y Xurxo González Rodríguez (pp. 105-126). -- Revisión de la etiqueta "Novo Cinema Galego". Testimonios de autor / Beli Martínez Martínez (pp. 127-152). -- El cine de no ficción en los cortometrajes de Kimuak: evoluación, tendencias y nuevas propuestas creativas / Ainhoa Fernández de Arroyabe Olaorut, Nekane E. Zubiaur Gorozika y Iñaki Lazkano Arrillaga (pp. 153-179). -- Cosas que hacen "crack". Emociones y cinefilia en Color perro que huye (Andrés Duque, 2011) / Miguel Fernández Labayen y Elena Oroz (pp. 181- 204). -- Estudio evolutivo del lenguaje narrativo, desde los primeros documentales a las transmedia / Begoña Gutiérrez San Miguel (pp. 207-244). -- La participación ciudadana en el documental colaborativo: hacia nuevas narrativas audiovisuales / Gloria Rosique Cedillo (pp. 245-263). -- Del documental lineal al webdocumental: enunciación y experiencia espectatorial en Gare du Nord de Claire Simon / Amanda Rueda (pp. 265-274). -- El documental multimedia interactivo. Un estudio de caso: En el reino del plomo (En Portada y Lab de RTVE.es, 2013) / Irene Liberia Vayá y Cristina Pérez de Algaba Chicano (pp. 275-299). -- Aproximación a la no ficción interactiva: panorámica del webdocumental español en la era digital / Robert Arnau Roselló (pp. 301-323)

Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients

OBJECTIVE: CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. METHODS: The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. RESULTS: T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis. CONCLUSION: The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients