El Catastro Español: localización, morfologías y dinámicas de las oficinas de la región metropolitana de Madrid

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The Spanish Cadastre: office location, morphologies and dynamics in metropolitan Madrid

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Catalytic Asymmetric α-Functionalization of α-Branched Aldehydes

Aldehydes constitute a main class of organic compounds widely applied in synthesis. As such, catalyst-controlled enantioselective α-functionalization of aldehydes has attracted great interest over the years. In this context, α-branched aldehydes are especially challenging substrates because of reactivity and selectivity issues. Firstly, the transient trisubstituted enamines and enolates resulting upon treatment with an aminocatalyst or a base, respectively, would exhibit attenuated reactivity; secondly, mixtures of E- and Z-configured enamines/enolates may be formed; and third, effective face-discrimination on such trisubstituted sp2 carbon intermediates by the incoming electrophilic reagent is not trivial. Despite these issues, in the last 15 years, several catalytic approaches for the α-functionalization of prostereogenic α-branched aldehydes that proceed in useful yields and diastereo- and enantioselectivity have been uncovered. Developments include both organocatalytic and metal-catalyzed approaches as well as dual catalysis strategies for forging new carbon–carbon and carbon–heteroatom (C-O, N, S, F, Cl, Br, …) bond formation at Cα of the starting aldehyde. In this review, some key early contributions to the field are presented, but focus is on the most recent methods, mainly covering the literature from year 2014 onward.This research was funded by Basque Government (grant IT-1583-22) and by MCIN/AEI/10.13039/501100011033 (grant PID2019-109633GB-C21)

N-(Diazoacetyl)oxazolidin-2-thiones as Sulfur Donor Reagents: Asymmetric Synthesis of Thiiranes from Aldehydes

Financial support was provided by the University of the Basque Country UPV/EHU (UFI 11/22), Basque Government (GV grant No IT-291-07), and Ministerio de Ciencia e Innovación (MICINN, Grant CTQ2007-68095-C02), Spain. A. L. thanks MICINN and European Social Foundation for a Ramón y Cajal contract. I. O. thanks MCINN for a fellowship. We also thank SGIker (UPV/EHU) for providing NMR, HRMS, X-Ray, and computational resources

Preclinical evaluation of the antimicrobial-immunomodulatory dual action of xenohormetic molecules against haemophilus influenzae respiratory infection

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammation and impaired airway immunity, providing an opportunistic platform for nontypeable Haemophilus influenzae (NTHi) infection. In this context, therapies targeting not only overactive inflammation without significant adverse effects, but also infection are of interest. Increasing evidence suggests that polyphenols, plant secondary metabolites with anti-inflammatory and antimicrobial properties, may be protective. Here, a Cistus salviifolius plant extract containing quercetin, myricetin, and punicalagin was shown to reduce NTHi viability. Analysis of these polyphenols revealed that quercetin has a bactericidal effect on NTHi, does not display synergies, and that bacteria do not seem to develop resistance. Moreover, quercetin lowered NTHi airway epithelial invasion through a mechanism likely involving inhibition of Akt phosphorylation, and reduced the expression of bacterially-induced proinflammatory markers il-8, cxcl-1, il-6, pde4b, and tnfα. We further tested quercetin’s effect on NTHi murine pulmonary infection, showing a moderate reduction in bacterial counts and significantly reduced expression of proinflammatory genes, compared to untreated mice. Quercetin administration during NTHi infection on a zebrafish septicemia infection model system showed a bacterial clearing effect without signs of host toxicity. In conclusion, this study highlights the therapeutic potential of the xenohormetic molecule quercetin against NTHi infection

Organocatalytic Michael Addition of Unactivated α-Branched Nitroalkanes to Afford Optically Active Tertiary Nitrocompounds

The direct, asymmetric conjugate addition of unactivated α-branched nitroalkanes is developed based on the combined use of chiral amine/ureidoaminal bifunctional catalysts and a tunable acrylate template to provide tertiary nitrocompounds in 55–80% isolated yields and high enantioselectivity (e.r. up to 96:4). Elaboration of the ketol moiety in thus obtained adducts allows a fast entry to not only carboxylic and aldehyde derivatives but also nitrile compounds and enantioenriched 5,5-disubstituted γ-lactams.We thank the Basque Government (EJ, grant IT1583-22) and Agencia Estatal de Investigación (grants PID2019-109633GB and PID2022-137153NB-C21/AEI/10.13039/501100011033) for financial support. A.G.-U. thanks EJ; B.L. thanks the Navarra Government, and M.E.-V. thanks UPNA (PJUPNA18-2022). Authors also thank SGIker (UPV/EHU/ERDF, EU) for providing NMR, HRMS, and X-ray resources

CHL1 hypermethylation as a potential biomarker of poor prognosis in breast cancer

The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplastic biopsies from 142 patients with invasive BC and compared with that of non-neoplastic tissues. We found higher CHL1 methylation levels in breast tumours than in non-neoplastic tissues, either from mammoplasties or adjacent-to-tumour, which correlated with lower levels of protein expression in tumours measured by immunohistochemistry. A panel of five BC cell lines was treated with two epigenetic drugs, and restoration of CHL1 expression was observed, indicating in vitro dynamic epigenetic regulation. CHL1 was silenced by shRNA in immortalized but non-neoplastic mammary cells, and enhanced cell proliferation and migration, but not invasion, were found by real-time cell analysis. The prognostic value of CHL1 hypermethylation was assessed by the log-rank test and fitted in a Cox regression model. Importantly, CHL1 hypermethylation was very significantly associated with shorter progression-free survival in our BC patient series, independent of age and stage (p = 0.001). In conclusion, our results indicate that CHL1 is downregulated by hypermethylation and that this epigenetic alteration is an independent prognostic factor in BC

Instrumentos de financiación empresarial

Este trabajo pretende ser de utilidad para cualquier, en general, persona que precise conocer las alternativas de financiación de las que dispone una empresa. En particular puede ser utilizado como material docente en asignaturas, tanto de la Licenciatura en Administración y Dirección de Empresas como de la Licenciatura en Economía, que aborden la financiación empresarial. El material se estructura en tres partes: •La primera parte, compuesta por un único capitulo se presenta la necesidad de conocer las distintas alternativas de financiación existentes y los criterios que se han de seguir para su elección: coste, vencimiento, propiedad y origen. •En la segunda parte, subdividida en cinco capítulos, se analizan cinco alternativas de financiación a corto plazo, presentando tanto sus características como el procedimiento para calcular su coste. •En la tercera parte, formada por dos capítulos, se estudian dos de las principales fuentes de financiación ajenas a largo plazo.Se pretende caracterizar de las distintas formulas de financiación empresarial ajenas. Se trata en definitiva de dilucidar la conveniencia, o no, del uso de las distintas fuentes financiación ajenas a las que puede acudir el responsable financiero de una empresa con el fin de establecer una estructura financiera adecuada a las necesidades de una empres