Palladium and Bimetallic Palladium–Nickel Nanoparticles Supported on Multiwalled Carbon Nanotubes: Application to Carbon–Carbon Bond-Forming Reactions in Water

Palladium and bimetallic Pd–Ni nanoparticles (NPs) protected by polyvinylpyrrolidone were prepared by the reduction-by-solvent method and deposited on multiwalled carbon nanotubes (MWCNTs). The catalytic activity of these NPs to carbon–carbon bond-forming reactions was studied by using 0.1 mol % Pd loading, at 120 °C for 1 h and water as a solvent under ligand-free conditions. The Suzuki–Miyaura reaction took place quantitatively for the cross-coupling of 4-bromoanisole with phenylboronic acid, better than those obtained with potassium phenyltrifluoroborate, with Pd50Ni50/MWCNTs as a catalyst and K2CO3 as a base and TBAB as an additive, with good recyclability during 4 cycles with some Ni leaching. The Hiyama reaction of 4-iodoanisole with trimethoxyphenylsilane, under fluoride-free conditions using 50 % aqueous NaOH solution, was performed with Pd/MWCNTs as a catalyst in 83 % yield with low recyclability. For the Mizoroki-Heck reaction 4-iodoanisole and styrene gave the corresponding 4-methoxystilbene quantitatively with Pd50Ni50/MWCNTs using K2CO3 as a base and TBAB as an additive although the recycle failed. In the case of the Sonogashira-Hagihara reaction, Pd/MWCNTs had to be used as a catalyst and pyrrolidine as a base for the coupling of 4-iodoanisole with phenylacetylene under copper-free conditions. The corresponding 4-methoxytolane was quantitatively obtained allowing the recycling of the catalyst during 3 cycles.The Spanish Ministerios de Ciencia e Innovación (MICINN) and Economía y Competitividad (MINECO) (projects CTQ 2007-62771/BQU, CTQ2010-20387, CTQ2013-43446-P, Consolider Ingenio 2010, CSD2007-00006, CTQ2014-51912-REDC, CTQ2012-31762 and RyC-2009-03813 fellowship), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/010, and PROMETEOII/2014/017) and the University of Alicante are gratefully acknowledged for financial support

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

At low temperature and in the presence of an acid catalyst, SO2 adds to 1,3-dienes equilibrating with the corresponding 3,6-dihydro-1,2-oxathiin-2-oxides (sultines). These compounds are unstable above -60 °C and equilibrate with the more stable 2,5-dihydrothiophene 1,1-dioxides (sulfolenes). The hetero-Diels-Alder additions of SO2 are suprafacial and follow the Alder endo rule. The sultines derived from 1-oxy-substituted and 1,3-dioxy-disubstituted 1,3-dienes cannot be observed at -100 °C but are believed to be formed faster than the corresponding sulfolenes. In the presence of acid catalysts, the 6-oxy-substituted sultines equilibrate with zwitterionic species that react with electron-rich alkenes such as enoxysilanes and allylsilanes, generating β,γ-unsaturated silyl sulfinates that can be desilylated and desulfinylated to generate polypropionate fragments containing up to three contiguous stereogenic centers and an (E)-alkene unit. Alternatively, the silyl sulfinates can be reacted with electrophiles to generate polyfunctional sulfones (one-pot, four-component synthesis of sulfones), or oxidized into sulfonyl chlorides and reacted with amines, then realizing a one-pot, four-component synthesis of polyfunctional sulfonamides. Using enantiomerically enriched dienes such as 1-[(R)- or 1-(S)-phenylethyloxy]-2-methyl-(E,E)-penta-1,3-dien-3-yl isobutyrate, derived from inexpensive (R)- or (S)-1-phenylethanol, enantiomerically enriched stereotriads are obtained in one-pot operations. The latter are ready for further chain elongation. This has permitted the development of expeditious total asymmetric syntheses of important natural products of biological interest such as the baconipyrones, rifamycin S, and apoptolidin

Estudio epidemiológico en una muestra clínica de mujeres a través del dis

La investigación epidemiológica llevada a cabo en las últimas décadas en nuestro país ha demostrado, de manera inequívoca, la existencia de marcadas diferencias en la morbilidad psicopatológica y en el patrón de conducta de enfermedad desarrollados según el sexo (Vázquez-Barquero, Diez Manrique, Peña, Quintanal y Labrador López, 1986; Herrera, Antonell, Espagnolo, Domenech y Martín, 1987; Herrera, Antonell, Spagnolo y Gispert, 1990). Este hecho, unido a la constatación de que la prevalencia psicopatológica en la mujer es mucho mayor que en el hombre y que el riesgo de padecer un trastorno mental puede ser casi del doble en el sexo femenino (Muñoz, 1979; Herrera et al., 1987; Vázquez-Barquero, Diez Manrique y Peña, 1987), nos hacen plantear la presente investigación con el objetivo de conocer el tipo de desórdenes psicológicos que afectan de forma preferente a la población femenina, objetivo éste enmarcado en un planteamiento metodológico de tipo epidemiológico descriptivo

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

At low temperature and in the presence of an acid catalyst, SO2 adds to 1,3-dienes equilibrating with the corresponding 3,6-dihydro-1,2-oxathiin-2-oxides (sultines). These compounds are unstable above -60 degrees C and equilibrate with the more stable 2,5-dihydrothiophene 1,1-dioxides (sulfolenes). The hetero-Diels-Alder additions of SO2 are suprafacial and follow the Alder endo rule. The sultines derived from 1-oxy-substituted and 1,3-dioxy-disubstituted 1,3-dienes cannot be observed at -100 degrees C but are believed to be formed faster than the corresponding sulfolenes. In the presence of acid catalysts, the 6-oxy-substituted sultines equilibrate with zwitterionic species that react with electron-rich alkenes such as enoxysilanes and allylsilanes, generating beta,gamma-unsaturated silyl sulfinates that can be desilylated and desulfinylated to generate polypropionate fragments containing up to three contiguous stereogenic centers and an (E)-alkene unit. Alternatively, the silyl sulfinates can be reacted with electrophiles to generate polyfunctional sulfones (one-pot, four-component synthesis of sulfones), or oxidized into sulfonyl chlorides and reacted with amines, then realizing a one-pot, four-component synthesis of polyfunctional sulfonamides. Using enantiomerically enriched dienes such as 1-[(R)- or 1-(S)-phenylethyloxyl-2-methyl-(E,E)-penta-1,3-dien-3-yl isobutyrate, derived from inexpensive (R)- or (S)-1-phenylethanol, enantiomerically enriched stereotriads are obtained in one-pot operations. The latter are ready for further chain elongation. This has permitted the development of expeditious total asymmetric syntheses of important natural products of biological interest such as the baconipyrones, rifamycin S, and apoptolidin A

Retos de la investigación psicológica en salud mental

The magnitude and impact of mental disorders does not correspond to the resources devoted to research and attention. Although we have made significant progress in their understanding and the efficacy of the psychological treatments, we are still far from an optimal situation. This paper focuses on one of the major issues which we consider fundamental challenges and needs in this area, the increase in research focusing on psychopathology, especially on the mechanisms and processes that explain and maintain mental disorders, as a key point for the design and development of new psychological interventions for the prevention, treatment, and promotion of mental health. The aim is to promote discussion among all stakeholders and debate on those lines we think as a priority.La magnitud y el impacto que suponen los trastornos mentales no se corresponden con los recursos que se dedican a su investigación y atención. Aunque hemos avanzado notablemente en su comprensión y en la eficacia de los tratamientos psicológicos que intentan paliarlos, estamos aún lejos de la situación óptima. Este trabajo se centra en uno de los retos y una de las necesidades que consideramos fundamentales, el incremento de la investigación focalizada en psicopatología, especialmente sobre los mecanismos y procesos que explican y mantienen estos problemas, como eje básico para el desarrollo de nuevas intervenciones psicológicas, tanto para la prevención como para el tratamiento y promoción de la salud mental. El objetivo es promover la discusión entre los agentes implicados y reflexionar sobre las líneas de trabajo que creemos prioritarias.Este trabajo ha sido financiado por el Ministerio Español de Economía y Competitividad (MINECO), a través de la Red de Excelencia PROMOSAM financiada por el MINECO (PSI2014-56303-REDT)

Teaching linguistic politeness: a methodological proposal

The aim of this article is to explore theoretical and methodological aspects of the teaching of pragmatics in a second language. Taking as point of departure the pragmatic continuum, which includes pragmalinguistics and sociopragmatics, we focus on the promotion of sociopragmatic knowledge in classroom contexts. More specifically, it is argued that a revised contextual and interactional view of Brown and Levinson¿s (1987) model of linguistic politeness, related to such notions as genre and politeness systems, offers suitable tools of pragmatic description for use in teaching and learning second languages. We start with a brief overview of linguistic politeness from a socio-cognitive framework. Then, we revise the main methodological approaches to the teaching of pragmatic knowledge in general and the specific teaching of linguistic politeness in particular. Finally, we make a methodological proposal for use in foreign language instruction

Anti-TNF-a therapy in refractory uveitis associated with sarcoidosis: multicenter study of 17 patients

OBJECTIVES: To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. METHODS: Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. RESULTS: A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber [interquartile range-IQR] 0.5 [0-2] versus 0 [0-0] (p = 0.003), vitritis 0 [0-1.25] versus 0 [0-0] (p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) (p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily [interquartile range] dose of prednisone was also reduced from 10 [0-30]mg at the onset of the anti-TNF-α therapy to 0 [0-0]mg at 2 years (p = 0.02). Significant reduction was also achieved in the immunosuppressive load. CONCLUSION: Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.Funding: This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from ‘‘Instituto de Salud Carlos III’’ (ISCIII) (Spain) Acknowledgments: This work was partially supported by RETICS Program, RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Risk of cancer in family members of patients with lynch-like syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk

Microglia regulate learning and memory through NF-κB

Resumen del póster presentado al 19th Meeting Spanish Society of Neuroscience, celebrado en Lleida del 3 al 5 de noviembre de 2021.Microglia, the resident immune cells of the CNS, have been implicated in brain plasticity and function. However, the mechanisms remain largely unknown. Here, we show that Cre-dependent removal of the RelA subunit of the NF-κB transcription factor from adult microglia results in impaired learning and long-term potentiation. Depletion of RelA elicits changes in chromatin accessibility and transcriptome landscapes of microglia associated with specific gene regulatory programs driving the activation of specific microglia phenotypes. Our findings suggest that NF-κB gene products drive specific microglia phenotypes modulating neuronal circuits for learning and memory.Peer reviewe

First Description of Natural and Experimental Conjugation between Mycobacteria Mediated by a Linear Plasmid

Background: in a previous study, we detected the presence of a Mycobacterium avium species-specific insertion sequence, IS1245, in Mycobacterium kansasii. Both species were isolated from a mixed M. avium-M. kansasii bone marrow culture from an HIV-positive patient. the transfer mechanism of this insertion sequence to M. kansasii was investigated here.Methodology/Principal Findings: A linear plasmid (pMA100) was identified in all colonies isolated from the M. avium-M. kansasii mixed culture carrying the IS1245 element. the linearity of pMA100 was confirmed. Other analyses suggested that pMA100 contained a covalently bound protein in the terminal regions, a characteristic of invertron linear replicons. Partial sequencing of pMA100 showed that it bears one intact copy of IS1245 inserted in a region rich in transposase-related sequences. These types of sequences have been described in other linear mycobacterial plasmids. Mating experiments were performed to confirm that pMA100 could be transferred in vitro from M. avium to M. kansasii. pMA100 was transferred by in vitro conjugation not only to the M. kansasii strain from the mixed culture, but also to two other unrelated M. kansasii clinical isolates, as well as to Mycobacterium bovis BCG Moreau.Conclusions/Significance: Horizontal gene transfer (HGT) is one of most important mechanisms leading to the evolution and diversity of bacteria. This work provides evidence for the first time on the natural occurrence of HGT between different species of mycobacteria. Gene transfer, mediated by a novel conjugative plasmid, was detected and experimentally reproduced.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Cooperacion Interuniversitaria UAM-Banco Santander con America Latina (CEAL), UAM, SpainConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilLab Nacl Comp Cient, Petropolis, BrazilUniv Autonoma Madrid, Fac Med, Dept Prevent Med, Madrid, SpainInst Adolfo Lutz Registro, Nucleo TB & Micobacterioses, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilFAPESP: FAPESP - 06/01533-9Web of Scienc