Exploring mutasynthesis to increase structural diversity in the synthesis of highly oxygenated polyketide lactones

The enantioselective synthesis of (2R,3R,4E,8E)-3-hydroxy-2,4,8-trimethyldeca-4,8-dienolide (5) by ring-closing metathesis is described. This compound is an analogue of 3,4-dihydroxy-2,4,6,8-tetramethyldec- 8-enolide (4) which is a rare 11-membered lactone produced by the fungus, Botrytis cinerea. Mutasynthetic studies with compound 5 using two mutants of B. cinerea led to the isolation of four new highly oxygenated 11-membered lactones (11–14) in which compound 5 has been stereoselectively epoxidized and hydroxylated at sites that were not easily accessible by classical synthetic chemistry

The synthesis of 3-hydroxy-2,4,8-trimethyldec- 8-enolides and an approach to 3,4-dihydroxy- 2,4,6,8-tetramethyldec-8-enolide

The synthesis of several derivatives of 3-hydroxy-2,4,8-trimethyldec-8-enolide and attempts at the synthesis of 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide (1), a structure which has been assigned to a metabolite of the phytopathogenic fungus, Botrytis cinerea, gave products whose spectroscopic data had significant differences from those reported for the natural product 1. The rare 11-membered lactone rings were constructed by ring-closing metathesis reactions. The increase in conformational restrictions imposed by the substituents has a high influence on the stereochemistry of the ring-closing metathesis reaction and gives rise to a decrease in the yield for the synthesis of 11-membered lactones. The predominant alkene which was obtained was the (Z)-isomer. The observed spectroscopic differences between the synthesized lactones and the natural product and the spectroscopic data of its acetylated derivative 26a allowed us to revise the structure 1 to that of the γ-butyrolactone 26

Association of aromatase and estrogen receptor gene polymorphisms with hip fractures

Producción CientíficaSummary Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. Introduction Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fracture

Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study

Producción CientíficaIn comparison with hip fractures, increased expression of genes in the Wnt pathway and increased Wnt activity were found in bone samples and osteoblast cultures from patients with osteoarthritis, suggesting the involvement of this pathway in subchondral bone changes. No consistent differences were found in the genetic association study

Efectos sobre la salud humana de los campos magnéticos y eléctricos de muy baja frecuencia (ELF)

El presente documento, promovido por la Dirección General de Seguridad y Salud Laboral de la Consejería de Empleo de la Junta de Andalucía, dentro de la Acción 77 del Plan General de Prevención de Riesgos Laborales 2003-2008, pretende establecer el marco teórico actual de conocimiento sobre los campos ELF; explicar los conceptos fundamentales de los mismos y las fuentes que los generan; establecer los principales efectos biológicos que se producen en los seres humanos a causa de su exposición, y las posibles enfermedades que son motivo de estudio. Asimismo, se establece una comparación entre las dos guías comentadas anteriormente sobre niveles de exposición, y que tienen un reconocimiento importante a nivel internacional. También son objeto de análisis los principales tipos de estudios (epidemiológicos, de laboratorio, etc…); los niveles de exposición poblacionales, tanto para el público en general como para el ocupacional; los métodos de medida e instrumentación empleados; las posibles medidas de protección y prevención; y la normativa relacionada con los campos magnéticos ELF. Se citan además las líneas de investigación recomendadas por la Organización Mundial de la Salud para completar las lagunas existentes de la base científica desarrollada. Finalmente, cabe decir que se ha pretendido citar los principales documentos de recopilaciones bibliográficas, cuya consulta pueda proporcionar información más detallada cuando ésta se requiera.Consejería de Empleo. Junta de Andalucía. Españ

Diseño de micropartículas de alginato con maíz con matriz prebiótica de aloe vera para la encapsulación de Lactobacillus plantarum.

Hoy en día el uso de bacterias probióticas ha aumento notablemente el interés en la industria de los alimentos, ya que estos consiguen obtener efectos beneficiosos para la mejora en la salud de la población en general, de igual manera, la tendencia de preferencia en la población ha ido aumentando para con los productos alimenticios que nos ofrecen considerables beneficios nutricionales y en la salud. Para que estas bacterias probióticas intervengan de la manera apropiada y esperada, es de gran importancia que lleguen vivas al intestino en un número adecuado. En los productos probióticos el cambio persistente en la viabilidad de las distintas bacterias que son utilizadas, es un inconveniente significativo y de gran consideración; dicha viabilidad podrá ser protegida mediante el procedimiento de una microencapsulación, en donde dicha técnica, hará que las bacterias probióticas queden atrapadas dentro de unas cápsulas, para así, producir partículas con un diámetro de unos cuantos nanómetros a unos pocos milímetros. En los productos alimenticios en los que se les han incorporado bacterias probióticas, es de gran ayuda la incorporación de alginatos y/o diversos geles para elaborar la microencapsulación de las bacterias, y así con esta técnica, los microorganismos queden protegidos frente al entorno desfavorable de los procesos digestivos y así mismo poder conservar su actividad metabólica. En la presente investigación, se utilizó Aloe vera (Aloe barbadensis Miller) y alginato de sodio para la elaboración de la matriz encapsulante mediante la técnica de extrusión, para la obtención de microcápsulas; por lo tanto el objetivo central de esta investigación es el diseño óptimo de microcápsulas a base de estos materiales, así como la evaluación del potencial que tiene el Aloe vera como matriz prebiótica

Planck intermediate results. XXXVI. Optical identification and redshifts of Planck SZ sources with telescopes at the Canary Islands observatories

Catalogs and data.-- et al.We present the results of approximately three years of observations of Planck Sunyaev-Zeldovich (SZ) sources with telescopes at the Canary Islands observatories as part of the general optical follow-up programme undertaken by the Planck Collaboration. In total, 78 SZ sources are discussed. Deep-imaging observations were obtained for most of these sources; spectroscopic observations in either in long-slit or multi-object modes were obtained for many. We effectively used 37.5 clear nights. We found optical counterparts for 73 of the 78 candidates. This sample includes 53 spectroscopic redshift determinations, 20 of them obtained with a multi-object spectroscopic mode. The sample contains new redshifts for 27 Planck clusters that were not included in the first Planck SZ source catalogue (PSZ1).The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, JA and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). A.S., R.B., H.L., and J.A.R.M. acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) under the 2011 Severo Ochoa Program MINECO SEV-2011-0187, and the Consolider-Ingenio project CSD2010-00064 (EPI: Exploring the Physics of Inflation).Peer Reviewe

CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington's disease

Huntington’s disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins 1 to 4 (CPEB1 to CPEB4) are RNA binding proteins that repress or activate translation of CPE-containing transcripts by shortening or elongating their poly(A) tail. Here, we found increased CPEB1 and decreased CPEB4 protein in the striatum of patients and mouse models with HD. This correlated with a reprogramming of polyadenylation in 17.3% of the transcriptome, markedly affecting neurodegeneration-associated genes including PSEN1, MAPT, SNCA, LRRK2, PINK1, DJ1, SOD1, TARDBP, FUS, and HTT and suggesting a new molecular mechanism in neurodegenerative disease etiology. We found decreased protein content of top deadenylated transcripts, including striatal atrophy–linked genes not previously related to HD, such as KTN1 and the easily druggable SLC19A3 (the ThTr2 thiamine transporter). Mutations in SLC19A3 cause biotin-thiamine–responsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD