The Degenerating Substantia Nigra as a Susceptible Region for Gene Transfer-Mediated Inflammation

Parkinson's disease (PD) is characterized by the progressive degeneration of neurons in the substantia nigra pars compacta (SN). The naïve SN is highly susceptible to inflammation. In addition, microglial activation in the degenerating SN displays distinct characteristics that increase the reactivity of the region towards inflammatory stimuli. On the other hand, gene therapy for PD has recently move forward into clinical settings, with PD being the neurodegenerative disorder with the highest number of Phase I/II gene therapy clinical trials approved and completed. These clinical trials are not targeting the SN, but this region is a certain candidate for future gene therapy interventions. Here, the unique immune-related properties of the degenerating SN in the context of a putative gene therapy intervention are reviewed. Several variables affecting the host response to gene delivery such as vector type and dosage, age and stage of disease of patients, and method of gene delivery and transgene used are discussed. Finally, approaches to diminish the risk of immune-mediated toxicity by gene transfer in the SN are presented

Mapeo litológico y mineralógico del batolito devónico Cerro Áspero, usando imágenes ASTER, Sierras Pampeanas Orientales, Argentina

The present study evaluates ASTER image processing as a technique to assist the lithological and mineralogical mapping oflarge granitic bodies and associated hydrothermal alteration assemblages related to the Cerro Áspero batholith, in Sierra de Comechingones, Argentina. This batholith was formed by the successive emplacement of several sub circular, high-level crust plutons that intruded, in the Upper Devonian, to metamorphic sequences of high to medium grade reworked by shear zones. Each of these plutons developed internal, external and roof units, and dyke swarms. Internal units are composed by porphyritic biotite monzogranites and external, roof units and dyke swarms are dominated by two-mica and muscovite leucocratic monzogranites to quarz-rich alkali-feldspar granites. The main associated mineralizations are W-Mo magmatic-hydrothermaldeposits and postbatholith epithemal fluorite deposits of cretaceous age. Supervised classification, principal component analyses and emissivity calculations were made to identify lithological composition and variations within the different plutons that comprise the Cerro Áspero batholith. This methodology allowed us to have a better and precise mapping of the study area as well as the contacts between the different plutons that comprise the Cerro Áspero batholith. The classification with spectral angle mapper methods allowed to identify the different sectors with hydrothermal alteration (argillic and silicification). The argillic alteration is mainly associated with epithermal fluorite deposits74339440

Mapeo litológico y mineralógico del batolito devónico Cerro Áspero, usando imágenes ASTER, Sierras Pampeanas Orientales, Argentina

En este trabajo se presentan los resultados obtenidos utilizando técnicas de procesamiento de imágenes Aster para asistir al mapeo litológico y mineralógico de grandes cuerpos graníticos y de la alteración hidrotermal asociada al batolito Cerro Áspero, Sierra de Comechingones, Argentina. Este batolito fue construido por el emplazamiento sucesivo de varios plutones subcirculares, epizonales, que intruyeron en el Devónico Superior, a secuencias metamórficas de alto a mediano grado retrabajadas por fajas de deformación. Cada uno de estos plutones desarrolló unidades internas, externas, cuspidales y enjambres de diques. Las unidades internas están compuestas de monzogranitos porfídicos con biotita y las unidades externas, cuspidales y los enjambres de dique están dominados por leucogranitos cuyas composiciones varían desde monzogranítica hasta granitos alcali-feldespáticos, ricos en cuarzo. Las principales mineralizaciones asociadas son depósitos magmáticoshidrotermales de W-Mo y depósitos de fluorita epitermal, post-batolíticos, de edad cretácica. Para identificar la composición litológica y las variaciones en los plutones que lo componen se realizó clasificación supervisada, análisis de componentes principales y cálculos de emisividad. Esta metodología permitió un mejor y más detallado mapeo en el área de estudio, así como precisar los contactos entre los plutones que componen el batolito. La clasificación obtenida con el método SAM (spectral angle mapper) permitió la determinación de diferentes alteraciones hidrotermales (argílica y sílicificación). La alteración argílica está asociada principalmente con depósitos de fluorita epitermal.The present study evaluates ASTER image processing as a technique to assist the lithological and mineralogical mapping of large granitic bodies and associated hydrothermal alteration assemblages related to the Cerro Áspero batholith, in Sierra de Comechingones, Argentina. This batholith was formed by the successive emplacement of several sub circular, high-level crust plutons that intruded, in the Upper Devonian, to metamorphic sequences of high to medium grade reworked by shear zones. Each of these plutons developed internal, external and roof units, and dyke swarms. Internal units are composed by porphyritic biotite monzogranites and external, roof units and dyke swarms are dominated by two-mica and muscovite leucocratic monzogranites to quarz-rich alkali-feldspar granites. The main associated mineralizations are W-Mo magmatic-hydrothermal deposits and postbatholith epithemal fluorite deposits of cretaceous age. Supervised classification, principal component analyses and emissivity calculations were made to identify lithological composition and variations within the different plutons that comprise the Cerro Áspero batholith. This methodology allowed us to have a better and precise mapping of the study area as well as the contacts between the different plutons that comprise the Cerro Áspero batholith. The classification with spectral angle mapper methods allowed to identify the different sectors with hydrothermal alteration (argillic and silicification). The argillic alteration is mainly associated with epithermal fluorite deposits.Fil: Radice, Stefania. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pinotti, Lucio Pedro. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Maffini, María Natalia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Campanella, Osvaldo Hector. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; ArgentinaFil: Ducart, Diego F.. Universidade Estadual do Campinas. Instituto de Geociencias; BrasilFil: Coniglio, Jorge Enrique. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; ArgentinaFil: Demartis, Manuel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: D'eramo, Fernando Javier. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Klebsiella pneumoniae Carbapenemase–2, Buenos Aires, Argentina

Fil: Pasteran, Fernando. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Otaegui, Luis. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Guerriero, Leonor. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Radice, Gabriel. Sanatorio Trinidad Mitre; Argentina.Fil: Maggiora, Ricardo. Sanatorio Trinidad Mitre; Argentina.Fil: Rapoport, Melina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Faccone, Diego. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: di Martino, Ana. Sanatorio Trinidad Mitre; Argentina.Fil: Galas, Marcelo F. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina

Antimicrobial susceptibility testing in clinically relevant non-fermenting gram-negative bacilli: recommendations from the Antimicrobial Agents Subcommittee of the Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología

En este documento se dan a conocer una serie de recomendaciones para el ensayo, la lectura, la interpretación y el informe de las pruebas de sensibilidad a los antimicrobianos para los bacilos gram negativos no fermentadores (BGNNF) que se aíslan en humanos. Se adoptaron como base las recomendaciones internacionales, las de la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas y las de un grupo de expertos invitados. Se incluye, además, la nomenclatura actualizada de los BGNNF y la descripción de algunas de sus características individuales, de sus resistencias naturales o habituales a los antimicrobianos de uso clínico y de los mecanismos responsables de tales resistencias. También se indican los agentes antimicrobianos que se deberían ensayar frente a las distintas especies, con la especificación de cuáles deberían ser informados, y su ubicación estratégica en las placas de cultivo para poder detectar los mecanismos de resistencia más frecuentes y relevantes. Por último, se detallan los métodos de detección y de confirmación fenotípica de la presencia de b-lactamasas emergentes en Argentina, como las carbapenemasas clases A y B.This document contains the recommendations for antimicrobial susceptibility testing of the clinically relevant non-fermenting gram-negative bacilli (NFGNB), adopted after conforming those from international committees to the experience of the Antimicrobial Agents Subcommittee members and invited experts. This document includes an update on NFGNB classification and description, as well as some specific descriptions regarding natural or frequent antimicrobial resistance and a brief account of associated resistance mechanisms. These recommendations not only suggest the antimicrobial drugs to be evaluated in each case, but also provide an optimization of the disk diffusion layout and a selection of results to be reported. Finally, this document also includes a summary of the different methodological approaches that may be used for detection and confirmation of emerging b-lactamases, such as class A and B carbapenemases.Fil: Radice, Marcela Alejandra. Asociación Argentina de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Marin, Marcelo. Asociación Argentina de Microbiología; ArgentinaFil: Giovanakis, Marta. Asociación Argentina de Microbiología; ArgentinaFil: Vay, Carlos.Fil: Almuzara, Marisa.Fil: Limansky, Adriana.Fil: Casellas, José M.. Asociación Argentina de Microbiología; ArgentinaFil: Famiglietti, Angela. Asociación Argentina de Microbiología; ArgentinaFil: Quinteros, Mirta. Asociación Argentina de Microbiología; ArgentinaFil: Bantar, Carlos. Asociación Argentina de Microbiología; ArgentinaFil: Galas, Marcelo.Fil: Kovensky Pupko, Jaime. Asociación Argentina de Microbiología; ArgentinaFil: Nicola, Federico. Asociación Argentina de Microbiología; ArgentinaFil: Pasteran, Fernando. Asociación Argentina de Microbiología; ArgentinaFil: Soloaga, Rolando. Asociación Argentina de Microbiología; ArgentinaFil: Gutkind, Gabriel Osvaldo. Asociación Argentina de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Geology and geocronology of predevonic laminar and irregular intrusions in the central portion of Sierras de Córdoba

El basamento gnéisico-migmático del sector centro-norte de la Sierra Chica y parte oriental de la Sierra Grande de Córdoba, se encuentra asociado a una gran cantidad de intrusiones ígneas, las cuales hasta el momento poseían escasos antecedentes de investigación. En este trabajo, se identificaron cinco litologías ígneas que se agruparon en dos asociaciones en base a su morfología, reología y relaciones de campo. La primera, comprende intrusiones de morfología irregular, que incluyen monzogranitos, tonalitas y pegmatitas (denominadas de tipo I). Estos cuerpos poseen bordes lobulados y contactos transicionales con su roca encajante y su origen posiblemente se vincula con los procesos de anatexis cortical ocurridos durante el ciclo Orogénico Pampeano. La segunda asociación, comprende intrusiones laminares (diques), que incluyen tonalitas-trondhjemitas y pegmatitas (llamadas de tipo II). Se caracterizan por presentar bordes rectos y contactos netos con su roca de caja y se encuentran asociados espacialmente con fajas de cizalla discretas estabilizadas en facies de anfibolitas. A su vez, estas rocas intruyen de manera discordante a las intrusiones irregulares y al basamento gnéisico migmático, por lo que su emplazamiento ha sido posterior. A partir de sus relaciones de yacencia, emplazamiento sin-cinemático con fajas de cizalla (estabilizadas en facies de anfibolita) y las edades Ar/Ar obtenidas en este trabajo (450,92±1,41 Ma y 434,53±3,16 Ma), la generación y el emplazamiento de los cuerpos laminares habría ocurrido durante el Ciclo Orogénico Famatiniano.A large amount of igneous intrusions hosted by a gneissic-migmatic metamorphic basement crop out in the central-north part of the Sierra Chica and eastern boundary of the Sierra Grande de Córdoba. In this contribution, five igneous lithologies were identified and grouped into two distinctive rock groups according to their morphologies, rheology and field relationships. The first group includes irregular-shaped monzogranites, tonalites and pegmatites (called type-I), having lobate and diffuse contacts with their surrounding host rocks. Field relationships suggest that these intrusions originated from crustal anatexis processes of different protoliths, correlated with similar processes occurred during the Pampean Orogeny. The second group includes laminar-shaped (dykes) tonalite-trondhjemites and pegmatites (called type-II), having straight and sharp contacts with their host rocks. They are spatially associated with narrow and localized shear zones stabilized in amphibolite facies. These igneous rocks invariably crosscut the irregular-shaped intrusives of the first group as well as gneissic and migmatic metamorphic host rocks of the basement, clearly reflecting a younger age of emplacement.Fil: Boffadossi, María Alejandra. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: D'eramo, Fernando Javier. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Demartis, Manuel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Pinotti, Lucio Pedro. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Coniglio, Jorge Enrique. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Muratori, María Eugenia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Maffini, María Natalia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Radice, Stefania. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; Argentin

Return to sport soccer after anterior cruciate ligament reconstruction: ISAKOS consensus

Many factors can affect the return to pivoting sports, after an Anterior Cruciate Ligament Reconstruction. Prehabilitation, rehabilitation, surgical and psychological aspects play an essential role in the decision to return to sports. The purpose of this study is to reach an international consensus about the best conditions for returning to sports in soccer-one of the most demanding level I pivoting sports after anterior cruciate ligament (ACL) reconstruction

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype

"BMC Cancer 2014 14:734"BACKGROUND: Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers.Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia. METHODS: Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1a stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1a signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting. RESULTS: We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1a, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1a stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1a, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population. CONCLUSIONS: Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolismo.This work was funded by FEDER funds through the COMPETE Program (Programa Operacional Factores de Competitividade) and by national funds through FCT (Portuguese Foundation for Science and Technology, Portugal), mainly in the context of the scientific project PTDC/SAU-GMG/120049/2010-FCOMP-01-0124-FEDER-021209, and partially by PTDC/SAU-FCF/104347/2008. FCT funded the research grants of BS (SFRH/BD/69353/2010), ASR (SFRH/BPD/75705/2011), ARN (grant from the project PTDC/SAU-GMG/120049/2010), CP (SFRH/BPD/69479/2010), AV (SFRH/BPD/90303/2012), as well as JP, with Programa Ciencia 2007 (Contratacao de Doutorados para o SCTN - financiamento pelo POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, comparticipado pelo Fundo Social Europeu e por fundos nacionais do MCTES) and Programa IFCT (FCT Investigator). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT

P-cadherin expression in breast cancer: a review

P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumour aggressiveness. In addition, expression of P-cadherin is well established as an indicator of poor prognosis in human breast cancer, which has stimulated our interest in studying its role in this setting. This review describes the most important findings on P-cadherin expression and function in normal mammary tissue and breast cancer cells, emphasizing that further research is required to elucidate the role played by this protein in human mammary tumours