Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads

Allosteric compounds that stimulate Hsp90 adenosine triphosphatase (ATPase) activity were rationally designed, showing anticancer potencies in the low micromolar to nanomolar range. In parallel, the mode of action of these compounds was clarified and a quantitative model that links the dynamic ligand-protein cross-talk to observed cellular and in vitro activities was developed. The results support the potential of using dynamics-based approaches to develop original mechanism-based cancer therapeutics

Caffeine inheritance in interspecific hybrids of Coffea arabica x Coffea canephora (Gentianales, Rubiaceae)

Caffeine inheritance was investigated in F2 and BC1F1 generations between Coffea arabica var. Bourbon Vermelho (BV) and Coffea canephora var. Robusta 4x (R4x). The caffeine content of seeds and leaves was determined during 2004 and 2005. Microsatellite loci-markers were used to deduce the meiotic pattern of chromosome pairing of tetraploid interspecific hybrids. Genetic analysis indicated that caffeine content in seeds was quantitatively inherited and controlled by genes with additive effects. The estimates of broad-sense heritability of caffeine content in seeds were high for both generations. In coffee leaves, the caffeine content (BSH) from the same populations showed transgressive segregants with enhanced levels and high BSH. Segregation of loci-markers in BC1F1 populations showed that the ratios of the gametes genotype did not differ significantly from those expected assuming random associations and tetrasomic inheritance. The results confirm the existence of distinct mechanisms controlling the caffeine content in seeds and leaves, the gene exchange between the C. arabica BV and C. canephora R4x genomes and favorable conditions for improving caffeine content in this coffee population312498504CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQsem informaçã

Microfábricas de areniscas eólicas de la Formación de la Cuesta (Pérmico), Sierra de Narváez, Provincia de Catamarca, República Argentina

En este trabajo se estudian las microfábricas de las areniscas eólicas de la Formación De La Cuesta (Pérmico, provincia de Catamarca). Sobre la base de las características texturales (tamaño de grano, selección y asimetría) y las microestructuras presentes, fueron identificadas seis microfábricas principales. La microfábrica 1 comprende a las láminas de paquetes entrecuzados formadas por flujo de grano, caracterizadas por el predominio de arena mediana con valores de media entre 300? y 460?. Las distribuciones granulométricas son unimodales, moderadamente bien seleccionadas y ligeramente asimétricas. La microfábrica 2, aparece estrechamente asociada a la microfábrica 1, y corresponde a las láminas originadas por caída de granos dentro de los sets entrecruzados. Predomina la arena fina y muy fina con distribuciones moderadamente bien seleccionadas. La microfábrica 3 aparece en estratos con laminación entrecruzada de bajo ángulo u horizontal, el tamaño de grano dominante es la arena mediana, siendo la distribución granulométrica en la mayoría de los casos unimodal y moderadamente seleccionada. La característica que distingue a esta microfábrica, es el desarrollo de láminas milimétricas con gradación inversa, producidas por la migración de óndulas eólicas donde se producían tanto el impacto-proyección como el impacto-reptaje de clastos. Similares características texturales son mostradas por la microfábrica 4, aunque en este caso la gradación inversa está ausente, muy probablemente debido a la falta de arena gruesa que registre el transporte por impacto-reptaje de clastos durante la migración de las óndulas. Areniscas masivas, de grano muy fino y mostrando óndulas de adhesión, son incluidas en la microfábrica 5 que dominan tanto en los depósitos de interduna como de extraduna. Estas areniscas se caracterizan por el abundante cemento eodiagenético temprano de carbonato, que promovió la preservación de fábricas abiertas. La microfábrica 6 corresponde a areniscas de tamaño de grano más fino, en ellas domina la fracción arena muy fina (72% en promedio) con porcentajes variables de limo grueso (17% en promedio). Los bancos son masivos, con laminación horizontal u ondulosa. Las microfábricas enumeradas aparecen en asociaciones específicas dentro de los depósitos eólicos. Las microfábricas 1 y 2 forman la mayor parte de los paquetes entrecruzados en subambientes de dunas, mientras que las microfábricas 3 y 4 caracterizan a los ambientes de extraduna-interduna seca. Por otro lado las microfábricas 5 y 6 prevalecen en los subambientes de extraduna-interduna húmedas. Los estudios sobre microfábricas resultan útiles no solo para obtener una completa y más precisa información sobre los mecanismos de transporte eólicos, sino también para interpretar los cambios en propiedades petrofísicas tales como porosidad y permeabilidad. Asimismo estos análisis pueden ser empleados como herramientas útiles en la descripción e interpretación de testigos de corona

Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

Comparative and Prospective Analysis of Three Different Approaches for Live-Donor Nephrectomy

PURPOSE: Living donor nephrectomy is usually performed by a retroperitoneal flank incision. Due to the significant morbidity and long recovery time for a flank incision, anterior extra peritoneal sub-costal and transperitoneal video-laparoscopic methods have been described for donor nephrectomy. We prospectively compare the long-term results of donors as well as functional recipients submitted to these three approaches. MATERIALS AND METHODS: A total of 107 live donor renal transplantations were prospectively evaluated from May 2001 to January 2004. Donors were compared with regard to operative and warm ischemia time, postoperative pain, analgesic requirements, and complications. Recipients were compared with regard to graft function, acute cellular rejection, surgical complications, and graft and recipient survival. RESULTS: The mean operative and warm ischemia times were longer in the video-laparoscopic group (p<0.001), whereas patients of the flank incision group presented more postoperative pain (p=0.035), required more analgesics (p<0.001), had longer hospital stays (p<0.001), and suffered more pain on the 90th day after surgery (p=0.006). In the sub-costal and flank incision groups, there was a larger number of paraesthesias and abdominal wall asymmetries (p<0.001). Recipient groups were demographically comparable and presented similar acute tubular necrosis incidence and delayed graft function. The incidence of acute cellular rejection was higher in the video-laparoscopic and flank incision groups (p=0.013). There was no difference in serum creatinine levels, surgical complications, or recipient or graft survival between groups. CONCLUSIONS: The video-laparoscopic and sub-costal approaches proved to be safe, and to provide donor advantages relative to the flank incision approach. Among recipients, the complication rate, graft survival, and recipient survival were similar in all groups

Findings of intraformational striated pavements in the late carboniferous glacial deposits of the Andean Precordillera, Argentina

One of the most important glacial events in the history of the Earth took place during the Late Paleozoic when large areas of the Gondwana Supercontinent were covered by ice-masses (Crowell, 1978; Hambrey and Harland, 1981; Isbell et al., 2003a,b; Rocha Campos et al., 2008; Fielding et al., 2008; López Gamundí, 2010). Though this glacial event was initially considered a large and unique episode spanning a great part of the Carboniferous and Permian in Gondwana, new geological evidence suggests that the glacial period was not continuous, but rather punctuated by several interglacial events. In this way, López Gamundí (1997) and later Isbell et al. (2003b) divided the Late Paleozoic Ice Age (LPIA) into four major glacial intervals corresponding to the Early Carboniferous (LPIA 1), Late Carboniferous- Early Permian (LPIA 2), Early Permian (LPIA 3) and Late Permian (LPIA 4). This division adequately describes the record of the glacial deposits in Gondwana and allows for the proposal of a general stratigraphy for the glacial deposits demonstrating the existence of low-frequency climatic changes. In this paper we describe two subglacial basal contact surfaces found in the lower part of the Guandacol Formation (Frenguelli, 1944; Cuerda, 1965) in the Central Precordillera (northwestern Argentina). The Guandacol Formation is well known for containing glacial deposits, including diamictites and resedimented diamictites at the lower third of the unit (Limarino et al., 2006; Marenssi et al., 2002; Marenssi et al., 2005). According to paleontological (palynological) information, and some radiometric dating, the age of the glacial deposits is Late Visean- Early Bashkirian and therefore fits into the LPIA 2 interval of Isbell et al. (2003b)

Geology and petrogenetic considerations of the Loma Marcelo skarn, Neoproterozoic basement of the Ventania System, Argentina

The Late Precambrian–Early Palaeozoic crystalline basement of the Ventania System is mainly composed of Neoproterozoic S-type granites, Early Cambrian alkaline granites, and Middle Cambrian peralkaline rhyolites. The Neoproterozoic granites (ca. 607–581 Ma) crop out in the Cerro Pan de Azúcar-Cerro del Corral area and host the Loma Marcelo Ca/Mg skarn, composed of calc-silicate- and chondrodite-bearing assemblages. Petrographical, geochemical, and geochronological data indicate that the skarn was formed from carbonate xenoliths of sedimentary nature incorporated during the intrusion of the Neoproterozoic granites and that it is the result of three successive metamorphic events. The first one is related to the incorporation of carbonate xenoliths by the intrusion and the associated contact metamorphism. The second event is linked to the crystallization of the Early Cambrian granites and related post-magmatic processes. They are responsible for fluorine influx into the Neoproterozoic basement, which resulted in the formation of high-F minerals in the Loma Marcelo skarn (e.g. vesuvianite, chondrodite). The Sm-Nd garnet-whole rock isochron age of 526.8 ± 12.0 Ma in the skarn confirms its relationship with the Early Cambrian magmatism. The last event corresponds to a regional metamorphism assigned to the Late Devonian–Early Carboniferous on the basis of a LA-ICP-MS U-Pb age of 353.4 ± 6.7 Ma determined on zircons of the skarn as well as a Rb-Sr quartz-sericite isochron age of 364.4 ± 3.6 Ma obtained from a quartz vein that post-tectonically cuts the already mylonitized granites. The different chemical compositions of the carbonate protoliths determined the formation of two types of skarns of calcic and magnesian compositions. A single date of the calcic skarn defined a LA-ICP-MS U-Pb upper intercept age of 648 ± 21 Ma, providing the maximum sedimentation age for the calcic protolith of the Loma Marcelo skarn. The minimum sedimentation age is provided by the crystallization age of the S-type granite surrounding the skarn (ca. 607 Ma). The Loma Marcelo skarn reveals the occurrence of underground Neoproterozoic carbonate (meta-?) sedimentary rocks as part of the basement of the Ventania System. These rocks could correlate with the carbonate sequences of the neighbouring Claromecó Basin and Tandilia System.Facultad de Ciencias Naturales y MuseoInstituto de Recursos MineralesCentro de Investigaciones Geológica

Contaminantes orgánicos persistentes en leche materna de centros urbanos de la provincia de Buenos Aires

Due to their chemical persistence and high lipophilicity, persistent organic pollutants (POPs) have a tendency to accumulate and biomagnify in the food chain. Because of its easy noninvasive collection and high-fat content, human milk is a good indicator POPs in human populations. The aim of our study was to evaluate human exposure to POPs (PCBs, DDTs and its metabolites, α, β y γ HCHs, CHLDs: heptachlor, heptachlor epoxide, trans- and cis-chlordanes and nonachlors) in 59 human milk samples collected during 2010-2011 in Punta Lara, Ensenada, Florencio Varela and Buenos Aires.Los contaminantes orgánicos persistentes (COPs) se acumulan en matrices ricas en materia grasa como la leche materna, que es un buen indicador de sus niveles en poblaciones humanas debido a su fácil y no invasiva extracción. Con el objeto de evaluar la exposición a COPs en la provincia de Buenos Aires y compararla con otras áreas, se analizaron bifenilos policlorados (PCBs), diclorodifeniltricloroetano (DDT) y sus metabolitos (DDT, TDE), hexaclorociclohexanos (α, β y γ-HCH) y clordanos (CHLDs: heptaclor y su epóxido, trans y cis clordanos y nonaclors) en muestras de leche materna colectadas durante 2010 y 2011 en Punta Lara, Ensenada, Florencio Varela y Capital Federal

Sites for gamma-ray astronomy in Argentina

We have searched for possible sites in Argentina for the installation of large air Cherenkov telescope arrays and water Cherenkov systems. At present seven candidates are identified at altitudes from 2500 to 4500 m. The highest sites are located at the NW of the country, in La Puna. Sites at 2500 and 3100 m are located in the West at El Leoncito Observatory, with excellent infrastructure. A description of these candidate sites is presented with emphasis on infrastructure and climatology.Fil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Allekotte, Ingomar. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Bertou, Xavier Pierre Louis. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Colombo, E.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Etchegoyen, A.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Garcia, B.. Universidad Tecnológica Nacional; ArgentinaFil: Garcia Lambas, Diego Rodolfo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Levato, Orlando Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; ArgentinaFil: Medina, M. C.. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Muriel, Hernan. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Recabarren, Pablo Genaro Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad Nacional de Córdoba; Argentin