El mezcal en Sonora, México, más que una bebida espirituosa. Etnobotánica de Agave angustifolia Haw

¿Cómo sería la vida de los sonorenses sin el mezcal? La interrogante guía el propósito general del trabajo, orientado a identificar la importancia que tradicionalmente ha revestido el Agave angustifolia en la vida cotidiana de los sonorenses. En su mayor parte, los estudios existentes en Sonora en torno a esta especie se enfocan, básicamente, en su uso para la elaboración industrial del licor, popularmente conocido como bacanora. La investigación pretende contribuir, en alguna medida, al mayor conocimiento del valor biológico y cultural de la planta. Con ese objetivo se recurre a la etnobotánica para obtener una mirada más completa de las formas en las que los hombres y mujeres se han relacionado con el agave. La región de estudio comprende dos zonas mezcaleras: la sierra orien-te, donde la mayor parte de la población es mestiza, y la zona sur, donde los grupos indígenas Mayo y Guarijío cohabitan con mestizos. Se realizaron entrevistas a profundidad a diversos pobladores, así como a investigadores y otros estudiosos de la planta. Se consultaron las fuentes históricas disponibles. Los resultados muestran la existencia de diferencias regionales en los usos del agave y técnicas de preparación, determinadas por un número de factores estrechamente vinculados con el grupo étnico de los pobladores y su historia

A switching-regimen model for the Spanish inflation : 1962-1997

En este documento se estima un modelo de cambio de regimen para describir la evolucion de la inflacion durante el periodo 1965-1997. De este modo es posible identificar tanto las diferentes fechas en las que la inflacion cambia de regimen como la probabilidad asignada a cada registro de inflacion observada de pertenecer a un regimen u otro. Estas circunstancias resultan de especial interes para relacionar la evolucion y caracteristicas de cada regimen de inflacion con el momento de implantacion de las mencionadas estrategias antiinflacionistas. (jah) (glk) (dls) (mac

Mitochondrial bioenergetics and distribution in living human osteoblasts grown on implant surfaces

Osseointegration of implants is crucial for the long-term success of oral implants. The periimplant bone formation by osteoblasts is strongly dependent on the local mechanical environment in the interface zone. Robust demands for energy are placed on osteoblasts during the adhesion process to solid surfaces, and mitochondria are capital organelles in the production of most of the ATP needed for the process. We have assessed the relationship between osteoblast differentiation and mitochondrial bioenergetics in living cells grown on two different titanium surfaces, in order to provide valuable information for the design of material surfaces required for the development of the most appropriate osteogenic surface for osteoblastic anchorage. Combined backscattered and fluorescence confocal microscopy showed that in flat cells grown on a machined surface, highly energized mitochondria were distributed along the cell body. In contrast, cells grown on the rough surface emitted long protrusions in search of surface roughness, with actin stress fibers clearly polarized and highly energized mitochondria clustered at focal adhesion sites. This report using normal human osteoblastic cells indicates that these cells are especially sensitive to surface cues through energy production that enhances the necessary adhesion required for a successful osseointegration

Multi-modal ultrasound imaging for breast cancer detection

This work describes preliminary results of a two-modality imaging system aimed at the early detection of breast cancer. The first technique is based on compounding conventional echographic images taken at regular angular intervals around the imaged breast. The other modality obtains tomographic images of propagation velocity using the same circular geometry. For this study, a low-cost prototype has been built. It is based on a pair of opposed 128-element, 3.2 MHz array transducers that are mechanically moved around tissue mimicking phantoms. Compounded images around 360 degrees provide improved resolution, clutter reduction, artifact suppression and reinforce the visualization of internal structures. However, refraction at the skin interface must be corrected for an accurate image compounding process. This is achieved by estimation of the interface geometry followed by computing the internal ray paths. On the other hand, sound velocity tomographic images from time of flight projections have been also obtained. Two reconstruction methods, Filtered Back Projection (FBP) and 2D Ordered Subset Expectation Maximization (2D OSEM), were used as a first attempt towards tomographic reconstruction. These methods yield useable images in short computational times that can be considered as initial estimates in subsequent more complex methods of ultrasound image reconstruction. These images may be effective to differentiate malignant and benign masses and are very promising for breast cancer screening. (C) 2015 The Authors. Published by Elsevier B.V

Production Performance of Local Village Chicken Fed by Agriculture by-product Supplemented with Herbal Probiotics and Mud Clams Extract (Polymesoda erosa) in Kendari-South-East Sulawesi

Ninety head day old chick (DOC) of local village chicken was used in this experiment to evaluate the effect of agricultural by product-based feed supplemented with herbal probiotics (HP) and mud clams extract (MC) on production performance of local village chicken. A completely randomized design was used with 5 treatments and 4 replications. The treatments consisted of control (R0), 0.75%HP+1.5%MC (R1), 1.5%HP+3%MC (R2), 2.25%HP+4.5%MC (R3), and 3.0%HP+6.0%MC (R4). All chicken was kept in a group of five flocks equipped with feeding and water supply apparatus. The results showed that local village chicken got R2 treatment gave a significantly higher response in feed consumption (32.5gd-1) compared to R0 (23.1gd-1), R1 (23.9gd-1), R3 (24.0gd-1), and R4 (21.3gd-1). The daily gain of local village chicken was also significantly higher in R2 treatment (7.4g-1) compared to R0 (4.6gd-1), R1 (4.9gd-1), R3 (4.6gd-1), and R4 treatment (4.1gd-1). However, feed conversion resulted from those treatments did not show a significant difference. The lower feed conversion gain in this experiment has existed in R2 treatment (4.0) followed by treatment R1 (4.9), R0 (5.0), R4 (5.2), and treatment R3 (5.4). Therefore, it was concluded that the treatments had a significant effect on feed consumption and daily gain but had no effect on feed conversion of local village chicken. The inclusion level of 1.5% herbal probiotics and 3% mud clams extract gave better effect on both feed consumption and daily gain of local village chicken

Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism

Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73a oncosuppressors. We show that p.P187S causes structural and dynamic changes communicated to functional sites far from the mutated site, affecting the FAD binding site located at the N-terminal domain (NTD) and accelerating proteasomal degradation through dynamic effects on the C-terminal domain (CTD). Structural protein:protein interaction studies reveal that the cancer-associated polymorphism does not abolish the interaction with p73a, indicating that oncosuppressor destabilization largely mirrors the low intracellular stability of p.P187S. In conclusion, we show how a single disease associated amino acid change may allosterically perturb several functional sites in an oligomeric and multidomain protein. These results have important implications for the understanding of loss-of-function genetic diseases and the identification of novel structural hot spots as targets for pharmacological intervention

Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism

In humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT-1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity.This work was supported by the Spanish Ministry of Science and Innovation (CSD2009-00088, BIO2012-34937 and SAF2011-23933), the Junta de Andalucia (P11-CTS-7187), and the Oxalosis and Hyperoxaluria Foundation (OHF2012 to B.C.). A.L.P. acknowledges a Ramon y Cajal research contract (RyC2009-04147) from the Spanish Ministry of Science and Innovation and the University of Granada. N. M-T acknowledges a FPI predoctoral fellowship from the Spanish Ministry of Science and Innovation. A.C.C. and N.T. were supported by the grant IOS-1353845 from the National Science Foundation (NSF). N.T. acknowledges the Tetelman Fellowship for International Research on the Sciences awarded by Yale University.Peer Reviewe

Counterintuitive structural and functional effects due to naturally occurring mutations targeting the active site of the disease-associated NQO1 enzyme*

Our knowledge on the genetic diversity of the human genome is exponentially growing. However, our capacity to establish genotype–phenotype correlations on a large scale requires a combination of detailed experimental and computational work. This is a remarkable task in human proteins which are typically multifunctional and structurally complex. In addition, mutations often prevent the determination of mutant high-resolution structures by X-ray crystallography. We have characterized here the effects of five mutations in the active site of the disease-associated NQO1 protein, which are found either in cancer cell lines or in massive exome sequencing analysis in human population. Using a combination of H/D exchange, rapid-flow enzyme kinetics, binding energetics and conformational stability, we show that mutations in both sets may cause counterintuitive functional effects that are explained well by their effects on local stability regarding different functional features. Importantly, mutations predicted to be highly deleterious (even those affecting the same protein residue) may cause mild to catastrophic effects on protein function. These functional effects are not well explained by current predictive bioinformatic tools and evolutionary models that account for site conservation and physicochemical changes upon mutation. Our study also reinforces the notion that naturally occurring mutations not identified as disease-associated can be highly deleterious. Our approach, combining protein biophysics and structural biology tools, is readily accessible to broadly increase our understanding of genotype–phenotype correlations and to improve predictive computational tools aimed at distinguishing disease-prone against neutral missense variants in the human genome