Overproduction of PDR3 Suppresses Mitochondrial Import Defects Associated with a TOM70 Null Mutation by Increasing the Expression of TOM72 in Saccharomyces cerevisiae

Most mitochondrial proteins are synthesized with cleavable amino-terminal targeting signals that interact with the mitochondrial import machinery to facilitate their import from the cytosol. We previously reported that the presequence of the F1-ATPase beta subunit precursor (pre-F1beta ) acts as an intramolecular chaperone that maintains the precursor in an import-competent conformation prior to import (P. Hajek, J. Y. Koh, L. Jones, and D. M. Bedwell, Mol. Cell. Biol. 17:7169-7177, 1997). We also found that a mutant form of pre-F1beta with a minimal targeting signal (Delta 1,2 pre-F1beta) is inefficiently imported into mitochondria because it rapidly folds into an import-incompetent conformation. We have now analyzed the consequences of reducing the pre-F1beta targeting signal to a minimal unit in more detail. We found that Delta 1,2 pre-F1beta is more dependent upon the Tom70p receptor for import than WT pre-F1beta is, resulting in a growth defect on a nonfermentable carbon source at 15°C. Experiments using an in vitro mitochondrial protein import system suggest that Tom70p functions to maintain a precursor containing the Delta 1,2 pre-F1beta import signal in an import-competent conformation. We also identified PDR3, a transcriptional regulator of the pleiotropic drug resistance network, as a multicopy suppressor of the mitochondrial import defects associated with Delta 1,2 pre-F1beta in a tom70Delta strain. The overproduction of PDR3 mediated this effect by increasing the import of Delta 1,2 pre-F1beta into mitochondria. This increased the mitochondrial ATP synthase activity to the extent that growth of the mutant strain was restored under the selective conditions. Analysis of the transcription patterns of components of the mitochondrial outer membrane import machinery demonstrated that PDR3 overproduction increased the expression of TOM72, a little studied TOM70 homologue. These results suggest that Tom72p possesses overlapping functions with Tom70p and that the pleiotropic drug resistance network plays a previously unappreciated role in mitochondrial biogenesis

Procesos de alteración y paleosuelos ligados a la sedimentación miocena del NE. de Segovia, depresión del Duero

Se ha realizado un análisis mineral6gico y micromorfol6gico en la zona de confluencia de las partes distales de los sistemas de abanicos aluviales miocenos procedentes de los relieves de Somosierra- Ayllón, al SE., y de Honrubia, al NO. En él, se constatan diferencias entre los procesos edhficos que afectaron a uno y otro sistema, asi como en los grados de evolución de los perfiles edhficos. Los depósitos procedentes de Honrubia se caracterizan por los frecuentes episodios de  encostramiento, a los que se asocia la presencia de esmectitas o de palygorskita en función del menor o mayor grado evolutivo y del menor o mayor confinamiento. Los depósitos del sistema de abanicos aluviales de Somosierra-Ayllón están, generalmente, menos afectados por las alteraciones edáficos, a consecuencia de la mayor intensidad de los procesos sedimentarios. Las interrupciones del depósito sólo dieron lugar a la formación de palygorskita. En los medios lagunares ubicados en la unión nororiental de ambos sistemas tuvo lugar el desarrollo de fases silicatadas ricas en magnesio: sepiolita y esmectitas hipermagnesianas. Por último, la silicificación responde a una cementación tardia en un medio desconfinado, o bien a un reemplazamiento del sustrato en medio confinado (nódulos de silex)

Democracia y política exterior : Fuerzas Armadas y funcionarios alfonsinistas a 30 años de la consulta popular por el Beagle

Fil: Zurita, María Delicia. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina

pH Dependence and Stoichiometry of Binding to the Fc Region of IgG by the Herpes Simplex Virus Fc Receptor gE-gI

Herpes simplex virus type 1 encodes two glycoproteins, gE and gI, that form a heterodimer on the surface of virions and infected cells. The gE-gI heterodimer has been implicated in cell-to-cell spread of virus and is a receptor for the Fc fragment of IgG. Previous studies localized the gE-gI-binding site on human IgG to a region near the interface between the CH2 and CH3 domains of Fc, which also serves as the binding site for bacterial and mammalian Fc receptors. Although there are two potential gE-gI-binding sites per Fc homodimer, only one gE-gI heterodimer binds per IgG in gel filtration experiments. Here we report production of recombinant human Fc molecules that contain zero, one, or two potential gE-gI-binding sites and use them in analytical ultracentrifugation experiments to show that two gE-gI heterodimers can bind to each Fc. Further characterization of the gE-gI interaction with Fc reveals a sharp pH dependence of binding, with KD values of ~340 and ~930 nM for the first and second binding events, respectively, at the slightly basic pH of the cell surface (pH 7.4), but undetectable binding at pH 6.0. This strongly pH-dependent interaction suggests a physiological role for gE-gI dissociation from IgG within acidic intracellular compartments, consistent with a mechanism whereby herpes simplex virus promotes intracellular degradation of anti-viral antibodies

Thinking outside the beamspot: Other SUSY searches at the LHC (long-lived particles and R-parity violation)

Supersymmetric particles that are long-lived or violate R-parity could evade many conventional searches for supersymmetry. This talk presents the latest results of searches for supersymmetry with long-lived particles or R-parity violation performed by the ATLAS and CMS collaborations using $\sim$20 fb$^{-1}$ of proton-proton collisions at center-of-mass energy of 8 TeV delivered by the LHC.Comment: Submitted to Proceedings of Rencontres de Moriond QCD 201

Screening of Fusarium graminearum isolates for enzymes extracellular and deoxynivalenol production

Fusarium graminearum, the main etiological agent of Fusarium Head Bligh, has high intraspecific genetic diversity, which is related to the variability in the aggressiveness among isolates against wheat. The aggressiveness involves different mechanisms as the production and liberation of extracellular enzymes and mycotoxins. In the present report, several F. graminearum isolates obtained from wheat spikes from Pampas region, Argentina, were screened for polygalacturonase (pectinase), proteolytic and lipase extracellular enzymatic activities production, as well as by the capacity to produce deoxynivalenol. The enzymatic production in terms of magnitude was varied among isolates, which could be related to a differential capacity to infect wheat. Both polygalacturonase as proteolytic activities had a maximum activity in the first days of incubation. Instead, the lipase activity reached its maximum activity advanced incubation time. Deoxynivalenol production was delayed over time with respect to the first enzymatic activities, which would infer its relation with the progress of the disease in the host, more than with the early stages of infection. The characterization carried out in this research, would allow us to apply a selection criterion among isolates for further research.Fil: Ortega, Leonel Maximilano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Fermentaciones Industriales (i); ArgentinaFil: Alconada Magliano, Teresa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Fermentaciones Industriales (i); ArgentinaFil: Astoreca, Andrea Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Fermentaciones Industriales (i); ArgentinaFil: Kikot, Gisele Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Fermentaciones Industriales (i); Argentin

Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer

Background About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients. Methods CTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn’s post-test was used for comparisons between groups. Statistical significance was set at p < 0.05. Results EpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis. Conclusions Our results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing