The chaperone TRAP1 as a modulator of the mitochondrial adaptations in cancer cells

Mitochondria can receive, integrate, and transmit a variety of signals to shape many biochemical activities of the cell. In the process of tumor onset and growth, mitochondria contribute to the capability of cells of escaping death insults, handling changes in ROS levels, rewiring metabolism, and reprograming gene expression. Therefore, mitochondria can tune the bioenergetic and anabolic needs of neoplastic cells in a rapid and flexible way, and these adaptations are required for cell survival and proliferation in the fluctuating environment of a rapidly growing tumor mass. The molecular bases of pro-neoplastic mitochondrial adaptations are complex and only partially understood. Recently, the mitochondrial molecular chaperone TRAP1 (tumor necrosis factor receptor associated protein 1) was identified as a key regulator of mitochondrial bioenergetics in tumor cells, with a profound impact on neoplastic growth. In this review, we analyze these findings and discuss the possibility that targeting TRAP1 constitutes a new antitumor approach

Ferromagnetic and multiferroic interfaces in granular perovskite composite xLa0.5Sr0.5CoO3-(1-x)BiFeO3

of ferromagnetic La0.5Sr0.5CoO3 (LSCO) and multiferroic BiFeO3 (BFO) were synthesized by spray pyrolysis method. Different compositions of multiferroic xLSCO-(1-x)BFO composites were synthesized at 800 °C for 2 h. Scanning electron microscopy and energy dispersive spectroscopy elemental mapping were performed to study the morphology of composites. Ferri/ferromagnetic responses above TC (LSCO) are observed, which are associated with the interfaces LSCO/BFO. This interface presents a different behavior compared to the original perovskites, and the magnitude of the magnetization depends on x. Electrical DC conductivity as a function of temperature for LSCO nanopowder (x = 1) presents a different behavior than that reported in bulk material. For x = 1 and 0.9, the model by Glazman and Matveev [Zh. Eksp. Teor. Fiz. 94, 332 (1988)] is proposed to describe the electrical conductivity. On the other hand, x = 0, 0.1, and 0.5 present a variable range hopping behavior. Complex impedance spectroscopy as a function of frequency indicates a pure resistive behavior for x ≥ 0.5 compositions, while a complex resistive-capacitive behavior is observed for low x values (0, 0.1). In these samples, low values of magnetoelectric coupling were measured with an AC lock-in technique.Fil: Lohr, Javier Hernán. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Lopez, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Saleta, Martin Eduardo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Sanchez, Rodolfo Daniel. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentin

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

Shade delays flowering in Medicago sativa

Shade intolerant plants respond to the decrease in the red (R) to far-red light (FR) ratio (R:FR) occurring under shade by elongating stems and petioles and re-positioning leaves, in a race to out-compete neighbors for the sunlight resource. In some annual species, these shade-avoidance responses (SAS) are accompanied by the early induction of flowering. Anticipated flowering is viewed as a strategy to set seeds before the resources become severely limiting. Little is known about the molecular mechanisms of SAS in perennial forage crops like alfalfa (Medicago sativa). To study SAS in alfalfa, we exposed alfalfa plants to simulated shade by supplementing with FR. Low R:FR produced a classical SAS, such as increased internode and petiole length but, unexpectedly, delayed flowering. To understand the molecular mechanisms involved in uncoupling SAS from early flowering, we used a transcriptomic approach. SAS were likely mediated by increased expression of msPIF3 and msHB2 in low R:FR. Constitutive expression of these genes in Arabidopsis led to SAS, including early flowering, strongly suggesting their roles are conserved. Delayed flowering was likely to be mediated by the downregulation of msSPL3, which promotes flowering in both Arabidopsis and alfalfa. Shade-delayed flowering in alfalfa may be important to extend the vegetative phase under sub-optimal light conditions and thus assure the accumulation of reserves necessary to resume growth after the next season. This article is protected by copyright. All rights reserved.Fil: Lorenzo, Christian Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Iserte, Javier Alonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sanchez Lamas, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Antonietti, Mariana Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Garcia Gagliardi, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Hernando, Carlos Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Dezar, Carlos Alberto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Agrobiotecnología de Rosario; ArgentinaFil: Vazquez, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Agrobiotecnología de Rosario; ArgentinaFil: Casal, Jorge José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Yanovsky, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cerdan, Pablo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Distribution and Demographics of Fuchsia Excorticata, Nelson Lakes National Park

The small tree Fuchsia excorticata (Onagraceae) is found on disturbed riparian sites throughout New Zealand. Spatial distribution and demographic changes in populations of F. excorticata were surveyed in the Rotoiti Nature Recovery Project (RNRP) area, and an associated non-treatment reference area, Nelson Lakes National Park, over the period 2005 to 2007. The RNRP is an intensively managed "mainland island" project in mixed beech (Nothofagus) forest, pest animal species especially possums (Trichosurus vulpecula), rodents, and mustelids are controlled. The aim of this study was to survey the condition of F. excorticata in the managed and reference areas to determine if any differences could be detected between the populations over time. The only significant (p<0.05) difference between the two areas was in sapling abundance, which was higher in the RNRP management area. This was tentatively attributed to pest management; however the concurrence of complex environmental influences, and a lack of management replication, prevented a simple interpretation of the data. There was no significant difference in recruitment, growth, mortality, and tree or seedling abundance between the managed and reference areas. Growth rate, especially of saplings, was significantly greater at lower elevations in the RNRP managed area, however the inverse held for the reference area. Mammalian herbivory was light; the main affect being to restrict seedling growth through hedging. Periodic heavy flooding was responsible for much of the mortality, however many newly disturbed sites were rapidly populated with fuchsia seedlings. The need for rigour in establishing ecologically comparable reference sites for comparative studies was evident. There were inherent difficulties in establishing causal relationships between ecological changes and management practices where management was not replicated geographically

Easy to synthesize, robust organo-osmium asymmetric transfer hydrogenation catalysts

Asymmetric transfer hydrogenation (ATH) is an important process in organic synthesis for which the Noyori-type RuII catalysts [(arene)Ru(Tsdiamine)] are now well established and widely used. We now demonstrate for the first time the catalytic activity of the osmium analogues. X-ray crystal structures of the 16-electron OsII catalysts are almost identical to those of RuII. Intriguingly the precursor complex was isolated as a dichlorido complex with a monodentate amine ligand. The OsII catalysts are readily synthesised (within 1 h) and exhibit excellent enantioselectivity in ATH reactions of ketones