BRASIL. Mapas generales (1770). 1:66000

Presenta la zona comprendida desde el río Amazonas hacia el surEscala hallada a partir de 1 minuto [= 2,8 cm]. Coordenadas referidas unicamente a la latitudTabla de signos convencionalesCopia digital. Madrid : Ministerio de Cultura. Dirección General del Libro, Archivos y Bibliotecas, 201

Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus

A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules

Alcances e obstáculos do accountability midiático na América Latina após a Terceira Onda da Democratização

Una de las más clásicas funciones normativas de los medios de comunicación en las democracias es la de ser vigilantes del poder, tanto para servir como defensores de la ciudadanía como para que la opinión pública tome correctas decisiones. El presente trabajo discute desde una posición crítica la accountability mediática en América Latina tras la Tercera Ola de la Democracia hasta el presente, la que si bien ha tenido una importante labor denunciante e investigativa en determinados casos de corrupción política, se postula como limitada por dos razones: la primera, la alta concentración de la propiedad de los sistemas de medios regionales ha provocado un bajo pluralismo informativo que puede poner en duda los verdaderos alcances e intenciones de la vigilancia que realizan los medios al poder y su aporte a las democracias. Por otra parte, y como segunda razón, las reformas de los últimos años llevadas a cabo por algunos gobiernos de liderazgo progresista o populista no han creado un ambiente propicio para esta función, al contrario, han propiciado carencias para la libertad informativa, principio básico para la accountability mediática. A modo de conclusión, se reflexiona sobre la importancia de fomentar el pluralismo informativo y la libertad de expresión como bases para la vigilancia de los medios al poder en la región latinoamericana.One of the most classic normative functions of media in democracies is to be vigilant of power, both to serve as defenders of the citizens and for the public opinion to make correct decisions. This paper discusses from a critical perspective the accountability of the media in Latin America from the Third Wave of Democracy up to date, which has been important in denouncing and investigating certain cases of political corruption, but has been limited for two reasons: the first is the high concentration of ownership of regional media systems, have led to a very low level of informative pluralism which calls into question the true scope and intentions of the surveillance that the media can carry out of power and its contribution to democracy. On the other hand, the second reason is the reforms carried out in recent years by the leadership of some progressive or populist governments that have not created a proper environment for this function, and on the contrary, have provided shortcomings for the freedom of information, a basic principle for media accountability. As a conclusion, this paper reflects on the importance of promoting informative pluralism and freedom of expression as the basis of media surveillance of power in the Latin American region.Uma das mais clássicas funções normativas dos meios de comunicação nas democracias é a de ser vigilantes do poder, tanto para servir como defensores da cidadania quanto para que a opinião pública tome decisões corretas. Este trabalho discute, sob uma posição crítica, o accountability midiático na América Latina após a Terceira Onda da Democratização até o presente, a que, embora tenha tido um importante trabalho denunciante e investigativo em determinados casos de corrupção política, apresenta-se como limitada por duas razões: a alta concentração da propriedade dos sistemas de meios regionais que provoca um baixo pluralismo informativo que pode colocar em dúvida os verdadeiros alcances e intenções da vigilância realizados pelos meios ao poder e sua contribuição para a democracia; por outro lado, e como segunda razão, as reformas dos últimos anos realizadas por alguns governos de liderança progressista ou populista que não criaram um ambiente propício para essa função; ao contrário, promoveram carências para a liberdade informativa, princípio básico para o accountability midiático. Como conclusão, reflexiona-se sobre a importância de fomentar o pluralismo informativo e a liberdade de expressão como bases para a vigilância dos meios ao poder na região latino-americana.https://revistas.udem.edu.co/index.php/anagramas/article/view/194

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Neurospora from natural populations: Population genomics insights into the Life history of a model microbial Eukaryote

The ascomycete filamentous fungus Neurospora crassa played a historic role in experimental biology and became a model system for genetic research. Stimulated by a systematic effort to collect wild strains initiated by Stanford geneticist David Perkins, the genus Neurospora has also become a basic model for the study of evolutionary processes, speciation, and population biology. In this chapter, we will first trace the history that brought Neurospora into the era of population genomics. We will then cover the major contributions of population genomic investigations using Neurospora to our understanding of microbial biogeography and speciation, and review recent work using population genomics and genome-wide association mapping that illustrates the unique potential of Neurospora as a model for identifying the genetic basis of (potentially adaptive) phenotypes in filamentous fungi. The advent of population genomics has contributed to firmly establish Neurospora as a complete model system and we hope our review will entice biologists to include Neurospora in their research

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al

The Soluble Recombinant Neisseria meningitidis Adhesin NadAΔ351–405 Stimulates Human Monocytes by Binding to Extracellular Hsp90

The adhesin NadA favors cell adhesion/invasion by hypervirulent Neisseria meningitidis B (MenB). Its recombinant form NadAΔ351–405, devoid of the outer membrane domain, is an immunogenic candidate for an anti-MenB vaccine able to stimulate monocytes, macrophages and dendritic cells. In this study we investigated the molecular mechanism of NadAΔ351–405 cellular effects in monocytes. We show that NadAΔ351–405 (against which we obtained polyclonal antibodies in rabbits), binds to hsp90, but not to other extracellular homologous heat shock proteins grp94 and hsp70, in vitro and on the surface of monocytes, in a temperature dependent way. Pre-incubation of monocytes with the MenB soluble adhesin interfered with the binding of anti-hsp90 and anti-hsp70 antibodies to hsp90 and hsp70 at 37°C, a condition in which specific cell-binding occurs, but not at 0°C, a condition in which specific cell-binding is very diminished. Conversely, pre-incubation of monocytes with anti-hsp90 and anti-hsp70 antibodies did not affected NadAΔ351–405 cell binding in any temperature condition, indicating that it associates to another receptor on their plasma membrane and then laterally diffuses to encounter hsp90. Consistently, polymixin B interfered with NadAΔ351–405 /hsp90 association, abrogated the decrease of anti-hsp90 antibodies binding to the cell surface due to NadAΔ351–405 and inhibited adhesin-induced cytokine/chemokine secretion without affecting monocyte-adhesin binding. Co-stimulation of monocytes with anti-hsp90 antibodies and NadAΔ351–405 determined a stronger but polymixin B insensitive cell activation. This indicated that the formation of a recombinant NadA/hsp90/hsp70 complex, although essential for full monocyte stimulation, can be replaced by anti-hsp90 antibody/hsp90 binding. Finally, the activation of monocytes by NadAΔ351–405 alone or in the presence of anti-hsp90 antibodies were both inhibited by neutralizing anti-TLR4 antibodies, but not by anti-TLR2 antibodies. We propose that hsp90-dependent recruitment into an hsp90/hsp70/TLR4 transducing signal complex is necessary for the immune-stimulating activity of NadAΔ351–405 anti-MenB vaccine candidate

Plant-Inspired Polyaleuritate–Nanocellulose Composite Photonic Films

Plant epidermis is a complex composite material composed by the cuticle and the epidermal cells. In order to prevent dehydration the cuticle is a water barrier composed of an outer layer (proper cuticle) connected to the cell wall of the epidermal cells via a complex matrix often referred to as cutinised cell wall, that acts as compatibilizer for the water repellent cutin and the hydrophilic polysaccharides in the cell walls. Here, biomimetic plant epidermis-inspired films with selective reflection properties were prepared by formation of an aliphatic polyester coating on chiral nematic cellulose nanocrystal (CNC) films. Aleuritic acid, a polyhydroxylated fatty acid, was sprayed on CNC films and polymerized by hot-pressing. The micromorphology of the resultant samples was characterized by scanning electron microscopy (SEM). Polarised optical microscopy confirmed the CNCs helicoidal organization in the films, responsible for the reflection of circularly polarised light, before and after the hot-pressing. The chemical analysis by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) confirmed the polymerization of aleuritic acid into polyaleuritate with differences between filter paper and woodpulp substrates that were ascribed to water elimination during polycondensation. The characterization of the mechanical (Young’s modulus and hardness from nanoindentation tests) and hydrodynamic (water uptake and water vapor transmission rate) properties indicated that this process enhances the robustness and waterproof behaviour of CNC films. These properties were comparable to those of commercial and biodegradable materials commonly used in packaging such as polyesters and cellulose derivatives, thus making these natural composite ideal for optically responsive packaging applications.J.A.H.-G. acknowledges the funding by the Spanish “Ministerio de Ciencia, Innovación y Universidades”, project numbers RTI2018-096896-J-I00 and RYC2018-025079-I