Voltage-Driven DNA Translocations through a Nanopore

We measure current blockade and time distributions for single-stranded DNA polymers during voltage-driven translocations through a single α-hemolysin pore. We use these data to determine the velocity of the polymers in the pore. Our measurements imply that, while polymers longer than the pore are translocated at a constant speed, the velocity of shorter polymers increases with decreasing length. This velocity is nonlinear with the applied field. Based on this data, we estimate the effective diffusion coefficient and the energy penalty for extending a molecule into the pore.Molecular and Cellular Biolog

El Sistema Nacional de Fomento Musical. Un modelo de política cultural

La política cultural que impulsa el Estado mexicano no sólo se centra en el apoyo, promoción y difusión de la actividad artística, sino se interesa por todas aquellas manifestaciones que fortalecen la identidad nacional, regional y local. Por ello, son también de interés las tradiciones y las expresiones populares, la cultura masiva y todos los recursos que abrigan la vida en común. Si alguna vez hubo un dilema entre la cultura circunscrita al arte y la cultura pensada como aquello que da sentido a la convivencia social, las instituciones culturales del país, tanto las federales como las estatales y locales, han tratado de difuminar esa frontera adoptando una postura de largo aliento en el trabajo cultural

Planeación cultural, la asignatura pendiente: El caso del Distrito Federal en México

Este texto revisa el tema de la planeación cultural, un tema pendiente de las políticas culturales de México y de gran parte de Latinoamérica. Tres temas se han tratado bajo este rubro: la planeación cultural urbana, las ciudades creativas y en general la creatividad artística. La segunda parte del texto trata de los programas de cultura de México y en especial lo que se ha hecho en este sentido en el Distrito Federal. Muchas son los déficits existentes que podrían ser llenados con una planeación que incorpore los aspectos financieros y de evaluación de los programas culturales. PALABRAS-CLAVE: Planeación cultural; Programas de cultura; Políticas culturales de México. Planejamento cultural, a marca pendente: O caso do Distrito Federal, no México Este texto faz, inicialmente, uma revisão sobre o tema do planejamento cultural, um tema pendente nas políticas culturais do México e em grande parte da América Latina. Três questões são tratadas sob essa rubrica: o planejamento cultural urbano; as cidades criativas e, num aspecto mais geral, a criatividade artística. Em seguida, trata dos programas de cultura do México e o que tem sido feito, nesse sentido, no Distrito Federal. São muitos os déficits que poderiam ser reduzidos com um planejamento que incorporasse os aspectos financeiros e de avaliação dos programas culturais. PALAVRAS-CHAVE: Planejamento cultural. Programas de Cultura. Políticas culturais no México. Cultural Planning, the pending mark: The Federal District matter, in Mexico This text, initially, makes a review concerning the cultural planning theme, something pending in the cultural policies in México and in the greatest part of the Latin America. Three matters are discussed under this signature: the urban cultural planning; the creative cities and, in a general aspect, the artistic creativity. As it follows, it discusses the culture programs in Mexico and what has been done, in this sense, in the Federal District. There are many deficits that could be reduced with a planning that would incorporate the financial and evaluation aspects of the cultural programs. KEYWORDS: Cultural Planning. Culture Programs. Cultural Policies in Mexico

Hsp27 (HspB1) and αB-crystallin (HspB5) as therapeutic targets

AbstractHsp27 and αB-crystallin are molecular chaperones that are constitutively expressed in several mammalian cells, particularly in pathological conditions. These proteins share functions as diverse as protection against toxicity mediated by aberrantly folded proteins or oxidative-inflammation conditions. In addition, these proteins share anti-apoptotic properties and are tumorigenic when expressed in cancer cells. This review summarizes the current knowledge about Hsp27 and αB-crystallin and the implications, either positive or deleterious, of these proteins in pathologies such as neurodegenerative diseases, myopathies, asthma, cataracts and cancers. Approaches towards therapeutic strategies aimed at modulating the expression and/or the activities of Hsp27 and αB-crystallin are presented

Computational design of a red fluorophore ligase for site-specific protein labeling in living cells

Chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of the intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies.National Institutes of Health (U.S.) (Grant DP1 OD003961)National Institutes of Health (U.S.) (R01 GM072670)American Chemical Societ

Analysis of Ballast Transport in the Event of Overflowing of the Drainage System on High Speed Lines

The transport of ballast caused by the overflowing of longitudinal drains is a prime example of the interactions between the railway track and its environment. In such conditions, water flowing from the platform, along with debris, may drag the ballast off the track foundation. The rate of ballast erosion rises when obstacles are placed along the platform. To better understand the phenomenon of ballast transport, research was undertaken in collaboration with Ecole Polytechnique Fédérale de Lausanne (EPFL). Systematic tests were performed on a physical model, using a 1:3 scale factor, under both normal and severe operational conditions, as well as in the case of a platform obstructed by obstacles. Numerical simulations were also run to evaluate different optimised configurations for the drainage system of the platform. The obtained results have improved the understanding of the phenomenon of ballast transport and have made it possible to identify at risk areas where the overflowing may negatively affect the railway traffic

Probing the structural hierarchy and energy landscape of an RNA T-loop hairpin

The T-loop motif is an important recurrent RNA structural building block consisting of a U-turn sub-motif and a UA trans Watson–Crick/Hoogsteen base pair. In the presence of a hairpin stem, the UA non-canonical base pair becomes part of the UA-handle motif. To probe the hierarchical organization and energy landscape of the T-loop, we performed replica exchange molecular dynamics (REMD) simulations of the T-loop in isolation and as part of a hairpin. Our simulations reveal that the isolated T-loop adopts coil conformers stabilized by base stacking. The T-loop hairpin shows a highly rugged energy landscape featuring multiple local minima with a transition state for folding consisting of partially zipped states. The U-turn displays a high conformational flexibility both when the T-loop is in isolation and as part of a hairpin. On the other hand, the stability of the UA non-canonical base pair is enhanced in the presence of the UA-handle. This motif is apparently a key component for stabilizing the T-loop, while the U-turn is mostly involved in long-range interaction. Our results suggest that the stability and folding of small RNA motifs are highly dependent on local context

The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted