Re-examining the spectra of macromolecules. Current practice of spectral quasi B-factor flattening.

The analysis of structure factors in 3D cryo-EM Coulomb potential maps and their “enhancement” at the end of the reconstruction process is a well-established practice, normally referred to as sharpening. The aim is to increase contrast and, in this way, to help tracing the atomic model. The most common way to accomplish this enhancement is by means of the so-called B-factor correction, which applies a global filter to boost high frequencies with some dampening considerations related to noise amplification. The results are maps with a better visual aspect and a quasiflat spectrum at medium and high frequencies. This practice is so widespread that most map depositions in the Electron Microscopy Data Base (EMDB) only contain sharpened maps. Here, the use in cryoEM of global B-factor corrections is theoretically and experimentally analyzed. Results clearly illustrate that protein spectra present a falloff. Thus, spectral quasi-flattening may produce protein spectra with distortions when compared with experimental ones, this fact, combined with the practice of reporting only sharpened maps, generates a sub-optimal situation in terms of data preservation, reuse and reproducibility. Now that the field is more advanced, we put forward two suggestions: (1) to use methods which keep more faithfully the original experimental signal properties of macromolecules when “enhancing” the map, and (2) to further stress the need to deposit the original experimental maps without any postprocessing or sharpening, not only the enhanced maps. In the absence of access to these original maps data is lost, preventing their future analysis with new methods.The authors would like to acknowledge economical support from The Spanish Ministry of Economy and Competitiveness through Grants BIO2016-76400-R(AEI/FEDER, UE), the “Comunidad Autónoma de Madrid” through Grant: S2017/BMD-3817

Developing Transdermal Applications of Ketorolac Tromethamine Entrapped in Stimuli Sensitive Block Copolymer Hydrogels

Purpose: In order to obtain dermal vehicles of ketorolac tromethamine (KT) for the local treatment of inflammation and restrict undesirable side effects of systemic levels hydrogels (HGs) of poloxamer and carbomer were developed. Methods: KT poloxamer based HG (KT-P407-HG) and KT carbomer based HG (KT-C940-HG) were elaborated and characterized in terms of swelling, degradation, porosity, rheology, stability, in vitro release, ex vivo permeation and distribution skin layers. Finally, in vivo anti-inflammatory efficacy and skin tolerance were also assessed. Results: HGs were transparent and kept stable after 3 months exhibiting biocompatible near neutral pH values. Rheological patterns fitted to Herschel-Bulkley for KT-C940-HG and Newton for KT-P407-HG due to its low viscosity at 25°C. Rapid release profiles were observed through first order kinetics. Following the surface the highest concentration of KT from C940-HG was found in the epidermis and the stratum corneum for P407-HG. Relevant anti-inflammatory efficacy of KT-P407-HG revealed enough ability to provide sufficient bioavailability KT to reach easily the site of action. The application of developed formulations in volunteers did not induce any visual skin irritation. Conclusions: KT-P407-HG was proposed as suitable formulation for anti-inflammatory local treatment without theoretical systemic side effect

Quién nos hubiera dicho : Guadalajara, 22 de abril

Obra que analiza la movilización civil que se produjo en Guadalajara como consecuencia de la tragedia vivida por la ciudad con las explosiones del 22 de abril de 1992. Además de la crónica de la tragedia, los textos incluyen artículos respecto de la demora de las autoridades en dictaminar sobre los responsables del desastre. A la vez, se enfatiza el papel jugado por distintos sectores de la sociedad civil en las tareas inmediatamente posteriores a las explosiones, así como en la reconstrucción a más largo plazo