Prion protein (PrPC) biosynthesis involves a multi-step process that includes translation and post-translational modifications. While PrP has been widely investigated, for the homolog Doppel (Dpl), limited knowledge is available. In this study, we focused on a vital step of eukaryotic protein biosynthesis: targeting by the signal recognition particle (SRP). Taking the ovine Dpl (OvDpl(1-30)) peptide as a template, we studied its behavior in two different hydrophobic environments using CD and NMR spectroscopy. In both trifluoroethanol (TFE) and dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC), the OvDpl(1-30) peptide revealed to fold in an alpha-helical conformation with a well-defined central region extending from residue Cys8 until Ser22. The NMR structure was subsequently included in a computational docking complex with the conserved M-domain of SRP54 protein (SRP54M), and further compared with the N-terminal structures of mouse Dpl and bovine PrPC proteins. This allowed the determination of (i) common predicted N-terminal/SRP54M polar contacts (Asp331, Gln335, Glu365 and Lys432) and (ii) different N–C orientations between prion and Dpl peptides at the SRP54M hydrophobic groove, that are in agreement with each peptide electrostatic potential. Together, these findings provide new insights into the biosynthesis of prion-like proteins. Besides they also show the role of protein conformational switches in signalization toward the endoplasmic membrane, a key event of major significance in the cell cycle. They are thus of general applicability to the study of the biological function of prion-like as well as other proteins.

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We report a method to obtain electrospun fibers based on ionic liquids and gelatin, exhibiting antimicrobial properties.

Non-catalytic cellulosomal carbohydrate-binding modules (CBMs) are responsible for increasing the catalytic efficiency of cellulosic enzymes by selectively putting the substrate (a wide range of poly- and oligosaccharides) and enzyme into close contact. In the present work we carried out an atomistic rationalization of the molecular determinants of ligand specificity of a family 11 CBM from thermophilic C. thermocellum (CtCBM11), based on a NMR and molecular modeling approach. We have determined the NMR solution structure of CtCBM11 at 25 and 50 ºC and derived information on the residues of the protein involved in ligand recognition and on the influence of the length of the saccharide chain on binding. We obtained models of the CtCBM11/cellohexaose and CtCBM11/cellotetraose complexes by docking in accordance with the NMR experimental data. Specific ligand/protein CH-π and Van der Waals interactions were found to be determinant for the stability of the complexes and for defining specificity. Using the order parameters derived from backbone dynamics analysis in the presence and absence of ligand and at 25 and 50 ºC, we determined that the protein’s backbone conformational entropy is slightly positive. This data in combination with the negative binding entropy calculated from ITC studies supports a selection mechanism where a rigid protein selects a defined oligosaccharide conformation.

No abstract is available for this item.

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Technology assessment is essentially an approach, a collective of the systematic methods used to scientifically investigate the conditions for and the consequences of technology and technicising and to denote their societal evaluation. It is an investigation about the technological developments as well as an evaluation of its potential impacts on society. The assessment of emerging technologies, however, requires special attention. Brain-Computer Interface (BCI) is an emerging technology which allows for the direct communication between the brain and an external device. It is a truly direct connection, with no use of the normal output pathways of peripheral nerves and muscles, allowing for the brain to have control over objects and software without intermediates. To address these kinds of technologies at early stages of development, Constructive Technology Assessment (CTA), a member of Technology Assessment approaches, has been considered as one of the most fitting approaches. As an emerging technology, BCI is at its early stages of research and thus many challenges are still ahead. Mainstream adoption is not expected in least 10 years many challenges are yet to be overcome. Therefore, the objective of this article is to discuss and present a methodological approach to assess brain-computer interface technology considering constructive technology assessment and future oriented technology analysis as the main processes to undertake the assessment. The assessment will focus only on the non-invasive type of BCI and for medical applications in three defined areas: Communication & Control, Motor Substitution and Motor Recovery for a time horizon of 10 years, 2022. These areas were chosen based on the capability of BCI to serve as a replacement of normal neuromuscular pathways. That makes it one of the best technologies to help people in activating and controlling assistive technologies which enable communication and control of the environment. However, the real impacts o

Tuberculosis (TB) remains one of the most serious infectious diseases in the world and the rate of new cases continues to increase. The development of cheap and simple methodologies capable of identifying TB causing agents belonging to the Mycobacterium tuberculosis Complex (MTBC), at point-of-need, in particular in resource-poor countries where the main TB epidemics are observed, is of paramount relevance for the timely and effective diagnosis and management of patients. TB molecular diagnostics, aimed at reducing the time of laboratory diagnostics from weeks to days, still require specialised technical personnel and labour intensive methods. Recent nanotechnology-based systems have been proposed to circumvent these limitations. Here, we report on a paper-based platform capable of integrating a previously developed Au-nanoprobe based MTBC detection assay-we call it {"}Gold on Paper{"}. The Au-nanoprobe assay is processed and developed on a wax-printed microplate paper platform, allowing unequivocal identification of MTBC members and can be performed without specialised laboratory equipment. Upon integration of this Au-nanoprobe colorimetric assay onto the 384-microplate, differential colour scrutiny may be captured and analysed with a generic {"}smartphone{"} device. This strategy uses the mobile device to digitalise the intensity of the colour associated with each colorimetric assay, perform a Red Green Blue (RGB) analysis and transfer relevant information to an off-site lab, thus allowing for efficient diagnostics. Integration of the GPS location metadata of every test image may add a new dimension of information, allowing for real-time epidemiologic data on MTBC identification.

Tuberculosis remains one of the most serious infectious diseases worldwide requiring new tools to circumvent current molecular diagnostics limitations. Nanodiagnostics, i.e. nanotechnology based diagnostics, may do just that by decreasing the time needed for the molecular characterisation of the infecting agent, and allowing for miniaturisation and portability for point-of-need adapted to remote regions without suitable lab equipment.