Engineered spider silk-based 2D and 3D materials prevent microbial infestation

Biofilm formation, especially of antimicrobiotic-resistant microbial strains, are a major problem in health care. Therefore, there is great interest in developing advanced materials that are selectively inhibiting microbial adhesion to surfaces, but at the same time promoting mammalian cell growth. In nature, some spider silks have evolved to repel microbes, a feature that could be used in biomaterials. To unravel how microbe repellence can be achieved in engineered spider silk, different recombinant spider silk proteins based on the consensus sequences of Araneus diadematus dragline silk proteins (fibroin 3 and 4) were processed into 2D-patterned films and 3D-hydrogels. Strikingly, protein structure characteristics on the nanoscale are the basis for the detected microbe-repellence. Designed spider silk materials promoted mammalian cell attachment and proliferation while inhibiting microbial infestation, demonstrating the great potential of these engineered spider silk-based materials as bio-selective microbial-resistant coatings in biomedical as well as technical applications

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

Forced Moves or Good Tricks in Design Space? Landmarks in the Evolution of Neural Mechanisms for Action Selection

This review considers some important landmarks in animal evolution, asking to what extent specialized action-selection mechanisms play a role in the functional architecture of different nervous system plans, and looking for “forced moves” or “good tricks” (see Dennett, D., 1995, Darwin’s Dangerous Idea, Penguin Books, London) that could possibly transfer to the design of robot control systems. A key conclusion is that while cnidarians (e.g. jellyfish) appear to have discovered some good tricks for the design of behavior-based control systems—largely lacking specialized selection mechanisms—the emergence of bilaterians may have forced the evolution of a central ganglion, or “archaic brain”, whose main function is to resolve conflicts between peripheral systems. Whilst vertebrates have many interesting selection substrates it is likely that here too the evolution of centralized structures such as the medial reticular formation and the basal ganglia may have been a forced move because of the need to limit connection costs as brains increased in size

Germline and somatic cancer-associated mutations in the ATP-binding motifs of PTEN influence its subcellular localization and tumor suppressive function

Germline and somatic PTEN mutations are found in Cowden syndrome (CS) and multiple sporadic malignancies, respectively. PTEN function appears to be modulated by subcellular compartmentalization, and mislocalization may affect function. We have shown that cellular ATP levels affect nuclear PTEN levels. Here, we examined the ATP-binding capabilities of PTEN and functional consequences, relevant to cancer-associated mutations. PTEN mutation analysis of CS patients and sporadic colorectal carcinomas and comparative aminoacid analysis were utilized to identify mutations in ATP-binding motifs. The ability of wild-type (WT) or mutant PTEN to bind ATP was assessed by ATP–agarose-binding assays. Subcellular fractionation, western blotting, confocal microscopy and growth assays were used to determine relative nuclear-cytoplasmic localization and function. Somatic colorectal carcinoma-derived PTEN missense mutations were associated with nuclear mislocalization. These mutations altered cellular proliferation, apoptosis and anchorage-dependent growth. Examination of PTEN's amino acid sequence revealed these mutations resided in previously undescribed ATP-binding motifs (c.60–73; c.122–136). In contrast to WT PTEN, both cancer-associated somatic and germline-derived PTEN missense mutations, which lie within the ATP-binding motifs, result in mutant PTEN that does not bind ATP efficiently. We also show that CS patients with germline ATP-binding motif-mutations had nuclear PTEN mislocalization. Of four unrelated patients with functional germline ATP-binding domain mutations, all three female patients had breast cancers. Germline and somatic mutations within PTEN's ATP-binding domain play important pathogenic roles in both heritable and sporadic carcinogenesis by PTEN nuclear mislocalization resulting in altered signaling and growth. Manipulation of ATP may represent novel therapies in tumors with such PTEN alterations

Optimized distillation coupled with state-of-the-art membranes for propylene purification

The growing production of polyolefins, mainly polyethylene and polypropylene, currently demands increasing outputs of polymer-grade light olefins. The most commonly adopted process for the separation of olefin/paraffin mixtures is performed by energy intensive high pressure or cryogenic distillation, which is considered the most expensive operation in the petrochemical industry. The use of membrane technology offers a compact and modular solution for capital and energy savings, thanks to process intensification. In this work, we move one step forward in the design of hybrid propane/propylene separation systems, using computer aided modeling tools to identify economically optimal combinations of distillation and state-of-the-art membranes. A model is proposed to optimize a hybrid configuration, whereby the membrane performs the bulk separation and the distillation column is intended for the final product polishing, accounting for membrane investment cost and process operating expenses. The decision variables are the membrane area and the column reflux ratio, and the model is able to calculate the optimal feed trays. The upper-bound properties of selected membranes, which define their performance and reliability criteria, have been studied, benchmarking the economic evaluation against conventional distillation in order to assess the expedience of a hybrid system implementation.Financial support from the Spanish Ministry of Science under the projects CTQ2015-66078-R and CTQ2016-75158-R (MINECO, Spain-FEDER 2014–2020) is gratefully acknowledged. Raúl Zarca also thanks the Universidad de Cantabria for a postgraduate fellowship