Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid

Background: Nanoparticles in contact with biological fluids interact with proteins and other biomolecules, thus forming a dynamic corona whose composition varies over time due to continuous protein association and dissociation events. Eventually equilibrium is reached, at which point the continued exchange will not affect the composition of the corona. Results: We developed a simple and effective dynamic model of the nanoparticle protein corona in a body fluid, namely human plasma. The model predicts the time evolution and equilibrium composition of the corona based on affinities, stoichiometries and rate constants. An application to the interaction of human serum albumin, high density lipoprotein (HDL) and fibrinogen with 70 nm N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles is presented, including novel experimental data for HDL. Conclusions: The simple model presented here can easily be modified to mimic the interaction of the nanoparticle protein corona with a novel biological fluid or compartment once new data will be available, thus opening novel applications in nanotoxicity and nanomedicine

Altered glucose-dependent secretion of glucagon and ACTH is associated with insulin resistance, assessed by population analysis

This study aimed to characterize how the dysregulation of counter-regulatory hormones can contribute to insulin resistance and potentially to diabetes. Therefore, we investigated the association between insulin sensitivity and the glucose- and insulin-dependent secretion of glucagon, adrenocorticotropic hormone (ACTH), and cortisol in non-diabetic individuals using a population model analysis. Data, from hyperinsulinemic–hypoglycemic clamps, were pooled for analysis, including 52 individuals with a wide range of insulin resistance (reflected by glucose infusion rate 20–60 min; GIR 20–60min). Glucagon secretion was suppressed by glucose and, to a lesser extent, insulin. The GIR20–60min and BMI were identified as predictors of the insulin effect on glucagon. At no rmoglycemia (5 mmol/L), a 90% suppression of glucagon was achieved at insulin concentrations of 16.3 and 43.4 μU/mL in individuals belonging to the highest and lowest quanti les of insulin sensitivity, respectively. Insulin resistance of glucagon secretion explained the elevated fasting glucagon for individuals with a low GIR20–60min. ACTH secretion was suppressed by glucose and not affected by insulin. The GIR20–60min was superior to other measures as a predictor of glucose-dependent ACTH secretion, with 90% suppression of ACTH secretion by glucose at 3.1 and 3.5 mmol/L for insulin-sensitive and insulin-resista nt individuals, respectively. This difference may appear small but shifts the suppression rang e into normoglycemia for individuals with insulin resistance, thus, leading to earli er and greater ACTH/cortisol response when the glucose falls. Based on modeling of pooled glucose-clamp data, insulin resistance was associated with generally elevated glucagon and a potentiated cortisol-axis response to hypoglycemia, and over time both hormonal pathways may therefore contribute to dysglycemia and possibly type 2 diabetes

Infrared emission towards SN 1987A 11 years after outburst: Measurements with ISOCAM

We present measurements of the mid-infrared (MIR) emission from SN 1987A, made using the Infrared Space Observatory (ISO) 11 years after outburst. They are the only late epoch detections of this source in the thermal IR regime. The position of the source, determined from an offset to an IR-emitting star, suggests that the emission is associated with SN 1987A or its extended supernova remnant (SNR). A predominantly circumstellar origin is however suggested by the size and orientation of the IR-emitting region, which is comparable with the extension of the inner ring seen with the Hubble Space Telescope (HST). The emission is most probably from collisionally-heated circumstellar grains embedded in shocked gas downstream of the blast wave. The MIR extent is consistent with the hypothesis that the blast wave was propagating into material of moderate density interior to the thick inner ring at the epoch of the ISOCAM observations

Infrared emission towards 11 years after outburst: Properties of the circumstellar dust

Detailed models are presented for the late epoch mid infrared (MIR) emission from collisionally heated grains in the shocked circumstellar gas around SN 1987A. Thermal dust emission from a region of moderate density interior to the thick inner ring seen with the Hubble Space Telescope (HST) is found to be a natural explanation for the MIR spectral energy distribution measured by ISOCAM. The MIR-spectrum can be reproduced by a mixture of silicate-iron or silicate-graphite grains or by a composition of pure graphite grains. A composition of pure iron grains on the other hand can be excluded and a pure silicate composition does not seem to be very likely. The dust-to-gas ratio in the interaction zone is ~0.01%, an order of magnitude lower than estimates for dust abundances in the winds of red supergiant (RSG) stars in the LMC. This low dust abundance can be accounted for by a combination of evaporation through the UV-flash from the supernova outburst and subsequent sputtering in the shocked gas. For this explanation to hold, dust in the pre-supernova circumstellar medium (CSM) would have to have been predominantly composed of grains other than graphite, with a maximum size smaller than ~0.1 microns

Revisiting INTEGRAL/SPI observations of 44^44Ti from Cassiopeia A

T. Siegert, R. Diehl, M. G. H. Krause, and J. Greiner, “Revisiting INTEGRAL/SPI observations of 44Ti from Cassiopeia A”, Astronomy & Astrophysics, Vol. 579, July 2015. This version of record is available online at: https://doi.org/10.1051/0004-6361/201525877 Reproduced with Permission from Astronomy and Astrophysics, © ESO 2015.Context. The 340-yr old supernova remnant Cassiopeia A, located at 3.4 kpc distance, is the best-studied young core-collapse super- nova remnant. Nucleosynthesis yields in radioactive isotopes have been studied with different methods, in particular for production and ejection of 44Ti and 56Ni, which originate in the innermost regions of the supernova. 44Ti was first discovered in this remnant, but is not seen consistently in other core-collapse sources. Aims. We aim to measure radioactive 44Ti ejected in Cassiopeia A and to place constraints on velocities of these ejecta by determining X- and γ-ray line-shape parameters of the emission lines. Methods. We analyzed the observations made with the SPI spectrometer on INTEGRAL together with an improved instrumental background method, to achieve a high spectroscopic resolution that enables interpretation for a velocity constraint on 44Ti ejecta from the 1.157 MeV γ-ray line of the 44Sc decay. Results. We observe both the hard X-ray line at 78 keV and the γ-ray line at 1157 keV from the 44Ti decay chain at a combined significance of 3.8σ. Measured fluxes are (2.1 ± 0.4) × 10−5 ph cm−2 s−1 and (3.5 ± 1.2) × 10−5 ph cm−2 s−1, which corresponds to (1.5 ± 0.4) × 10−4 and (2.4 ± 0.9) × 10−4 M⊙ of 44Ti, respectively. The measured Doppler broadening of the lines implies expansion velocities of 4300 and 2200 km s−1 , respectively. By combining our results with previous studies, we determine a more precise esti- mate of ejected 44Ti of (1.37 ± 0.19) × 10−4 M⊙. Conclusions. The measurements of the two lines are consistent with previous studies. The flux in the line originating from excited 44Ca is significantly higher than the flux determined in the lines from 44Sc. Cosmic-ray acceleration within the supernova remnant may be responsible for an additional contribution to this line from nuclear de-excitation following energetic particle collisions in the remnant and swept-up material.Peer reviewe

The USDA Barley Core Collection:Genetic Diversity, Population Structure, and Potential for Genome-Wide Association Studies

New sources of genetic diversity must be incorporated into plant breeding programs if they are to continue increasing grain yield and quality, and tolerance to abiotic and biotic stresses. Germplasm collections provide a source of genetic and phenotypic diversity, but characterization of these resources is required to increase their utility for breeding programs. We used a barley SNP iSelect platform with 7,842 SNPs to genotype 2,417 barley accessions sampled from the USDA National Small Grains Collection of 33,176 accessions. Most of the accessions in this core collection are categorized as landraces or cultivars/breeding lines and were obtained from more than 100 countries. Both STRUCTURE and principal component analysis identified five major subpopulations within the core collection, mainly differentiated by geographical origin and spike row number (an inflorescence architecture trait). Different patterns of linkage disequilibrium (LD) were found across the barley genome and many regions of high LD contained traits involved in domestication and breeding selection. The genotype data were used to define 'mini-core' sets of accessions capturing the majority of the allelic diversity present in the core collection. These 'mini-core' sets can be used for evaluating traits that are difficult or expensive to score. Genome-wide association studies (GWAS) of 'hull cover', 'spike row number', and 'heading date' demonstrate the utility of the core collection for locating genetic factors determining important phenotypes. The GWAS results were referenced to a new barley consensus map containing 5,665 SNPs. Our results demonstrate that GWAS and high-density SNP genotyping are effective tools for plant breeders interested in accessing genetic diversity in large germplasm collections

Mapping the CDIO Syllabus to the UNESO Key Competences for Sustainability

In this paper a framework of key competencies for sustainability defined by UNESCO is used\ua0to evaluate the relevance of the CDIO Syllabus for promoting engineering education for\ua0sustainable development. The evaluation is performed in two steps. First, topics, terms and\ua0concepts in the CDIO Syllabus that corresponds to the different UNESCO key competencies\ua0are identified. The second step is a qualitative discussion where areas of strong mapping are\ua0highlighted and aspects that could be better visualized or strengthened in, or added to, the\ua0Syllabus are identified. Differences in definitions of various concepts between the CDIO\ua0Syllabus and the UNESCO key competencies and the overall relation between the two\ua0frameworks are discussed. It is concluded that the CDIO Syllabus is rather well aligned with\ua0the UNESCO framework, however several opportunities (not to say needs) for strengthening\ua0the Syllabus in relation to the key competencies are identified. The UNESCO key\ua0competencies are found to be useful instruments for scrutinizing and updating the CDIO\ua0Syllabus. Other opportunities for knowledge and methods transfer between the Education for\ua0Sustainable Development (ESD) domain and the Engineering Education domain are\ua0identified. The paper is proposed to be used as basis for updating the CDIO Syllabus into a\ua0version 3.0 for maintaining its relevance in a changing world

Protein C Inhibitor—A Novel Antimicrobial Agent

Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequently leads to their permeabilization. As shown by negative staining electron microscopy, treatment of Escherichia coli or Streptococcus pyogenes bacteria with PCI triggers membrane disruption followed by the efflux of bacterial cytosolic contents and bacterial killing. The antimicrobial activity of PCI is located to the heparin-binding site of the protein and a peptide spanning this region was found to mimic the antimicrobial activity of PCI, without causing lysis or membrane destruction of eukaryotic cells. Finally, we show that platelets can assemble PCI on their surface upon activation. As platelets are recruited to the site of a bacterial infection, these results may explain our finding that PCI levels are increased in tissue biopsies from patients suffering from necrotizing fasciitis caused by S. pyogenes. Taken together, our data describe a new function for PCI in innate immunity

Human Centric Facial Expression Recognition

Facial expression recognition (FER) is an area of active research, both in computer science and in behavioural science. Across these domains there is evidence to suggest that humans and machines find it easier to recognise certain emotions, for example happiness, in comparison to others. Recent behavioural studies have explored human perceptions of emotion further, by evaluating the relative contribution of features in the face when evaluating human sensitivity to emotion. It has been identified that certain facial regions have more salient features for certain expressions of emotion, especially when emotions are subtle in nature. For example, it is easier to detect fearful expressions when the eyes are expressive. Using this observation as a starting point for analysis, we similarly examine the effectiveness with which knowledge of facial feature saliency may be integrated into current approaches to automated FER. Specifically, we compare and evaluate the accuracy of ‘full-face’ versus upper and lower facial area convolutional neural network (CNN) modelling for emotion recognition in static images, and propose a human centric CNN hierarchy which uses regional image inputs to leverage current understanding of how humans recognise emotions across the face. Evaluations using the CK+ dataset demonstrate that our hierarchy can enhance classification accuracy in comparison to individual CNN architectures, achieving overall true positive classification in 93.3% of cases

Interaction of β-Sheet Folds with a Gold Surface

The adsorption of proteins on inorganic surfaces is of fundamental biological importance. Further, biomedical and nanotechnological applications increasingly use interfaces between inorganic material and polypeptides. Yet, the underlying adsorption mechanism of polypeptides on surfaces is not well understood and experimentally difficult to analyze. Therefore, we investigate here the interactions of polypeptides with a gold(111) surface using computational molecular dynamics (MD) simulations with a polarizable gold model in explicit water. Our focus in this paper is the investigation of the interaction of polypeptides with β-sheet folds. First, we concentrate on a β-sheet forming model peptide. Second, we investigate the interactions of two domains with high β-sheet content of the biologically important extracellular matrix protein fibronectin (FN). We find that adsorption occurs in a stepwise mechanism both for the model peptide and the protein. The positively charged amino acid Arg facilitates the initial contact formation between protein and gold surface. Our results suggest that an effective gold-binding surface patch is overall uncharged, but contains Arg for contact initiation. The polypeptides do not unfold on the gold surface within the simulation time. However, for the two FN domains, the relative domain-domain orientation changes. The observation of a very fast and strong adsorption indicates that in a biological matrix, no bare gold surfaces will be present. Hence, the bioactivity of gold surfaces (like bare gold nanoparticles) will critically depend on the history of particle administration and the proteins present during initial contact between gold and biological material. Further, gold particles may act as seeds for protein aggregation. Structural re-organization and protein aggregation are potentially of immunological importance