Adsorption of Fibrinogen on Silica Surfaces-The Effect of Attached Nanoparticles

When a biomaterial is inserted into the body, proteins rapidly adsorb onto its surface, creating a conditioning protein film that functions as a link between the implant and adhering cells. Depending on the nano-roughness of the surface, proteins will adsorb in different amounts, with different conformations and orientations, possibly affecting the subsequent attachment of cells to the surface. Thus, modifications of the surface nanotopography of an implant may prevent biomaterial-associated infections. Fibrinogen is of particular importance since it contains adhesion epitopes that are recognized by both eukaryotic and prokaryotic cells, and can therefore influence the adhesion of bacteria. The aim of this study was to model adsorption of fibrinogen to smooth or nanostructured silica surfaces in an attempt to further understand how surface nanotopography may affect the orientation of the adsorbed fibrinogen molecule. We used a coarse-grained model, where the main body of fibrinogen (visible in the crystal structure) was modeled as rigid and the flexible α C-chains (not visible in the crystal structure) were modeled as completely disordered. We found that the elongated fibrinogen molecule preferably adsorbs in such a way that it protrudes further into solution on a nanostructured surface compared to a flat one. This implicates that the orientation on the flat surface increases its bio-availability

Atomically Resolved Interfacial Analysis of Bone-Like Hydroxyapatite Nanoparticles on Titanium

Titanium is commonly used for medical devices, including osseointegrating implants, owing to its biocompatibility and mechanical properties. Nanostructuring titanium implants is known to enhance the healing process by promoting bone growth on the implant surface. Hydroxyapatite nanoparticles, resembling natural bone mineral, have been used to further improve osseointegration. While previous studies have investigated the osseointegration of titanium implants using atom probe tomography, limited research has focused on the attachment of synthetic hydroxyapatite to titanium. Herein, electron microscopy and atom probe tomography are used to reveal the assembly of synthetic hydroxyapatite nanoparticles in the titanium oxide surface. By sputter coating with chromium, a suitable matrix is formed for detailed interfacial analysis. The results demonstrate the diffusion of calcium, phosphorus, and carbon from hydroxyapatite nanoparticles into the titanium oxide surface. Titanium is commonly used for medical devices, owing to its biocompatibility and mechanical properties. Nanostructuring titanium implants with hydroxyapatite nanoparticles, resembling natural bone mineral, enhances the healing process by promoting bone growth on the implant surface. Herein, atom probe tomography reveals the assembly of synthetic hydroxyapatite nanoparticles in the titanium oxide surface.image & COPY; 2023 WILEY-VCH Gmb

Formulation of polyphthalaldehyde microcapsules for immediate UV-light triggered release

Triggered release from responsive drug reservoirs activated by remote stimuli is desired in a range of fields. Critical bottlenecks are cost-efficient formulation avenues applicable for industrial scale-up, viable triggers and immediate release rather than continuous release upon activation. UV-sensitive microcapsules based on self-immolating polymers in combination with thin shells and morphological weak spots should allow for immediate triggered release. Polyphthalaldehyde-based microcapsules were prepared using several variations of the internal phase separation route. In addition, a fluorescence microscopy method was developed to study both the microcapsule morphology and the triggered release in-situ. The microcapsule formation was driven by the surface activity of the stabilizer, effectively lowering the high polymer-water interfacial tension, which is in sharp contrast to conventional encapsulation systems. Contrary to previous findings, a core–shell morphology was obtained via slow emulsion-to-suspension transformation. Rapid transformation captured intermediate inverted core–shell structures. The capsules were highly sensitive to both acid- and UV-mediated triggers, leading to an unzipping and rupturing of the shell that released the core content. Poly(methacrylic acid)-stabilized microcapsules displayed immediate UV-triggered release provided by their stimuli-sensitive blueberry morphology. Both capsules in aqueous and dry environment started to lose their core content after less than one minute of UV light exposure

"Man måste brinna för att bli bränd" - en studie om en grupp kvinnors upplevelse av utbrändhet

ABSTRACT Author: Aferdita Haxha, Anna-lena Hulander Title: ”Man måste brinna för att bli bränd” – en studie om en grupp kvinnors upplevelse av utbrändhet Supervisor: Anders Lundberg Assessor: Mats Hilte The aim with this essay was to examine seven women’s experiences regarding burn-out. Furthermore we looked at what emotions these women experienced during their burn-out period and how their recovery was perceived. When summoned our material we found that burn-out seemed to be a less valid illness, in some cases we noticed a sense of shame connected to the sickness. Burn-out is an unclear expression that causes confusion because it’s a vague word with many meanings. The term has also been criticized for the reason that it refers to something that is burnt down, never to recover. The information our analysis is based upon is gathered through qualitative semi-structured interviews. We have applied Christina Maslach theory concerning burn-out to better understand and gather further knowledge regarding burn-out. Our conclusion is that burn-out is complex phenomenon which is caused by both work-related issues as well as personal traits

Immune complement activation is attenuated by surface nanotopography

The immune complement (IC) is a cell-free protein cascade system, and the first part of the innate immune system to recognize foreign objects that enter the body. Elevated activation of the system from, for example, biomaterials or medical devices can result in both local and systemic adverse effects and eventually loss of function or rejection of the biomaterial. Here, the researchers have studied the effect of surface nanotopography on the activation of the IC system. By a simple nonlithographic process, gold nanoparticles with an average size of 58 nm were immobilized on a smooth gold substrate, creating surfaces where a nanostructure is introduced without changing the surface chemistry. The activation of the IC on smooth and nanostructured surfaces was viewed with fluorescence microscopy and quantified with quartz crystal microbalance with dissipation monitoring in human serum. Additionally, the ability of pre-adsorbed human immunoglobulin G (IgG) (a potent activator of the IC) to activate the IC after a change in surface hydrophobicity was studied. It was found that the activation of the IC was significantly attenuated on nanostructured surfaces with nearly a 50% reduction, even after pre-adsorption with IgG. An increase in surface hydrophobicity blunted this effect. The possible role of the curvature of the nanoparticles for the orientation of adsorbed IgG molecules, and how this can affect the subsequent activation of the IC, are discussed. The present findings are important for further understanding of how surface nanotopography affects complex protein adsorption, and for the future development of biomaterials and blood-contacting devices

Dietary biomarkers and food records indicate compliance to study diets in the ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) trial

Background: In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported intake of trial foods from telephone interviews. The aim of this study was to evaluate compliance using objective dietary biomarkers for whole grain, fruit and vegetables, margarine and oil, seafood and overall fat quality, as well as reported intake from food records of key components of the study diets. Methods: Fifty patients with rheumatoid arthritis were randomized to begin with the intervention diet (rich in whole grain, fruit and vegetables, margarine/oil and seafood) or the control diet (rich in meat and high-fat dairy) for 10 weeks, followed by a ~ 4 months wash-out period, and then switched diet. Compliance was evaluated using plasma alkylresorcinols (AR) as biomarkers for intake of whole grain wheat and rye, serum carotenoids for fruit and vegetables, plasma linoleic acid (LA, 18:2 n-6) and -α-linolenic acid (18:3, n-3) for margarine and cooking oil, plasma eicosapentaenoic acid (EPA, 20:5 n-3), −docosahexaenoic acid (DHA 22:6, n-3) and -docosapentaenoic acid (22:5 n-3) for seafood, and plasma fatty acid pattern for the overall dietary fat quality. Reported intake of whole grain, fruit, berries and vegetables, seafood, red meat, and fat quality was extracted from 3-d food records. Results: Plasma AR C21:0 and C23:0, LA, EPA, and DHA were higher while total serum carotenoids were lower after the intervention diet period compared to the control diet period (AR and carotenoids: p = <0.05, fatty acids: p = <0.001). Reported intake of whole grain, fruit, berries and vegetables, and seafood was higher and reported intake of red meat was lower during the intervention diet period compared to the control diet period (p = <0.001). Plasma- and reported fatty acid pattern differed as intended between the diet periods

Stable trapping of multiple proteins at physiological conditions using nanoscale chambers with macromolecular gates

The possibility to detect and analyze single or few biological molecules is very important for understanding interactions and reaction mechanisms. Ideally, the molecules should be confined to a nanoscale volume so that the observation time by optical methods can be extended. However, it has proven difficult to develop reliable, non-invasive trapping techniques for biomolecules under physiological conditions. Here we present a platform for long-term tether-free (solution phase) trapping of proteins without exposing them to any field gradient forces. We show that a responsive polymer brush can make solid state nanopores switch between a fully open and a fully closed state with respect to proteins, while always allowing the passage of solvent, ions and small molecules. This makes it possible to trap a very high number of proteins (500-1000) inside nanoscale chambers as small as one attoliter, reaching concentrations up to 60 gL−1. Our method is fully compatible with parallelization by imaging arrays of nanochambers. Additionally, we show that enzymatic cascade reactions can be performed with multiple native enzymes under full nanoscale confinement and steady supply of reactants. This platform will greatly extend the possibilities to optically analyze interactions involving multiple proteins, such as the dynamics of oligomerization events

The Forkhead Transcription Factor Foxi1 Is a Master Regulator of Vacuolar H+-ATPase Proton Pump Subunits in the Inner Ear, Kidney and Epididymis

The vacuolar H+-ATPase dependent transport of protons across cytoplasmic membranes in FORE (forkhead related) cells of endolymphatic epithelium in the inner ear, intercalated cells of collecting ducts in the kidney and in narrow and clear cells of epididymis require expression of several subunits that assemble into a functional multimeric proton pump. We demonstrate that expression of four such subunits A1, B1, E2 and a4 all co-localize with the forkhead transcription factor Foxi1 in a subset of epithelial cells at these three locations. In cells, of such epithelia, that lack Foxi1 we fail to identify any expression of A1, B1, E2 and a4 demonstrating an important role for the transcription factor Foxi1 in regulating subunit availability. Promoter reporter experiments, electrophoretic mobility shift assays (EMSA) and site directed mutagenesis demonstrate that a Foxi1 expression vector can trans-activate an a4-promoter reporter construct in a dose dependent manner. Furthermore, we demonstrate using chromatin immunoprecipitation (ChIP) assays that Foxi1-dependent activation to a large extent depends on cis-elements at position −561/−547 in the a4 promoter. Thus, we provide evidence that Foxi1 is necessary for expression of at least four subunits in three different epithelia and most likely is a major determinant for proper assembly of a functional vacuolar H+-ATPase complex at these locations

Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: Implications for human CHARGE syndrome

CHD7 is a chromodomain gene mutated in CHARGE syndrome, a multiple anomaly condition characterized by ocular c oloboma, h eart defects, a tresia of the choanae, r etarded growth and development, g enital hypoplasia, and e ar defects including deafness and semicircular canal dysgenesis. Mice with heterozygous Chd7 deficiency have circling behavior and semicircular canal defects and are an excellent animal model for exploring the pathogenesis of CHARGE features. Inner ear vestibular defects have been characterized in heterozygous Chd7 -deficient embryos and early postnatal mice, but it is not known whether vestibular defects persist throughout adulthood in Chd7 -deficient mice or whether the vestibular sensory epithelia and their associated innervation and function are intact. Here we describe a detailed analysis of inner ear vestibular structures in mature mice that are heterozygous for a Chd7 -deficient, gene-trapped allele ( Chd7 Gt/+ ). Chd7 Gt/+ mice display variable asymmetric lateral and posterior semicircular canal malformations, as well as defects in vestibular sensory epithelial innervation despite the presence of intact hair cells in the target organs. These observations have important functional implications for understanding the clinical manifestations of CHD7 mutations in humans and for designing therapies to treat inner ear vestibular dysfunction. J. Comp. Neurol. 504:519–532, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56115/1/21460_ftp.pd