Self-association of a highly charged, arginine-rich cell-penetrating peptide

Small angle X-ray scattering (SAXS) measurements reveal a striking difference in intermolecular interactions between two short, highly charged peptides, namely deca-arginine (R10) and deca-lysine (K10). Comparison of SAXS curves at high and low salt concentration shows that R10 self-associates, while interactions between K10 chains are purely repulsive. The self-association of R10 occurs to a larger extent at low ionic strength indicating that the attraction between R10 molecules has an important electrostatic component. SAXS data is complemented by potentials of mean force between the peptides calculated by means of umbrella sampling molecular dynamics (MD) simulations. Atomistic MD simulations elucidate the origin of the R10-R10 attraction by providing structural information on the dimeric state: the last two C-terminal residues of R10 constitute an adhesive patch achieved by stacking of the side chains of two arginine residues and by salt bridges formed between the like-charge ion-pair and C-terminal carboxyl groups. A statistical analysis of the protein data bank reveals that this mode of interaction commonly occurs in proteins. Please click Additional Files below to see the full abstract

Dynamical Oligomerisation of Histidine Rich Intrinsically Disordered Proteins Is Regulated through Zinc-Histidine Interactions

Intrinsically disordered proteins (IDPs) can form functional oligomers and in some cases, insoluble disease related aggregates. It is therefore vital to understand processes and mechanisms that control pathway distribution. Divalent cations including Zn2+ can initiate IDP oligomerisation through the interaction with histidine residues but the mechanisms of doing so are far from understood. Here we apply a multi-disciplinary approach using small angle X-ray scattering, nuclear magnetic resonance spectroscopy, calorimetry and computations to show that that saliva protein Histatin 5 forms highly dynamic oligomers in the presence of Zn2+. The process is critically dependent upon interaction between Zn2+ ions and distinct histidine rich binding motifs which allows for thermodynamic switching between states. We propose a molecular mechanism of oligomerisation, which may be generally applicable to other histidine rich IDPs. Finally, as Histatin 5 is an important saliva component, we suggest that Zn2+ induced oligomerisation may be crucial for maintaining saliva homeostasis

Livet efter en hjärtinfarkt : En litteraturöversikt som belyser patientens upplevelse.

Bakgrund: Hjärtinfarkt är en global folksjukdom som främst kan förebyggas genom hälsosamma levnadsvanor. Efter att ha drabbats av en hjärtinfarkt är en stor och betydelsefull del av behandlingen att patienten ändrar till hälsosamma levnadsvanor utefter risk-och friskfaktorer. För att få patienter att eftersträva en hälsosammare livsstil har sjuksköterskan en betydelsefull roll genom personcentrerad och hälsofrämjande omvårdnad som vägleder, informerar och stöttar patienten. Att drabbas av en hjärtinfarkt kan väcka många olika känslor och upplevelser där sjuksköterskan ska möta och bekräfta dessa. Patienten ska ses som en jämlikpart och vara delaktig i sin vård.  Syfte: Syftet var att belysa livet efter en hjärtinfarkt med fokus på förändrade levnadsvanor. Metod: En litteraturöversikt med kvalitativ metod och induktiv ansats valdes för att besvara syftet. Tio artiklar granskades och analyserades. Resultat: Dataanalysen som syfte till att identifiera likheter och skillnader i artiklarna skapade tre huvudkategorier förändrade levnadsvanor, den nya livssituationen ochstödets betydelse. Med underkategorier att sluta röka, att förändra sin fysiska aktivitet, att förändra kosten, acceptera den nya livssituationen, rädsla och oro, information och stöttning från vården samtnärståendes påverkan.Slutsats: Patienternas upplevelse av att förändra sina levnadsvanor efter en hjärtinfarkt bidrog till många känslor och upplevelser som kunde påverka patienten positivt och negativt. En koppling kunde dras till att de negativa upplevelserna kan förebyggas genom ökat stöd, information och personcentread vård från sjukvården. Nyckelord:Hjärtinfarkt, information, kvalitativ, levnadsvanor, livsstilsförändring, patient, upplevelse

Konstruktioner av moderskap och faderskap: En kvalitativ studie om hur föreställningar om moderskap och faderskap interagerar med andra bedömningskriterier på Familjerätten

The aim of our study was to examine how concepts of motherhood and fatherhood interact with other determining factors in child custody investigations. Emanating from our own work experience in social work, we began to consider the prevalent values surrounding parenting, in particular, those terms related to motherhood and fatherhood. Thus our central issues of examination are which assessment criteria affect a social worker with regards to questions of child custody, residence and access; how a social worker constructs parents in his or her reasoning and judgments; and if he or she reproduces society's perceptions of motherhood and fatherhood. We started with a social constructivist approach in which sex is seen as being socially constructed. This approach also makes use of Yvonne Hirdman’s theory of the gender system. Our results were analyzed based on these theories. We chose to interview seven social workers using a semi-structured interview technique, in which we also used a vignette as an interview tool. We found that the prevailing notions in society regarding maternity and paternity according to the social workers are based on traditional gender roles, which means that it is still the mother who is deemed to have primary responsibility for childcare. This was evident in the reasoning of the social workers, where the parents were constructed in accordance with societal standards. Since the continuity of the child was highlighted as a key evaluation criterion, we believe that it is difficult for family secretaries to free themselves from notions of maternity and paternity when the mother is the one who stood for the continuity. This is when the mother, according to traditional gender roles, was seen as the primary care giver

Utilizing Coarse-Grained Modeling and Monte Carlo Simulations to Evaluate the Conformational Ensemble of Intrinsically Disordered Proteins and Regions

In this study, we have used the coarse-grained model developed for the intrinsically disordered saliva protein (IDP) Histatin 5, on an experimental selection of monomeric IDPs, and we show that the model is generally applicable when electrostatic interactions dominate the intra-molecular interactions. Experimental and theoretically calculated small-angle X-ray scattering data are presented in the form of Kratky plots, and discussions are made with respect to polymer theory and the self-avoiding walk model. Furthermore, the impact of electrostatic interactions is shown and related to estimations of the conformational ensembles obtained from computer simulations and “Flexible-meccano.” Special attention is given to the form factor and how it is affected by the salt concentration, as well as the approximation of using the form factor obtained under physiological conditions to obtain the structure factor

Molecular Dynamics Simulations of Intrinsically Disordered Proteins: Force Field Evaluation and Comparison with Experiment

An increasing number of studies using molecular dynamics (MD) simulations of unfolded and intrinsically disordered proteins (IDPs) suggest that current force fields sample conformations that are overly collapsed. Here, we study the applicability of several state-of-the-art MD force fields, of the AMBER and GROMOS variety, for the simulation of Histatin 5, a short (24 residues) cationic salivary IDP with antimicrobial and antifungal properties. The quality of the simulations is assessed in three complementary analyses: (i) protein shape and Size comparison with recent experimental small-angle X-ray scattering data; (ii) secondary structure prediction; (iii) energy landscape exploration and conformational Class analysis. Our results show that, indeed, standard force fields sample conformations that are too compact, being systematically unable to reproduce experimental evidence such as the scattering function, the shape of the protein as compared with the Kratky plot, and intrapeptide distances obtained through the pair distance distribution function, p(r). The consistency of this deviation suggests that the problem is not mainly due to protein-protein or water-water interactions, whose parametrization varies the most between force fields and water models. In fact, as originally proposed in [Best et al. J. Chem. Theory Comput. 2014, 10, 5113-5124.], balanced protein-water interactions may be the key to solving this problem. Our simulations using this approach produce results in very good agreement with experiment

Coarse-grained modelling of the intrinsically disordered protein Histatin 5 in solution. Monte Carlo simulations in combination with SAXS.

Monte Carlo simulations and coarse-grained modelling have been used to analyze Histatin 5, which is an unstructured short cationic salivary peptide known to have anti-candidical properties. The calculated scattering functions have been compared with intensity curves and the distance distribution function P(r) obtained from SAXS, at both high and low salt concentrations. The aim is to achieve a molecular understanding and a physico-chemical insight of the obtained SAXS results and to gain information of conformational changes of Histatin 5 due to altering salt content, charge distribution, and net charge. From a modelling perspective, the accuracy of the electrostatic interaction is of special interest. The used coarse-grained model is based on the primitive model in which charged hard spheres differing in charge and in size represent the ionic particles, and the solvent only enters the model through its relative permittivity. The Hamiltonian of the model comprises three different contributions: (i) excluded volumes, (ii) electrostatic, and (iii) van der Waals interactions. Even though the model can be considered as gross omitting atomistic details, a great correspondence is obtained with experimental results. This article is protected by copyright. All rights reserved

Underlying mechanisms behind adhesion of fermented milk to packaging surfaces

Fermented milk is commonly eaten during breakfast or as a snack between meals either in one-portion cups or from a bowl with a spoon. Approximately 5-10% of the fermented milk remains in the packages upon pouring, which during the last years, has received attention in public media as newspapers and television. This is a problem, not only from an economical point of view, but also from an ecological and unethical perspective. In this study, we have investigated the influence of rheology, surface characteristics, and storage time; on product adhesion, and this study is a continuation of an earlier study published in this journal. The physical properties of the surface as roughness and morphology were determined by Scanning Electron Microscopy, Interferometry, contact angle measurements, and Fourier Transform Infrared/Attenuated Total Reflectance Spectroscopy. After incubation, the adhered amount was determined by gravimetrical studies. The results have shown that there are two mechanisms over different time scales that predominate. Initially (seconds-minutes) the excess product is drained of the surfaces until the gravity is opposed by the rheological strength such as the yield stress and the apparent viscosity. The second mechanism occurs on a longer time scale (minutes-hours) and it includes dewatering of the product residue at the surface. Concluded in this work is that the rheological properties of fermented milk is of major importance and that the problem with fermented milk remaining in the packages could be regarded as a flow and dewatering problem rather than an adsorption problem. (C) 2014 Elsevier Ltd. All rights reserved

Bovine β-casein has a polydisperse distribution of equilibrium micelles

β-casein, a self-associating protein, has been extensively studied over the years, and it is a molecule that is of academic, industrial, and clinical relevance. Therefore it is of interest to understand the structural and conformational properties of the assemblies, also denoted micelles. Here we show that β-casein possess a polydisperse distribution of equilibrium micelles, which has, to the authors knowledge, not been published before