Peptide-Based Coacervate-Core Vesicles with Semipermeable Membranes

Coacervates droplets have long been considered as potential protocells to mimic living cells. However, these droplets lack a membrane and are prone to coalescence, limiting their ability to survive, interact, and organize into higher-order assemblies. This work shows that tyrosine-rich peptide conjugates can undergo liquid–liquid phase separation in a well-defined pH window and transform into stable membrane-enclosed protocells by enzymatic oxidation and cross-linking at the liquid–liquid interface. The oxidation of the tyrosine-rich peptides into dityrosine creates a semipermeable, flexible membrane around the coacervates with tunable thickness, which displays strong intrinsic fluorescence, and stabilizes the coacervate protocells against coalescence. The membranes have an effective molecular weight cut-off of 2.5 kDa, as determined from the partitioning of small dyes and labeled peptides, RNA, and polymers into the membrane-enclosed coacervate protocells. Flicker spectroscopy reveals a membrane bending rigidity of only 0.1kBT, which is substantially lower than phospholipid bilayers despite a larger membrane thickness. Finally, it is shown that enzymes can be stably encapsulated inside the protocells and be supplied with substrates from outside, which opens the way for these membrane-bound compartments to be used as molecularly crowded artificial cells capable of communication or as a vehicle for drug delivery.publishedVersio

Advancing Models and Theories for Digital Behavior Change Interventions

To be suitable for informing digital behavior change interventions, theories and models of behavior change need to capture individual variation and changes over time. The aim of this paper is to provide recommendations for development of models and theories that are informed by, and can inform, digital behavior change interventions based on discussions by international experts, including behavioral, computer, and health scientists and engineers. The proposed framework stipulates the use of a state-space representation to define when, where, for whom, and in what state for that person, an intervention will produce a targeted effect. The "state" is that of the individual based on multiple variables that define the "space" when a mechanism of action may produce the effect. A state-space representation can be used to help guide theorizing and identify crossdisciplinary methodologic strategies for improving measurement, experimental design, and analysis that can feasibly match the complexity of real-world behavior change via digital behavior change interventions

Endocytosis of coacervates into liposomes

[Image: see text] Recent studies have shown that the interactions between condensates and biological membranes are of functional importance. Here, we study how the interaction between complex coacervates and liposomes as model systems can lead to wetting, membrane deformation, and endocytosis. Depending on the interaction strength between coacervates and liposomes, the wetting behavior ranged from nonwetting to engulfment (endocytosis) and complete wetting. Endocytosis of coacervates was found to be a general phenomenon: coacervates made from a wide range of components could be taken up by liposomes. A simple theory taking into account surface energies and coacervate sizes can explain the observed morphologies. Our findings can help to better understand condensate–membrane interactions in cellular systems and provide new avenues for intracellular delivery using coacervates

Behavior change interventions: the potential of ontologies for advancing science and practice

A central goal of behavioral medicine is the creation of evidence-based interventions for promoting behavior change. Scientific knowledge about behavior change could be more effectively accumulated using "ontologies." In information science, an ontology is a systematic method for articulating a "controlled vocabulary" of agreed-upon terms and their inter-relationships. It involves three core elements: (1) a controlled vocabulary specifying and defining existing classes; (2) specification of the inter-relationships between classes; and (3) codification in a computer-readable format to enable knowledge generation, organization, reuse, integration, and analysis. This paper introduces ontologies, provides a review of current efforts to create ontologies related to behavior change interventions and suggests future work. This paper was written by behavioral medicine and information science experts and was developed in partnership between the Society of Behavioral Medicine's Technology Special Interest Group (SIG) and the Theories and Techniques of Behavior Change Interventions SIG. In recent years significant progress has been made in the foundational work needed to develop ontologies of behavior change. Ontologies of behavior change could facilitate a transformation of behavioral science from a field in which data from different experiments are siloed into one in which data across experiments could be compared and/or integrated. This could facilitate new approaches to hypothesis generation and knowledge discovery in behavioral science

Prediction of torsional failure in 22 cadaver femora with and without simulated subtrochanteric metastatic defects: a CT scan-based finite element analysis

BACKGROUND: In metastatic bone disease, prophylactic fixation of impending long bone fracture is preferred over surgical treatment of a manifest fracture. There are no reliable guidelines for prediction of pathological fracture risk, however. We aimed to determine whether finite element (FE) models constructed from quantitative CT scans could be used for predicting pathological fracture load and location in a cadaver model of metastatic bone disease. MATERIAL AND METHODS: Subject-specific FE models were constructed from quantitative CT scans of 11 pairs of human femora. To simulate a metastatic defect, a transcortical hole was made in the subtrochanteric region in one femur of each pair. All femora were experimentally loaded in torsion until fracture. FE simulations of the experimental set-up were performed and torsional stiffness and strain energy density (SED) distribution were determined. RESULTS: In 15 of the 22 cases, locations of maximal SED fitted with the actual fracture locations. The calculated torsional stiffness of the entire femur combined with a criterion based on the local SED distribution in the FE model predicted 82% of the variance of the experimental torsional failure load. INTERPRETATION: In the future, CT scan-based FE analysis may provide a useful tool for identification of impending pathological fractures requiring prophylactic stabilization

Viruses: incredible nanomachines. New advances with filamentous phages

During recent decades, bacteriophages have been at the cutting edge of new developments in molecular biology, biophysics, and, more recently, bionanotechnology. In particular filamentous viruses, for example bacteriophage M13, have a virion architecture that enables precision building of ordered and defect-free two and three-dimensional structures on a nanometre scale. This could not have been possible without detailed knowledge of coat protein structure and dynamics during the virus reproduction cycle. The results of the spectroscopic studies conducted in our group compellingly demonstrate a critical role of membrane embedment of the protein both during infectious entry of the virus into the host cell and during assembly of the new virion in the host membrane. The protein is effectively embedded in the membrane by a strong C-terminal interfacial anchor, which together with a simple tilt mechanism and a subtle structural adjustment of the extreme end of its N terminus provides favourable thermodynamical association of the protein in the lipid bilayer. This basic physicochemical rule cannot be violated and any new bionanotechnology that will emerge from bacteriophage M13 should take this into account

Конкуренція університетів: світовий досвід і українські реалії

Досліджено процеси конкуренції вищих навчальних закладів; обґрунтовано основні критерії формування рейтингів університетів; виявлено взаємозв’язок між високим рейтингом університету і показником його елітності; розкрито значення капіталізації в конкурентних перевагах вищих навчальних закладів; визначено роль елітних університетів у постіндустріальному розвитку суспільства.Исследованы процессы конкуренции высших учебных заведений; обоснованы основные критерии формирования рейтингов университетов; показана взаимосвязь между высоким рейтингом университета и показателем его элитности; раскрыто значение капитализации в конкурентных преимуществах высших учебных заведений; определена роль элитных университетов в постиндустриальном развитии общества.The processes of competition of universities are studi ed, proved the main criteria for the formation of university rankings, found the relationship between highly-rated university and the rate of its elite, disclosed the value of capitalization in the competitive advantages of higher education institutions, and determined the role of elite universities in the post-industrial development

5-Formylcytosine can be a stable DNA modification in mammals.

5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA modification. These results suggest that 5fC has functional roles in DNA that go beyond being a demethylation intermediate.This work was supported by the Cancer Research UK (C14303/A17197, S.B.), The Wellcome Trust (WT099232, S.B.; WT095645/Z/11/Z, W.R.) and the BBSRC (BB/K010867/1, W.R.).This is the accepted manuscript. It is currently embargoed pending publication

Subchondral bone changes after joint distraction treatment for end stage knee osteoarthritis

Objective: Increased subchondral cortical bone plate thickness and trabecular bone density are characteristic of knee osteoarthritis (OA). Knee joint distraction (KJD) is a joint-preserving knee OA treatment where the joint is temporarily unloaded. It has previously shown clinical improvement and cartilage regeneration, indicating reversal of OA-related changes. The purpose of this research was to explore 3D subchondral bone changes after KJD treatment using CT imaging. Design: Twenty patients were treated with KJD and included to undergo knee CT imaging before, one, and two years after treatment. Tibia and femur segmentation and registration to canonical surfaces were performed semi-automatically. Cortical bone thickness and trabecular bone density were determined using an automated algorithm. Statistical parametric mapping (SPM) with two-tailed F-tests was used to analyze whole-joint changes. Results: Data was available of 16 patients. Subchondral cortical bone plate thickness and trabecular bone density were higher in the weight-bearing region of the most affected compartment (MAC; mostly medial). Especially the MAC showed a decrease in thickness and density in the first year after treatment, which was sustained towards the second year. Conclusions: KJD treatment results in bone changes that include thinning of the subchondral cortical bone plate and decrease of subchondral trabecular bone density in the first two years after treatment, potentially indicating a partial normalization of subchondral bone