The respiratory syncytial virus nucleoprotein–RNA complex forms a left-handed helical nucleocapsid

Respiratory Syncytial Virus (RSV) is an important human pathogen. Its nucleocapsid (NC), which comprises the negative sense RNA viral genome coated by the viral nucleoprotein N, is a critical assembly that serves as template for both mRNA synthesis and genome replication. We have previously described the X-ray structure of a nucleocapsid-like structure: a decameric ring formed of N-RNA that mimics one turn of the helical NC. In the absence of experimental data we had hypothesized that the NC helix would be right-handed, as the N-N contacts in the ring appeared to more easily adapt to that conformation. We now unambiguously show that the RSV NC is a left-handed helix. We further show that the contacts in the ring can be distorted to maintain key N-N protein interactions in a left-handed helix, and discuss the implications of the resulting atomic model of the helical NC for viral replication and transcription

Амбивалентно - эквилибраторное действие слабоминерализованных кремниевых вод на показатели водно-солевого обмена у жнвотных с моделью экспериментального предиабета

In the experiment on white rats with the model of pre-diabetes changes of water-salt exchange and their correction by internal course introduction of low-miniralization of silicic waters is grounded

Internet of tangibles:Exploring the interaction-attention continuum

There is an increasing interest in the HCI research community to design richer user interactions with the Internet of Things (IoT). This studio will allow exploring the design of tangible interaction with the IoT, what we call Internet of Tangibles. In particular, we aim at investigating the full interaction-attention continuum, with the purpose of designing IoT tangible interfaces that can switch between peripheral interactions that do not disrupt everyday routines, and focused interactions that support user's reflections. This investigation will be conducted through hands-on activities where participants will prototype tangible IoT objects, starting by a paper prototyping phase, supported by design cards, and followed by an Arduino prototype phase. The purpose of the studio is also establishing a community of researchers and practitioners, from both academy and industry, interested in the field of tangible interaction with the Internet of Things

LOOP:A physical artifact to facilitate seamless interaction with personal data in everyday life

We investigated how a physical artifact could support seamless interaction with personal activity data in everyday life. We introduce LOOP (Figure 1), a physical artifact that changes its shape according to the activity data of the owner, providing an abstract visualization. This paper reports on the design process of LOOP that was informed by interviews and co-creation sessions with end users. We conclude with future work on the evaluation of the concept. This paper makes two main contributions. Firstly, LOOP is proposed as an example of an alternative approach to physically represent activity data. Secondly, the design process and rationale behind LOOP are presented as design knowledge

Nanoencapsulation of bacteriophages in liposomes prepared using microfluidic hydrodynamic flow focusing

Increasing antibiotic resistance in pathogenic microorganisms has led to renewed interest in bacteriophage therapy in both humans and animals. A ‘Trojan Horse’ approach utilising liposome encapsulated phages may facilitate access to phagocytic cells infected with intracellular pathogens residing therein, e.g. to treat infections caused by Mycobacterium tuberculosis, Listeria, Salmonella and Staphyloccocus. Additionally, liposome encapsulated phages may adhere to and diffuse within mucosa harbouring resistant bacteria which are challenges in treating respiratory and gastrointestinal infections. Orally delivered phages tend to have short residence times in the gastrointestinal tract due to clinical symptoms such as diarrhoea; this may be addressed through mucoadhesion of liposomes. In the present study we have evaluated the use of a microfluidic based technique for the encapsulation of bacteriophages in liposomes having mean sizes between 100–300 nm. Encapsulation of two model phages was undertaken, an Escherichia coli T3 podovirus (size ~65 nm) and a myovirus Staphylococcus aureus phage K (capsid head ~80 nm and phage tail length ~200 nm). The yield of encapsulated T3 phages was 109 PFU/ml and for phage K was much lower at 105 PFU/ml. The encapsulation yield for E. coli T3 phages was affected by aggregation of T3 phages. S. aureus phage K was found to interact with the liposome lipid bilayer resulting in large numbers of phages bound to the outside of the formed liposomes instead of being trapped inside them. We were able to inactivate the liposome bound S. aureus K phages whilst retaining the activity of the encapsulated phages in order to estimate the yield of microfluidic encapsulation of large tailed phages. Previous published studies on phage encapsulation in liposomes may have overestimated the yield of encapsulated tailed phages. This overestimation may affect the efficacy of phage dose delivered at the site of infection. Externally bound phages would be inactivated in the stomach acid resulting in low doses of phages delivered at the site of infection further downstream in the gastrointestinal tract

An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles

Virus-like particles composed of the core antigen of hepatitis B virus (HBcAg) have been shown to be an effective platform for the display of foreign epitopes in vaccine development. Heterologous sequences have been successfully inserted at both amino and carboxy termini as well as internally at the major immunodominant epitope. We used cryogenic electron microscopy (CryoEM) and three-dimensional image reconstruction to investigate the structure of VLPs assembled from an N-terminal extended HBcAg that contained a polyhistidine tag. The insert was seen to form a trimeric spike on the capsid surface that was poorly resolved, most likely owing to it being flexible. We hypothesise that the capacity of N-terminal inserts to form trimers may have application in the development of multivalent vaccines to trimeric antigens. Our analysis also highlights the value of tools for local resolution assessment in studies of partially disordered macromolecular assemblies by cryoEM

Beyond butyrate:microbial fiber metabolism supporting colonic epithelial homeostasis

Human gut bacteria produce metabolites that support energy and carbon metabolism of colonic epithelial cells. While butyrate is commonly considered the primary fuel, it alone cannot meet all the carbon requirements for cellular synthetic functions. Glucose, delivered via circulation or microbial metabolism, serves as a universal carbon source for synthetic processes like DNA, RNA, protein, and lipid production. Detailed knowledge of epithelial carbon and energy metabolism is particularly relevant for epithelial regeneration in digestive and metabolic diseases, such as inflammatory bowel disease and type 2 diabetes. Here, we review the production and role of different colonic microbial metabolites in energy and carbon metabolism of colonocytes, also critically evaluating the common perception that butyrate is the preferred fuel.</p

Computer-aided detection of fasciculations and other movements in muscle with ultrasound:Development and clinical application

Objective: To develop an automated algorithm for detecting fasciculations and other movements in muscle ultrasound videos. Fasciculation detection in muscle ultrasound is routinely performed online by observing the live videos. However, human observation limits the objective information gained. Automated detection of movement is expected to improved sensitivity and specificity and increase reliability.Methods: We used 42 ultrasound videos from 11 neuromuscular patients for an iterative learning process between human observers and automated computer analysis, to identify muscle ultrasound movements. Two different datasets were selected from this, one to develop the algorithm and one to validate it. The outcome was compared to manual movement identification by clinicians. The algorithm also quantifies specific parameters of different movement types, to enable automated differentiation of events.Results: The algorithm reliably detected fasciculations. With algorithm guidance, observers found more fasciculations compared to visual analysis alone, and prescreening the videos with the algorithm saved clinicians significant time compared to reviewing full video sequences. All videos also contained other movements, especially contraction pseudotremor, which confused human interpretation in some.Conclusions: Automated movement detection is a feasible and attractive method to screen for fasciculations in muscle ultrasound videos.Significance: Our findings affirm the potential clinical usefulness of automated movement analysis in muscle ultrasound