HIV protease inhibition seen by X-ray diffraction and molecular dynamics

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Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse.

Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse

The impact of solvent characteristics on performance and process stability of printed carbon resistive materials

Carbon conductive pastes deposited by screen printing are used in many commercial applications including sensors, PCB, batteries, and PV, and as such represent an important value-added coating. An experimental investigation was carried out into the role of the solvent on the drying characteristics, conductivity, and process consistency in screen printed carbon pastes. Four materials with solvent boiling points between 166 and 219°C were deposited at film thickness between 6 and 16 μm, and the sheet resistance and film thickness were measured after successive passes through an industrial dryer operating with an air temperature of 155°C. Sheet resistances of 14 Ω/sq. were obtained with the thicker films while thinner films produced a sheet resistance of 46 Ω/sq. Thinner films achieved a stable resistivity within a 2.5-min residence time, while the thicker films required a residence time in excess of 12.5 min to achieve a stable resistivity. As well as prolonging drying times, the higher boiling point increased the resistivity of the cured film. It is postulated that the lower resistance of the faster drying materials is a result of film stressing increasing inter particle contact. Process models indicate that multiple thin layers are a more efficient means of manufacture for the process parameters examined

A brief guide to polymer characterization: structure (IUPAC technical report)

To bolster the series of Brief Guides released by International Union of Pure and Applied Chemistry (IUPAC), here we introduce the first Brief Guide to Polymer Characterization. This article provides a concise overview of characterization methods for teachers, students, non-specialists, and newcomers to polymer science as well as being a useful manual for researchers and technicians. Unlike pure low molar mass chemical substances, polymers are not composed of identical molecules. The macromolecules which comprise a single polymer sample vary from one another, primarily in terms of size and shape, but often also in the arrangement or positioning of atoms within macromolecules (e.g., chain branching, isomerism, etc.). Polymer properties are often drastically different from those of other substances and their characterization relies on specialist equipment and/or common equipment used in a specialized way (e.g., particular sample preparation or data analysis). This Brief Guide focuses uniquely on the structural characterization (i.e., analyzing the molecular and multi-molecular aspects) of polymers. The complex nature of the structural variables possible in macromolecular materials often presents a challenge with regard to the detailed structural characterization of polymers. This Brief Guide provides a useful starting point to direct the reader to the most commonly used and useful techniques to characterize these structural variables

Opportunities and hurdles of edible insects for food and feed

Entomophagy, the consumption of insects, is promoted as an alternative sustainable source of protein for humans and animals. Seminal literature highlights predominantly the benefits, but with limited empirical support and evaluation. We highlight the historical significance of entomophagy by humans and key opportunities and hurdles identified by research to date, paying particular attention to research gaps. It is known that insects present a nutritional opportunity, being generally high in protein and key micronutrients, but it is unclear how their nutritional quality is influenced by what they are fed. Research indicates that, in ideal conditions, insects have a smaller environmental impact than more traditional Western forms of animal protein; less known is how to scale up insect production while maintaining these environmental benefits. Studies overall show that insects could make valuable economic and nutritional contributions to the food or feed systems, but there are no clear regulations in place to bring insects into such supply systems. Future research needs to examine how the nutritional value of insects can be managed systematically, establish clear processing and storage methodology, define rearing practices and implement regulations with regard to food and feed safety. Each of these aspects should be considered within the specifics of concrete supply and value chains, depending on whether insects are intended for food or for feed, to ensure insects are a sound economic, nutritional and sustainable protein alternative – not just a more expensive version of poultry for food, or soya for feed

Histone Deacetylase Activity Modulates Alternative Splicing

There is increasing evidence to suggest that splicing decisions are largely made when the nascent RNA is still associated with chromatin. Here we demonstrate that activity of histone deacetylases (HDACs) influences splice site selection. Using splicing-sensitive microarrays, we identified ∼700 genes whose splicing was altered after HDAC inhibition. We provided evidence that HDAC inhibition induced histone H4 acetylation and increased RNA Polymerase II (Pol II) processivity along an alternatively spliced element. In addition, HDAC inhibition reduced co-transcriptional association of the splicing regulator SRp40 with the target fibronectin exon. We further showed that the depletion of HDAC1 had similar effect on fibronectin alternative splicing as global HDAC inhibition. Importantly, this effect was reversed upon expression of mouse HDAC1 but not a catalytically inactive mutant. These results provide a molecular insight into a complex modulation of splicing by HDACs and chromatin modifications

Modeling of mechanical properties of macroporous hydrogel

The research is supported by the Grant Agency of the Czech Republic by project No GA17-08531S Computational design of hydrogel cell scaffolds.Macroporous hydrogels with controlled morphology are widely used in biomedical fields, as drug delivery, tissue engineering, analytical and technical separations or responsive constructs. Porosity can be achieved by several methods. In the preparation of physical experiments it is made by salt crystals which are extracted from the hydrogel after polymerization. The salt crystals have different sizes and shapes. The pore sizes and their distribution affects the final mechanical properties. Such polymer structure is designed by simulations. The simulated structure is than transfered into ANSYS environment and its mechanical properties are examined and compared with experiments

Modelling of swelling and deformations of homogeneous hydrogel

Grant agency of Czech Republic by project No 17-08531S Computationally designed hydrogel cell supports. Additional support provider is Student Grant Competition by project No SGS19/157/OHK2/3T/12 Modelling, control and design of mechanical system 201

In-silico study of flow-mediated thrombosis in portal vein reconstructions

No. CZ.02.1.01/0.0/0.0/17 048/0007280, e-INFRA CZ ID:9014