High-Resolution Crystal Structure of Muscle Phosphoglycerate Mutase Provides Insight into Its Nuclear Import and Role

Phosphoglycerate mutase (PGAM) is a glycolytic enzyme converting 3-phosphoglycerate to 2-phosphoglycerate, which in mammalian cells is expressed in two isoforms: brain (PGAM1) and muscle (PGAM2). Recently, it was shown that besides its enzymatic function, PGAM2 can be imported to the cell nucleus where it co-localizes with the nucleoli. It was suggested that it functions there to stabilize the nucleolar structure, maintain mRNA expression, and assist in the assembly of new pre-ribosomal subunits. However, the precise mechanism by which the protein translocates to the nucleus is unknown. In this study, we present the first crystal structure of PGAM2, identify the residues involved in the nuclear localization of the protein and propose that PGAM contains a “quaternary nuclear localization sequence (NLS)”, i.e., one that consists of residues from different protein chains. Additionally, we identify potential interaction partners for PGAM2 in the nucleoli and demonstrate that 14-3-3ζ/δ is indeed an interaction partner of PGAM2 in the nucleus. We also present evidence that the insulin/IGF1–PI3K–Akt–mTOR signaling pathway is responsible for the nuclear localization of PGAM2.     

N-Terminally Lipidated Sialorphin Analogs—Synthesis,Molecular Modeling,In Vitro Effect on Enkephalins Degradation by NEP and Treatment of Intestinal Inflammation in Mice

Pharmacotherapy for inflammatory bowel disease (IBD) is difficult, and some patients do not respond to currently available treatments. Therefore, the discovery of novel anti-IBD agents is imperative. Our aim was the synthesis of lipidated analogs of sialorphin and the in vitro characterization of their effect on the degradation of Met-enkephalin by neutral endopeptidase (NEP). We also investigated in vivo whether the most active inhibitor (peptide VIII) selected in the in vitro studies could be a potential candidate for the treatment of colitis. Peptides were synthesized by the solid-phase method. Molecular modeling technique was used to explain the effect of fatty acid chain length in sialorphin analogs on the ligand–enzyme interactions. The anti-inflammatory effect was evaluated in the dextran sulphate sodium (DSS)-induced model of colitis in mice. Peptide VIII containing stearic acid turned out to be in vitro the strongest inhibitor of NEP. We have also shown that the length of the chain of stearic acid fits the size of the grove of NEP. Peptides VII and VIII exhibited in vivo similar anti-inflammatory activity. Our results suggest that lipidation of sialorphin molecule is a promising direction in the search for NEP inhibitors that protect enkephalins.     

Serum Level of MMP-3 and MMP-9 in Patients with Diabetes Mellitus Type 2 Infected with Epstein-Barr Virus

Diabetes mellitus type 2 (DM2) has recently become one of the most important health problems in the world. Patients with DM2 with long-term glycaemia are more likely to become infected than the healthy population. Matrix metalloproteinases (MMPs) play a key role in tissue remodeling during various physiological processes. However, it has been reported that certain MMPs are overexpressed during the development of various human diseases. In this study, we analyzed the levels of MMP-3 and MMP-9 in the serum of DM2 patients with and without Epstein-Barr virus (EBV) infection. The study included 115 patients with DM2 hospitalized in the Internal Ward of the Masovian Specialist Hospital in Radom, Poland, who were divided into two groups: EBV-positive and EBV-negative. The levels of MMP-3 and MMP-9 were tested in the serum of patients using the ELISA method, while the presence of EBV in saliva was tested by polymerase chain reaction (PCR). The presented studies showed a significant difference in the concentration of both MMPs in diabetic patients additionally infected with EBV compared to the group of non-infected individuals. It seems that MMPs may be useful biomarkers in the diagnosis, prognosis, and monitoring of diabetes associated with EBV infection.     

Metropolis–Hastings Monte Carlo Method for Neutron Emissivity Tomographic Inversion in Tokamak Plasma

The article presents a new approach to plasma neutron emissivity reconstruction based on the Metropolis–Hastings Monte Carlo algorithm. The algorithm is based on a biased random walk. A dedicated computer code generates pseudo-random samples within the domain that contains the solution. The properly chosen objective function ensures convergence to the desired solution. The method allows to overcome the problem of trapping in local minima by accepting, with some finite probability, changes in the direction opposite to that indicated by the objective function. The developed method was tested using a synthetic data set. The results show that the method provides reliable reconstructions and thus can be used as an alternative or complementary method to the commonly applied ones. The method capabilities were also tested against noise present in the line-integrated projections.     

Exploring the circularity potential regarding the multiple use of residual material

Clean Technologies and Environmental Policy - Building on recent insights in exploring material circularity, this study attempts to develop a methodological approach toward allocating an available...     

Permeability of carbon refractory materials used in a blast furnace hearth

Permeability of experimental and standard micropore carbon materials, before and after the heat treatment at 1550 °C, was investigated using gas permeability measurements (GP) and mercury intrusion porosimetry (MIP). Permeability of both materials increased after the annealing. Experimental micropore carbon material was less permeable than standard one, both before and after the heat treatment. Measured gas permeabilities were compared with permeabilities determined based on MIP measurements using two different models: Hagen?Poiseuille and Carman?Kozeny equation. Using the inverse problem approach, for the first time Carman?Kozeny constant was determined for micropore carbon materials. Carman?Kozeny model gave more accurate results (i.e. close to gas permeability measurements) than Hagen?Poiseuille model. Performed investigations showed that mercury intrusion porosimetry might be alternative method to investigate infiltration resistance of low permeable materials.     

Iron Complexes of Flavonoids-Antioxidant Capacity and Beyond

Flavonoids are common plant natural products able to suppress ROS-related damage and alleviate oxidative stress. One of key mechanisms, involved in this phenomenon is chelation of transition metal ions. From a physiological perspective, iron is the most significant transition metal, because of its abundance in living organisms and ubiquitous involvement in redox processes. The chemical, pharmaceutical, and biological properties of flavonoids can be significantly affected by their interaction with transition metal ions, mainly iron. In this review, we explain the interaction of various flavonoid structures with Fe(II) and Fe(III) ions and critically discuss the influence of chelated ions on the flavonoid biochemical properties. In addition, specific biological effects of their iron metallocomplexes, such as the inhibition of iron-containing enzymes, have been included in this review.     

Changes in the Flower and Leaf Proteome of Common Buckwheat (Fagopyrum esculentum Moench) under High Temperature

Common buckwheat (Fagopyrum esculentum Moench), a pseudocereal crop, produces a large number of flowers, but this does not guarantee high seed yields. This species demonstrates strong abortion of flowers and embryos. High temperatures during the generative growth phase result in an increase in the degeneration of embryo sacs. The aim of this study was to investigate proteomic changes in flowers and leaves of two common buckwheat accessions with different degrees of heat tolerance, Panda and PA15. Two-dimensional gel electrophoresis and mass spectrometry techniques were used to analyze the proteome profiles. Analyses were conducted for flower buds, open flowers capable of fertilization, and wilted flowers, as well as donor leaves, i.e., those growing closest to the inflorescences. High temperature up-regulated the expression of 182 proteins. The proteomic response to heat stress differed between the accessions and among their organs. In the Panda accession, we observed a change in abundance of 17, 13, 28, and 11 proteins, in buds, open and wilted flowers, and leaves, respectively. However, in the PA15 accession there were 34, 21, 63, and 21 such proteins, respectively. Fifteen heat-affected proteins were common to both accessions. The indole-3-glycerol phosphate synthase chloroplastic-like isoform X2 accumulated in the open flowers of the heat-sensitive cultivar Panda in response to high temperature, and may be a candidate protein as a marker of heat sensitivity in buckwheat plants.     

Mechanical properties of illite-based ceramics with controlled porosity studied by modern in situ techniques

Deformation tests combined with modern in situ acoustic emission (AE) and digital image correlation (DIC) techniques were applied to monitor low strain rate compressive behavior of illite-based ceramics with controlled porosity (P). A strong effect of porosity on the mechanical performance was observed: Young's modulus decreased linearly from 29.4 ± 1.1 GPa (P = 14 vol%) to 3.0 ± 0.5 GPa (P = 55 vol%) and compressive strength decreased from 307 ± 13.6 MPa (P = 14 vol%) to 27.7 ± 1.0 MPa (P = 55 vol%). The AE and DIC techniques revealed a transition from brittle fracture to gradual localized crushing with increasing porosity. The AE signals possessed high-energy burst-like characteristics typical of brittle fracture and (micro)cracking. The AE data showed continuous activity from the beginning of loading, suggesting that true elasticity does not occur in this material. The combination of mechanical tests with in situ techniques, therefore, proved to be particularly effective in providing additional information on the deformation dynamics in ceramics.