RNA sample optimization for cryo-EM analysis.

RNAs play critical roles in most biological processes. Although the three-dimensional (3D) structures of RNAs primarily determine their functions, it remains challenging to experimentally determine these 3D structures due to their conformational heterogeneity and intrinsic dynamics. Cryogenic electron microscopy (cryo-EM) has recently played an emerging role in resolving dynamic conformational changes and understanding structure-function relationships of RNAs including ribozymes, riboswitches and bacterial and viral noncoding RNAs.

Unravelling the potential of yolkin for nutraceutical use: the origin, structure, and functional insights of a hen egg yolk polypeptide complex.

Nutraceuticals can reduce the risk of many diseases, such as cardiovascular disease, immune deficiencies, neurodegeneration, and others. Their delivery remains a challenge because it depends on many factors, most notably the stability of the bioactive compounds. Yolkin is a peptide complex isolated from hen egg yolk with immunomodulatory and neuroprotective potential.

Conserved structures and dynamics in 5'-proximal regions of Betacoronavirus RNA genomes.

Betacoronaviruses are a genus within the Coronaviridae family of RNA viruses. They are capable of infecting vertebrates and causing epidemics as well as global pandemics in humans. Mitigating the threat posed by Betacoronaviruses requires an understanding of their molecular diversity.

Kartogenin-loaded liposomes coated with alkylated chondroitin sulfate for cartilage repair.

Cartilage loss is a common clinical problem, which leads to significant pain, dysfunction, and even disability. As a result, there is growing interest in using small, non-protein molecules to protect or repair cartilage. Kartogenin (KGN), a small hydrophobic molecule, shows chondroprotective and chondrogenic properties.

Autophagy of Candida albicans cells after the action of earthworm Venetin-1 nanoparticle with protease inhibitor activity.

The present studies show the effect of the Venetin-1 protein-polysaccharide complex obtained from the coelomic fluid of the earthworm Dendrobaena veneta on Candida albicans cells. They are a continuation of research on the mechanisms of action, cellular targets, and modes of cell death. After the action of Venetin-1, a reduced survival rate of the yeast cells was noted.

Silmitasertib (CX-4945), a Clinically Used CK2-Kinase Inhibitor with Additional Effects on GSK3β and DYRK1A Kinases: A Structural Perspective.

A clinical casein kinase 2 inhibitor, CX-4945 (silmitasertib), shows significant affinity toward the DYRK1A and GSK3β kinases, involved in down syndrome phenotypes, Alzheimer's disease, circadian clock regulation, and diabetes. This off-target activity offers an opportunity for studying the effect of the DYRK1A/GSK3β kinase system in disease biology and possible line extension. Motivated by the dual inhibition of these kinases, we solved and analyzed the crystal structures of DYRK1A and GSK3β with CX-4945.

Measurements of Energetic States Resulting from Ion Exchanges in the Isomorphic Crystals of Apatites and Bioapatites.

Developments in the field of nanostructures open new ways for designing and manufacturing innovative materials. Here, we focused on new original ways of calculating energy changes during the substitution of foreign ions into the structure of apatites and bioapatites. Using these tools, the energetic costs of ion exchanges were calculated for the exemplary cases known from the literature.

Novel Venetin-1 nanoparticle from earthworm coelomic fluid as a promising agent for the treatment of non-small cell lung cancer.

The present research shows the antitumor activity of a protein-polysaccharide complex Venetin-1 obtained from the coelomic fluid of Dendrobaena veneta earthworms against A549 cancer cells. The investigations are a continuation of experiments on the antitumor activity of coelomic fluid obtained from this species. The Venetin-1 nanoparticle was obtained after thermal treatment of the coelomic fluid, separation from coelomocytes, filtration, and lyophilization.

Destabilization of mutated human PUS3 protein causes intellectual disability.

Pseudouridine (Ψ) is an RNA base modification ubiquitously found in many types of RNAs. In humans, the isomerization of uridine is catalyzed by different stand-alone pseudouridine synthases (PUS). Genomic mutations in the human pseudouridine synthase 3 gene (PUS3) have been identified in patients with neurodevelopmental disorders.

Hierarchy of Bioapatites.

Apatites are one of the most intensively studied materials for possible biomedical applications. New perspectives of possible application of apatites correspond with the development of nanomaterials and nanocompounds. Here, an effort to systematize different kinds of human bioapatites forming bones, dentin, and enamel was undertaken.

Novel diagnostic and prognostic factors for the advanced melanoma based on the glycosylation-related changes studied by biophysical profiling methods.

Melanoma is a life-threatening disease due to the early onset of metastasis and frequent resistance to the applied treatment. For now, no single histological, immunohistochemical or serological biomarker was able to provide a precise predictive value for the aggressive behavior in melanoma patients. Thus, the search for quantifying methods allowing a simultaneous diagnosis and prognosis of melanoma patients is highly desirable.

Evaluation of Xa inhibitors as potential inhibitors of the SARS-CoV-2 Mpro protease.

Based on previous large-scale in silico screening several factor Xa inhibitors were proposed to potentially inhibit SARS-CoV-2 Mpro. In addition to their known anticoagulants activity this potential inhibition could have an additional therapeutic effect on patients with COVID-19 disease. In this study we examined the binding of the Apixaban, Betrixaban and Rivaroxaban to the SARS-CoV-2 Mpro with the use of the MicroScale Thermophoresis technique.

Investigation of Thiocarbamates as Potential Inhibitors of the SARS-CoV-2 Mpro.

In the present study we tested, using the microscale thermophoresis technique, a small library of thionocarbamates, thiolocarbamates, sulfide and disulfide as potential lead compounds for SARS-CoV-2 Mpro drug design. The successfully identified binder is a representative of the thionocarbamates group with a high potential for future modifications aiming for higher affinity and solubility. The experimental analysis was extended by computational studies that show insufficient accuracy of the simplest and widely applied approaches and underline the necessity of applying more advanced methods to properly evaluate the affinity of potential SARS-CoV-2 Mpro binders.

Studies of Peculiar Mg-Containing and Oscillating Bioapatites in Sheep and Horse Teeth.

New types of biological apatites have been discovered in molar sheep and horse teeth and are divided in two types. In the first and more general type, the release of Mg ions is parallel to the changes in composition of apatite leading to a final stoichiometric ratio of Ca to P ions, going from dentin depth towards the boundary of enamel with air. Inside dentin, another apatite sub-types were discovered with alternating layers of Mg-rich and C-rich apatites.

Opportunities of combinatorial thin film materials design for the sustainable development of magnesium-based alloys.

Magnesium-based lightweight structural materials exhibit potential for energy savings. However, the state-of-the-art quest for novel compositions with improved properties through conventional bulk metallurgy is time, energy, and material intensive. Here, the opportunities provided by combinatorial thin film materials design for the sustainable development of magnesium alloys are evaluated.

Novel Approach to Tooth Chemistry. Quantification of the Dental-Enamel Junction.

The dentin-enamel junction (DEJ) is known for its special role in teeth. Several techniques were applied for the investigation of the DEJ in human sound molar teeth. The electron (EPMA) and proton (PIXE) microprobes gave consistent indications about the variability of elemental concentrations on this boundary.

Novel Approach to Tooth Chemistry: Quantification of Human Enamel Apatite in Context for New Biomaterials and Nanomaterials Development.

A series of linear profiles of the elements of the enamel in human molar teeth were made with the use of an electron microprobe and a Raman microscope. It is postulated that the enamel can be treated as the superposition of variable "overbuilt" enamel on the stable "core" enamel at the macro-, micro- and nanoscale level. The excessive values characterize the "overbuilt enamel".

Radioactivity of the gas pipeline network in Poland.

The paper presents the study of the radioactivity connected with the transport of natural gas by the gas pipeline network in the selected points in Poland. In the scope of the study the measurements of activity concentration of radon (Rn) in the gas samples, radiolead (Pb) in spent filter cartridges and dust samples (black powder) collected from the gas pipeline network were performed. The results show that the Rn activity concentration in natural gas varies from the detection limit of the applied method (30 Bq/m) to around 1400 Bq/m.

RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination.

Background: TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized.

Radioactivity in wastes generated from shale gas exploration and production - North-Eastern Poland.

In the present study, the K-40, U-238, Ra-226, Pb-210, Ra-228 and Th-228 activity concentrations were measured in 64 samples of wastes generated from shale gas exploration in North-Eastern Poland. The measured samples consist of drill cuttings, solid phase of waste drilling muds, fracking fluids, return fracking fluids and waste proppants. The measured activity concentrations in solid samples vary in a wide range from 116 to around 1100 Bq/kg for K-40, from 14 to 393 Bq/kg for U-238, from 15 to 415 Bq/kg for Ra-226, from 12 to 391 Bq/kg for Pb-210, from a few Bq/kg to 516 Bq/kg for Ra-228 and from a few Bq/kg to 515 Bq/kg for Th-228.

Determination of the self-attenuation based on the sample composition in gamma-ray spectrometry of Pb: requirements for the scope of chemical analyses.

In the presented paper analysis of sensitivity of self-attenuation correction to the accuracy of chemical composition analysis is presented. The analyses were done by means of Monte Carlo simulation for cylindrical samples and for four sample materials: peat, water, ash and soil. For each of these materials the major elements were selected whose determination in the analysed material is necessary.

Radon as a potential health hazard for clients and workers of selected thermal spas in Poland.

The radiation exposure due to 222Rn and its progeny inhalation for clients and employees of selected thermal water spas was assessed. The radon risk was calculated using the measured 222Rn activity concentrations in the investigated thermal waters and radon transfer coefficient, defined as a fraction of radon released from the swimming pool water to the indoor air of swimming pool. The total radon in air concentration was not measured.

Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.

Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a.