Silver is not equal to silver : synthesis and evaluation of silver nanoparticles with low biological activity, and their incorporation into C12C_{12}alanine-based hydrogel

A new type of silver nanoparticles (AgNPs) was prepared and comprehensively studied. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses indicated that 24 nm AgNPs with narrow size distribution were obtained while Z-potential confirms their good stability. The composites of the obtained AgNPs with nontoxic-nature-inspired hydrogel were formed upon cooling of the aqueous solution AgNPs and C12Ala. The thermal gravimetric analysis (TGA) and the differential scanning calorimetry (DSC) do not show significant shifts in the characteristic temperature peaks for pure and silver-enriched gels, which indicates that AgNPs do not strongly interact with C12Ala fibers, which was also confirmed by SEM. Both AgNPs alone and in the assembly with the gelator C12Ala were almost biologically passive against bacteria, fungus, cancer, and nontumor human cells, as well as zebra-fish embryos. These studies proved that the new inactive AgNPs-doped hydrogels have potential for the application in therapy as drug delivery media

The Link between Protein Kinase CK2 and Atypical Kinase Rio1

The atypical kinase Rio1 is widespread in many organisms, ranging from Archaebacteria to humans, and is an essential factor in ribosome biogenesis. Little is known about the protein substrates of the enzyme and small-molecule inhibitors of the kinase. Protein kinase CK2 was the first interaction partner of Rio1, identified in yeast cells. The enzyme from various sources undergoes CK2-mediated phosphorylation at several sites and this modification regulates the activity of Rio1. The aim of this review is to present studies of the relationship between the two different kinases, with respect to CK2-mediated phosphorylation of Rio1, regulation of Rio1 activity, and similar susceptibility of the kinases to benzimidazole inhibitors

The Link between Protein Kinase CK2 and Atypical Kinase Rio1

The atypical kinase Rio1 is widespread in many organisms, ranging from Archaebacteria to humans, and is an essential factor in ribosome biogenesis. Little is known about the protein substrates of the enzyme and small-molecule inhibitors of the kinase. Protein kinase CK2 was the first interaction partner of Rio1, identified in yeast cells. The enzyme from various sources undergoes CK2-mediated phosphorylation at several sites and this modification regulates the activity of Rio1. The aim of this review is to present studies of the relationship between the two different kinases, with respect to CK2-mediated phosphorylation of Rio1, regulation of Rio1 activity, and similar susceptibility of the kinases to benzimidazole inhibitors

Catalytic activity of mutants of yeast protein kinase CK2α

Yeast CK2 is a highly conserved member of the protein kinase CGMC subfamily composed of two catalytic (α and α') and two regulatory (β and β') subunits. The amino-acid sequences of both catalytic subunits are only 60% homologous. Modelling of the tertiary structure of the CK2α displays additional α-helical structures not present in the CK2α' subunit, connecting the ATP-binding loop with the catalytic and activation loops. Deletion of this part causes drastic structural and enzymatic changes of the protein (CK2αΔ91-128) with characteristics similar to yeast CK2α' (low sensitivity to salt, heparin and spermine). Additionally, the deletion causes an over 5-fold decrease of the binding affinity for ATP and ATP-competitive inhibitors (TBBt and TBBz). The structural basis for TBBt and TBBz selectivity is provided by the hydrophobic pocket adjacent to the ATP/GTP binding site, which is smaller in CK2 than in the majority of other protein kinases. The importance of hydrophobic interactions in the binding of specific inhibitors was investigated here by mutational analysis of CK2α residues whose side chains contribute to reducing the size of the hydrophobic pocket. Site-directed mutagenesis was used to replace Val67 and Ile213 by Ala. The kinetic properties of the single mutants CK2αVal67Ala and CK2αIle213Ala, and the double mutant CK2Val67Ala Ile213Ala were studied with respect to ATP, and both inhibitors TBBt and TBBz. The Km values for ATP did not change or were very close to those of the parental kinase. In contrast, all CK2α mutants analysed displayed higher Ki values towards the inhibitors (10 to 12-fold higher with TBBt and 3 to 6-fold with TBBt) comparing to recombinant wild-type CK2α

The concept of a sustainable business model: Opportunities and challenges

The concept of sustainable development is considered one of the most important and urgent challenges facing humanity today. Therefore, solutions that promote sustainable business are of particular importance. The purpose of this article was to explore the concept of a business model as a potentially promising way of shaping the contribution of businesses to sustainable development. A systematic literature review method was used to identify, analyze and critically evaluate the first theoretical proposals for the concept of a sustainable business model. Fundamental differences between the proposed conceptualizations were identified, stemming from different understandings of the business model concept on the one hand, and from its embedding in different, partly contradictory approaches, to corporate contributions to sustainable development, on the other. The article adapts the holistic approach of corporate sustainability and the understanding of the business model as a representation of the essence of business including the proposition, creation, delivery and capture of value. As a result, key elements of the emerging new ontology of the sustainable business model have been identified and defined. The proposed concept of a sustainable business model primarily means adopting a different logic of business, and the basis for defining the various elements of the business model is the reconstruction of the concept of value. The sustainability of a business model is thus referred to the extent to which this model maximizes benefits while reducing economic, social, and environmental damage, and creates value not only for the company and its customers but also for various stakeholder groups. The main part of the article is a systematic identification of the opportunities and challenges associated with the new proposal. These are discussed according to the key elements of the sustainable business model, which are: the value proposition, value creation and value capture.The concept of sustainable development is considered one of the most important and urgent challenges facing humanity today. Therefore, solutions that promote sustainable business are of particular importance. The purpose of this article was to explore the concept of a business model as a potentially promising way of shaping the contribution of businesses to sustainable development. A systematic literature review method was used to identify, analyze and critically evaluate the first theoretical proposals for the concept of a sustainable business model. Fundamental differences between the proposed conceptualizations were identified, stemming from different understandings of the business model concept on the one hand, and from its embedding in different, partly contradictory approaches, to corporate contributions to sustainable development, on the other. The article adapts the holistic approach of corporate sustainability and the understanding of the business model as a representation of the essence of business including the proposition, creation, delivery and capture of value. As a result, key elements of the emerging new ontology of the sustainable business model have been identified and defined. The proposed concept of a sustainable business model primarily means adopting a different logic of business, and the basis for defining the various elements of the business model is the reconstruction of the concept of value. The sustainability of a business model is thus referred to the extent to which this model maximizes benefits while reducing economic, social, and environmental damage, and creates value not only for the company and its customers but also for various stakeholder groups. The main part of the article is a systematic identification of the opportunities and challenges associated with the new proposal. These are discussed according to the key elements of the sustainable business model, which are: the value proposition, value creation and value capture

Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery

Five-membered 1,2,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bioisosteric properties and an unusually wide spectrum of biological activities. Thus, it is a perfect framework for the novel drug development. After a century since the 1,2,4-oxadiazole have been discovered, the uncommon potential attracted medicinal chemists’ attention, leading to the discovery of a few presently accessible drugs containing 1,2,4-oxadiazole unit. It is worth noting that the interest in a 1,2,4-oxadiazoles’ biological application has been doubled in the last fifteen years. Herein, after a concise historical introduction, we present a comprehensive overview of the recent achievements in the synthesis of 1,2,4-oxadiazole-based compounds and the major advances in their biological applications in the period of the last five years as well as brief remarks on prospects for further development

Different properties of four molecular forms of protein kinase CK2 from Saccharomyces cerevisiae

CK2 is a pleiotropic constitutively active serine/threonine protein kinase composed of two catalytic α- and two regulatory β-subunits, whose regulation is still not well understood. It seems to play an essential role in regulation of many cellular processes. Four active forms of CK2, composed of αα'ββ', α2ββ', α'2ββ', and a free α'-subunit were isolated from wild-type yeast and strains containing a single deletion of the catalytic subunit. Each species exhibits properties typical for CK2, but they differ in substrate specificity and sensitivity to inhibitors. This suggests that each CK2 isomer may regulate different process or may differ in the way of its regulation