Reactive trityl derivatives: stabilised carbocation mass-tags for life sciences applications

The rational design of novel triarylmethyl (trityl)-based mass tags (MT) for mass-spectrometric (MS) applications is described. We propose a "pKR+ rule" to correlate the stability of trityl carbocations with their MS performance: trityls with higher pKR+ values ionise and desorb better. Trityl blocks were synthesised that have high pKR+ values and are stable in conditions of MS analysis; these MTs can be ionised by matrix as well as irradiation with a 337 nm nitrogen laser. 13C-Labelled tags were prepared for MS quantitation applications. Moreover, the tags were equipped with a variety of functional groups allowing conjugation with different functionalities within (bio)molecules to enhance the MS characteristics of the latter. The MS behaviour of model polycationic trityl compounds with and without the matrix was studied to reveal that poly-trityl clusters are always singly charged under the (MA)LDI-TOF conditions. Several peptide-trityl conjugates were prepared and comparisons revealed a beneficial effect of trityl tags on the conjugate detection in MS. Trityl compounds containing para-methoxy- and dimethylamine groups, as well as a xanthene fragment, showed considerable enhancement in MS detection of model peptides; thus they are promising tools for proteomic applications. Dimethoxytrityl derivatives allow one to distinguish between Arg- and Lys-containing peptides. Maleimido trityl derivatives are suitable for the efficient derivatisation of thiol-containing peptides in pyridine

Radial solitons in armchair carbon nanotubes

Radial solitons are investigated in armchair carbon nanotubes using a generalized Lennard-Jones potential. The radial solitons are found in terms of moving kink defects whose velocity obeys a dispersion relation. Effects of lattice discreteness on the shape of kink defects are examined by estimating the Peierls stress. Results suggest that the typical size for an unpinned kink phase is of the order of a lattice spacing.Comment: 11 pages, 3(eps) figure

Correlation between actual nutrition and lipid peroxidation and antioxidant defense parameters in aged 14–17 years adolescents living in rural area

The aim of the study was to reveal the relationship between the parameters of actual nutrition and the lipid peroxidation and antioxidant defense system in adolescents aged 14–17 in a rural area. Material and methods. 76 adolescents aged 14–17 of the Irkutsk region were examined by the cross-sectional study method. Actual nutrition was studied by the 24-hour nutrition reproduction method. The content of substrates with unsaturated double bonds (DB), diene conjugates (DC), ketodienes and conjugated trienes (KD and CT), thiobarbituric acid reacting species (TBARS), α-tocopherol, retinol, reduced (GSH) and oxidized glutathione (GSSG), total blood antioxidant activity (TAA), superoxide dismutase (SOD) activity in blood by spectrophotometry and fluorometry methods were analyzed. Results. The adolescents’ diet did not meet the principles of a balanced diet – there was reduced protein intake, an imbalance of unsaturated fatty acids, A, C, D, B vitamins deficiency. An excessive element in the diet was sodium. The content of substrates with DB, KD and CT and TBARS increased significantly in the studied group of adolescents, the concentration of DC decreased. Parameters of antioxidant defense both decreased (TAA, retinol content) and increased (α-tocopherol, GSH concentration). Correlation analysis showed relationships between DB and vitamin B1, B2 content; DC level and calories, carbohydrate and vitamin B1 content; concentration of KD and CT and fats, TAA and vitamin A and β-carotene level; level of α-tocopherol in blood and vitamin E in food; GSH and vitamin K; SOD activity and vitamin H content. Multiple negative correlations were between GSSG and fat, vitamins B1, B9, C, K food concentration were found.Conclusions. The calculated vitamin consumption indicators allow to reveal nutritional deviations in adolescents and to connect them with the real provision of the body with these metabolites

Clinical and epidemiological characteristics and effectiveness of antiviral therapy for COVID-19 in children: The experience of the first year of the pandemic

Background. The use of antiviral agents can shorten the duration of the viral infection. The aim: to study the clinical and epidemiological features and the effectiveness of antiviral therapy for new coronavirus infection (COVID-19) in outpatient children.Materials and methods. From April 2020 to March 2021, 9334 outpatient children aged from 0 months to 17 years were randomly tested for new coronavirus infection. SARS-CoV-2 RNA was detected in oropharyngeal and nasal material by PCR. Patients with confirmed new coronavirus infection were prescribed interferon-alpha (IFN-α) intranasally, antiviral agents of systemic action. The control group consisted of children with COVID-19 who did not receive treatment.Results. When examining clinically healthy contact children, SARS-CoV-2 RNA was detected in 7.4 % of cases. In the structure of ARI, the specific weight of COVID-19 was 12.3 % with the peak incidence in April-May (up to 22.8 %) and NovemberDecember (up to 30.0 %). In half of the cases, children became infected in the family, and usually adults were the index patient. In 47.7 % of cases, an asymptomatic form of COVID-19 was registered without significant differences in patients of different ages. In one third of children with concomitant pathology, the disease was asymptomatic, in half it was mild, in other cases moderate severity was diagnosed. The clinical picture of COVID-19 did not differ from other ARIs. Anosmia (9.4 %) in half of the cases was combined with ageusia (4.4 %) and was significantly more common in boys. The duration of clinical manifestations in children of the control group and those who received antiviral therapy did not statistically significantly differ in mild and severity of the disease. Also, various antiviral therapy options did not significantly affect the duration of SARS-CoV-2 detection in children with various forms of COVID-19.Conclusion. In the first year of the pandemic, the novel coronavirus infection did not dominate the pattern of respiratory diseases in outpatient children. Further research is required to develop pediatric guidelines for the treatment of COVID-19 at the outpatient stage

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

cisRED: a database system for genome-scale computational discovery of regulatory elements

We describe cisRED, a database for conserved regulatory elements that are identified and ranked by a genome-scale computational system (). The database and high-throughput predictive pipeline are designed to address diverse target genomes in the context of rapidly evolving data resources and tools. Motifs are predicted in promoter regions using multiple discovery methods applied to sequence sets that include corresponding sequence regions from vertebrates. We estimate motif significance by applying discovery and post-processing methods to randomized sequence sets that are adaptively derived from target sequence sets, retain motifs with p-values below a threshold and identify groups of similar motifs and co-occurring motif patterns. The database offers information on atomic motifs, motif groups and patterns. It is web-accessible, and can be queried directly, downloaded or installed locally

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

Critical analysis of information security culture definitions

This article aims to advance the understanding of information security culture through a critical reflection on the wide-ranging definitions of information security culture in the literature. It uses the hermeneutic approach for conducting literature reviews. The review identifies 16 definitions of information security culture in the literature. Based on the analysis of these definitions, four different views of culture are distinguished. The shared values view highlights the set of cultural value patterns that are shared across the organization. An action-based view highlights the behaviors of individuals in the organization. A mental model view relates to the abstract view of the individual’s thinking on how information security culture must work. Finally, a problem-solving view emphasizes a combination of understanding from shared value-based and action-based views. The paper analyzes and presents the limitations of these four views of information security culture definitions

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins