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

Comparison of REMS, NEWS, qSOFA and SIRS criteria scales for sepsis prediction in patients with diagnosis “SARS-CoV-2, virus unidentified”: a retrospective observational study

Background. Despite ample research on the coronavirus infection sequence and therapy, the incidence of adverse outcomes remains very high. Sepsis stands among the major factors greatly complicating treatment and increasing the risk of death. A timely identification of highrisk sepsis patients is a cornerstone of effective sepsis prevention.Objectives. A comparative prognostic power assessment between the quick Sequential Organ Failure Assessment (qSOFA) scale, National Early Warning Score (NEWS), Initial Prehospital Rapid Emergency Medicine Score (REMS) and the Systemic Inflammatory Response Syndrome (SIRS) criteria for sepsis detection in anaesthetic intensive care patients with a diagnosis: SARS-CoV-2, virus unidentified.Methods. A retrospective observational study included 166 patients over 18-year age with unconfirmed infection (ICD-10 code U07.2). The qSOFA, NEWS, REMS and SIRS point estimates were obtained from each patient. The patients were retrospectively divided in two cohorts by sepsis presence (Sepsis-3 criteria) to determine the express scales power in evaluating the risk of sepsis (estimated as area under ROC curve, AUROC).Results. Data on 102 patients were included in the final analysis. Fifty-eight (57%) patients were terminal, and 55 (54%) developed sepsis. The estimates are as follows: NEWS — AUROC 0.848 [95% confidence interval (CI) 0.764–0.912], sensitivity 76.36% [95% CI 63.0–86.8], specificity 82.98% [95% CI 69.2–92.4], optimal cut-off threshold >5 points; qSOFA — AUROC 0.700 [95% CI 0.602–0.787], sensitivity 76.36% [95% CI 63.0–86.8], specificity 61.70% [95% CI 46.4–75.5], optimal cut-off threshold >0 points; REMS — AUROC 0.739 [95% CI 0.643–0.821], sensitivity 69.09% [95% CI 55.2–80.9], specificity 65.96% [95% CI 50.7–79.1], optimal cut-off threshold >5 points; SIRS criteria — AUROC 0.723 [95% CI 0.626–0.807], sensitivity 98.18% [95% CI 90.3–100.0], specificity 31.91% [95% CI 19.1–47.1], optimal cut-off threshold >0 points.Conclusion. The NEWS scale revealed a good prognostic power to estimate the risk of sepsis in patients with suspected COVID-19 disease. The qSOFA, REMS scales and SIRS criteria possess a good calibration capacity, albeit insufficient resolution, which limits their prognostic value

Comprehensive analysis of the 5-HTTLPR allelic polymorphism effect on behavioral and neurophysiological indicators of executive control in people from different ethnic groups in Siberia

The allelic polymorphism of the serotonin transporter’s gene 5-HTTLPR is considered as one of the factors determining an individual genetic predisposition to the development of a wide range of affective disorders, including depression. Many studies have shown that the climatic and social conditions of people’s life can have a significant impact on the connections of 5-HTTLPR with the risk of depression. The stop-signal paradigm (SSP) is an experimental method allowing evaluating an individual ability to the self-control of behavior in a changing environment. In the SSP experiment, a subject should either press one of several buttons quickly after the appearance of the target stimuli or suppress the already started movement if an inhibitory signal follows the target stimulus. The aim of this study is a research of associations between the allelic the 5-HTTLPR polymorphism and the individual scores of the personal anxiety level, as well as the behavioral and neurophysiological indicators of the ability to self-control over motor reactions in the SSP. The study was conducted among people from three ethno-regional groups: healthy Caucasoids from Novosibirsk, the Mongoloid groups of the indigenous population of the Tuva Republic and Sakha Republic (Yakutia). Genetic, ethnographic, and psychological influences on an individual’s ability to control motor responses were compared. The amplitude of the premotor peak of the evoked brain potential was used as a neurophysiological marker of the person’s readiness to the execution of target-directed activity. It was revealed that the frequency of the S-allele polymorphism 5-HTTLPR was significantly higher for both mongoloid groups compared to the Caucasoids. The S/S genotype was associated with an increased level of personal anxiety and at the same time with a better ability to the self-control of behavior in the SSP experiment. Anxiety level, participants’ sex, ethnicity, and allelic polymorphism 5-HTTLPR had a statistically significant effect on the amplitude of the premotor readiness potential recorded under the SSP conditions in the frontal and parietal-occipital cortical regions. Our data support the hypothesis that the S/S genotype of the 5-HTTLPR polymorphism may be associated with more success in adapting to the climatic conditions connected with high life risk in comparison to L/L and L/S genotypes

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

Сравнение адсорбционных свойств оксида цинка и шунгита в связи с их действием в качестве активаторов серной вулканизации

Determination of the adsorption characteristics of zinc oxide and shungite with respect to benzene vapor adsorption was carried out by the BET method. The specific surface area was calculated, the curves of pore volumes distribution according to their size were constructed. The possibility of using shungite as an activator of sulfur vulcanization of butadiene-nitrile rubbers was shown.Проведено определение адсорбционных характеристик оксида цинка и шунгита по адсорбции паров бензола методом БЭТ. Рассчитаны удельные поверхности, построены кривые распределения объемов пор по их размерам. Показана возможность применения шунгита в качестве активатора серной вулканизации бутадиен-нитрильных каучуко

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