ВОЛЬТАМПЕРОМЕТРИЧЕСКАЯ МУЛЬТИСЕНСОРНАЯ СИСТЕМА НА ОСНОВЕ МОДИФИЦИРОВАННЫХ ПОЛИАРИЛЕНФТАЛИДАМИ СТЕКЛОУГЛЕРОДНЫХ ЭЛЕКТРОДОВ ДЛЯ РАСПОЗНАВАНИЯ И ОПРЕДЕЛЕНИЯ ВАРФАРИНА

Voltammetric sensors and sensory system based on glassy carbon electrodes modified by polyarylenephthalides (chlorinated polyphthalidylidenefluorene, polyphthalidylidene diphenyl and brominated polyphthalidylidene diphenyl) were developed for the recognition and determination of warfarin. The electrochemical and analytical characteristics of the sensors were studied. The optimal conditions for recording voltammograms of warfarin oxidation were established: the range of working potentials was 0.5 ÷ 1.2 V, scan rate was 20 mVs-1, the electrode holding time in the analyzed solution was 30s, and the pH of the supporting electrolyte was 6.86 (Na2HPO4 + KH2PO4). Using the values of the slope of the dependence log ip = log v + const (Δlg ip / Δlg v = 0.7 ÷ 0.9), it was found that the rate-controlling step of warfarin oxidation was the depolarizer adsorption on the surface of the polymer modifier. The linear range of the dependence of the maximum of warfarin oxidation peak on the concentration was 0.3×10-6 ÷ 0.5×10-3 М. Using the “added-found” method, the accuracy of determining the warfarin content in the model solutions was evaluated. The relative standard deviation and relative measurements error didn’t exceed 4.63% and 11.1% respectively. By the means of chemometrics methods (principal components analysis and SIMCA) the possibility of the recognition of warfarin preparations without isolating the active substances in dosage forms was shown, which made it possible to distinguish pharmaceutical preparations from the different manufacturers. At the same time, the sample preparation procedure was significantly simplified, and the cost and time of the analysis were reduced. It was also shown that the use of the multisensory system of the “electronic tongue” type significantly increased the percentage of correctly recognized samples in comparison to the registration of voltammograms on the single sensor. The proportion of correctly recognized samples was 97-100%.Keywords: warfarin, voltammetry, polyarylenephthalide, modified electrodes, sensor system(Russian) DOI: http://dx.doi.org/10.15826/analitika.2019.23.4.003R.A. Zilberg, Yu.A. Yarkaeva, D.I. Dubrovsky, L.R. Zagitova, V.N. MaistrenkoBashkir State University, Department of Chemistry,32, Validy Str., Ufa, 450076, Russian FederationРазработаны вольтамперометрические сенсоры и сенсорная система на основе стеклоуглеродных электродов, модифицированных полиариленфталидами – хлорированными полифталидилиденфлуореном, полифталидилидендифенилом и бромированным полифталидилидендифенилом, для распознавания и определения варфарина. Изучены электрохимические и аналитические характеристики сенсоров. Установлены оптимальные условия регистрации вольтамперограмм варфарина: диапазон рабочих потенциалов 0.5 ÷ 1.2 В, скорость развертки потенциалов 20 мВ/с, время выдерживания электрода в анализируемом растворе 30 с, pH фонового электролита 6.86 (Na2HPO4 + KH2PO4). По  значениям тангенса угла наклона зависимости lg ip = lg v + const (Δlg ip/Δlg v = 0.7÷ 0.9) установлено, что лимитирующей стадией процесса окисления варфарина является преимущественно адсорбция деполяризатора на поверхности полимерного модификатора. Линейный характер зависимости максимального тока окисления варфарина от концентрации сохраняется в диапазоне 0.3·10-6 ÷ 0.5·10-3 М. При определении содержания варфарина в модельных растворах методом «введено-найдено», относительное стандартное отклонение не превышает 4.6 %, относительная погрешность не превышает 11.1 %. С использованием методов хемометрики: метода главных компонент (МГК) и метода формального независимого моделирования аналогий классов (SIMCA) показана возможность распознавания препаратов варфарина без выделения действующих веществ в лекарственных формах, что позволяет различать лекарственные средства различных производителей. При этом заметно упрощается процедура пробоподготовки, снижаются стоимость и время анализа. Показано, что использование мультисенсорной системы типа «электронный язык» существенно повышает процент правильно распознанных образцов по сравнению с регистрацией вольтамперограмм на одном сенсоре. Доля правильно распознанных образцов составляет 97-100 %.Ключевые слова: варфарин, вольтамперометрия, полиариленфталид, модифицированные электроды, сенсорная системаDOI: http://dx.doi.org/10.15826/analitika.2019.23.4.00

proGenomes2: an improved database for accurate and consistent habitat, taxonomic and functional annotations of prokaryotic genomes

Microbiology depends on the availability of annotated microbial genomes for many applications. Comparative genomics approaches have been a major advance, but consistent and accurate annotations of genomes can be hard to obtain. In addition, newer concepts such as the pan-genome concept are still being implemented to help answer biological questions. Hence, we present proGenomes2, which provides 87 920 high-quality genomes in a user-friendly and interactive manner. Genome sequences and annotations can be retrieved individually or by taxonomic clade. Every genome in the database has been assigned to a species cluster and most genomes could be accurately assigned to one or multiple habitats. In addition, general functional annotations and specific annotations of antibiotic resistance genes and single nucleotide variants are provided. In short, proGenomes2 provides threefold more genomes, enhanced habitat annotations, updated taxonomic and functional annotation and improved linkage to the NCBI BioSample database. The database is available at http://progenomes.embl.de/

Riddling : Chimera’s dilemma

We wish to acknowledge the support: Sao Paulo Research Foundation (FAPESP) under Grants 2011/19296-1, 2015/05186-0, 2015/07311-7, 2015/50122-0, and 2017/20920-8, Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (CNPq), and Coordena¸cao de Aperfei¸coamento de Pessoal de Nıvel Superior (CAPES).Peer reviewedPublisher PD

Differential diagnosis of primary and metastatic ovarian carcinomas

Ovarian tumors constitute 3.4 % of the structure of oncological diseases in women worldwide. However, the ovaries are also a common target for metastasis of carcinoma from other organs. Conducting differential diagnosis between primary carcinoma and metastasis is often challenging. The aim of this study is to highlight the issues of morphological and immunohistochemical differential diagnosis of primary ovarian carcinomas and metastases from carcinomas of various organs to the ovaries. Materials and methods. Data analysis of clinical and pathohistological studies of 381 patients. Paraffin sections for pathohistological studies were stained with hematoxylin and eosin using standard methodology. Immunohistochemical studies were conducted in 161 cases using a panel of antibodies: cytokeratins, estrogen receptors, progesterone receptors, CA125, TTF1, Vimentin, CDX2, Villin, Chromogranin A, Synaptophysin, CD56, GATA, p53, Inhibin A, FOXL-2, PAX-8, Ki-67. The specimens were examined and analyzed using the Axioskop 40 microscope (Zeiss) with the AxioCam MRc camera (Zeiss). Results. The article discusses key issues of differential diagnosis of primary and metastatic ovarian carcinomas based on a large clinical and operational material. The application of an adequate panel of immunohistochemical antibodies for verification is considered. The results of the frequency of occurrence of different histological variants of ovarian carcinomas and metastases to the ovaries from carcinomas of other organs are provided based on our own research from 2019 to 2023. The main morphological and immunohistochemical indicators for practical use in the work of a pathologist in the verification of ovarian tumors are presented. An example of forming an antibody panel, taking into account clinical and morphological indicators in a specific clinical case from our own practice, is given. Conclusions. Metastases of carcinomas from other organs to the ovaries constitute half of all cases requiring immunohistochemical investigation based on morphological structure. The most common are metastases from breast and colorectal cancers. However, the diagnosis of metastatic intestinal carcinoma is particularly challenging, as there is usually no clear clinical picture. In the differential diagnosis of primary and metastatic ovarian tumors, a comprehensive approach to analyzing the clinical presentation, microscopic structure of the tumor, and the surrounding tissue plays a significant role. Additionally, the formation of an antibody panel, taking into account these data, is crucial. The article provides a list of antibodies that have demonstrated greater effectiveness in our work

Landscape of mobile genetic elements and their antibiotic resistance cargo in prokaryotic genomes

Prokaryotic Mobile Genetic Elements (MGEs) such as transposons, integrons, phages and plasmids, play important roles in prokaryotic evolution and in the dispersal of cargo functions like antibiotic resistance. However, each of these MGE types is usually annotated and analysed individually, hampering a global understanding of phylogenetic and environmental patterns of MGE dispersal. We thus developed a computational framework that captures diverse MGE types, their cargos and MGE-mediated horizontal transfer events, using recombinases as ubiquitous MGE marker genes and pangenome information for MGE boundary estimation. Applied to ∼84k genomes with habitat annotation, we mapped 2.8 million MGE-specific recombinases to six operational MGE types, which together contain on average 13% of all the genes in a genome. Transposable elements (TEs) dominated across all taxa (∼1.7 million occurrences), outnumbering phages and phage-like elements (<0.4 million). We recorded numerous MGE-mediated horizontal transfer events across diverse phyla and habitats involving all MGE types, disentangled and quantified the extent of hitchhiking of TEs (17%) and integrons (63%) with other MGE categories, and established TEs as dominant carriers of antibiotic resistance genes. We integrated all these findings into a resource (proMGE.embl.de), which should facilitate future studies on the large mobile part of genomes and its horizontal dispersal

Проектирование доступа для адреналэктомии с применением компьютерно-томографического 3D-моделирования

Introduction. In the literature, the insufficient attention is paid to preoperative planning of access to adrenal masses using modern computed tomographic navigation capabilities. The purpose. To demonstrate the possibilities of designing a safe access for adrenalectomy with the appliation of three-dimensional printed models based on the integral assessment of preoperative computed tomographic data. Materials and methods. The possibilities of preoperative design of access for adrenalectomy were studied in 362 patients with adrenal tumors, for whom computed tomography was performed on an Aquillion 64 (Toshiba, Japan). Results. Reliable anthropometric (BMI, body shape) and CT criteria for designing surgical access to the right and left NP were determined. Three patients with a borderline number of risk criteria for the development of vascular complications associated with technical difficulties of adrenalectomy (for the right AP, ≥4, for the left AP, ≥3) underwent CT-segmentation of images followed by the creation of three-dimensional plates — a model of the AP tumor with adjacent organs and vessels. Conclusion. Preoperative computed tomographic access design, taking into account the criteria of the risk of complications and the application of three-dimensional printed models, make it possible to reasonably use endoscopic and open adrenalectomy options, significantly improving the immediate results of patient treatment.Введение. Дооперационному планированию доступа к образованиям надпочечников при помощи современных возможностей компьютерно-томографической навигации в литературе уделяется недостаточно внимания. Цели и задачи: продемонстрировать возможности проектирования безопасного доступа для адреналэктомии с использованием трехмерных печатных моделей, основанных на интегральной оценке предоперационных компьютерно-томографических данных. Материалы и методы. Изучены возможности дооперационного проектирования доступа для адреналэктомии у 362 больных опухолями надпочечников, которым компьютерная томография выполнена на установке Aquillion 64 (Toshiba, Япония). Результаты. Определены достоверные антропометрические (ИМТ, форма телосложения) и КТ-критерии проектирования хирургического доступа к правому и левому НП. Трем больным с пограничным числом критериев риска развития сосудистых осложнений, связанных с техническими трудностями адреналэктомии (для правого НП  ≥4, для левого НП  ≥3), была проведена КТ-сегментация изображений с последующим созданием трехмерных пластинатов — модель опухоли НП с соседними органами и сосудами. Заключение. Дооперационное компьютерно-томографическое проектирование доступа с учетом критериев риска развития осложнений и использование трехмерных печатных моделей позволяют обоснованно применять эндоскопические и открытые варианты адреналэктомии, достоверно улучшая непосредственные результаты лечения больных

SPIRE: a Searchable, Planetary-scale mIcrobiome REsource

Meta'omic data on microbial diversity and function accrue exponentially in public repositories, but derived information is often siloed according to data type, study or sampled microbial environment. Here we present SPIRE, a Searchable Planetary-scale mIcrobiome REsource that integrates various consistently processed metagenome-derived microbial data modalities across habitats, geography and phylogeny. SPIRE encompasses 99 146 metagenomic samples from 739 studies covering a wide array of microbial environments and augmented with manually-curated contextual data. Across a total metagenomic assembly of 16 Tbp, SPIRE comprises 35 billion predicted protein sequences and 1.16 million newly constructed metagenome-assembled genomes (MAGs) of medium or high quality. Beyond mapping to the high-quality genome reference provided by proGenomes3 (http://progenomes.embl.de), these novel MAGs form 92 134 novel species-level clusters, the majority of which are unclassified at species level using current tools. SPIRE enables taxonomic profiling of these species clusters via an updated, custom mOTUs database (https://motu-tool.org/) and includes several layers of functional annotation, as well as crosslinks to several (micro-)biological databases. The resource is accessible, searchable and browsable via http://spire.embl.de