Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome

Accurate chromosome segregation, controlled by kinetochore-mediated chromatid attachments to the mitotic spindle, ensures the faithful inheritance of genetic information. Kinetochores assemble onto specialized CENP-A nucleosomes (CENP-ANuc) of centromeric chromatin. In humans, this is mostly organized as thousands of copies of an ~171 bp α-satellite repeat. Here, we describe the cryo-EM structure of the human inner kinetochore CCAN (Constitutive Centromere Associated Network) complex bound to CENP-ANuc reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, while a linker DNA segment of the α-satellite repeat emerges from the fully-wrapped end of the nucleosome to thread through the central CENP-LN channel which tightly grips the DNA. The CENP-TWSX histone-fold module, together with CENP-HIKHead, further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of the α-satellite repeat linker DNA by CCAN provides a robust mechanism by which the kinetochore withstands the pushing and pulling of centromeres associated with chromosome congression and segregation forces.

Power consumption management method objects of the regional electrotechnical complex based on the accounting of an additional resource

В настоящей статье рассматривается метод управления электропотреблением объектов регионального электротехнического комплекса на основе учёта добавочного ресурса. Актуальность его разработки обусловлена существующими тенденциями развития цифровой экономики во всех отраслях региональной экономики, в том числе - в припортовых комплексах региона. Важной составляющей современной цифровой экономики выступает цифровая энергетика, позволяющая регулировать управление бизнес-процессами в энергетической сфере. Обеспечение электроэнергией регионального припортового комплекса осуществляется с помощью двух подсистем регионального электроэнергетического комплекса: регионального транспортно-сетевого комплекса и регионального электротехнического комплекса. Важной задачей развития цифровой энергетики является разработка и внедрение цифровых сервисов. На сегодняшний день в региональных транспортно-сетевом и электротехническом комплексах внедрено значительное число цифровых сервисов. Однако они носят преимущественно «учётный» характер, в результате чего не способны в полной мере реализовать управление энергетическими процессами, существенно сократить затраты и повысить уровень энергоэффективности. Предлагаемый метод включает в себя модель и методики, позволяющие установить границы начала и завершения бифуркационных процессов, реализовать прогнозирование электропотребления объектов РТСК и РЭК на основе учёта добавочного ресурса и осуществить режимное нормирование электропотребления объектов, не нарушая технологического процесса. Применение данного метода может быть осуществлено в рамках динамического моделирования процесса электропотребления, исследования бифуркационных процессов, а также в качестве теоретической основы для создания сервисного программного обеспечения цифровых платформ управления электропотреблением для РТСК, РЭК и региональных припортовых комплексов. This article discusses the method of managing the electrical consumption of a regional electrical complex based on the accounting of an additional resource. The relevance of its development is due to the existing trends in the development of the digital economy in all sectors of the region, including in regional port complexes. An important component of the digital economy is digital energy, which allows regulating the management of business processes in the energy sector. The provision of electricity to the regional port complex is carried out with the help of two subsystems of the regional electric power complex: the regional transport and network complex and the regional electrical complex. An important task of the development of digital energy is the development and implementation of digital services. To date, a fairly large number of digital services have been introduced in RTSC and REC. However, they are more "accounting" in nature and are unable to fully implement the management of energy processes in order to increase energy efficiency and reduce costs. The proposed method includes a model and methods that allow determining the boundaries of the beginning and completion of bifurcation processes, implementing forecasting of electrical consumption of RTSC and REC facilities based on accounting for additional resources and implementing regime rationing of electrical consumption of facilities without disrupting the technological process. The application of this method can be carried out within the framework of dynamic modeling of the electrical consumption process, the study of bifurcation processes, as well as a theoretical basis for creating service software for digital electrical consumption management platforms for the regional transport and network complex, regional electrical grid complex and regional port complexes.

Endophytic Fungal Community of Tobacco Leaves and Their Potential Role in the Formation of “Cherry-Red” Tobacco

“Cherry-red” tobacco is the superior variant of tobacco, appearing with the apperance of red dapples on cured leaves due to the demethylation of nicotine to nornicotine during maturation and curing. Fungi are known to have the capacity to convert nicotine to nornicotine. However, an endophytic fungal community of “cherry-red” tobacco has never been reported to our best knowledge. Here, we sampled mature leaves from both “cherry-red” and ordinary tobacco at lower, center, and upper plant sections, and we analyzed the ITS diversity using high-throughput sequencing. Results revealed a significantly different fungal community of foliar endophyte in “cherry-red” and ordinary tobacco. In comparison to the ordinary control, higher diversity and a co-occurrence network complex were found in “cherry-red” samples, especially in the center and upper leaves, where the red dapples mainly emerged. More taxa were enriched in the “cherry-red” than ordinary tobacco leaves at all plant sections. In particular, Aspergillus, some strains of which are reported capable of converting nicotine to nornicotine, was specifically enriched in upper “cherry-red” tobacco leaves, which showed most red dapples after curing. A less robust network structure was detected in the “cherry-red” tobacco compared to ordinary tobacco. The nearest taxon index (NTI) and β NTI indicated that the local community structuration of tobacco endophytic fungi mainly driven by deterministic process, while the community turnover among plant sections was stochastic. In conclusion, our study provides the earliest information of endophytic fungal community in “cherry-red” tobacco leaf, and the community diversity, composition, and network features are synchronously varied with the appearance of red dapples, which is suggestive of their relationship to the formation of “cherry-red” tobacco.

Development of an Information-Network Complex to Support Production Operations of Control, Diagnostics and Adjustment of the Accuracy Characteristics of Solid-State Wave Gyroscopes

Статья посвящена разработке информационно-сетевого комплекса (ИСК) для сопровождения производственных операций контроля, диагностики и настройки точностных характеристик твердотельных волновых гироскопов с целью повышения качества изделий и эффективности технологических процессов.Для этого сначала проведен анализ существующих информационных систем сопровождения автоматизации технологических процессов и их контроля. Обсуждается возможность использования таких систем в производстве твердотельных волновых гироскопов.В результате предложена структура ИСК, разделяющаяся на физическую и информационную подсистемы. В ней физическая подсистема представляет собой набор коммутирующих устройств в виде стендов с промышленными компьютерами, узлов связи, серверов и персональных компьютеров и других периферийных устройств. А информационная подсистема включает программное обеспечение для автоматизации технологических операций и анализа получаемых данных. Предполагается, что программное обеспечение анализа данных будет также производить запросы к базе данных и обрабатывать большие объемы информации с использованием алгоритмов машинного обучения.Для повышения эффективности всей системы организуется автоматический сбор физических и точностных параметров изделий на разных этапах их производства. Среди основных планируемых результатов работы ИСК выделены: оптимизация технологических процессов и выявление сложных многофакторных нелинейных зависимостей параметров качества от параметров технологических операций, а также автоматическое оперативное выявление неисправного оборудования с выработкой рекомендаций по его ремонту и автоматический оперативный контроль уровня квалификации операторов с регулировщиками.Отдельно обсуждаются способы интегрирования ИСК в производственный процесс изготовления твердотельного волнового гироскопа.

Machine intelligence design of 2019-nCoV drugs

Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed.

Identification of Key Genes and Candidated Pathways in Human Autosomal Dominant Polycystic Kidney Disease by Bioinformatics Analysis

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic form of kidney disease. High-throughput microarray analysis has been applied for elucidating key genes and pathways associated with ADPKD. Most genetic profiling data from ADPKD patients have been uploaded to public databases but not thoroughly analyzed. This study integrated 2 human microarray profile datasets to elucidate the potential pathways and protein-protein interactions (PPIs) involved in ADPKD via bioinformatics analysis in order to identify possible therapeutic targets. Methods: The kidney tissue microarray data of ADPKD patients and normal individuals were searched and obtained from NCBI Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified, and enriched pathways and central node genes were elucidated using related websites and software according to bioinformatics analysis protocols. Seven DEGs were validated between polycystic kidney disease and control kidney samples by quantitative real-time polymerase chain reaction. Results: Two original human microarray datasets, GSE7869 and GSE35831, were integrated and thoroughly analyzed. In total, 6,422 and 1,152 DEGs were extracted from GSE7869 and GSE35831, respectively, and of these, 561 DEGs were consistent between the databases (291 upregulated genes and 270 downregulated genes). From 421 nodes, 34 central node genes were obtained from a PPI network complex of DEGs. Two significant modules were selected from the PPI network complex by using Cytotype MCODE. Most of the identified genes are involved in protein binding, extracellular region or space, platelet degranulation, mitochondrion, and metabolic pathways. Conclusions: The DEGs and related enriched pathways in ADPKD identified through this integrated bioinformatics analysis provide insights into the molecular mechanisms of ADPKD and potential therapeutic strategies. Specifically, abnormal decorin expression in different stages of ADPKD may represent a new therapeutic target in ADPKD, and regulation of metabolism and mitochondrial function in ADPKD may become a focus of future research.