bluuebunny/crossref_metadata_2025 huggingface dataset:
The formation of legal policy of Ukraine at the present stage.
Authors: Khodakivskyi Mykhailo
Published: August 2021

Introduction. Legal policy as a means of regulating the political and legal sphere of society is a prerequisite for optimizing political, economic, social and other relations in society. At the present stage, politics is considered through the prism of its governance function, and in turn, law is a means of normalizing and governing public relations.

In this approach, legal policy is a strategic means of transforming society, which regulates the complex relationship between society and the state and ensures human and civil rights and freedoms. Most domestic research papers on legal policy cover some of its various aspects and expressions, but focus primarily on its theoretical foundations.

The aim of the article. Today there is a certain lack of applied research in legal policy. We shall try to consider the applied aspects of legal policy at the present stage of development of Ukraine, regarding it as a set of governance tasks and political and legal decisions that regulate various social relations by legal means.

Results. The process of Ukrainian eurointegration stimulates the development of a civilized legal policy. Its basic characteristics are laid down in the Association Agreement between the European Union and the European Atomic Energy Community and their Member States, of the one part, and Ukraine, of the other part. The institutional basis of this policy is the Ministry of Justice of Ukraine, which is becoming a national center for the formation of state legal policy. Further steps in this direction include the reorganization of its structure in such a way as to provide an institutional opportunity for the formation of state legal policy in all public spheres, which should be regulated by legal means.

Conclusions. The key means of transforming legal policy at the present stage is the commitment made by Ukraine during the signing of the Association Agreement with the European Union. Ukrainian modern legal policy is based on such values as democratic principles, the rule of law, good governance, and so on. The structural elements of modern legal policy are the proper institutional basis for its making and the necessary content of social transformations. At the present stage, the institutional mechanism of introducing and making legal policy is being formed, based on the activity of the Ministry of Justice of Ukraine as the single national center for forming state legal policy, integrating structural subdivisions of other central executive bodies. The next stage of the reform of Ukrainian legal policy should be its content, which will also be carried out in the context of Ukrainian eurointegration.
Elements of Political-Legal Development of Ukraine Strategy: Aspects of Actualization and Scholarly Comprehension
Authors: Tarasyuk Volodymyr
Published: August 2021

and Scholarly Comprehension
The unbalanced state apparatus in the conditions of the law enforcement system inaction and the chaotic actions of the authorities aimed at overcoming the crisis caused by the resistance of oligarchic capital eloquently testify to the need to implement systematic programs to restore and develop strategic directions of the state.
Strengthening and separating regional elites from the center weakens the role and discredits central governments; the loss of control over the strategic sectors of the economy monopolized by the oligarchs requires the government to constantly seek a compromise between the interests of the state and meet the needs of corrupt capital; lack of own (national) programs for the development of education and science, national security and defense, information policy – led to the introduction of foreign ideas and concepts, sometimes outdated and sometimes irrelevant to modern Ukrainian conditions (for example, the introduction of restrictive economic instruments contribute to the destruction of countries, unable to provide their needs with their own resources at least 90%).
The constant reduction of financial, natural, and human resources has led to growing public discontent with the oligarchs who «colonized Ukraine» in the late 1990s and early 2000s and, depending on Russian markets, pursue their own mercantile interests contrary to state interests.
Elite change is one of the most pressing and painful issues related to the restoration of subjectivity and statehood in the Ukrainian state. None of the previous mass protests, the Orange Revolution and the Revolution of Dignity, led to a change of elites as the primary, basic cause of mass discontent. Policy inclusiveness and economic monopolization do not help restore public confidence in government actions and decisions. Domestic elites are in one way or another closely connected (dependent) with oligarchic capital – whether financial, political or media. Thus, Ukrainian elites can be confidently called pro-oligarchic, and oligarchs – representatives of domestic elites.
The public demand for the de-elitization of the oligarchs has every reason to grow into another Maidan. In Ukraine, during the thirty years of independence, no conditions have been created for the professional realization of educators, scientists, doctors, journalists, engineers, etc. All so-called non-profit professions are in deep decline. Market relations have gradually transformed into market thinking – a liberal economy turns us into a market society. When measuring education, medicine, politics, friendship or family relations according to the standards of market thinking – the market suffers, and public relations, and education, medicine, science, politics, etc. – none of these categories can be market by definition.
Electronic payment system as an object of criminal encroachment
Authors: Vasylenko Oleksandr
Published: August 2021

Introduction. In recent years, the number of payment transactions carried out using electronic payment systems has grown rapidly. Despite the steady growth of electronic payments among both individuals and legal entities, a number of problems remain unresolved, which primarily include ensuring the security of electronic payment transactions by the state at the legislative level and the development of effective means of combating and preventing crime. in the specified area. The current criminal legislation contains certain rules that can ensure the security of the electronic payment system. But insufficient research of some theoretical aspects of criminal liability for this type of criminal offenses significantly reduces the effectiveness of criminal law protection of this area of life. One such aspect is the theoretical uncertainty of the object that falls under the protection of criminal law. In particular, there is a lack of theoretical definition of the system of electronic payments in terms of the object, which is placed under the protection of criminal law.
The aim of the article. The importance of the researched problems and the need to increase the efficiency of the current Criminal Code of Ukraine determine the purpose of this study, which is to define the concept of electronic payment system as an object of criminal protection.
Results. Criminal offenses committed in the system of electronic payments belong to a qualitatively new type of mercenary crime in the banking sector, which is directly related to the modernization of economic relations in society. They cover the sphere of economic interests of the state as a whole, individual legal entities, as well as individuals who use the electronic payment system in their own interests. There is a need to develop a universal criminal law terminology in order to improve the regulatory framework governing relations in the field of electronic payments. Unfortunately, the definition of electronic payment system (electronic payment system) has not been properly developed either in the financial and economic sphere or in jurisprudence, and the existing definitions are not clear and contain a list of essential features of such systems.
Conclusions. The system of electronic payments as an object of criminal encroachment - is regulated by law the order of public relations for the transfer of funds between participants in the payment system through a special payment mechanism, which is a set of methods, tools, methods to make calculations for effective and safe transfer of funds from the payer to the recipient in time and space and regulated by a special law and payment rules, are implemented on the basis of the contract against which the criminal encroachment is directed. This definition indicates the specifics of the electronic payment system as an object of crime, and also contains a list of all the most important features of this system, which will further contribute to the correct classification of crimes committed in this area.
Violent crime of juveniles: features of group behavior
Authors: Kvasha Roman
Published: August 2021

Introduction. Prevention of juvenile delinquency is always one of the priorities of Ukraine's legal policy, as children are one of the most criminally affected segments of the population. The preamble to the Law of Ukraine "On Child Protection" states that the protection of children in Ukraine is a strategic national priority, which is important for ensuring the national security of Ukraine, the effectiveness of domestic policy. It should be noted that neither society nor the state has created an effective system for preventing juvenile delinquency, including violence. Today, the level of juvenile delinquency among Ukrainians and its increased public danger is of concern to scholars, practitioners, and ordinary citizens alike.
The aim of the article. Establishing the features of group violent juvenile delinquency.
Conclusions features of the group nature of violent juvenile delinquency: the desire for community and imitation as normal psychophysiological age traits; greater degree of cruelty and abuse of the victim; incitement to suicide; increased group dependence; insufficient social self-control; conformism; ease of quick informal integration; the need for communication and self-affirmation; group cohesion; dominant group motive. When committing group violent crimes by minors in the group, despite the presence of different motives of its participants, the group motive is dominant. Such a group motive determines the qualification of the crime committed by minors. The group through the system of its intragroup relations determines certain personal characteristics of its members.
A promising area of further research in this area is to determine the nature and content of group motive, as well as the role of the leader in the mechanism of group violent behavior of minors.
The Doctrine of Legal Regulation: Approaches to Understanding
Authors: Tarakhonych Tetiana
Published: August 2021

The article describes the scientific approaches to understanding of the doctrine, the legal doctrine, and the legal regulation doctrine.
The article states that the public relations’ reformation, the current needs of legal practice require fundamentally new approaches to legal doctrine not only as one of the sources of law, but also as an important component of the process of law-making, law enforcement and legal interpretation.
The research focuses on the fact that the legal doctrine in general and the doctrine of legal regulation in particular belongs to a key position both in the general and theoretical legal science and in the science of industry direction.
It is emphasized that theorists of law analyze the legal doctrine due to the application of the methodological potential of philosophy and theory of law through the prism of the interaction of legal doctrine and the doctrine of legal regulation.
The author provides the definition of the legal regulation’s doctrine as a component of legal doctrine based on previous knowledge and is the result of fundamental scientific research, a set of scientific ideas, views, concepts, theories recognized by the scientific community, that can be applied in law-making, law-enforcement and legal interpretation activities.
The important attention is paid to the peculiarities of the legal regulation’s doctrine. It is aimed at a certain object of knowledge; is a certain set of ideas, views, principles of scientific knowledge, concepts, theories, etc.; requires a set of generalizations; is formed under the influence of needs and social interests; has a communicative, informational orientation; is in close cooperation with law-making, law-enforcement and legal interpretation activities; has a certain structure, cognitive and strong-willed components, is formed in society and the state by generalization of scientific knowledge, etc.
The research defines the factors that influence the formation and development of the doctrine of legal regulation. They are divided into factors of both objective and subjective nature.
The particular attention is paid to the main functions of the doctrine of legal regulation, namely: cognitive, informational, prognostic, communication, etc.
Presepsin ve COVID 19: Literatürün gözden geçirilmesi
Authors: ALKAN Sevil , YILDIZ Emel , ÇİNPOLAT Havva Yasemin , OĞUZ MIZRAKÇI Serpil
Published: August 2021

Günümüzde hakkında global olarak çok sayıda araştırmalar devam eden Koronavirüs hastalığı (COVID-19) hastalığının da prognozunun belirlenmesinde, patolofizyolojisinin anlaşılmasında biyobelirteçlerin rol alabileceği düşünülmektedir. Presepsin de bu biyobelirteçlerden olup, kritik COVID-19 vakalarının erken tespitinde ve mortalite riskinin değerlendirmesinde kullanılabileceği iddia edilmiştir. Biz de çalışmamızda Koronavirüs COVID-19 ve presepsin ilişkisini literatür eşliğinde irdelemeyi amaçladık. Sınırlı sayıdaki bilimsel makale mevcut olup, mevcut veriler kısıtlı hasta sayılarını içermektedir. Sonuç olarak presepsinin COVID 19 da kullanılabilecek bir biyomarker olduğu konusunda henüz kesin bilimsel kanıtlar bulunmamaktadır. Daha fazla hastayı içerem ileriye dönük çalışmalara ihtiyaç duyulmaktadır.
GIDA KAYNAKLI AKRİLAMİDİN FETOTOKSİK ETKİLERİ VE AKRİLAMİD TOKSİSİTESİNE KARŞI KORUYUCU ÖNLEMLER
Authors: ERDEMLİ Zeynep
Published: August 2021

Akrilamid, insanlar üzerinde toksik etkilerinin gözlenebileceği dozların tam olarak bilinemediği kimyasallar grubunda değerlendirilmektedir. Akrilamidi de kapsayan bu grup kimyasal maddeler, çok düşük konsantrasyonlarda bile sağlık riski taşıyabilmektedir ve tamamen zararsız kabul edilmeleri mümkün değildir. Gıdaların yüksek sıcaklıklarda kızartılması ve fırınlanması sonucu bol miktarda akrilamid oluşmakta, bu gıdaları tüketen insanlar her gün belli miktarlarda akrilamide maruz kalmaktadır. Gebe kadınlar da gebelik boyunca gıda kaynaklı akrilamide maruz kalmakta ve bebekleri muhtemelen bundan etkilenmektedir. Gelişmekte olan beynin çeşitli kimyasallara karşı daha hassas olması ve akrilamidin beyin gelişimi için toksik olduğunun ve öğrenme fonksiyonunun gelişmesini bozabileceğinin rapor edilmesi gebelik boyunca gıdalarla alınan akrilamidi daha da önemli kılmakta ve ciddi endişeye yol açmaktadır. Güncel araştırmalarda, enterik mikrobiyata ve beyin fonksiyonu arasında bağlantı olduğunun ortaya konması ile gebelikte sindirilemeyen oligosakkaritlerin takviyesinin faydalı mikrobiyata stimulasyonu yoluyla insan sağlığını olumlu etkilediği gösterilmiştir. Gebe kadınların, akrilamidin gebelik süresince fetus üzerinde meydana getirebileceği toksik etkilerden ve gebelik sonrasında oluşabilecek bilişsel fonksiyon bozukluklarından yavrularını korumak için; yoğun akrilamid içeren kızartılmış ve fırınlanmış yiyeceklerden mümkün olduğunca uzak durmalarını, plasentayı ve kan‐beyin bariyerini kolaylıkla geçebilen ve akrilamidin fetotoksik etkilerini önemli oranda azaltan E vitamini gibi antioksidanları günlük olarak yeterli düzeyde almalarını, kendi gıdalarını hazırlarken gıdalarda akrilamid oluşumunu önemli oranda azaltan yöntemleri uygulamalarını öneriyoruz.
Analisis Postingan di Twitter Mengenai Vaksinasi Covid-19: Perilaku Sosial Terhadap Vaksinasi Covid-19 guna Pencegahan Penularan Covid-19
Authors: Khoirun Nisa Aulia Sukmani
Published: August 2021

Pandemi Covid-19 merupakan peristiwa baru yang dialami oleh seluruh masyarakat Indonesia dan juga dunia. Pandemi ini muncul dengan pola dan masalah baru yang memengaruhi perilaku sosial manusia sebagai individu dan masyarakat. Informasi merupakan hal penting yang harus diketahui oleh manusia untuk menghadapi perubahan pola dan masalah yang terjadi. Di era pandemi ini, manusia aktif berinteraksi di media sosial sebagai bentuk pelarian dari kebijakan pelarangan interaksi fisik untuk mengurangi penularan virus. Interaksi yang terjadi antarmanusia merupakan bentuk saling berbagi pengalaman dan pengetahuan yang dimiliki untuk kepentingan manusia itu sendiri. Bagaimana ini dijelaskan? interaksi sebagai perilaku sosial harus dimaknai lebih dalam sebagai proses manusia untuk mencari pengetahuan dan pengalaman yang memiliki maksud dan tujuan di dalamnya. Tujuan ini sebenarnya untuk memastikan bahwa manusia itu sendiri memiliki pengetahuan untuk menghadapi perubahan yang terjadi akibat munculnya pandemi Covid-19. Metode social media ethnography digunakan untuk melihat proses interaksi di media sosial secara terus menerus hingga akhirnya manusia dapat membuktikan bahwa dirinya memiliki kemampuan dan pengetahuan untuk memahami dan berperilaku di era pandemi Covid-19. Media sosial Twitter digunakan untuk melihat interaksi yang terjadi antarnetizen Indonesia terkait kejadian Covid-19, khususnya vaksinasi Covid-19 yang dilakukan di Indonesia. Interaksi berulang yang dilakukan membentuk bukti diri yang digunakan untuk mengonfirmasi dan mengamati peristiwa dengan lebih baik dengan pengetahuan sebelumnya. Pengetahuan ini merupakan bentuk acuan yang digunakan manusia untuk bertindak ketika menghadapi peristiwa tertentu, dalam hal ini menanggapi setiap peristiwa selama pandemi Covid-19.
Pengampunan Pidana dalam Mewujudkan Keadilan, Kepastian, dan Kemanfaatan
Authors: A.Rachmat Wirawan  , Avelyn Pingkan Komuna
Published: August 2021

Tulisan ini mencoba memberikan perspektif dari penyelenggaraan sistem hukum pidana Indonesia saat ini. Bagaimana keadilan, kepastian dan kemanfaatan merupakan satu wujud utuh dari tujuan hukum pidana itu sendiri. Bukan hanya dari perspektif korban, juga harus diperhatikan dari perspektif terdakwa. Namun realita penyelenggaraan sistem hukum pidana, lebih menitik beratkan pada konsep keadilan dan kepastian. Seolah mengenyampingkan asas kemanfaatan dari tujuan hukum yang sudah lama terpatri. Hasilnya banyak pihak tidak merasakan wujud dari  keadilan yang sejati. Keadilan adalah ketika perkara putus dipengadilan menjadi sebuah doktrinisasi. Penyelenggaraan norma yang cenderung postivis menggiring opini bahwa penegakan hukum hanya sekedar corong dari undang-undang. Penyelesaian perkara hanya dipandang dalam dimensi "adil dan pasti". "Adil" dengan penjatuhan sanksi sedang "pasti" dengan putusan hakim pengadilan yang sifatnya mengikat. Sedang asas manfaat belum menemukan wujudnya yang hakiki. Untuk itu perlu dilakukan transformasi dari sistem hukum pidana saat ini. Penerapan sistem hukum yang tidak hanya bertumpuh pada adil dan pasti juga memperoleh manfaat bagi para pihak. Adapun metode penelitian yang digunakan adalah deskriptif kualitatif dengan pendekatan normative konseptual yang melakukan perbandingan hukum dengan berbagai kajian hukum dan contoh kasus terkait. Dengan hasil yang ingin dicapai adalah terwujudnya keadilan, kepastian dan kemanfaatan secara utuh dengan asas pengampunan pidana.
Factors Affecting Low Academic Achievement of Open University's Students in Indonesia
Authors: Wahyudi Heri
Published: August 2021

This research aims to analyze the factors that cause low student academic achievement. To achieve these objectives, this research used a survey design to collect data from respondents. Before the research, the researchers conducted a pre-survey interview technique to several respondents in order to obtain information to formulate a construct that will be analyzed as well as to determine the research instruments. This research was conducted in regional office Denpasar with students from Non-Pendas Program with low academic achievement as the respondents. There were 71 respondents with a response rate of 92.5%. Based on these results, there are some important things that can be concluded: Lack of motivation, lack of study time and no teaching materials are factors which lead to low academic achievement with low impact.Not following the online tutorial, not forming a study group, lack of test preparation and lack of enrichment of the materials are factors which lead to low academic achievement with quite high impact.Not supportive learning situation and the lack of study planning are the factors that lead to low academic achievement with low impact.
НЕИЗВЕСТНЫЕ ИЗДАНИЯ И НОВЫЕ ФОРМЫ ПЕЧАТИ МОСКОВСКОГО ПЕЧАТНОГО ДВОРА ВО ВТОРОЙ ПОЛОВИНЕ XVII ВЕКА
Authors: Поздеева Ирина Васильевна
Published: August 2021

Аннотация. В статье на основании анализа репертуара Московского Печатного двора второй половины XVII века, составленного по данным архива Приказа книгопечатного дела, показаны новые формы печатных изданий, новые задачи Государева Печатного двора и их успешное решение. В результате показано, что Московский Печатный двор в исследуемый период стал важнейшим инструментом подготовки страны и ее населения к петровским реформам, ознаменовавшим наступление в России новой эпохи.
Abstract. Based on the analysis of the repertoire of the Moscow Printing House of the second half of the 17th century, compiled from the data of the archive of the Order of the Printing Industry, the article shows new forms of printed publications, new tasks of the Tsar’s Printing House and their successful solution. As a result, it is shown that the Moscow Printing House during the period under study became the most important tool for preparing the country and its population for the Peter’s reforms, which marked the onset of a new era in Russia.
МОИ ВОСПОМИНАНИЯ О МАРИНЕ МИХАЙЛОВНЕ ГРОМЫКО И ЕЕ РАССКАЗ О СВОЕЙ ЖИЗНИ
Authors: Матханова Наталья Петровна
Published: August 2021

Аннотация. Текст включает в себя воспоминания о М. М. Громыко как научном руководителе автора статьи, а также запись интервью, где воспроизводятся важные биографические данные из жизни Громыко и академической среды Новосибирска 1960–1970-х годов. Автор отмечает причины, по которым Громыко не писала своей биографии, в том числе – в связи с репрессиями, через которые прошли семья ее отца и ее родственники, и сложностью жизни советского времени для вынесения определенных оценок происходящего.
Abstract. The text includes memories of M. M. Gromyko, as the scientific advisor of the author of the article, but includes a recording of an interview, which reproduces important biographical data from the life of Gromyko and the academic environment of 1960–1970s in Novosibirsk. The author notes the reasons why Gromyko did not write her biography, due to the repressions through which the family of her father and their relatives went through, the complexity of life in Soviet times for making certain assessments of what was happening.
Somatic Sex: On the Origin of Neoplasms With Chromosome Counts in Uneven Ploidy Ranges
Authors: Haas Oskar A.
Published: August 2021

Stable aneuploid genomes with nonrandom numerical changes in uneven ploidy ranges define distinct subsets of hematologic malignancies and solid tumors. The idea put forward herein suggests that they emerge from interactions between diploid mitotic and G0/G1 cells, which can in a single step produce all combinations of mono-, di-, tri-, tetra- and pentasomic paternal/maternal homologue configurations that define such genomes. A nanotube-mediated influx of interphase cell cytoplasm into mitotic cells would thus be responsible for the critical nondisjunction and segregation errors by physically impeding the proper formation of the cell division machinery, whereas only a complete cell fusion can simultaneously generate pentasomies, uniparental trisomies as well as biclonal hypo- and hyperdiploid cell populations. The term “somatic sex” was devised to accentuate the similarities between germ cell and somatic cell fusions. A somatic cell fusion, in particular, recapitulates many processes that are also instrumental in the formation of an abnormal zygote that involves a diploid oocyte and a haploid sperm, which then may further develop into a digynic triploid embryo. Despite their somehow deceptive differences and consequences, the resemblance of these two routes may go far beyond of what has hitherto been appreciated. Based on the arguments put forward herein, I propose that embryonic malignancies of mesenchymal origin with these particular types of aneuploidies can thus be viewed as the kind of flawed somatic equivalent of a digynic triploid embryo.
ANXA1 as a Prognostic and Immune Microenvironmental Marker for Gliomas Based on Transcriptomic Analysis and Experimental Validation
Authors: Lin Zhongxiao , Wen Min , Yu Enxing , Lin Xiao , Wang Hua , Chen Jiayu , Yao ChaoJie , Zhang Hengli , Ru Junnan , Wang Kankai , Zhang Ying , Huang Lijie , Zhuge Qichuan , Yang Su
Published: August 2021

The tumor microenvironment (TME) plays an important role in the growth and invasion of glioma. This study aimed to analyze the composition of the immune microenvironment in glioma samples and analyze the important differentially expressed genes to identify novel immune-targeted therapy for glioma. We downloaded transcriptomic data of 669 glioma samples from The Cancer Genome Atlas database. CIBERSORT and ESTIMATE methods were used to calculate the proportion of tumor-infiltrating immune cells and ratio of immune and stromal components in the TME. The differentially expressed genes (DEGs) were screened by comparing the genes expressed by both stromal and immune cells. Annexin A1 (ANXA1) was determined to be an important prognostic indicator through the common overlap of univariate Cox regression analysis and protein–protein interaction network analysis. The proportion of tumor-infiltrating immune cells, calculated by CIBERSORT algorithm, had a significant difference in distribution among the high and low ANXA1 expression groups, indicating that ANXA1 could be an important immune marker of TME. Furthermore, ANXA1 level was positively correlated with the histopathological factors and negatively related to the survival of glioma patients based on the analysis of multiple databases. Finally, in vitro experiments verified that antagonizing ANXA1 expression promoted cell apoptosis and inhibited the invasion and migration capacities of glioma cells. Therefore, ANXA1 due to its immune-related functions, can be an important prognostic indicator and immune microenvironmental marker for gliomas. Further studies are warranted to confirm ANXA1 as a potential immunotherapeutic target for gliomas.
Meta-Analysis-Assisted Detection of Gravity-Sensitive Genes in Human Vascular Endothelial Cells
Authors: Liang Yin , Wang Mengxue , Liu Yun , Wang Chen , Takahashi Ken , Naruse Keiji
Published: August 2021

Gravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized that it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells (HUVEC) to simulated microgravity (SMG) using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin (PG) transporter gene SLCO2A1 decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level of SLCO2A1, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.
Uncharged Components of Single-Stranded DNA Modulate Liquid–Liquid Phase Separation With Cationic Linker Histone H1
Authors: Mimura Masahiro , Tomita Shunsuke , Sugai Hiroka , Shinkai Yoichi , Ishihara Sayaka , Kurita Ryoji
Published: August 2021

Liquid–liquid phase separation (LLPS) of proteins and DNAs has been recognized as a fundamental mechanism for the formation of intracellular biomolecular condensates. Here, we show the role of the constituent DNA components, i.e., the phosphate groups, deoxyribose sugars, and nucleobases, in LLPS with a polycationic peptide, linker histone H1, a known key regulator of chromatin condensation. A comparison of the phase behavior of mixtures of H1 and single-stranded DNA-based oligomers in which one or more of the constituent moieties of DNA were removed demonstrated that not only the electrostatic interactions between the anionic phosphate groups of the oligomers and the cationic residues of H1, but also the interactions involving nucleobases and deoxyriboses (i) promoted the generation of spherical liquid droplets via LLPS as well as (ii) increased the density of DNA and decreased its fluidity within the droplets under low-salt conditions. Furthermore, we found the formation of non-spherical assemblies with both mobile and immobile fractions at relatively higher concentrations of H1 for all the oligomers. The roles of the DNA components that promote phase separation and modulate droplet characteristics revealed in this study will facilitate our understanding of the formation processes of the various biomolecular condensates containing nucleic acids, such as chromatin organization.
Zebrafish Models in Therapeutic Research of Cardiac Conduction Disease
Authors: Gao Rui , Ren Jie
Published: August 2021

Malfunction in the cardiac conduction system (CCS) due to congenital anomalies or diseases can cause cardiac conduction disease (CCD), which results in disturbances in cardiac rhythm, leading to syncope and even sudden cardiac death. Insights into development of the CCS components, including pacemaker cardiomyocytes (CMs), atrioventricular node (AVN) and the ventricular conduction system (VCS), can shed light on the pathological and molecular mechanisms underlying CCD, provide approaches for generating human pluripotent stem cell (hPSC)-derived CCS cells, and thus improve therapeutic treatment for such a potentially life-threatening disorder of the heart. However, the cellular and molecular mechanisms controlling CCS development remain elusive. The zebrafish has become a valuable vertebrate model to investigate early development of CCS components because of its unique features such as external fertilization, embryonic optical transparency and the ability to survive even with severe cardiovascular defects during development. In this review, we highlight how the zebrafish has been utilized to dissect the cellular and molecular mechanisms of CCS development, and how the evolutionarily conserved developmental mechanisms discovered in zebrafish could be applied to directing the creation of hPSC-derived CCS cells, therefore providing potential therapeutic strategies that may contribute to better treatment for CCD patients.
PP2A Phosphatase as an Emerging Viral Host Factor
Authors: Barski Michal Slawomir , Minnell Jordan James , Maertens Goedele Noella
Published: August 2021

Protein phosphatase 2A (PP2A) is one of the most ubiquitous cellular proteins and is responsible for the vast majority of Ser/Thr phosphatase activity in eukaryotes. PP2A is a heterotrimer, and its assembly, intracellular localization, enzymatic activity, and substrate specificity are subject to dynamic regulation. Each of its subunits can be targeted by viral proteins to hijack and modulate its activity and downstream signaling to the advantage of the virus. Binding to PP2A is known to be essential to the life cycle of many viruses and seems to play a particularly crucial role for oncogenic viruses, which utilize PP2A to transform infected cells through controlling the cell cycle and apoptosis. Here we summarise the latest developments in the field of PP2A viral targeting; in particular recent discoveries of PP2A hijacking through molecular mimicry of a B56-specific motif by several different viruses. We also discuss the potential as well as shortcomings for therapeutic intervention in the face of our current understanding of viral PP2A targeting.
TAVR in Cancer Patients: Comprehensive Review, Meta-Analysis, and Meta-Regression
Authors: Marmagkiolis Konstantinos , Monlezun Dominique J. , Cilingiroglu Mehmet , Grines Cindy , Herrmann Joerg , Toutouzas Konstantinos Pavlos , Ates Ismail , Iliescu Cezar
Published: August 2021

Objectives: This study sought to systematically analyze the available clinical evidence on TAVR therapy in cancer patients with symptomatic severe AS.

Background: Aortic stenosis is the most common valvular heart disease in the world. TAVR has expanded the treatment options for this lethal disease process. The safety and efficacy of TAVR in cancer patients has not yet been reliably established. We thus conducted the largest known multi-center meta-analysis on TAVR and cancer status.

Methods: We performed a literature search using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from January 2015 to 2020. Studies that compared the use of TAVR in patients with severe symptomatic aortic stenosis and cancer against patients without cancer were included. Meta-regression was also conducted to determine if common clinical factors modified the possible association between cancer status and TAVR mortality.

Results: Five studies with 11,129 patients in the cancer group and 41,706 patients in the control group met inclusion criteria. The short-term mortality in the cancer group was 2.4% compared with 3.3% in the control group (odds ratio: 0.72, 95% confidence interval: 0.63–0.82; p < 0.0001). The frequency of stroke was 2.4% compared with 2.7% (odds ratio of 0.87, 95% confidence interval: 0.76–0.99; p < 0.04). The frequency of AKI was 14.2% in cancer patients vs. 16.4% (odds ratio of 0.81, 95% confidence interval: 0.76–0.85; p < 0.04). The rates of bleeding and need for new pacemaker implantation were not significantly different. Meta-regression demonstrated there was no significant association modifying.

Conclusions: On the basis of the results of this meta-analysis TAVR may be a safe and effective therapeutic option for patients with cancer and symptomatic severe aortic stenosis. Larger, longer, and randomized trials are required to adequately test this above hypothesis.
Deep Dehydration as a Plausible Mechanism of the 2013 Mw 8.3 Sea of Okhotsk Deep-Focus Earthquake
Authors: Zhang Hao , van der Lee Suzan , Bina Craig R. , Ge Zengxi
Published: August 2021

The rupture mechanisms of deep-focus (>300 km) earthquakes in subducting slabs of oceanic lithosphere are not well understood and different from brittle failure associated with shallow (<70 km) earthquakes. Here, we argue that dehydration embrittlement, often invoked as a mechanism for intermediate-depth earthquakes, is a plausible alternative model for this deep earthquake. Our argument is based upon the orientation and size of the plane that ruptured during the deep, 2013 Mw 8.3 Sea of Okhotsk earthquake, its rupture velocity and radiation efficiency, as well as diverse evidence of water subducting as deep as the transition zone and below. The rupture process of this earthquake has been inferred from back-projecting dual-band seismograms recorded at hundreds of seismic stations in North America and Europe, as well as by fittingP-wave trains recorded at dozens of globally distributed stations. If our inferences are correct, the entirety of the subducting Pacific lithosphere cannot be completely dry at deep, transition-zone depths, and other deep-focus earthquakes may also be associated with deep dehydration reactions.
Structural Inheritance Controls Strain Distribution During Early Continental Rifting, Rukwa Rift
Authors: Kolawole Folarin , Phillips Thomas B. , Atekwana Estella A. , Jackson Christopher A.-L.
Published: August 2021

Little is known about rift kinematics and strain distribution during the earliest phase of extension due to the deep burial of the pre-rift and earliest rift structures beneath younger, rift-related deposits. Yet, this exact phase of basin development ultimately sets the stage for the location of continental plate divergence and breakup. Here, we investigate the structure and strain distribution in the multiphase Late Paleozoic-Cenozoic magma-poor Rukwa Rift, East Africa during the earliest phase of extension. We utilize aeromagnetic data that image the Precambrian Chisi Shear Zone (CSZ) and bounding terranes, and interpretations of 2-D seismic reflection data to show that, during the earliest rift phase (Permo-Triassic ‘Karoo’): 1) the rift was defined by the Lupa border fault, which exploited colinear basement terrane boundaries, and a prominent intra-basinal fault cluster (329° ± 9.6) that trends parallel to and whose location was controlled by the CSZ (326°); 2) extensional strain in the NW section of the rift was accommodated by both the intra-basinal fault cluster and the border fault, where the intra-basinal faulting account for up to 64% of extension; in the SE where the CSZ is absent, strain is primarily focused on the Lupa Fault. Here, the early-rift strain is thus, not accommodated only by the border fault as suggested by existing magma-poor early-rift models; instead, strain focuses relatively quickly on a large border fault and intra-basinal fault clusters that follow pre-existing intra-basement structures; 3) two styles of early-rift strain localization are evident, in which strain is localized onto a narrow discrete zone of basement weakness in the form of a large rift fault (Style-1 localization), and onto a broader discrete zone of basement weakness in the form of a fault cluster (Style-2 localization). We argue that the CSZ and adjacent terrane boundaries represent zones of mechanical weakness that controlled the first-order strain distribution and rift development during the earliest phase of extension. The established early-rift structure, modulated by structural inheritance, then persisted through the subsequent rift phases. The results of our study, in a juvenile and relatively well-exposed and data-rich rift, are applicable to understanding the structural evolution of deeper, buried ancient rifts.
Combination Usage of AdipoCount and Image-Pro Plus/ImageJ Software for Quantification of Adipocyte Sizes
Authors: Hu Yepeng , Yu Jian , Cui Xiangdi , Zhang Zhe , Li Qianqian , Guo Wenxiu , Zhao Cheng , Chen Xin , Meng Meiyao , Li Yu , Guo Mingwei , Qiu Jin , Shen Fei , Wang Dongmei , Ma Xinran , Xu Lingyan , Shen Feixia , Gu Xuejiang
Published: August 2021

In recent decades, the prevalence of obesity has been rising. One of the major characteristics of obesity is fat accumulation, including hyperplasia (increase in number) and hypertrophy (increase in size). After histological staining, it is critical to accurately measure the number and size of adipocytes for assessing the severity of obesity in a timely fashion. Manual measurement is accurate but time-consuming. Although commercially available adipocyte counting tools, including AdipoCount, Image-Pro Plus, and ImageJ were helpful, limitations still exist in accuracy and time consuming. In the present study, we introduced the protocol of combined usage of these tools and illustrated the process with histological staining slides from adipose tissues of lean and obese mice. We found that the adipocyte sizes quantified by the tool combination were comparable as manual measurement, whereas the combined methods were more efficient. Besides, the recognition effect of monochrome segmentation image is better than that of color segmentation image. Overall, we developed a combination method to measure adipocyte sizes accurately and efficiently, which may be helpful for experimental process in laboratory and also for clinic diagnosis.
Responses of Withania frutescens (L.) Pauquy (Solanaceae) Growing in the Mediterranean Area to Changes in the Environmental Conditions: An Approach of Adaptation
Authors: Moussaoui Abdelfattah El , Bourhia Mohammed , Jawhari Fatima Zahra , Khalis Hind , Chedadi Mohamed , Agour Abdelkrim , Salamatullah Ahmad Mohammad , Alzahrani Abdulhakeem , Alyahya Heba Khalil , Alotaibi Asdaf , Bousta Dalila , Bari Amina
Published: August 2021

Background

Flora growth is always influenced by the environmental conditions that surround the plant.

The Objective of the Study

The present research work was undertaken to study the response of Withania frutescens (L.) Pauquy to changes in the environmental conditions by investigating topographical, climatological, morphological, histological, and phytochemical aspects influencing the plant’s growth.

Materials and Methods

The topography of the study area was described using the Digital Terrain Model (DTM). The bioclimatic study was carried out using a climatological database (TerraClimate) used for an old period 1960–1970 (OP) and a new period 2000–2019 (NP). The histological study on stems, leaves, and roots was investigated according to protocols as described in the present study. The phytochemical analysis was assessed using a gas chromatograph coupled to a mass spectrophotometer after silylation.

Results

The topographical study showed that the selected stations varied in terms of topographical characteristics. The average annual precipitation recorded for the study area was 624 mm/year, and the thermal amplitude was around 34.64°C. The morphometrical study revealed that the plant had changes in length and width from one zone to another. The histometrical study of organs showed changes in tissue structure over time and location. The phytochemical content in the studied plants was also found to vary over time and location.

Conclusion

Based on the obtained results, we could confirm that W. frutescens has developed alternate strategies to mitigate increasingly harsh environmental conditions.
Significant Gene Biomarker Tyrosine Kinase Non-receptor 2 Mediated Cell Proliferation and Invasion in Colon Cancer
Authors: Ling Sunkai , He Yanru , Li Xiaoxue , Ma Yu , Li Yuan , Kong Bo , Huang Peilin
Published: August 2021

Objective: This study aimed to investigate the expression and biological functions of TNK2 and miR-125a-3p in colon cancer.

Materials and methods: The expression of TNK2 and miR-125a-3p in colon cancer tissues was analyzed using data deposited on public databases including UALCAN and ONCOMINE. We verified their expression in colon cancer cell lines by RT-qPCR and western blotting. By regulating the expression of TNK2 and miR-125a-3p in colon cancer cells, their functions and potential mechanisms were explored.

Results:TNK2 was overexpressed in colon cancer cell lines, and it was found to directly bind to miR-125a-3p, which was downregulated in these cell lines. Their expression affected the proliferation and invasion of colon cancer cells. Additionally, colon cancer patients with lower TNK2 expression had better prognoses than those with higher TNK2 expression.

Conclusion: Our results indicated that TNK2 and miR-125a-3p play critical roles in colon cancer, and could also serve as biomarkers for the diagnosis and prognosis of this malignant disease.
KLF4 Inhibits the Differentiation of Goat Intramuscular Preadipocytes Through Targeting C/EBPβ Directly
Authors: Xu Qing , Li Yanyan , Lin Sen , Wang Yong , Zhu Jiangjiang , Lin Yaqiu
Published: August 2021

Intramuscular fat (IMF) deposition is a complicated process, and most of the underlying regulators of this biological process are unknown. Here, we cloned the intact CDS of KLF4 gene, investigated the role of KLF4 by gaining or losing function in vitro and further explored the pathways of KLF4 regulating differentiation of intramuscular preadipocytes in goat. Our results show that goat KLF4 gene consists of 1,536 bp encoding a protein of 486 amino acids. The expression of KLF4 is higher in the lung while lower in the heart and muscle in goat. Knockdown of KLF4 mediated by siRNA technique significantly promotes intramuscular preadipocyte lipid accumulation and upregulates mRNA expression of adipogenic related genes including C/EBPα, C/EBPβ, and PPARγ in vivo cultured cells. Consistently, overexpression of KLF4 inhibits intramuscular adipocyte lipid accumulation and significantly downregulation gene expression of C/EBPβ, PPARγ, aP2, and Pref-1. Further, we found that other members of KLFs were upregulated or downregulated after interference or overexpression of KLF4, including KLF2 and KLF5–7. We also found that C/EBPβ was a potential target of KLF4, because it had an opposite expression pattern with KLF4 during the differentiation of intramuscular preadipocytes and had putative binding sites of KLF4. The dual-luciferase reporter assay indicated that overexpression of KLF4 inhibited the transcriptional activity of C/EBPβ. These results demonstrate that KLF4 inhibits the differentiation of intramuscular preadipocytes in goat by targeting C/EBPβ.
Identification of Candidate Genes Regulating the Seed Coat Color Trait in Sesame (Sesamum indicum L.) Using an Integrated Approach of QTL Mapping and Transcriptome Analysis
Authors: Li Chun , Duan Yinghui , Miao Hongmei , Ju Ming , Wei Libin , Zhang Haiyang
Published: August 2021

Seed coat color is an important seed quality trait in sesame. However, the genetic mechanism of seed coat color variation remains elusive in sesame. We conducted a QTL mapping of the seed coat color trait in sesame using an F2 mapping population. With the aid of the newly constructed superdense genetic linkage map comprised of 22,375 bins distributed in 13 linkage groups (LGs), 17 QTLs of the three indices (i.e., L, a, and b values) of seed coat color were detected in seven intervals on four LGs, with a phenotype variance explanation rate of 4.46–41.53%. A new QTL qSCa6.1 on LG 6 and a QTL hotspot containing at least four QTLs on LG 9 were further identified. Variants screening of the target intervals showed that there were 84 genes which possessed the variants that were high-impact and co-segregating with the seed coat color trait. Meanwhile, we performed the transcriptome comparison of the developing seeds of a white- and a black-seeded variety, and found that the differentially expressed genes were significantly enriched in 37 pathways, including three pigment biosynthesis related pathways. Integration of variants screening and transcriptome comparison results suggested that 28 candidate genes probably participated in the regulation of the seed coat color in sesame; of which, 10 genes had been proved or suggested to be involved in pigments biosynthesis or accumulation during seed formation. The findings gave the basis for the mechanism of seed coat color regulation in sesame, and exhibited the effects of the integrated approach of genome resequencing and transcriptome analysis on the genetics analysis of the complex traits.