bluuebunny/crossref_metadata_2025 huggingface dataset:
Cymantrene Derivatives Containing Imino Groups: Spectral and Photochemical Properties
Authors:   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, Moscow, 119991 Russia, Telegina L. N. , Borisov Yu. A. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, Moscow, 119991 Russia, Kelbysheva E. S. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, Moscow, 119991 Russia
Published: March 2021

The investigation of a photochemical behavior of imino derivatives of cymantrene reveals a possibility of formation of four-membered hemilabile chelate complexes. In the presence of external ligands, such as CO, MeCN, or PPh3, the ligand exchange between imino groups at the Mn atom in dicarbolyl chelates and the external ligand is observed. It is shown that MeCN or PPh3 can be substituted for CO under dark conditions, resulting in intermolecular photochromic systems between tricarbonyl complexes and dicarbonyl derivatives with MeCN and PPh3 ligand, respectively.
Ekspektasi Sosial Pemuda Sasak dalam Nasyid Ya Fata Sasak Karya Hamzanwadi
Authors: Rosidi Akhyar
Published: March 2021

This study aims to describe the youth’s social expectations of the nasyid text Ya Fata Sasak by T.G.K.H. Muhammad Zainuddin Abdul Majid. The research method used is semiotic that is qualitative interpretive with content analysis techniques that focus to the research on the latent content of nasyid text Ya Fat Sasak as data research on the latent content of the nasyid Ya Fata Sasak research. This technique is carried out by copying the nasyid Ya Fata Sasak manuscript to Indonesian, reading, writing, and coding into five codes of Rolands Barthes such as hermeneutic code, action code, symbolic code, semantics code, and referential code. So the social expectations of the Sasak youth are defined. The result of this research shows that Sasak youth have equal opportunities with other young people in Indonesia to expect both individually and collectively. Every social expectation carried  out by Sasak youth is certainly related to the interest of the people, nation and the state which is realized through the strengthening of critical and independent discourses to  maintain  their  idealism,  such  as  building self-confidence (character building) and carrying out social and religious values as brotherhood and unity, managing natural resources that can be utilized optimally, participating in various competitions of contestations, and instilling a spirit of nationalism as the one of foundations for maintaining and advancing the Indonesian people.
PENGGUNAAN APLIKASI VIDEOMAKER FX DALAM PENGEMBANGAN MEDIA PEMBELAJARAN BAHASA INDONESIA
Authors: Khairunnisa Naurah
Published: March 2021

Perkembangan zaman yang sangat pesat pastinya berpengaruh terhadap teknologi informasi dan komunikasi, termasuk pada bidang Pendidikan. Salah satu dari produk teknologi informasi dan komunikasi yang sangat menarik untuk dimanfaatkan dalam pembelajaran adalah aplikasi VideoMaker FX ini. Dalam pemanfaatan media, diperlukan kreativitas dan juga pertimbangan instruksional yang matang dari pengajar. Kenyataannya banyak pengajar yang menggunakan media pembelajaran seadanya tanpa pertimbangan pembelajaran. Penelitian ini bertujuan untuk menghasilkan media pembelajaran Bahasa Indonesia menggunakan aplikasi VideoMaker FX di sekolah yang praktis, mudah dan efektif terhadap pembelajaran siswa. Metode penelitian yang digunakan adalah metode kualitatif deskripsi, dengan cara mendeskripsikan penggunaan aplikasi VideoMaker FX sebagai pengembangan media video pembelajaran.
BETA KATSAYILARI AYLIK OLARAK DEĞİŞİR Mİ? KÖRFEZ ARAP ÜLKELERİ İŞBİRLİĞİ KONSEYİ ÜLKELERİ ÜZERİNE BİR ARAŞTIRMA
Authors: HATİPOĞLU Mercan
Published: March 2021

Bu çalışmanın amacı Körfez Arap Ülkeleri İşbirliği Konseyi (Bahreyn, Birleşik Arap Emirlikleri (BAE), Suudi Arabistan, Umman, Katar, Kuveyt) ülke borsaları için beta katsayılarının aylara göre değişip değişmediğinin araştırılmasıdır. Piyasa riskini temsil etmek için MSCI Dünya Borsaları endeksi kullanılmıştır. Çalışmada, Körfez Arap Ülkeleri İşbirliği Konseyi ülkeleri borsalarının aylık beta değerlerinin, uzun dönemli beta değerlerinden oldukça farklı olduğu bulgusuna ulaşılmıştır. Dolayısıyla, risk-getiri ilişkisi bu borsaların için aylık olarak değişkenlik arz etmektedir. Bu tarz anomalilerin finansal piyasalarda varlığı, gerek bireysel yatırımcılara gerekse portföy yöneticilerine aylık fiyat dalgalanmalarından yararlanarak piyasa üstü kazanç sağlama fırsatı sunmaktadır.
PERCERAIAN DI MASA PANDEMI COVID-19 DALAM PERSPEKTIF ILMU SOSIAL
Authors:   Program Pascasarjana Universitas Andalas, Tristanto Aris
Published: March 2021

Pandemi COVID-19 merupakan badai yang sempurna untuk menguji hubungan pasangan suami istri. Selama pandemi COVID-19 angka perceraian di Indonesia meningkat sebesar 5 persen. Tulisan ini merupakan kajian literatur yang bertujuan untuk menganalisis perceraian di masa pandemi COVID-19 dalam perspektif ilmu sosial. Analisis dalam tulisan ini dilakukan melalui kajian pustaka. Secara umum faktor penyebab perceraian pada masa pandemi COVID-19 terjadi karena adanya konflik dalam rumah tangga yang disebabkan oleh permasalahan ekonomi, ketidakseimbangan aktivitas dan waktu bersama, kekerasan dalam rumah tangga, berubah pola komunikasi, dan faktor usia dalam membina rumah tangga. Dari berbagai teori dalam ilmu sosial dapat diketahui bahwa dalam sebuah keluarga ada fungsi dan disfungsi yang terjadi antara keluarga. Dalam keluarga pun sering terjadi pertentangan atau konflik internal maupun eksternal anggota keluarga. Agar terhindar dari keretakan dalam rumah tangga dapat dilakukan dengan cara memberi ruang ke dalam hubungan sebaik yang dapat dilakukan. Selain itu penulis merekomendasikan kepada semua pasangan suami istri yang sering berkonflik di tengah pendemi, sebaiknya pasangan suami istri tersebut harus belajar untuk berdiskusi dengan menggunakan kata-kata yang lembut, dan membangun terutama pada saat mengatakan sesuatu yang sulit bagi pasangan untuk mendengarnya. Dalam berdiskusi penting untuk menerapkan perilaku 3M yaitu, mengalah, memaklumi, dan memaafkan.
دور البيئة التشريعية في تطبيق معايير الحلال في المنتجات والخدمات وملائمة النظام القانوني الليبي استرشادا ʪلمعايير الماليزية
Authors: Ahmed Ahmed Salem
Published: March 2021

Halal standards are based on religious values that are unique to other legal systems. Consequently, the legislation of the surrounding environment may have direct effects on the application of these standards, and that these effects become more complex the more the environment embodied in the contents clash with the Shariah-based Halal. In order to show the importance of the Halal sector in both religious and investment aspects, this paper examined the contribution of the legislative environment to Halalization and how Halal standards could be adopted in the products and services by the existing legal systems of the countries that have not adopted them, through comparison between legal systems. The paper used the Libyan legal system as a case study because its system is less concerned about Halalization. After analyzing the laws related to Halal products and services, it was found that the Libyan legislative environment is rich with the contents of Halalization; even if the Halalization is not codified in the contemporary concept just as stated in the Malaysian standards that the paper adopts as a criterion for the comparison, it implicitly includes most of the contents of these standards. The paper recommends that the Libyan system should adopt the Halal standards to benefit from this sector.
Qualitative Indicators of Irrigated Gray-Meadow Soils of Mugan-Salyan Steppe of Azerbaijan
Authors: Nuriyeva K.
Published: March 2021

This article discusses the general physical and geographical location, geological, geomorphological and soil-climatic conditions of the region. The methodological instructions are consecrated, the qualitative indicators of soils and their assessment according to the appraisal scores of the dominant irrigated gray earth soils are analyzed.
Trends in the Evolution of Visual Communication in the Context of Book Design
Authors:   Kharkiv State Academy of Design and Arts, Velichko Nadiia
Published: March 2021

The article reviews the stages and factors of evolution in visual communication. It also analyzes the basic principles in construction of such communication. Features of a book as a communicative carrier are reviewed. The article reveals current trends of visual communication evolution, their origins and historical analogues. The author proves that changes in communication technologies are closely related to changes in the principles of information consumption. Modern features of communicative space development are revealed. They include interactivity, multimedia, and hypertextuality. Due to these factors, expansion of the role of the visual component and its more active use as the main carrier in the communicative culture keeps going on in recent years. Analysis of the modern communicative space indicates not only the tendency to visualize. Firstly, a distinctive feature of modern communications is an easy access of almost any information accumulated by mankind. Secondly, general acceleration of the pace of life pushes to the need to learn and relearn, gain new knowledge every day, spending as little time as possible. Third, the user has a habit to respond to any type of information interactively. This is one of the most important changes in the principles of transmission and perception of information, which involves the user in the process of perception and makes him a co‑author. The present research shows that visual communication uses not only modern approaches, such as hypertextuality, multimedia and interactivity, but also traditional methods of artistic practices, such as color, composition, shaping, etc. Modern trends in visual communication feature redefining of the techniques inherent in visual communication for a long time. At the same time, there is a certain interpenetration of techniques inherent in computer and print media. The development of methods of information transfer is continuing. The emerging of new forms is possible, which may serve as a topic for further research.
Design Methodology: From the Achievements of Historical Development to the Problems of Modern Functioning
Authors:   Cherkasy State Technological University, Sergeieva Natalia
Published: March 2021

The research presents a general analysis of the design methodology development, which deals with the main global trends, but still appeals more to the design property and problems of the post-Soviet countries. The purpose of the present study is to analyze modern manifestations of the crisis in design methodology. It is based on the topicality of performance of its important role in providing thought and organizing design practice. The implementation of the research goal became possible owing to general logical methods of analysis and synthesis, the historical method, and methods of induction and deduction. The study found that the achievements of the USSR design methodology, which had been developed and tested in the 1960–80s of the twentieth century, have not become in demand in modern science. On the other hand, a more detailed analysis revealed the proximity of their essential content to modern design approaches, which had been proposed after the 1990s by researchers and experts of Western design. In particular, it is a question of comparison of the “Design-program” approach and the principles of so-called “Design-thinking”, which is popular nowadays; the concept of the environmental approach and the thesis of “Environmental design”; experiments on the emotional image formation in design and the concept of “Emotional design”. In addition to stating lost opportunities and time, broken ties of scientific heredity, etc., it is important to realize the reasons of this case. It is also essential to become aware that along with objective circumstances of ideological, organizational or material causes, there are also subjective ones, which are significant too. So, the subconscious feeling that your own values are more important than others will neither contribute to the development of a National Design Model (in the context of globalization of the world cultural space), nor to the formation of the functioning methodology accordingly. Particularly, when this feeling is combined with a super-loyal and uncritical attitude to other people’s opinions.
Art of Fire of Ukraine in the Context of European Artistic Process (Exemplified by National and International Competitive Exhibitions of Ceramic Art and Glass Art)
Authors:   Institute of Art Studies, Folkloristics and Ethnology, Chegusova Zoia
Published: March 2021

The article presents a detailed analysis of achievements of Ukrainian artists working in the field of art of fire, in particular professional ceramics and glassworks, while attracting close attention in the general artistic process of the 1980s to 2010s. Losses of the art industry in Ukraine in the 1990s did not stop the artists from searching the ways to streamline decorative imagery, as well as non‑standard approaches to materials in the individual work of artists in this field. European and global biennials and triennials of decorative art considerably contributed to finding new ways of the art of fire development. During such events masters of various artistic trends and schools exchanged their experience. And that proved to be the most powerful stimulus for both intensification of creativity and strengthening experimental activities in exposition works of Ukrainian artists at the turn of the 20th and 21st centuries. Since then, Ukrainian masters of ceramics and glassworks have begun mastering the heritage of artists from other countries, which contributed to the diversification of formal techniques of Ukrainian artists of decorative art. This, in its turn, has led to the emergence of various conceptual works, installations, and complicated spatial compositions. The author also carefully considers national competitive exhibitions, all‑Ukrainian presentations and symposia, which helped to introduce the latest artistic ideas and technologies of the art of fire masters. This study is actualized by globalization processes taking place in civilization. Stating specific challenges posed by the globalization to national culture, the author, at the same time, finds arguments in favor of its positive effects on art. A rapid entry of Ukrainian ceramic and glass artists into the global context at the turn of the 20th – 21st centuries, does not bring about a danger of dissolving in it, given the nature of professional decorative art of Ukraine. The art of fire is perceived as a powerful branch in the field of national culture with its inherent features of authentic spiritual genetics, as a dynamic balance of centuries‑old traditions and modern fine arts. It is paradoxical, the author believes, that globalization generates the opposite process as well: it directs Ukrainian artists to search for archetypes of their own culture, returns to their national historical heritage, and stimulates the preservation of national identity, as a result of which the art of fire becomes an important factor of national and cultural identification. In the context of professional decorative art problems and from the viewpoint of national and cultural identification in the conditions of globalization processes in Ukraine, such an aspect of studying the art of fire within the field of art history science is considered for the first time.
The Cultural Landscape of Norway: to the Question of Aesthetics and Ecology of the Environment
Authors:   Kyiv National University of Culture and Arts, Som-Serdyukova Olena
Published: March 2021

In the realities of Norway, a cultural landscape is an element of mass consciousness and one of the key definitions. The cultural landscape presupposes the relationship between the past, through the present, to the future. Layering and changes in the cultural landscape are permanent. The task of modernity is to fix and preserve the cultural landscape. The interdisciplinary, integrated work of specialists of various profiles is realized with responsibility for the future. The way of understanding the cultural landscape, its analysis, and interpretation influences the development of historical memory. A rational understanding and emotional attitude to the cultural landscape is formed at the intersection of time with space, culture with art, landscape with history. A look at the cultural landscape through the prism of local and national history helps to understand the past, builds the meanings of the authentic and identical. Design is the tool to combine the main requirements of modernity to the cultural landscape – aesthetics, and ecology. The attitude to nature is understood, not as an urgent economic need, but as the property of future generations from which we just borrow it. The formation of a new ethic, based on the preservation of the environment, a meaningful attitude to nature, taking personal responsibility for it, shapes the aesthetics inspired by the forms and colors of nature. The author analyzed the main types of Norwegian cultural landscapes, which included coast, mountain, and town. The place of church edifices in such a landscape was also identified. Using specific examples, the author outlined the characteristics, and defined the role of the environment design. Comments on the cultural landscape are made through a number of literary reflections. The author came to conclusions which gave grounds to thinking about a unique place of such a definition as a cultural landscape in the socio-cultural life of Norway.
‘Indian Gowns Small and Great’: Chintz Banyans Ready Made in the Coromandel, c. 1680–c. 1780
Authors: Fennetaux Ariane
Published: March 2021

The article focuses on the close study of a group of eighteenth-century chintz nightgowns that were ready-made or partly ready-made in India for the European market. Whereas nightgowns are usually associated with the taste for the exotic and the spread of the fashion is sometimes linked to the availability of the garment on the ready-made market, the production of ready-made gowns in India and the methods put in place to manufacture these commodities have not been studied. Based on a close reading of surviving chintz nightgowns, the article attempts to understand production techniques put in place by Indian craftsmen to meet European demand. Material evidence suggests streamlined production processes were in place in India from the end of the seventeenth century that had no real equivalent in Europe. The article thus sheds further light on the idea of Europe's ‘Indian apprenticeship’, showing that Indian mastery of colour was coupled with production methods combining artisanal, non-mechanized work with a level of bulk production and enhanced efficiency.
Variability in inflectional forms of attributive-appositive composite lexical units in Polish
Authors: Cetnarowska Bożena
Published: March 2021

This paper examines inflectional markers (signalling number, case and gender) of selected types of NN complexes in Polish, which can be regarded as attributive-appositive (ATAP) lexical units in the cross-linguistic classification of compounds proposed by Scalise & Bisetto (2009) . Polish compounds proper show externalization of inflection and take inflectional markers on their right-hand constituents only. In contrast, Polish juxtapositions are expected to display double inflectional marking (on both their components). However, data from the National Corpus of Polish demonstrate that ATAP juxtapositions containing the lexeme widmo ‘ghost, phantom’ as their right-hand component exhibit variability in their inflectional paradigms. The right-hand (i.e. the modifier) constituent of such juxtapositions either shows number and case agreement with the head noun, or it appears in the default (nom.sg) form. Potential reasons for the instability of inflectional paradigms of such NN juxtapositions are considered.
Pilot Scale Elimination of Phenolic Cellulase Inhibitors From Alkali Pretreated Wheat Straw for Improved Cellulolytic Digestibility to Fermentable Saccharides
Authors: Haq Ikram ul , Nawaz Ali , Liaqat Badar , Arshad Yesra , Fan Xingli , Sun Meitao , Zhou Xin , Xu Yong , Akram Fatima , Jiang Kankan
Published: March 2021

Depleting supplies of fossil fuel, regular price hikes of gasoline and environmental deterioration have necessitated the search for economic and eco-benign alternatives of gasoline like lignocellulosic biomass. However, pre-treatment of such biomass results in development of some phenolic compounds which later hinder the depolymerisation of biomass by cellulases and seriously affect the cost effectiveness of the process. Dephenolification of biomass hydrolysate is well cited in literature. However, elimination of phenolic compounds from pretreated solid biomass is not well studied. The present study was aimed to optimize dephenoliphication of wheat straw using various alkalis i.e., Ca(OH)2 and NH3; acids i.e., H2O2, H2SO4, and H3PO4; combinations of NH3+ H3PO4 and H3PO4+ H2O2 at pilot scale to increase enzymatic saccharification yield. Among all the pretreatment strategies used, maximum reduction in phenolic content was observed as 66 mg Gallic Acid Equivalent/gram Dry Weight (GAE/g DW), compared to control having 210 mg GAE/g DW using 5% (v/v) combination of NH3+H3PO4. Upon subsequent saccharification of dephenoliphied substrate, the hydrolysis yield was recorded as 46.88%. Optimized conditions such as using 1%+5% concentration of NH3+ H3PO4, for 30 min at 110°C temperature reduced total phenolic content (TPC) to 48 mg GAE/g DW. This reduction in phenolic content helped cellulases to act more proficiently on the substrate and saccharification yield of 55.06% was obtained. The findings will result in less utilization of cellulases to get increased yield of saccharides by hydrolyzing wheat straw, thus, making the process economical. Furthermore, pilot scale investigations of current study will help in upgrading the novel process to industrial scale.
Induced Neurons for Disease Modeling and Repair: A Focus on Non-fibroblastic Cell Sources in Direct Reprogramming
Authors: Kim Kathryn M. , Thaqi Mentor , Peterson Daniel A. , Marr Robert A.
Published: March 2021

Direct cellular reprogramming exhibits distinct advantages over reprogramming from an induced pluripotent stem cell intermediate. These include a reduced risk of tumorigenesis and the likely preservation of epigenetic data. In vitro direct reprogramming approaches primarily aim to model the pathophysiological development of neurological disease and identify therapeutic targets, while in vivo direct reprogramming aims to develop treatments for various neurological disorders, including cerebral injury and cancer. In both approaches, there is progress toward developing increased control of subtype-specific production of induced neurons. A majority of research primarily utilizes fibroblasts as the donor cells. However, there are a variety of other somatic cell types that have demonstrated the potential for reprogramming into induced neurons. This review highlights studies that utilize non-fibroblastic cell sources for reprogramming, such as astrocytes, olfactory ensheathing cells, peripheral blood cells, Müller glia, and more. We will examine benefits and obstructions for translation into therapeutics or disease modeling, as well as efficiency of the conversion. A summary of donor cells, induced neuron types, and methods of induction is also provided.
Critical Response of High-Rise Buildings With Deformation-Concentration Seismic Control System Under Double and Multi Impulses Representing Pulse-Type and Long-Duration Ground Motions
Authors: Kawai Akira , Maeda Tatsuhiko , Takewaki Izuru
Published: March 2021

The critical responses are investigated for a high-rise building with a deformation-concentration seismic control system under double and multi impulses representing pulse-type and long-duration ground motions, respectively. The critical responses were studied for an elastic-plastic multi-degree-of-freedom (MDOF) shear building model under a double impulse and a multi impulse in the previous papers. However, it seems difficult to derive the critical response for a realistic three-dimensional (3-D) nonlinear frame model with a deformation-concentration seismic control system under such double and multi impulses. The criteria on the criticality of the double and multi impulses for the elastic-plastic MDOF shear building model derived in the previous research are extended to this realistic controlled 3-D frame model by regarding the sum of base story shear forces of both main and sub buildings as a key quantity. In the analysis, the concepts of “Double Impulse Pushover (DIP)” and “Multi Impulse Pushover (MIP)” introduced before are used effectively for clarifying the progressive performances for the increasing input level. The analyses of total input energy, frame hysteretic energy and damper dissipation energy are conducted and the criticality of the input derived based on the above-mentioned criteria is investigated in detail.
Connecting the Dots: Resolving the Bone Marrow Niche Heterogeneity
Authors: Dolgalev Igor , Tikhonova Anastasia N.
Published: March 2021

Single-cell sequencing approaches have transformed our understanding of stem cell systems, including hematopoiesis and its niche within the bone marrow. Recent reports examined the bone marrow microenvironment at single-cell resolution at steady state, following chemotherapy treatment, leukemic onset, and aging. These rapid advancements significantly informed our understanding of bone marrow niche heterogeneity. However, inconsistent representation and nomenclature among the studies hinder a comprehensive interpretation of this body of work. Here, we review recent reports interrogating bone marrow niche architecture and present an integrated overview of the published datasets.
Warburg’s Ghost—Cancer’s Self-Sustaining Phenotype: The Aberrant Carbon Flux in Cholesterol-Enriched Tumor Mitochondria via Deregulated Cholesterogenesis
Authors: Coleman Peter S. , Parlo Risa A.
Published: March 2021

Interpreting connections between the multiple networks of cell metabolism is indispensable for understanding how cells maintain homeostasis or transform into the decontrolled proliferation phenotype of cancer. Situated at a critical metabolic intersection, citrate, derived via glycolysis, serves as either a combustible fuel for aerobic mitochondrial bioenergetics or as a continuously replenished cytosolic carbon source for lipid biosynthesis, an essentially anaerobic process. Therein lies the paradox: under what conditions do cells control the metabolic route by which they process citrate? The Warburg effect exposes essentially the same dilemma—why do cancer cells, despite an abundance of oxygen needed for energy-generating mitochondrial respiration with citrate as fuel, avoid catabolizing mitochondrial citrate and instead rely upon accelerated glycolysis to support their energy requirements? This review details the genesis and consequences of the metabolic paradigm of a “truncated” Krebs/TCA cycle. Abundant data are presented for substrate utilization and membrane cholesterol enrichment in tumors that are consistent with criteria of the Warburg effect. From healthy cellular homeostasis to the uncontrolled proliferation of tumors, metabolic alterations center upon the loss of regulation of the cholesterol biosynthetic pathway. Deregulated tumor cholesterogenesis at the HMGR locus, generating enhanced carbon flux through the cholesterol synthesis pathway, is an absolute prerequisite for DNA synthesis and cell division. Therefore, expedited citrate efflux from cholesterol-enriched tumor mitochondria via the CTP/SLC25A1 citrate transporter is fundamental for sustaining the constant demand for cytosolic citrate that fuels the elevated flow of carbons from acetyl-CoA through the deregulated pathway of cholesterol biosynthesis.
EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells
Authors: Schelch Karin , Vogel Lisa , Schneller Anja , Brankovic Jelena , Mohr Thomas , Mayer Rupert L. , Slany Astrid , Gerner Christopher , Grusch Michael
Published: March 2021

Tumors and the tumor microenvironment produce multiple growth factors that influence cancer cell behavior via various signal transduction pathways. Growth factors, like transforming growth factor β (TGFβ) and epidermal growth factor (EGF), have been shown to induce proliferation, migration, and invasion in different cell models. Both factors are frequently overexpressed in cancer and will often act in combination. Although both factors are being used as rational targets in clinical oncology, the similarities and differences of their contributions to cancer cell migration and invasion are not fully understood. Here we compared the impact of treating A549 lung adenocarcinoma cells with TGFβ, EGF, and both in combination by applying videomicroscopy, functional assays, immunoblotting, real-time PCR, and proteomics. Treatment with both factors stimulated A549 migration to a similar extent, but with different kinetics. The combination had an additive effect. EGF-induced migration depended on activation of the mitogen-activated protein kinase (MAPK) pathway. However, this pathway was dispensable for TGFβ-induced migration, despite a strong activation of this pathway by TGFβ. Proteome analysis (data are available via ProteomeXchange with identifier PXD023024) revealed an overlap in expression patterns of migration-related proteins and associated gene ontology (GO) terms by TGFβ and EGF. Further, only TGFβ induced the expression of epithelial to mesenchymal transition (EMT)-related proteins like matrix metalloproteinase 2 (MMP2). EGF, in contrast, made no major contribution to EMT marker expression on either the protein or the transcript level. In line with these expression patterns, TGFβ treatment significantly increased the invasive capacity of A549 cells, while EGF treatment did not. Moreover, the addition of EGF failed to enhance TGFβ-induced invasion. Overall, these data suggest that TGFβ and EGF can partly compensate for each other for stimulation of cell migration, but abrogation of TGFβ signaling may be more suitable to suppress cell invasion.
The Role of Intestinal Flora in the Regulation of Bone Homeostasis
Authors: Li Chengxiang , Pi Guofu , Li Feng
Published: March 2021

Intestinal flora located within the intestinal tract comprises a large number of cells, which are referred to as the second gene pool of the human body and form a complex symbiotic relationship with the host. The knowledge of the complex interaction between the intestinal flora and various life activities of the host is a novel and rapidly expanding field. Recently, many studies are being conducted on the relationship between the intestinal flora and bone homeostasis and indicate that the intestinal flora can regulate bone homeostasis via the host immune, metabolic, and endocrine systems. What’s more, based on several clinical and preclinical pieces of evidence, changing the composition and function of the host intestinal flora through the application of probiotics, prebiotics, and fecal microbiota transplantation is being considered to be a potential novel target for the regulation of bone homeostasis. Here, we searched relevant literature and reviewed the role of the intestinal flora in the regulation of bone homeostasis and its modulating interventions.
Interaction of Trypanosoma cruzi Gp82 With Host Cell LAMP2 Induces Protein Kinase C Activation and Promotes Invasion
Authors: Onofre Thiago Souza , Rodrigues João Paulo Ferreira , Shio Marina Tiemi , Macedo Silene , Juliano Maria Aparecida , Yoshida Nobuko
Published: March 2021

The surface molecule gp82 of metacyclic trypomastigote (MT) forms of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, mediates the host cell invasion, a process critical for the establishment of infection. Gp82 is known to bind to the target cell in a receptor-dependent manner, triggering Ca2+ signal, actin cytoskeleton rearrangement and lysosome spreading. The host cell receptor for gp82 was recently identified as LAMP2, the major lysosome membrane-associated protein. To further clarify the mechanisms of MT invasion, we aimed in this study at identifying the LAMP2 domain that interacts with gp82 and investigated whether target cell PKC and ERK1/2, previously suggested to be implicated in MT invasion, are activated by gp82. Interaction of MT, or the recombinant gp82 (r-gp82), with human epithelial HeLa cells induced the activation of Ca2+-dependent PKC and ERK1/2. The LAMP2 sequence predicted to bind gp82 was mapped and the synthetic peptide based on that sequence inhibited MT invasion, impaired the binding of r-gp82 to HeLa cells, and blocked the PKC and ERK1/2 activation induced by r-gp82. Treatment of HeLa cells with specific inhibitor of focal adhesion kinase resulted in inhibition of r-gp82-induced PKC and ERK1/2 activation, as well as in alteration of the actin cytoskeleton architecture. PKC activation by r-gp82 was also impaired by treatment of HeLa cells with inhibitor of phospholipase C, which mediates the production of diacylglycerol, which activates PKC, and inositol 1,4,5-triphosphate that releases Ca2+ from intracellular stores. Taken together, our results indicate that recognition of MT gp82 by LAMP2 induces in the host cell the activation of phosholipase C, with generation of products that contribute for PKC activation and the downstream ERK1/2. This chain of events leads to the actin cytoskeleton disruption and lysosome spreading, promoting MT internalization.
De Novo Synthesis of Phosphatidylcholine Is Essential for the Promastigote But Not Amastigote Stage in Leishmania major
Authors: Moitra Samrat , Basu Somrita , Pawlowic Mattie , Hsu Fong-fu , Zhang Kai
Published: March 2021

Phosphatidylcholine (PC) is the most abundant type of phospholipids in eukaryotes constituting ~30% of total lipids in Leishmania. PC synthesis mainly occurs via the choline branch of the Kennedy pathway (choline ⇒ choline-phosphate ⇒ CDP-choline ⇒ PC) and the N-methylation of phosphatidylethanolamine (PE). In addition, Leishmania parasites can acquire PC and other lipids from the host or culture medium. In this study, we assessed the function and essentiality of choline ethanolamine phosphotransferase (CEPT) in Leishmania major which is responsible for the final step of the de novo synthesis of PC and PE. Our data indicate that CEPT is localized in the endoplasmic reticulum and possesses the activity to generate PC from CDP-choline and diacylglycerol. Targeted deletion of CEPT is only possible in the presence of an episomal CEPT gene in the promastigote stage of L. major. These chromosomal null parasites require the episomal expression of CEPT to survive in culture, confirming its essentiality during the promastigote stage. In contrast, during in vivo infection of BALB/c mice, these chromosomal null parasites appeared to lose the episomal copy of CEPT while maintaining normal levels of virulence, replication and cellular PC. Therefore, while the de novo synthesis of PC/PE is indispensable for the proliferation of promastigotes, intracellular amastigotes appear to acquire most of their lipids through salvage and remodeling.
Reduction of Emergency Calls and Hospitalizations for Cardiac Causes: Effects of Covid-19 Pandemic and Lockdown in Tuscany Region
Authors: D'Ascenzi Flavio , Cameli Matteo , Forni Silvia , Gemmi Fabrizio , Szasz Claudia , Fabrizio Valeria Di , Mechi Maria Teresa , Nocci Matteo , Mondillo Sergio , Valente Serafina
Published: March 2021

Introduction: Containment measures were established to flatten the curve of COVID-19 contagion in order to avoid a crash of the healthcare system. However, these measures influenced the rate of hospitalization of cardiac patients. In this study, we aimed to analyse the impact of COVID-19 and the effects of lockdown measures on hospital admissions and alerts of emergency medical system (EMS) for cardiac causes in the Tuscany region.

Methods: An observational, retrospective analysis from Italian Tuscany region was conducted. We evaluated consecutive patients contacting EMS or admitted to the 39 Emergency Departments (EDs) in Tuscany for cardiac causes in the first trimester of 2020. Data were compared with the same period in 2018/19.

Results: The alerts of EMS for cardiac causes significantly decrease in 2020 and the highest difference between 2018/19 and 2020 was found immediately after national lockdown (Δ = −47.4%, p < 0.001). The number of admissions for chest pain in the EDs also decreased, with a maximum difference of −67.6% (p < 0.001) vs. 2018/19. The number of hospital accesses for acute coronary syndromes, atrial fibrillation, and heart failure in the EDs significantly decreased in 2020 as compared to 2018/19 (maximum Δ = −58.9%, p < 0.001; maximum Δ = −63.0%, p < 0.001; maximum Δ = −72.7%, p < 0.001, respectively).

Conclusions: A significant decrease in the contacts to EMS for cardiac causes and in cardiac diagnoses was observed during the first trimester of 2020. Fear of contagion has likely played a relevant role. The lesson learnt from first wave of COVID-19 pandemic suggests that appropriate public information strategies and re-education of people are essential.
Service-Learning in Europe. Dimensions and Understanding From Academic Publication
Authors: Sotelino-Losada Alexandre , Arbués-Radigales Elena , García-Docampo Laura , González-Geraldo José L.
Published: March 2021

Service-learning began within the framework of the New School in which constructivist experiential methodologies were particularly important following various studies, such as those by John Dewey and his “Learning by Doing” approach. From then on, this pedagogical practice has spread all over the world at varying rates. In Europe it was slower to spread than in the Americas. In this regard it is especially interesting to look at the current state of the matter. The object of this study was to analyze the academic publication in Europe since the year 2000 with a detailed bibliographic review of publications with roots in Europe. We examined the main databases and used an analysis matrix with various content levels. We found that service-learning has different names in Europe, and that there have been uneven epistemological advances depending on the countries examined. We also noted that, in general, it was about higher education that most literature had been published. One of our significant conclusions was the exponential growth of contributions over the last 20 years, particularly in Spain, which produced the most academic literature on this topic. We believe that service-learning faces the challenge of effective consolidation based on educational quality criteria, and which includes combining elements of virtuality, reality, and academic rigor.
Prognostic Alternative mRNA Splicing in Adrenocortical Carcinoma
Authors: Liang Weiwei , Sun Fangfang
Published: March 2021

Background

This paper aims to identify alternative RNA splicing landscape and its prognostic value in adrenocortical carcinoma.

Methods

The alternative splicing events data with corresponding clinical information data of 79 ACC patients were obtained from the Cancer Genome Atlas and SpliceSeq package. Prognosis-associated AS events by using univariate Cox regression analysis were selected. Gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognosis-related splicing events were submitted to develop moderate predictors using Lasso regression model.

Results

One thousand five survival-associated alternative splicing events were identified. The prognostic genes included ATXN2L, MEIS1, IKBKB, COX4I1. Functional enrichment analysis suggested that prognostic splicing events are associated with Wnt signaling pathway. A prediction model including 12 alternative splicing events was constructed by Lasso regression using train set. ROC analysis showed good performance of the prediction model in test set. Then, a nomogram integrating the clinical-pathological factors and riskscore was constructed for predicting 1‐ and 3‐year survival rate.

Conclusion

Our data provide a comprehensive bioinformatics analysis of AS events in ACC, providing biomarkers for disease progression and a potentially rich source of novel therapeutic targets.
Oxidized Hyaluronic Acid Hydrogels as a Carrier for Constant-Release Clenbuterol Against High-Fat Diet-Induced Obesity in Mice
Authors: Chen Wei-Yao , Lin Feng-Huei
Published: March 2021

The global obesity population is increasing year-by-year, and the related cost is sharply increasing annually. There are several methods available to combat obesity; however, there is a lack of a single tool that is both safe and efficacious. The use of Clenbuterol in bodybuilding and by professional athletes is controversial owing to its side effects, including hepatotoxicity. This study administered Clenbuterol at a much lower dose than the established safety level, and rather than through oral administration, the treatments were delivered through controlled-release intra-adipose injection. The different dosing and mode of administration will lower the risk of side effects, increase the safety profile, and could facilitate use in the anti-obesity market. A thermo-sensitive hydrogel was used as the carrier uploaded with Clenbuterol to achieve controlled-release. In thein vitrostudy, the developed new formulae were not cytotoxic to 3T3-L1 cells and could inhibit lipogenesis effectively. In the animal study, the mice were fed a high-fat diet and treated with Clenbuterol by oral administration, or injected with Clenbuterol-modified hyaluronate hydrogel (HAC) regularly. Both groups showed reduction in whole-body, visceral, and gonadal fat contents and body weight. The abdominal fat was analyzed using MRI imaging in adipose mode and water mode. The abdominal fat ratio in the mice treated with normal diet and those given intra-adipose injections with HAC had the lowest value among the test groups. The mice treated with high-fat diet (HFD) showed the highest value of 53.78%. The chronic toxicityin-vivotest proved that controlled-release injections of 2–10 µg Clenbuterol daily were safe, as demonstrated in the blood elements and serological analyses. This study developed a new and promising method for anti-obesity treatment, using a monthly intra-adipose controlled-release injection of HAC. The developed new formulae of Clenbuterol not only effectively decreased body weight and body fat content but also inhibited lipogenesis on the harvested visceral tissue and reduced adipose tissue around the gonadal fat area. The side effects induced by traditional oral administration of Clenbuterol were not observed in this research; this has excellent potential to be a useful tool for future obesity treatment without safety concerns.
Use of Insulin Degludec/Insulin Aspart in the Management of Diabetes Mellitus: Expert Panel Recommendations on Appropriate Practice Patterns
Authors: Demir Tevfik , Turan Serap , Unluhizarci Kursad , Topaloglu Oya , Tukek Tufan , Gogas Yavuz Dilek
Published: March 2021

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (IDeg), which provides long-lasting basal insulin coverage, and insulin aspart (IAsp), which targets post-prandial glucose. This expert panel aimed to provide a practical and implementable guidance document to assist clinicians in prescribing IDegAsp in the diabetes management with respect to different patient populations including children and adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) as well as pregnant, elderly and hospitalized patients and varying practice patterns (insulin-naive, insulin-treated, switching from basal, basal bolus and premix regimens). The experts recommended that IDegAsp can be used in insulin-naive T2D patients with poor glycemic control (HbA1c >8.5%) despite optimal oral antidiabetic drugs (OADs) as well as in insulin-treated T2D patients by switching from basal insulin, basal-bolus therapy or premixed insulins in relation to lower risk of nocturnal hypoglycemia, fewer injections and lower intraday glycemic variability, respectively. The experts considered the use of IDegAsp in children with T2D as a basal bolus alternative rather than as an alternative to basal insulin after metformin failure, use of IDegAsp in adult T1D patients as a simplified basal bolus regimen with lesser nocturnal hypoglycemia, fewer injections and better fasting plasma glucose control and in children with T1D as an alternative insulin regimen with fewer injection to increase treatment adherence. The proposed expert opinion provides practical information on use of IDegAsp in different patient populations and practice patterns to assist clinicians, which seems to compensate the need for easily implementable guidance on this novel insulin regimen.
Case Report and Review of Literature: Thyroid Metastases From Breast Carcinoma
Authors: Wang Yichao , Zhou Shengliang , Yu Boyang , Zhou Ping , Zhu Jingqiang , Wei Tao , Li Zhihui
Published: March 2021

Rationale

The thyroid is a rare site for distant metastases from breast carcinoma. The incidence of thyroid metastases in fine needle aspiration biopsy (FNAB) was less than 0.2%.

Patient concerns

We report a case of 54-year-old woman with a history of breast carcinoma presented with diffuse scattered microcalcifications in thyroid and enlarged bilateral cervical lymph nodes detected on ultrasound (US). Physical examination of the patient revealed firm and enlarged thyroid lobes.

Diagnoses

FNAB and immunohistochemistry (IHC) of the thyroid lesion confirmed the thyroid metastases from breast cancer.

Interventions and Outcomes

Due to the comorbidities of breast carcinoma metastases to the right axillary, cervical lymph nodes and left chest wall, the patient received chemotherapy. After a follow-up of 19 months, the patient was alive without any new distant metastases.

Lessons

Our case highlights that thyroid metastases should be considered in a patient combined with thyroid lesions and a history of breast carcinoma. IHC played an important role in differentiating thyroid metastases from primary thyroid cancer.