bluuebunny/crossref_metadata_2025 huggingface dataset:
KEBERKESANAN BENGKEL DALAM MENINGKATKAN KEMAHIRAN TEKNOLOGI MAKLUMAT DAN MOTIVASI GURU TERHADAP PROSES PENILAIAN DALAM TALIAN
Authors: LETCHMANAN CHELVA , SAAD ASLINA
Published: April 2021

Workshops are an on-going approach to increase the Information Communication and Technology (ICT) skills and motivation of teachers in the implementation of 21st Century Learning. This study aims to design and implement an online assessments (OA) workshop as well as evaluating the effectiveness of workshops in enhancing the ICT skills and motivation level of Tamil language teachers. In addition, a survey of the motivational level of teachers towards OA before and after the workshop has been conducted. This study uses quantitative and qualitative research methodology. A total of 50 Tamil language teachers were selected as the research respondents through purposive sampling. The data collection was done through interviews, questionnaires, as well as pre and post-tests. The OA workshop was designed and carried out based on nine main themes derived from the interview instrument. The effectiveness of the workshop was analysed through an experimental method using the pre and post-test instruments. The results of the study using a Paired T-test have found significant differences with t(49) = -40.86, p = 0.000, p< 0.05 between pre-test and post-test on the level of ICT skills in OA among Tamil language teachers. Meanwhile, the motivation level of Tamil language teachers towards OA was evaluated through questionnaires and analysed via the Paired T-test. The analysis showed that t(49) = -8.373, p = 0.000, p<0.05 indicated a significant difference in the motivation level towards OA after attending the workshop. Correlation analysis, on the other hand, indicated a medium correlation value r(0.350) between ICT skills and the motivation level towards OA after the Tamil language teachers attended the OA workshop. This proves that the teachers’ motivation increases in tandem with the increase in ICT skills after attending the OA workshop. The implication of this study is that the implementation of workshops to guide teachers towards the adoption of ICT in OA as well as increasing the motivation among teachers is effective and extendable to other teachers.
TAMIḺ MOḺIK KAṞṞAL KAṞPITTALIL PĒCCUT TIṞAṈIṈ CELVĀKKUM ĀḶUMAIYUM [INFLUENCE AND PERSONALITY OF SPEAKING SKILLS IN TAMIL LANGUAGE LEARNING AND TEACHING]
Authors: NARAYANAN SAGAR
Published: April 2021

Speaking is one of the basic language skills. Personality is called ‘personality’. Therefore, it is very important to have influence on speech as well as how much physical and mental resources are essential for personality development. This study examines the extent to which personality skills are important for a teacher to be able to speak in the teaching of learning. This dissertation was based on a book review and an observation among Tamil teachers at school. Vocabulary is the ability to take the word. Vocabulary is required to be a leader in any field, no matter who you are. This study examines the importance or influence of speaking skills among teachers. Approaches such as observation and interview were carried out among the Tamil teachers in this study. Speaking skill in classroom teaching is an important part of every teacher. Conceptual speaking and clear speech will refine classroom teaching. Improving these elements will help students in the classroom and fully engage in their learning. This review was conducted from a number of angles for each teacher to dominate in speaking skill. This study shows that effective learning in teaching can be achieved if each teacher acquires an influential personality in speaking skills.
CABARAN PDPR BAHASA TAMIL DI SEKOLAH LUAR BANDAR [CHALLENGES OF TAMIL LANGUAGE PDPR IN RURAL SCHOOLS]
Authors: THANNIMALAI TAMILMULLAI , BALOH SALINI
Published: April 2021

This study is entitled Challenges of Tamil Language Pdpr in Rural Schools. This study uses a qualitative study with analysis of available journals from a variety of reliable sources. The objective of this study is to be a guide for students to follow PdPR optimally and a guide for teachers to implement PdPR in a structured and planned manner. There are several challenges in implementing PdPR, namely teachers are not prepared for the new norms of PdPR, students often get interrupted while implementing PdPR. The study found that PdPR is an implication of a holistic assessment. Several suggestions have been submitted for the improvement of PdPR, namely the improvement of the syllabus set by the MOE during the implementation period of PKP to better suit the needs of students.
Tieteenalan rajat ja niiden ylittäminen
Authors: Isopahkala-Bouret Ulpukka
Published: April 2021

Tieteenalojen rajojen ja identiteetin määrittely on jatkuva prosessi. Siihen eivät riitä tutkimuskohde

ja alan vakiintuneet menetelmät, ei edes ansiokas historia. Tieteenala pysyy elävänä ainoastaan, jos sen

ympärillä on vahva tiedeyhteisö, joka synnyttää uutta tutkimusta, kokee yhteenkuuluvuutta ja on valmis

puolustamaan alansa olemassaolon oikeutusta.
Tavoitteena turvallisuus
Authors: Mannila Erikka , Laajalahti Anne
Published: April 2021

Turvallisuuden varmistaminen on elintärkeä osa sairaaloiden jokapäiväistä toimintaa. Artikkelissa tarkastellaan turvallisuuskulttuurin rakentamista ja kriiseistä oppimisen tukemista sairaaloissa. Tutkimusaihetta lähestytään erityisesti sairaaloiden sisäisen kriisiviestinnän näkökulmasta. Tutkimuskysymykset ovat seuraavat: 1) Miten turvallisuuskulttuuria voidaan kehittää sairaaloissa? 2) Miten kriiseistä oppimista voidaan tukea sairaaloissa? Tutkimusaihetta lähestyttiin haastattelemalla kaikkien viiden Suomen yliopistollisen sairaalan turvallisuus- ja viestintäpäälliköitä (N = 10). Tulosten mukaan turvallisuuskulttuuria voidaan kehittää sairaaloissa 1) jaettua ymmärrystä turvallisuudesta synnyttämällä, 2) turvallisuusnäkökulmat kaikessa tekemisessä huomioimalla, 3) ohjeistuksia kehittämällä, 4) yhteistyötä tukemalla ja pirstaloitumista ehkäisemällä, 5) työntekijöitä osallistamalla sekä 6) johtamista kehittämällä. Turvallisuuskulttuuria kehitettäessä on olennaista pyrkiä tasapainoon 1) rutiinien ja joustavuuden, 2) korjaamisen ja ennakoinnin, 3) hierarkian ja vastuunjaon, 4) suunnitelmien ja käytännön sekä 5) sulkeutuneisuuden ja avoimuuden jännitteiden välillä. Tulosten mukaan kriiseistä oppimista voidaan tukea 1) koulutusta tarjoamalla, 2) avoimuutta lisäämällä, 3) tarkoituksenmukaiset viestintäkanavat varmistamalla sekä 4) tietoa ja kokemuksia jakamalla. Lisäksi on tärkeää painottaa kriiseistä selviämisen sijaan ennaltaehkäiseviä toimia ja oppimista kriisin jokaisessa vaiheessa.
Koulutuksen digitaalinen datafik(s)aatio
Authors: Mertala Pekka
Published: April 2021

Tässä kriittisessä esseessä luon yleiskatsauksen koulutuksen digitaalisen datafikaation erilaisiin muotoihin ja merkityksiin erityisesti kotimaisessa kontekstissa. Esseessä käyn läpi datafikaation suhdetta muihin koulutusta ohjaaviin trendeihin, erityisesti digitalisaatioon, oppimiskeskeisyyteen ja tulosvastuullisuuteen. Lisäksi tarkastelen datan ja datan diskursiivisen tuottamisen välistä epäsuhtaa, josta jatkan koulun dataintensiivisten käytäntöjen kautta tapahtuvan jatkuvan datankeruun luonnollistumisen tarkasteluun. Viimeisessä temaattisessa osiossa jäsennän elinikäisen oppimisen ideologian ja datafikaation välistä suhdetta. Esseen lopuksi esitän monilukutaidon pedagogiikkaan tukeutuen näkemykseni siitä, millä tavoin datafikaation ei-toivottuja lieveilmiöitä voidaan purkaa ja miten arkiset datakäytänteet voidaan uudelleenkehystää kriittisen datalukutaidon harjoitteluun.
Karakteristik Endapan Sedimen: Studi Kasus Pantai Parangkusumo Daerah Istimewa Yogyakarta
Authors: Arif Subhan , Adibrata Pamela Felita , Dzakiya Nurul
Published: April 2021

Keragaman karakteristik endapan sedimen berdasarkan perbedaan proses geomorfologinya memiliki tantangan dalam dunia eksplorasi yang berkaitan dengan batuan sedimen. Tujuan dari penelitian ini adalah untuk mengetahui karakteristik tekstur endapan sedimen berdasarkan perbedaan proses geomorfologi yang bekerja untuk menjadi sebuah analog. Metode yang digunakan dengan pengumpulan data lapangan, serta tahap pengolahan data berupa analisis granulometri di laboratorium. Hasil analisis menunjukkan bahwa sampel endapan pasir yang diambil pada daerah gumuk pasir memiliki rata-rata bentuk butir yang lebih menyerupai bentuk bola, kebundaran yang lebih membundar, ukuran butir yang lebih halus, sortasi yang lebih baik dan kedewasaan yang tingkatannya lebih dewasa dibandingkan dengan sampel endapan pasir pada daerah pasang surut
Efektivitas Sistem Pengendalian Internal pada Pengelolaan Persediaan Barang Habis Pakai (Alat Tulis Kantor) di Dinas Pertanian dan Pangan Kota Magelang
Authors: Ardiyanti Wiwit , Priyono Nuwun
Published: April 2021

Penelitian ini bertujuan untuk mengetahui efektivitas sistem pengendalian internal pada pengelolaan persediaan barang habis pakai di Kantor Dinas Pertanian dan Pangan Kota Magelang. Pengelolaan barang dikatakan efektif apabila dalam menyelengarakan dan dalam mengurus kegiatan tersebut tidak menimbulkan masalah yang tidak dikehendaki dan kegiatan tersebut telah sesuai dengan peraturan yang berlaku sehingga bisa mencapai tujuan perusahaan. Proses pengelolaan barang terdiri dari proses penerimaan, penyimpanan, pemeliharaan, pendistribusian atau pengeluaran, dan proses pengendalian. Penelitian ini menggunakan penelitian kualitatif dengan menggunakan metode deskriptif. Penelitian ini dilakukan di Bagian Umum dan Kepegawaian Dinas Pertanian dan Pangan Kota Magelang dan data diperoleh melalui wawancara dan kajian pustaka dengan Bagian pengelola gudang Dinas Pertanian dan Pangan Kota Magelang. Dalam penelitian ini disimpulkan bahwa sistem pengendalian internal sudah berjalan dengan baik dan efektif, karena telah menerapkan unsur-unsur pengendalian internal.
Evaluasi Penerapan SIMDA Keuangan pada Dinas Kepemudaan Olahraga dan Pariwisata Kota Magelang
Authors: Muthoharoh Siti , Nugraheni Agustina Prativi
Published: April 2021

Penelitian ini bertujuan untuk mengevaluasi penerapan sistem informasi manajemen daerah (SIMDA) keuangan di Dinas Kepemudaan Olahraga dan Pariwisata Kota Magelang. Selanjutnya, penelitian ini juga bertujuan untuk mengetahui langkah yang strategis untuk dilakukan oleh pemerintah daerah dalam penerapan SIMDA Keuangan dengan mengambil studi kasus pada Dinas Kepemudaan Olahraga Dan Pariwisata Kota Magelang. Kegiatan pengumpulan data penelitian ini menggunakan metode observasi dan wawancara dan menggunakan instrumen pendukung dalam bentuk e-formulir wawancara. Hasil penelitian ini dapat diketahui bahwa kualitas sistem yang dihasilkan SIMDA Keuangan secara keseluruhan sudah baik. Hasil yang diperoleh dari evaluasi penerapan SIMDA Keuangan pada Dinas Kepemudaan Olahraga dan Pariwisata Kota Magelang adalah dalam bentuk nilai persentase menggunakan perhitungan arikunto dengan hasil sebesar 68,52%. Lima kriteria kegunaan digunakan sebagai standar untuk menganalisis sejauh mana aplikasi SIMDA telah diterapkan, sehingga dapat diketahui apa kelemahan sistem dan dengan demikian dapat dilakukan perbaikan pada sistem.
Implementing Action Research in a Teacher Preparation Program: Opportunities and Limitations
Authors: L. Black Glenda
Published: April 2021

Action research has the potential to reconstruct schools into professional learning communities that are able to identify educational issues and develop appropriate solutions for 21st century learning. Increasingly, teacher education programs are providing action research experiences to encourage analytical thinking and problem-solving skills (Darling-Hammond, 2009, 2012). The purpose of this study was to critically examine the experiences of the teacher educator and teacher candidates involved in the implementation of an action research component over four years in a revised consecutive initial teacher preparation program. A case study design using action research methodology was used in the research, which provided the tools to explore a complex phenomenon within its context: the implementation of an action research assignment in a core course in a teacher preparation program. The perceptions of the faculty teaching the course and the teacher candidates (n=544) in each of the four years provided insight into challenges, benefits, and lessons learned.  The discussion centers on the implementation of action research in a compulsory course in a teacher education program; identifying opportunities and limitations settled into four main categories: structural incongruence, reflection, growth, and recommendations.
Stage Interpretation and Inner Transformations of the Image of the Hero in Baroque Art
Authors:   Saratov State L.V. Sobinov Conservatory, Alesenkova Victoria N.
Published: April 2021

The image of the Baroque hero — the martyr or righteous man — is of scholarly interest as an object of self-knowledge and a guide of the idea of inner transformations. The object of the research has been served to a great degree by Pedro Calderon’s play “The Constant Prince” and its stage manifestation, to a lesser degree Andreas Grifi us’ play “Catharina von Georgien.” The duplicity of inner nation typical of the baroque hero and the aspiration towards acquiring immortality are clearly refl ected in the mental scheme of the transition from death to resurrection. The protagonist’s outward suffering and death are perceived in this context as a symbolic refl ection of the inner sufferings of the soul capable of enlightenment and a mystical unifi cation with God. The scenic image of Don Fernando (“The Constant Prince”) is presented in the directorial images of Vsevolod Meyerhold (1915), Jerzy Grotowski (1965) and Boris Yukhananov (2013). This makes it possible to trace on various temporal stages the baroque hero’s change of perception from a positive to a negative scenario. Whereas the positive scenario of the image’s transformation asserts the process of attaining God, the negative scenario denies the possibility of spiritual reawakening and displaces God beyond the scope of the hero’s inner space, turning the hero from a savior into a victim.
The Characteristic Features of Vassily Titov’s Choral Music
Authors:   Moscow State Institute of Culture, Trukhanova Alexandra G.
Published: April 2021

Among the Russian composers of the turn of the 17th and 18th centuries a special position is held by the sacred choral works of Vassily Titov (ca. 1650 — ca. 1715), one of the bright representatives of the polyphonic part singing, in which the originality of the Russian Baroque musical culture. The music of Vassily Titov, an outstanding master of choral writing, is diverse in terms of its genres, it comprises nearly two hundred compositions, many of which predominated in the church music repertoire of Russian churches during the course of the 18th century. A study of Vassily Titov’s choral works has made it possible to disclose the characteristic features of the composer’s polyphonic style. The latter include the multi-choral presentation with its bright spatial effects, the antiphonic juxtapositions of large choral masses, the principles of concertizing based on the succession of solo voices and tutti, on the juxtaposition of the chordal-harmonic and the polyphonic exposition, as well as the skillful mastery of imitational counterpoint, up to polyphonic variation. Features of national originality reveal themselves most vividly in the musical thematicism of the compositions, where along with the ornamental design of the intertwining melodic lines and turns of an instrumental type, use is made of intonations of folk songs, cants and church chants. In his musical oeuvres Vassily Titov revised and reevaluated the basic characteristic traits and forms of Western European Baroque music in correspondence with the particularities of Russian musical culture, thereby preserving and enriching the traditions of the Russian national style.
Slovak music culture and music professions during Classicism era
Authors:   Academy of Arts, Strenacikova Sr. Maria , Strenacikova Jr. Maria ,   Academy of Arts
Published: April 2021

The Classicist period in Slovakia developed between 1760 and 1830. At that time Slovakia was a part of the territory of the Hungary. Musical culture during the reign of Maria Theresa, Joseph II and Francis I evolved in three stages under the infl uence of the European musical tradition and contacts with foreign composers from Austria, Germany and Czechia. People could listen to all sorts of music in opera houses, concert halls, noblemen’s courts, petty bourgeois salons and in the countryside. Musical professions in Slovakia were comparable with those in Central Europe. Musicians’ jobs included those of performers, composers, teachers, writers, theoreticians and organizers of cultural life. Usually, one person held two or more of these positions. Composers wrote works which were performed at various occasions. Music teachers taught at state-run music schools, pedagogical colleges and parochial schools. Manufacturers of musical instruments created a number of new instruments, especially wind instruments, violins and organs, many of which were regarded as being highly signifi cant throughout Europe.
The Ballet “Les Noces de Pelée et de Thetis” (1653) Preserved in Visual Images
Authors:   Moscow State P.I. Tchaikovsky Conservatory, Grutsynova Anna P.
Published: April 2021

The article is devoted to the ballet “Les Noces de Pelée et de Thetis” which was produced in 1693 in the Petit Bourbon Palace in Paris (according to the rules of the French theater of that time period) in order to complement the opera with the same name composed by Carlo Caproli. The basis for the plot of the production was the myth widely disseminated in art works about the mortal Peleus and the Nereid Thetis, transformed in correspondence with the aesthetics of that time. The Dance entrées followed each scene of the Italian opera and were connected with its each content, in its turn, forming a consistent, logically delineated narration. The published libretto conveys the plot, and at times the outer form of the action quite vividly and fi guratively. A description of the decorations and machines used in the ballet has also been preserved, as the result of which in our time it becomes possible to create a visual impression from the production. In addition, important defi ning details capable of providing a perception not only of the protagonists’ outward appearances, but also of a concrete distribution of roles between the performers are the sketches for numerous costumes preserved up to our time. Thereby, it turns out that in 17th century musical performance a considerable role is played by its visual solution, which, having been preserved in iconographic materials, is capable of helping create an impression from the overall conception of the production a few centuries after it happened.
Interview with Benjamin Bagby, Medieval Musician
Authors:   Manhattan School of Music, Green Edward
Published: April 2021

Benjamin (Ben) Bagby is one of the world’s distinguished medievalists, and is particularly well-known for his scholarly, yet passionate performances of the music of the medieval epoch — both with the ensemble Sequentia, which he co-founded, and as a soloist. In the fi eld of solo performance he is renowned for bringing to life the important Anglo-Saxon epic Beowulf — presenting it, as far as contemporary scholarship and vivid artistic imagination can allow, in an authentic “bardic” manner. This wide-ranging interview has much discussion of his career in both regards, as well as his experience as a professor at the Sorbonne. Readers who may wish, after reading this interview, to know more about this important musician and scholar can visit these two websites: www.BagbyBeowulf.com / www.Sequentia.org
Mark Belodubrovsky, a Versatile Contemporary Composer, Violinist and Educator
Authors:   Moscow State P.I. Tchaikovsky Conservatory, Rovner Anton А.
Published: April 2021

Mark Belodubrovsky is one of the most accomplished contemporary composers living presently in Moscow who has written a substantial amount of solo, chamber and vocal musical compositions of high quality, which are performed in Russia and in a number of other countries. His musical output is especially noted for its versatility of different styles of music: some of his compositions are traditional and romantic in their style and tonal in their harmony, with a strong infl uence of Russian folk music which the composer actively employs in a number of his compositions, while other works follow innovative avant-garde trends and incorporate serialism, including serial rhythm, sonoristics, aleatory technique and a number of other techniques. Some of his compositions are very accessible to a broad audience, containing memorable melodic and rhythmic traits, while others are written in a highly complex language, based on musical experimentation, comprehensible for the most part to a sophisticated audience well-versed in avantgarde trends in music. Some of his works are based on extroversive theatrical gestures and even contain comic elements, while others bear an inner philosophical discourse. Nonetheless, both of these contrasting features combine together to express a highly original style of the composer’s music which cannot be mistaken for that of anybody else. Belodubrovsky is known and highly regarded as a composer, a violinist, an enthusiastic cultural activist who discovered and popularized rare compositions of the early 20th century Russian modernist trend, the long-time director of the Nikolai Roslavetz and Nahum Gabo Festival for the Arts in Bryansk, and simply as a very open musician with a broad-minded approach towards various musical styles and directions. All of this has undoubtedly created an impact on his multifarious musical style which combines opposite stylistic directions. The article describes the life and the musical activities of Mark Belodubrovsky, then proceeds to describe an analyze his musical compositions. It is shown that notwithstanding the fact that his compositions pertain to different styles, they are all united by one individual stylistic trait which defi nes the composer’s artistic individuality.
The Idea of Russian Symbolism about the Synthesis of Cultural Forms in the Context of Postmodern Culture
Authors:   Far-Eastern State Technical Fisheries University, Tsareva Nadezhda A.
Published: April 2021

The relevance of the topic is due to the attention to trends in the development of culture. The synthesis of cultural forms is one of the important factors in the dynamics of culture. The teaching of Russian symbolism about the synthesis of cultures was analyzed in the scientifi c literature of the entire twentieth century. The novelty of the research is to compare the idea of art synthesis in the early twentieth and twenty-fi rst centuries. Two aspects of the idea of synthesis are considered: 1) the relevance of the idea of art synthesis in the postmodern era; 2) music and the visual series as organizing centers of art synthesis in the era of information technology. The purpose of this article is to examine the teaching of Russian symbolism about the integration of various forms of art and the features of synthesis in the postmodern era. The idea of integrating cultural forms was one of the key elements in Russian symbolism at the beginning of the twentieth century and was interpreted as a real prospect for the development of culture. In a broad sense, synthesis in symbolism meant the integrity of life, the integration of all spheres of human activity, the “organic connection” of cultures of the past and present. The synthesis can be realized on the basis of the art of symbolism, which can create a new culture. The synthesis of arts was understood as the beginning of the formation of a new culture. The core of the synthesis of arts, the symbolists saw music. Postmodern art is characterized by synthetism. Computer and information technologies create new forms of synthetic media art. The video series becomes the center of integration construction of postmodern audiovisual culture forms. The symbolist idea of the synthesis of arts as the beginning of cultural change in the postmodern era remains a utopian project. But the creation of new art forms in postmodern culture i s based on integration. New technologies are becoming a factor that determines the specifi cs of the synthesis of arts and infl uences the dynamics of culture. Both in Russian symbolism and in modern art, the goal of art synthesis is to present an integral image of the world, to form a system of worldview attitudes.
Fungal Endophytes of Tahiti Lime (Citrus citrus × latifolia) and Their Potential for Control of Colletotrichum acutatum J. H. Simmonds Causing Anthracnose
Authors: Muñoz-Guerrero Jaider , Guerra-Sierra Beatriz E. , Alvarez Javier C.
Published: April 2021

Colletotrichum acutatum is one of the causal agents of anthracnose in several crops, and of post-flowering fruit drop (PFD) in citrus and key lime anthracnose (KLA). The pathogen normally attacks flowers, causing lesions only in open flowers. Under very favorable conditions, however, it can also affect flower buds and small fruits, causing complete rotting of the fruit and a premature fall, resulting in major economic crop losses. We isolated endophytic fungi from Tahiti lime to evaluate its diversity, verify its antagonistic capacity against the phytopathogen Colletotrichum acutatum C-100 in dual tests, and evaluate the ability of various endophytic agents to control flowers with induced anthracnose. 138 fungal isolates were obtained from 486 fragments of branches, leaves, and fruit; from which 15 species were identified morphologically. A higher isolation frequency was found in branches and leaves, with a normal level of diversity compared to other citrus species. Of the 15 morphospecies, 5 were trialed against C. acutatum in antagonism tests, resulting in a finding of positive inhibition. 2 endophytic fungi from the antagonism tests demonstrated high inhibition of the phytopathogen, and were thus used in in vivo tests with Tahiti lime flowers, applied in a spore solution. Spore solutions of two molecularly identified species, Xylaria adscendens, and Trichoderma atroviride, reduced the lesions caused by the phytopathogen in these in vivo tests. The finding that these endophytes react antagonistically against C. acutatum may make them good candidates for further biological control research in an agroindustry that requires environmental sustainability.
Transcriptional Repression of MFG-E8 Causes Disturbance in the Homeostasis of Cell Cycle Through DOCK/ZP4/STAT Signaling in Buffalo Mammary Epithelial Cells
Authors: Verma Arvind K. , Ali Syed A. , Singh Parul , Kumar Sudarshan , Mohanty Ashok K.
Published: April 2021

The mammary gland is a unique apocrine gland made up of a branching network of ducts that end in alveoli. It is an ideal system to study the molecular mechanisms associated with cell proliferation, differentiation, and oncogenesis. MFG-E8, also known as Lactadherin, is a vital glycoprotein related to the milk fat globule membrane and initially identified to get secreted in bovine milk. Our previous report suggests that a high level of MFG-E8 is indicative of high milk yield in dairy animals. Here, we showed that MFG-E8 controls the cell growth and morphology of epithelial cells through a network of regulatory transcription factors. To understand the comprehensive action, we downregulated its expression in MECs by MFG-E8 specific shRNA. We generated a knockdown proteome profile of differentially expressed proteins through a quantitative iTRAQ experiment on a high-resolution mass spectrometer (Q-TOF). The downregulation of MFG-E8 resulted in reduced phagocytosis and cell migration ability, whereas it also leads to more lifespan to knockdown vis-a-vis healthy cells, which is confirmed through BrdU, MTT, and Caspase 3/7. The bioinformatics analysis revealed that MFG-E8 knockdown perturbs a large number of intracellular signaling, eventually leading to cessation in cell growth. Based on the directed network analysis, we found that MFG-E8 is activated by CX3CL1, TP63, and CSF2 and leads to the activation of SOCS3 and CCL2 for the regulation of cell proliferation. We further proved that the depletion of MFG-E8 resulted in activated cytoskeletal remodeling by MFG-E8 knockdown, which results in the activation of three independent pathways ZP4/JAK-STAT5, DOCK1/STAT3, and PIP3/AKT/mTOR. Overall, this study suggests that MFG-E8 expression in mammary epithelial cells is an indication of intracellular deterioration in cell health. To date, to the best of our knowledge, this is the first study that explores the downstream targets of MFG-E8 involved in the regulation of mammary epithelial cell health.
A Highly Conserved Shh Enhancer Coordinates Hypothalamic and Craniofacial Development
Authors: Crane-Smith Zoe , Schoenebeck Jeffrey , Graham Katy A. , Devenney Paul S. , Rose Lorraine , Ditzell Mark , Anderson Eve , Thomson Joseph I. , Klenin Natasha , Kurrasch Deborah M. , Lettice Laura A. , Hill Robert E.
Published: April 2021

Enhancers that are conserved deep in evolutionary time regulate characteristics held in common across taxonomic classes. Here, deletion of the highly conservedShhenhancer SBE2 (Shhbrain enhancer 2) in mouse markedly reducedShhexpression within the embryonic brain specifically in the rostral diencephalon; however, no abnormal anatomical phenotype was observed. Secondary enhancer activity was subsequently identified which likely mediates low levels of expression. In contrast, when crossing the SBE2 deletion with theShhnull allele, brain and craniofacial development were disrupted; thus, linking SBE2 regulatedShhexpression to multiple defects and further enabling the study of the effects of differing levels ofShhon embryogenesis. Development of the hypothalamus, derived from the rostral diencephalon, was disrupted along both the anterior-posterior (AP) and the dorsal-ventral (DV) axes. Expression of DV patterning genes and subsequent neuronal population induction were particularly sensitive toShhexpression levels, demonstrating a novel morphogenic context forShh. The role of SBE2, which is highlighted by DV gene expression, is to step-up expression ofShhabove the minimal activity of the second enhancer, ensuring the necessary levels ofShhin a regional-specific manner. We also show that lowShhlevels in the diencephalon disrupted neighbouring craniofacial development, including mediolateral patterning of the bones along the cranial floor and viscerocranium. Thus, SBE2 contributes to hypothalamic morphogenesis and ensures there is coordination with the formation of the adjacent midline cranial bones that subsequently protect the neural tissue.
METTL3-Mediated N6-Methyladenosine Modification Is Involved in the Dysregulation of NRIP1 Expression in Down Syndrome
Authors: Shi Weili , Yang Fan , Dai Ranran , Sun Yafei , Chu Yan , Liao Shixiu , Hao Bingtao
Published: April 2021

Down syndrome (DS) is a common genetic condition in which a person is born with an extra copy of chromosome 21. Intellectual disability is the most common characteristic of DS. N6-methyladenosine (m6A) is a common RNA modification that is implicated in many biological processes. It is highly enriched within the brain and plays an essential role in human brain development. However, the mRNA m6A modification in the fetal brain of DS has not been explored. Here, we report m6A mRNA profiles and mRNA expression profiles of fetal brain cortex tissue from DSs and controls. We observed that the m6A modification in DS brain tissues was reduced genome-wide, which may be due to decreased the m6A methyltransferase like 3 (METTL3) protein expression. The nuclear receptor-interacting protein 1 (NRIP1/RIP140) is coded by a highly conserved chromosome 21 (Hsa21) gene. Overexpression of NRIP1 is associated with mitochondrial dysfunction in DS. The NRIP1 mRNA increased in fetal brain tissues of DS, whereas the m6A modification of the NRIP1 mRNA significantly decreased. METTL3 knockdown reduced the m6A modification of NRIP1 mRNA and increased its expression, and an increase in NRIP1 m6A modification and a decrease in its expression were observed in METTL3-overexpressed cells. The Luciferase reporter assay confirmed that METTL3 regulates NRIP1 expression in an m6A-dependent manner. The decay rate of NRIP1 mRNA was significantly reduced in METTL3-knockdown cells but increased in METTL3-overexpressed cells. We proposed that the m6A modification of NRIP1 mRNA in DS fetal brain tissue is reduced, reducing its transcript degradation rate, resulting in abnormally increased expression of NRIP1, at least partially, in the DS brain. It provides a new mechanism for the molecular pathology of DS and leads to a new insight that may become therapeutically relevant.
Endothelial Glycocalyx Disorders May Be Associated With Extended Inflammation During Endotoxemia in a Diabetic Mouse Model
Authors: Sampei So , Okada Hideshi , Tomita Hiroyuki , Takada Chihiro , Suzuki Kodai , Kinoshita Takamasa , Kobayashi Ryo , Fukuda Hirotsugu , Kawasaki Yuki , Nishio Ayane , Yano Hirohisa , Muraki Isamu , Fukuda Yohei , Suzuki Keiko , Miyazaki Nagisa , Watanabe Takatomo , Doi Tomoaki , Yoshida Takahiro , Suzuki Akio , Yoshida Shozo , Kushimoto Shigeki , Ogura Shinji
Published: April 2021

In diabetes mellitus (DM) patients, the morbidity of infectious disease is increased, and these infections can easily progress from local to systemic infection. Sepsis is a characteristic of organ failure related to microcirculation disorders resulting from endothelial cell injury, whose most frequent comorbidity in patients is DM. The aim of the present study was to evaluate the influence of infection on DM-induced microvascular damage on inflammation and pulmonary endothelial structure using an experimental endotoxemia model. Lipopolysaccharide (LPS; 15 mg/kg) was injected intraperitoneally into 10-week-old male C57BLKS/J Iar- +leprdb/leprdb (db/db) mice and into C57BLKS/J Iar–m + / + leprdb (db/ +) mice, which served as the littermate non-diabetic control. At 48 h after LPS administration, the survival rate of db/db mice (0%, 0/10) was markedly lower (P < 0.05) than that of the db/ + mice (75%, 18/24), whereas the survival rate was 100% in both groups 24 h after LPS administration. In control mice, CD11b-positive cells increased at 6 h after LPS administration; by comparison, the number of CD11b-positive cells increased gradually in db/db mice until 12 h after LPS injection. In the control group, the number of Iba-1-positive cells did not significantly increase before and at 6, 12, and 24 h after LPS injection. Conversely, Iba-1-positive cells continued to increase until 24 h after LPS administration, and this increase was significantly greater than that in the control mice. Expression of Ext1, Csgalnact1, and Vcan related to endothelial glycocalyx synthesis was significantly lower in db/db mice than in the control mice before LPS administration, indicating that endothelial glycocalyx synthesis is attenuated in db/db/mice. In addition, ultrastructural analysis revealed that endothelial glycocalyx was thinner in db/db mice before LPS injection. In conclusion, in db/db mice, the endothelial glycocalyx is already injured before LPS administration, and migration of inflammatory cells is both delayed and expanded. This extended inflammation may be involved in endothelial glycocalyx damage due to the attenuation of endothelial glycocalyx synthesis.
Physiological and Aberrant γ-Globin Transcription During Development
Authors: Barbarani Gloria , Labedz Agata , Stucchi Sarah , Abbiati Alessia , Ronchi Antonella E.
Published: April 2021

The expression of the fetal Gγ- and Aγ-globin genes in normal development is confined to the fetal period, where two γ-globin chains assemble with two α-globin chains to form α2γ2tetramers (HbF). HbF sustains oxygen delivery to tissues until birth, when β-globin replaces γ-globin, leading to the formation of α2β2tetramers (HbA). However, in different benign and pathological conditions, HbF is expressed in adult cells, as it happens in the hereditary persistence of fetal hemoglobin, in anemias and in some leukemias. The molecular basis of γ-globin differential expression in the fetus and of its inappropriate activation in adult cells is largely unknown, although in recent years, a few transcription factors involved in this process have been identified. The recent discovery that fetal cells can persist to adulthood and contribute to disease raises the possibility that postnatal γ-globin expression could, in some cases, represent the signature of the fetal cellular origin.
Emerging Role of Exosomes in Retinal Diseases
Authors: Zhang Zhengyu , Mugisha Aime , Fransisca Silvia , Liu Qinghuai , Xie Ping , Hu Zizhong
Published: April 2021

Retinal diseases, the leading causes of vison loss and blindness, are associated with complicated pathogeneses such as angiogenesis, inflammation, immune regulation, fibrous proliferation, and neurodegeneration. The retina is a complex tissue, where the various resident cell types communicate between themselves and with cells from the blood and immune systems. Exosomes, which are bilayer membrane vesicles with diameters of 30–150 nm, carry a variety of proteins, lipids, and nucleic acids, and participate in cell-to-cell communication. Recently, the roles of exosomes in pathophysiological process and their therapeutic potential have been emerging. Here, we critically review the roles of exosomes as possible intracellular mediators and discuss the possibility of using exosomes as therapeutic agents in retinal diseases.
Melatonin Modulates Lipid Metabolism in Porcine Cumulus–Oocyte Complex via Its Receptors
Authors: Zhu Tianqi , Guan Shengyu , Lv Dongying , Zhao Mengmeng , Yan Laiqing , Shi Li , Ji Pengyun , Zhang Lu , Liu Guoshi
Published: April 2021

Lipid is a crucial energy resource for mammalian oocyte. Melatonin could benefit the maturation of porcine oocyte in vitro, but the related mechanism is not elucidated yet. In the current study, methods to monitor lipid metabolism in single live oocytes were firstly established using probes (Lipi-Blue and Lipi-Green). It was observed that both lipid biogenesis and lipolysis occurred in maturing oocyte, but the general level of lipids dropped. Then maturing oocytes stained with probes were treated with melatonin or lipid metabolic-related inhibitors (triacsin C, rotenone, or etomoxir). The results showed that the lipid metabolism and maturation of porcine oocytes were all disrupted and that melatonin rescued the oocytes treated with triacsin C or rotenone, but not those treated with etomoxir. Further investigation demonstrated that cumulus cells are able to transfer lipids to oocytes via gap junctions. It was also observed that melatonin receptors exist in cumulus cells and are required for oocytes to maintain lipid metabolism. Meanwhile, the global gene expressing in cumulus cells was also modulated by melatonin, especially the genes related to antioxidants (SOD1, GPX1, GPX3, GPX4, PRDX2, and PRDX5), lipid metabolism (FABP3, FABP5, ACACB, TECR, etc.), and mitochondrial respiration (GPD1, ETFB, CYC1, and the genes of ATP synthase). Altogether the current research demonstrates that melatonin modulates lipid metabolism in maturing oocytes through its receptors in cumulus cells and benefits the developmental competence of oocytes.
Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy
Authors: Wang Runze , Xu Yuerong , Zhang Wei , Fang Yexian , Yang Tiqun , Zeng Di , Wei Ting , Liu Jing , Zhou Haijia , Li Yan , Huang Zhan-peng , Zhang Mingming
Published: April 2021

High morbidity and mortality are the most typical characteristics of septic cardiomyopathy. We aimed to reveal the role of miR-22 in septic cardiomyopathy and to explore the underlying mechanisms. miR-22 cardiac-specific knockout (miR-22cKO) mice and miR-22 cardiac-specific transgenic (miR-22cOE) mice were subjected to a cecal ligation and puncture (CLP) operation, while a sham operation was used in the control group. The echocardiogram results suggested that miR-22cKO CLP mice cardiac dysfunction was alleviated. The serum LDH and CK-MB were reduced in the miR-22cKO CLP mice. As expected, there was reduced apoptosis, increased autophagy and alleviated mitochondrial dysfunction in the miR-22cKO CLP mice, while it had contrary role in the miR-22cOE group. Inhibiting miR-22 promoted autophagy by increasing the LC3II/GAPDH ratio and decreasing the p62 level. Additionally, culturing primary cardiomyocytes with lipopolysaccharide (LPS) simulated sepsis-induced cardiomyopathy in vitro. Inhibiting miR-22 promoted autophagic flux confirmed by an increased LC3II/GAPDH ratio and reduced p62 protein level under bafilomycin A1 conditions. Knocking out miR-22 may exert a cardioprotective effect on sepsis by increasing autophagy and decreasing apoptosis via sirt1. Our results revealed that targeting miR-22 may become a new strategy for septic cardiomyopathy treatment.
RNA Motifs and Modification Involve in RNA Long-Distance Transport in Plants
Authors: Wang Tao , Li Xiaojun , Zhang Xiaojing , Wang Qing , Liu Wenqian , Lu Xiaohong , Gao Shunli , Liu Zixi , Liu Mengshuang , Gao Lihong , Zhang Wenna
Published: April 2021

A large number of RNA molecules have been found in the phloem of higher plants, and they can be transported to distant organelles through the phloem. RNA signals are important cues to be evolving in fortification strategies by long-distance transportation when suffering from various physiological challenges. So far, the mechanism of RNA selectively transportation through phloem cells is still in progress. Up to now, evidence have shown that several RNA motifs including Polypyrimidine (poly-CU) sequence, transfer RNA (tRNA)-related sequence, Single Nucleotide Mutation bound with specific RNA binding proteins to form Ribonucleotide protein (RNP) complexes could facilitate RNA mobility in plants. Furthermore, some RNA secondary structure such as tRNA-like structure (TLS), untranslation region (UTR) of mRNA, stem-loop structure of pre-miRNA also contributed to the mobility of RNAs. Latest researchs found that RNA methylation such as methylated 5′ cytosine (m5C) played an important role in RNA transport and function. These studies lay a theoretical foundation to uncover the mechanism of RNA transport. We aim to provide ideas and clues to inspire future research on the function of RNA motifs in RNA long-distance transport, furthermore to explore the underlying mechanism of RNA systematic signaling.
BMSC-Derived Small Extracellular Vesicles Induce Cartilage Reconstruction of Temporomandibular Joint Osteoarthritis via Autotaxin–YAP Signaling Axis
Authors: Wang Yingnan , Zhao Miaomiao , Li Wen , Yang Yuzhi , Zhang Zhenliang , Ma Ruijie , Wu Mengjie
Published: April 2021

Background: Temporomandibular joint osteoarthritis (TMJOA) seriously affects the health of patients, and the current treatments are invasive and only used for advanced cases. Bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (BMSC-sEVs) may represent a safer and more effective treatment, but their role in TMJOA has not been elucidated. This study attempted to analyze the cartilage reconstruction effect of BMSC-sEVs on TMJOA and the mechanism underlying this effect.

Methods: BMSC-sEVs were isolated and purified by microfiltration and ultrafiltration and were subsequently characterized by nanoparticle tracking analysis, electron microscopy, and immunoblotting. TMJOA models were established in vivo and in vitro, and hematoxylin–eosin staining, immunohistochemistry, and histological scoring were performed to analyze the histological changes in TMJOA cartilage tissues treated with BMSC-sEVs. The proliferation, migratory capacity, and cell cycle distribution of TMJOA cartilage cells treated with BMSC-sEVs were detected. Furthermore, the related mechanisms were studied by bioinformatic analysis, immunoblotting, and quantitative PCR, and they were further analyzed by knockdown and inhibitor techniques.

Results: The acquisition and identification of BMSC-sEVs were efficient and satisfactory. Compared with the osteoarthritis (OA) group, the condylar tissue of the OA group treated with BMSC-sEV (OAsEV) showed an increase in cartilage lacuna and hypertrophic cartilage cells in the deep area of the bone under the cartilage. Significantly upregulated expression of proliferating cell nuclear antigen and cartilage-forming factors and downregulated expression of cartilage inflammation-related factors in OAsEV were observed. In addition, we found higher rates of cell proliferation and migratory activity and alleviated G1 stagnation of the cell cycle of OAsEV. Autotaxin was found in the BMSC-sEVs, and key factors of the Hippo pathway, Yes-associated protein (YAP), phosphorylated Yes-associated protein (p-YAP), etc. were upregulated in the OAsEV group. Treatment with BMSC-sEVs after autotaxin knockdown or inhibition no longer resulted in expression changes in cartilage-forming and inflammation-related factors and key factors of the Hippo pathway.

Conclusions: These results suggest that the autotaxin–YAP signaling axis plays an important role in the mechanism by which BMSC-sEVs promote cartilage reconstruction in TMJOA, which may provide guidance regarding their therapeutic applications as early and minimally invasive therapies for TMJOA, and provide insight into the internal mechanisms of TMJOA.
Molecular Components of Store-Operated Calcium Channels in the Regulation of Neural Stem Cell Physiology, Neurogenesis, and the Pathology of Huntington’s Disease
Authors: Latoszek Ewelina , Czeredys Magdalena
Published: April 2021

One of the major Ca2+ signaling pathways is store-operated Ca2+ entry (SOCE), which is responsible for Ca2+ flow into cells in response to the depletion of endoplasmic reticulum Ca2+ stores. SOCE and its molecular components, including stromal interaction molecule proteins, Orai Ca2+ channels, and transient receptor potential canonical channels, are involved in the physiology of neural stem cells and play a role in their proliferation, differentiation, and neurogenesis. This suggests that Ca2+ signaling is an important player in brain development. Huntington’s disease (HD) is an incurable neurodegenerative disorder that is caused by polyglutamine expansion in the huntingtin (HTT) protein, characterized by the loss of γ-aminobutyric acid (GABA)-ergic medium spiny neurons (MSNs) in the striatum. However, recent research has shown that HD is also a neurodevelopmental disorder and Ca2+ signaling is dysregulated in HD. The relationship between HD pathology and elevations of SOCE was demonstrated in different cellular and mouse models of HD and in induced pluripotent stem cell-based GABAergic MSNs from juvenile- and adult-onset HD patient fibroblasts. The present review discusses the role of SOCE in the physiology of neural stem cells and its dysregulation in HD pathology. It has been shown that elevated expression of STIM2 underlying the excessive Ca2+ entry through store-operated calcium channels in induced pluripotent stem cell-based MSNs from juvenile-onset HD. In the light of the latest findings regarding the role of Ca2+ signaling in HD pathology we also summarize recent progress in the in vitro differentiation of MSNs that derive from different cell sources. We discuss advances in the application of established protocols to obtain MSNs from fetal neural stem cells/progenitor cells, embryonic stem cells, induced pluripotent stem cells, and induced neural stem cells and the application of transdifferentiation. We also present recent progress in establishing HD brain organoids and their potential use for examining HD pathology and its treatment. Moreover, the significance of stem cell therapy to restore normal neural cell function, including Ca2+ signaling in the central nervous system in HD patients will be considered. The transplantation of MSNs or their precursors remains a promising treatment strategy for HD.