bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Nationality A Factor Affecting Serve Type, Serve Speed and Success In Professional Volleyball League?
Authors: Özünlü Pekyavaş Nihan , Cerezci Duygu Senay , Çınar-medeni Özge , Altundag Emre , Akarçeşme Cengiz , Çolakoğlu Filiz Fatma , Baltacı Gül
Published: January 2021

In professional volleyball, serving is one of the most important attacking options. A strong and qualified service is important to be successful in the game. There is limited research about comparison of native and foreign volleyball players and also no research was found about Turkish players. The aim of our study was to determine if being a national or a foreign player affects serve speed, serve type and success. Total of 6168 serve shots were included in our study. Four groups were determined as native woman players (n=1836), foreign woman players (n=1036), native man players (n=1886) and foreign man players (n=1410) serve shots. Serve speeds were measured by using Radar Gun (Pocket Radar, Santa Rosa, CA, USA). Serve types and serve efficiencies were recorded during game. There was significant difference between the groups in terms of serve speeds (F=1012.618 p≤0.01). Also statistically significant difference was found bet ween four groups for serve types (p≤0.01) and serve efficiencies (p=0.028). Our results might be a result of training type used from the beginning of sports life of the volleyball player. When we consider the findings, we think that the speed, type and effectiveness of serves should be evaluated and followed for training and tactical development.
Tratamento do efluente de uma caixa separadora água e óleo: potencial de reuso do efluente em um posto de gasolina
Authors: Borges Nayara Gabrielli de Freitas , Romão Ediene Monteiro , Jesus Fabrícia Nunes de
Published: February 2021

As atividades dos postos de gasolina têm em geral o maior potencial de causar danos ao meio ambiente por produtos químicos, gases, solventes, metais e combustíveis em especial. O armazenamento de combustíveis nas valas subterrâneas é o que mais provoca a contaminação do solo. Este estudo tem como objetivo analisar a estrutura de tratamento de efluentes de uma caixa separadora de água e subprodutos petroquímicos de um posto de gasolina, comparar os resultados com a legislação e avaliar seu potencial de reuso no processo. No Brasil, a legislação pertinente à atividade de armazenamento e distribuição de combustível data do ano 1997, com a edição da Resolução do Conselho Nacional do Meio Ambiente (CONAMA) nº. 237/97, que cita a atividade como sendo sujeita ao licenciamento ambiental e a CONAMA 430/2011 complementa e altera a Resolução nº 357/2005 que dispõe sobre as condições e padrões de lançamento de efluentes. No efluente de saída da caixa separadora, notamos que ainda ocorre anomalias, como o excesso de surfactantes e também na DBO, levando em consideração que esses dois parâmetros afetam a qualidade da água para o seu potencial reuso, e podendo causar contaminação no solo e lençol freático. Aconselhamos o uso do filtro com carvão ativado, por ser um método mais viável e que consegue atender as necessidades de devolver esse efluente dentro das normas padronizadas, possibilitando o reuso do efluente em descargas, jardinagem, lavar ambientes, dentre outros.
Users and health professionals perceptions of medication labels: a qualitative approach
Authors: Barroso Priscila Farfan , Moraes Cassia Garcia , Falavigna Maicon , Sirtori Lisana Reginini , Cruz Fernanda Horne da , Pons Emília da Silva
Published: February 2021

This study analyzed the labeling of medications in Brazil based on the perception of health professionals and users in order to propose modifications and improvements that avoided the error of medication use. The qualitative approach was used to collect data, and the semi-structured interview technique was performed among health professionals and the focal group technique among the users. This collection took place throughout 2017. The main difficulties encountered by drug product respondents were similar labels, the difficulty of finding the items on the labels, the different information on the primary and secondary packaging of the medicines and the difficulty in visualizing information in the labels. And the suggestions were to remove the unnecessary information labels that are considered obvious; and adding or highlighting the dosage information area, the route of administration, the mode of preparation of the medicines and storage form for preservation. About the general modifications there was agreement on the definition of color of the label according to the pharmacological action of the drug and on the standardization in the increase of letter of the main information of the label.
Violencia e mortalidade feminina por causas externas: observações nos dados de acidentes e agressões na Região Metropolitana de Manaus (RMM)
Authors: Sampaio Quézia Correa de Oliveira , Gomes Emilia dos Santos , Cruz Annebelle Pena Lima Magalhães , Farias Consuelo Pinheiro de , Guerreiro Ralyne Lima de Souza , Ferreira Rúbia Silene Alegre
Published: February 2021

O objetivo desta pesquisa consiste em observar violência e a mortalidade feminina por causas externas na Região Metropolitana de Manaus (RMM), no período de 1996 a 2018 e as ocorrências desta por etnina. As causas externas aqui observadas dizem respeito aos acidentes e agressões que acarretaram em mortes das mulheres amazonenses, neste recorte temporal. Os dados são provenientes do Sistema de Informações sobre Mortalidade do Datasus (SIM/DATASUS). Os resultados mostam que embora o volume de mortalidade por acidentes seja significativo, as mortes decorrentes da violencia contra a mulher são superiores. A conclusão é de que há uma necessidade de se tomar medidas que conjuntamente atuem no sentido de minimizar tão grande iniquidade.
Interview with Ge Gan-ru
Authors:   Manhattan School of Music, Green Edward
Published: February 2021

This interview is with the person rightlycalled China’s fi rst “avant-garde” composer,Ge Gan-ru. The honor is due to his 1983 compositionfor solo cello, Yi Feng (Lost Style), whichgrew out of his in-depth analysis of how Westernand Chinese music differ in their core presumptionsabout pitch, rhythm, timbre, and dynamics.A summary of that analysis is an important featureof this interview. Among other works discussedare his Wrong, Wrong, Wrong! for Voice,self-accompanied by a Toy Orchestra (2006), andhis Fifth String Quartet (2007), titled Fall of Baghdad.Interview with Ge Gan-ru for ICONI, conductedby Dr. Edward Green.
Interrelation of the Elements of Yakutia’s Natural and Cultural Heritage in the Region’s Positioning and the Development of Ethno-Cultural Tourism
Authors:   M.K. Ammosov North-Eastern Federal University, Fedorova Sardana N. , Konopleva Nina A. ,   Vladivostok State University of Economics and Service
Published: February 2021

The article presents the typological model of Yakutia’s natural and cultural heritage developed by the authors the substantial elements of which are natural objects and phenomena, material artifacts of culture, material and spiritual objects and spiritual elements of culture. This model demonstrates a rather stable sociocultural informational and value-conscious system, formed in the course of adaptation of the ethnicities inhabiting the region to the extremely severe environment of the North. The objects of natural cultural heritage create a system characterized in intrinsic relation by effective methods of environmental management, an original material and spiritual culture, a diversity of strategies of activity and managing. These reveal themselves in the rigid observation of natural rhythms, transfer to the subsequent generations of knowledge of features of the landscapes, natural resources, migrations of birds and animals, routes of nomadic wandering, places of settlements and nomadic housing, etc., as well as in the formation of a value-oriented spiritual bond with the primordial habitat, as well as the perception and celebration of its beauty and particularities.
Calligraphy as an Instrument of Development of the Designer’s Project-Oriented Thought
Authors:   Bashkir State Pedagogical University named after M. Akmulla, Vasilieva Anna Yu.
Published: February 2021

A project-oriented type of thought is very important for the profession of a designer. The article describes project-oriented thought as the chief element of its activity. Students studying design constantly polish their skills in practice when creating tutorial design projects and thereby develop project-oriented thought. Academic disciplines of the artistic cycle are directed at the development of project-oriented thought, and they include such an academic discipline as calligraphy. Knowledge, proficiency and skills developed by calligraphy are revealed by means of research. The article produces a complex structure of project-oriented thought based on Siegfried Begenau’s work and an analogy from the perspective of mastering calligraphy. On the basis of this analogy lies the principle of creation of a calligraphic work, from the idea to its realization. Study of calligraphic rules of writing develops manual dexterity, creativity and imagination and provides discipline, which is an important trait of the designer’s profession. Perfection of calligraphic elements and fonts in practice becomes conducive to elaboration of project-oriented thought. The conclusion is also arrived at that projectoriented thought is developed among designers faster after they undergo studies of a basic course of calligraphy.
The Musical Oeuvres of Nikolai Myaskovsky
Authors:   Saratov State L.V. Sobinov Conservatory, Demchenko Alexander I.
Published: February 2021

This lecture of Doctor of Arts, Professor Alexander I. Demchenko continues the cycle of lectures on Russian musical culture. In a maximally compact form the evolution of the musical oeuvres of composer Nikolai Ya. Myaskovsky is elucidated, the basic stages of which correspond to two sections of the text: “The 1910s and 1920” and “The 1930s and 1940s.” Just as in the previous cases, the exposition of the material presumes listening to a number of musical fragments, called upon to provide a general impression of the ranger of the composer’s artistic endeavors.
Visualization of Music as a Means for the Contemporary Composition to Function: Edison Denisov, “Three Pictures by Paul Klee”
Authors:   Tambov State Musical Pedagogical Institute named after S.V. Rachmaninov, Klimova Nataliya V.
Published: February 2021

This publication presents informational and analytic materials to a class in 7th grade of children’s music schools with commentaries and elucidations of the artistic style of German artist Paul Klee and the personal perspective of his art works by 20th century Russian composer. Examination is made of the questions of visualization as a means of impact on the perception of a contemporary classical musical composition. The central portion of the class material is taken up by an analysis of Klee’s works (the visual element) and the analysis of the musical score of Denisov’s cycle. The musical score and the illustrations of the artist’s works are projected on the screen, and the musical fl ow is superimposed on the visual depiction. Thereby, the content of Denisov’s chamber cycle is comprehended in interconnection with and through the components of the visual means of the composition’s functioning. As the result of the attempt of a synthetic perception of art, the visual element provides essential help in providing instruction at the elementary stage of musical education. The choice of the composition is stipulated by the revised content of the 7th grade textbook for children’s music schools by Olga Averyanova “Otechestvennaya muzyka XX veka” [“20th Century Russian Music”, Moscow, 2014]. The article suggests a consistent and interdependent examinations of the parameters of connections between music and painting and their refl ection in the individual, sonorous fl ow of the musical composition
The Musical Oeuvres of Dmitri Shostakovich
Authors:   Saratov State L.V. Sobinov Conservatory, Demchenko Alexander I.
Published: February 2021

This lecture of Doctor of Arts, Professor Alexander Demchenko illuminates in a maximally compact form the evolution of the music of the great composer, the main stages of which are corresponded to by the respective sections of the present text: “Early Works,” “Middle Period” and “Late Works,” which is supplemented by generalizations contained in the sections “The Issue of Humanism” and “The Artistic Constants.” The expounding of the lecture will be accompanied by listening to a number of fragments designed to give an overall impression of the range of the composer’s artistic quests.
Interview with Composer George Tsontakis
Authors:   Manhattan School of Music, Green Edward
Published: February 2021

This interview for the journal ICONI, taken by Dr. Edward Green, Professor at the Manhattan School of Music, is with one of the leading composers of the United States, George Tsontakis. A professor at Bard Conservatory of Music, he is the recipient of numerous awards for his work, including the prestigious Grawmeyer Award for his Second Violin Concerto. Professor Tsontakis’ work — nearly all of it commissioned — is wide-ranging in terms of genre, imaginative in its orchestrations, and always strongly emotional. Included in this interview are discussions of some of the biographical background to a number of his major pieces, including The Past, The Passion. Among the subjects discussed is the meaning of “concerto.” Several of his concertos and concerto-like compositions are specifically discussed in this interview, including Man of Sorrows (piano), and Sonnets (English Horn). The interview also touches upon his relations with two important American composers of earlier generation: George Rochberg, and Roger Sessions — who had been Tsontakis’ teacher of composition at Julliard.
Musical Computer
Authors:   Herzen State Pedagogical University of Russia, Gorbunova Irina B.
Published: February 2021

A new page in the manifestation and demonstration of expressive means of musical sound has been opened by the computer as a musical instrument, or the “musical computer.” Contemporary musicians have endeavored at the attempts at connecting composition with the theory of information, the unification of musical and acoustic parameters, having realized the idea of a regulated poly-dimensional sound space, a multilevel compositional model applied for sound generation with the use of concisely differentiated modulations of parameters of the level of frequencies, durations and dynamics. In the present lecture the author turns to the main stages of the evolution of the concept of “musical computer” reflecting the changes in the sound and the musical material during the course of the development of the practice of composition and music-making; questions are examined in connection with the particularities of development of the computer synthesis of sound; a retrospective analysis of technical and technological experiments made by musicians in their interactions with computer technologists, who have enhanced the development of the musical computer as a polyfunctional musical instrument, including the capabilities of its use as a means of providing the symphonic organization of music by means of stereophonic panorama setting of musical space; a broad range of issues is touched upon in connection with the peculiarities of musicians’ thinking and perception, including the impediments to a consistent acquisition of possibilities of the programmed musical instrument existent in the sphere.
The Melody of Form and Space: Music as a Source of Inspiration
Authors:   Bashkir State Pedagogical University named after Miftakhetdin Akmulla, Purik Elsa E. , Shakirova Marina G. ,   Birsk Branch of the Bashkir State University, Akhmadullin Mars L. ,   Ufa State Institute of Arts named after Zagir Ismagilov, Shakirov Vilur R. ,   Birsk Historical Museum
Published: February 2021

The article is devoted to the artistic legacy of Bashkir sculptor Ruslan Nigmatullin, one of the leading masters of contemporary visual arts in the republic. The relatedness of artistic expressive means of music with those in the plastic arts, their expressive elements become more apparent in the comparison of music and abstract art in the process of generation of the artistic image. The authors examine the artist’s oeuvres in the context of the particularity of sculpture as a peculiar art which requires from the viewer the knowledge of the laws of artistic form-generation and an understanding of their language, based on such elements as mass and space. The article presents an analysis of the artist’s works made of stone, metal or wood, while the artist himself sees their source as being connected with music. During the course of his entire artistic path Ruslan Nigmatullin has created sculptures in different directions: realism, decorative plastic and abstract art. The master’s art works, according to the authors of the article, are all unified by an inner figurative idea: when looking at the sculptor’s works it is possible to observe their inherent qualities: contemplation, abstraction and pure sound — natural, ethnic and sometimes purely songrelated, enhancing their relatedness to music. The artist considers one of the sources of his inspiration to be the historical Asian melodies, which share common roots with the ethnic music of the Bashkirs, Kazakhs and Tuvans. The authors provide an analogy between the folk songs of these peoples and their instrumental tunes, the latter being marked with a concise, measured rhythmic structure, and the artist’s works, his ability to create new forms, frequently just as abstract as the melodies with which it is associated.
The Middle Ages (from the Birth of Christ to the 13th Century). The East and the West
Authors:   Saratov State L.V. Sobinov Conservatory, Demchenko Alexander I.
Published: February 2021

The essence of the series of essays published by the journal is that with a maximum compactness of the presentation, it provides a summary of the main phenomena of world artistic culture, covered in its entirety both from the point of view of the general historical process, and in relation to the various arts (literature, the fi ne arts, architecture, music, theater and cinema). At the same time, the customary categorization according to national schools and the division into the separate respective arts with the genre specifi cation inherent in each of them are overcome, which answers the positive trends of globalization and provides a holistic view of artistic phenomena. The following artistic and historical periods are considered in stages: the Ancient world, the Greco-Roman world, the Middle Ages, the Renaissance era, the Baroque period, the Enlightenment, Romanticism, Post-romanticism, the fi rst, second and third Modern periods, Postmodernism, and, as an afterword, — “The Golden age of Russian artistic culture.”
Digital Musical Performance as the Refl ection of the Axiosphere of Culture and the Educational Space of the Digital Age
Authors:   Herzen State Pedagogical University of Russia, Petrova Natalia N.
Published: February 2021

The article examines performance on contemporary digital musical instruments, such as the keyboard synthesizer, the digital piano, the digital button and keyboard accordion and others, as a direction of artistic creativity in the contemporary sociocultural space on demand by numerous music lovers and professional performers. Evaluation is given to the possibilities of functioning for electronic musical creativity in the culturalcreative, communicative and educational angles. A phenomenological analysis of performance on electronic musical instruments is carried out and data is provided about the peculiarities of the sociocultural perception among various target auditoriums. The heuristic potential of electronic music-making for the young generation is highlighted in the refl ection of the demands of generation Z on poly-timbre and multi-genres in the artistic process. Examples are brought of successful attempts of realizing of individual and ensemble digital performance which has made it possible to manifest the fundamental functions of artistic culture, to create a system of moral and aesthetic values which would be relevant for society, and to form an aesthetically organized, highly technological sociocultural milieu.
The Semantic Explicitization of the Musical Text in Work with Beginner Guitarists
Authors:   S.M. Starikov Children’s Music School affi liated with the Tambov State Musical Pedagogical S.V. Rachmaninoff Institute, Okhotnikov Vladimir E.
Published: February 2021

The procedure of interpreting the content of the musical composition studied in a performance class is often reduced to reconstituting the version created by the instructor. The foundation of the joint interpretation with the pupil of the compositions may be served by the process of functioning of semantic fi gures in the context of the musical theme. Its semantic organization is impossible without turning to the foundational concept of semantic analysis — the intonational lexis, which summate the perceptions of the intonational vocabulary of the composer and the musical work he created. Thereby, the semantic explicitization must be the basis for objective analysis of the musical composition’s fi gurative-content aspect. The article examines the performers’ interpretations of musical compositions in beginners’ guitar classes on the basis of analyzing the musical text’s semantic structures in classical and contemporary music. For the beginner musician application of technique of semantic analysis will become a reliable source for a joint search for performance solution together with the instructor.
Renaissance (From the Middle of the 13th to the Middle of the 16th Century). Facets of Humanism
Authors:   Saratov State L.V. Sobinov Conservatory, Demchenko Alexander I.
Published: February 2021

The essence of the series of essays published by the magazine is that with a maximum compactness of presentation it provides a summary of the main phenomena of world artistic culture covered in general both from the point of view of the overall historical process, and in relation to various types of artistic creativity (literature, the visual arts, architecture, music, theater and cinema). At the same time, the customary categorization according to national schools and the division into separate types of art with the genre specifi cation inherent in each of them is overcome, which meets the positive tendencies of globalization and provides a holistic view of artistic phenomena.
Tibetan Culture of the Yellow River Basin in the Work of Contemporary Chinese Artists
Authors:   Far Eastern Federal University, Huang Yuanpeng , Alekseeva Galina V. ,   Far Eastern Federal University, Tingting Qin ,   China Academy of Arts
Published: February 2021

The Tibetan regions at the source of the Yellow River have recently become a new platform for painters which made it possible to convey the spirit, rituals, and national costumes of the people. Artists of the 21st century refl ect the humanistic beauty of the customs of the people of Tibet, their religious Buddhist beliefs, the values of the people living at the source of the main river of China. The authors analyze the colorful palette and other artistic means which allow such masters in China as Yang Feiyun, Lu Qinglong, Yu Xiaodong, Liu Xiaodong convey the world perception of the Tibetan people, their harmonious coexistence with the harsh nature of the region.
The Specificity of the Genesis of the National Television Series as an Original Cultural-Informational Phenomenon
Authors:   Vladivostok State University of Economics and Service, Ushanov Pavel V.
Published: February 2021

The article is devoted to the study of the formation of the television series as an independent cultural phenomenon, as well as a multifunctional means of mass communication. Based on the concept of Vladimir S. Sappak, the author examines the television series not simply as a form of the existence of art cinema in the space of television, but as a new cultural phenomenon which arose and continues to develop under the infl uence of a whole complex of types of visual culture and art. While studying the genesis of the television series, the author traces the process of the formation of the fi lm series as one of the basic components of the television series, which was also infl uenced by such types of visual popular culture as popular print and comics. Revealing the specifi city of the genesis of the television series, the author turns to Victor B. Shklovsky’s idea of defamiliarization as an artistic device aimed at creating a special perception of the subject by the audience. As a specifi c feature of the modern television series, the high degree of its dynamism distinguishes itself, the latter being due to the constant exchange of information with objects that also accumulate social information. Therefore, the television series becomes a space where the convergence of documentary and artistic communication fl ows is actively taking place. The results of this convergence can be attributed to the formation in the post-Soviet space of a unique phenomenon — a politically engaged television series.
The Principles of Organization of Career Enhancement Training Courses for Music Pedagogues in the Informational Educational Environment
Authors:   Herzen State Pedagogical University of Russia, Davletova Clara B.
Published: February 2021

The article examines the problems in organizing course preparations for a pedagogue musician’s, describes the aspects of actualizing the programs of career enhancement courses for specialists from the system of supplementary education for children. One of the main conditions for the organization of the courses is the use of the technical means — the computer and keyboard synthesizers, since particularly they open up the access to the necessary information, perfect the process of education and expand the forms, possibilities and technologies. The content of the supplementary professional programs of the career enhancement training courses correspond to the contemporary tendencies of development of Russian education and make it possible to use effectively the opportunities of the informational educational environment. The programs are developed with consideration of combining traditional musical education with innovational technologies. At the same time there appears the interdisciplinary integration: music — scholarship — informatics. Knowledge in the sphere of informational-communicational technologies is used as a tool for perfecting the instruction of the courses: mastery of the content of the material on the basis of utilization of the object environment and the present-day pedagogical technologies, including computer musical technologies and electronic musical instruments.
“Musical Informatics”. Program of the Discipline for Visually Impaired Students
Authors:   Herzen State Pedagogical University of Russia, Morozov Sergey A.
Published: February 2021

Thereunder is a publication the program of the discipline of “Musical Informatics” devoted to the theory and methodology of teaching student musicians with strong visual impairments. The methodological and content-rich components of study of this discipline in the federal state-run professional educational institution “Kursk Music Residential College for the Blind” of the Ministry of Labor and Social Protection of the Russian Federation are presented. The author of the article describes the special conditions for realizing the adapted program of the discipline of “Musical Informatics,” the thematic plan of the discipline, the methodological recommendations for teachers who implement the educational process within the walls of the college, the hardware-software, educational methodological and informational support for the realization of the educational process in specialized institutions the activities of which are directed at education, upbringing, rehabilitation and social adaptation of visually impaired invalids.
The Musical Oeuvres of Georgy Sviridov
Authors:   Saratov State L.V. Sobinov Conservatory, Demchenko Alexander I.
Published: February 2021

The previous issues of the journal featured publications of lectures about such outstanding 20th century Russian composers as Sergei Rachmaninoff, Igor Stravinsky, Sergei Prokofi ev, Nikolai Myaskovsky, Dmitri Shostakovich and Aram Khachaturian. This series is continued with a lecture about the music of Georgy Sviridov. After a general characterization of his musical legacy (in the preamble), the respective sections of the fi rst part of the lecture (The Musical Oeuvres of Sviridov in the Mid-20th Century, The Musical Oeuvres of Sviridov in the 1960s and 1970s, the Late Oeuvres of Sviridov) examines the foundational principles of the composer’s vivid individual style and evaluates the signifi cance of his contribution to the treasury of Russian art of the middle and second half of the 20th century. During the exposition of the lecture fragments of his musical compositions are presented for analysis in performances recommended by the author, in their sum, providing a perspective of the most substantial aspects of Sviridov’s musical legacy.
Phospho-Form Specific Substrates of Protein Kinase B (AKT1)
Authors: McKenna McShane , Balasuriya Nileeka , Zhong Shanshan , Li Shawn Shun-Cheng , O'Donoghue Patrick
Published: February 2021

Protein kinase B (AKT1) is hyper-activated in diverse human tumors. AKT1 is activated by phosphorylation at two key regulatory sites, Thr308 and Ser473. Active AKT1 phosphorylates many, perhaps hundreds, of downstream cellular targets in the cytosol and nucleus. AKT1 is well-known for phosphorylating proteins that regulate cell survival and apoptosis, however, the full catalog of AKT1 substrates remains unknown. Using peptide arrays, we recently discovered that each phosphorylated form of AKT1 (pAKT1S473, pAKT1T308, and ppAKT1S473,T308) has a distinct substrate specificity, and these data were used to predict potential new AKT1 substrates. To test the high-confidence predictions, we synthesized target peptides representing putative AKT1 substrates. Peptides substrates were synthesized by solid phase synthesis and their purity was confirmed by mass spectrometry. Most of the predicted peptides showed phosphate accepting activity similar to or greater than that observed with a peptide derived from a well-established AKT1 substrate, glycogen synthase kinase 3β (GSK-3β). Among the novel substrates, AKT1 was most active with peptides representing PIP3-binding protein Rab11 family-interacting protein 2 and cysteinyl leukotriene receptor 1, indicating their potential role in AKT1-dependent cellular signaling. The ppAKT1S473,T308 enzyme was highly selective for peptides containing a patch of basic residues at −5, −4, −3 and aromatic residues (Phe/Tyr) at +1 positions from the phosphorylation site. The pAKT1S473 variant preferred more acidic peptides, Ser or Pro at +4, and was agnostic to the residue at −5. The data further support our hypothesis that Ser473 phosphorylation plays a key role in modulating AKT1 substrate selectivity.
Vedolizumab: Potential Mechanisms of Action for Reducing Pathological Inflammation in Inflammatory Bowel Diseases
Authors: Luzentales-Simpson Matthew , Pang Yvonne C. F. , Zhang Ada , Sousa James A. , Sly Laura M.
Published: February 2021

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC), and Crohn’s disease (CD), are a group of disorders characterized by chronic, relapsing, and remitting, or progressive inflammation along the gastrointestinal tract. IBD is accompanied by massive infiltration of circulating leukocytes into the intestinal mucosa. Leukocytes such as neutrophils, monocytes, and T-cells are recruited to the affected site, exacerbating inflammation and causing tissue damage. Current treatments used to block inflammation in IBD include aminosalicylates, corticosteroids, immunosuppressants, and biologics. The first successful biologic, which revolutionized IBD treatment, targeted the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα). Infliximab, adalimumab, and other anti-TNF antibodies neutralize TNFα, preventing interactions with its receptors and reducing the inflammatory response. However, up to 40% of people with IBD become unresponsive to anti-TNFα therapy. Thus, more recent biologics have been designed to block leukocyte trafficking to the inflamed intestine by targeting integrins and adhesins. For example, natalizumab targets the α4 chain of integrin heterodimers, α4β1 and α4β7, on leukocytes. However, binding of α4β1 is associated with increased risk for developing progressive multifocal leukoencephalopathy, an often-fatal disease, and thus, it is not used to treat IBD. To target leukocyte infiltration without this life-threatening complication, vedolizumab was developed. Vedolizumab specifically targets the α4β7 integrin and was approved to treat IBD based on the presumption that it would block T-cell recruitment to the intestine. Though vedolizumab is an effective treatment for IBD, some studies suggest that it may not block T-cell recruitment to the intestine and its mechanism(s) of action remain unclear. Vedolizumab may reduce inflammation by blocking recruitment of T-cells, or pro-inflammatory monocytes and dendritic cells to the intestine, and/or vedolizumab may lead to changes in the programming of innate and acquired immune cells dampening down inflammation.
Revisiting Campylobacter jejuni Virulence and Fitness Factors: Role in Sensing, Adapting, and Competing
Authors: Elmi Abdi , Nasher Fauzy , Dorrell Nick , Wren Brendan , Gundogdu Ozan
Published: February 2021

Campylobacter jejuni is the leading cause of bacterial foodborne gastroenteritis world wide and represents a major public health concern. Over the past two decades, significant progress in functional genomics, proteomics, enzymatic-based virulence profiling (EBVP), and the cellular biology of C. jejuni have improved our basic understanding of this important pathogen. We review key advances in our understanding of the multitude of emerging virulence factors that influence the outcome of C. jejuni–mediated infections. We highlight, the spatial and temporal dynamics of factors that promote C. jejuni to sense, adapt and survive in multiple hosts. Finally, we propose cohesive research directions to obtain a comprehensive understanding of C. jejuni virulence mechanisms.
Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models
Authors: Tse Gary , Li Ka Hou Christien , Cheung Chloe Kwong Yee , Letsas Konstantinos P. , Bhardwaj Aishwarya , Sawant Abhishek C. , Liu Tong , Yan Gan-Xin , Zhang Henggui , Jeevaratnam Kamalan , Sayed Nazish , Cheng Shuk Han , Wong Wing Tak
Published: February 2021

Potassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to consolidate pre-clinical findings on the electrophysiological mechanisms underlying hypokalaemia-induced arrhythmogenicity. Both triggers and substrates are required for the induction and maintenance of ventricular arrhythmias. Triggered activity can arise from either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). Action potential duration (APD) prolongation can predispose to EADs, whereas intracellular Ca2+overload can cause both EADs and DADs. Substrates on the other hand can either be static or dynamic. Static substrates include action potential triangulation, non-uniform APD prolongation, abnormal transmural repolarization gradients, reduced conduction velocity (CV), shortened effective refractory period (ERP), reduced excitation wavelength (CV × ERP) and increased critical intervals for re-excitation (APD–ERP). In contrast, dynamic substrates comprise increased amplitude of APD alternans, steeper APD restitution gradients, transient reversal of transmural repolarization gradients and impaired depolarization-repolarization coupling. The following review article will summarize the molecular mechanisms that generate these electrophysiological abnormalities and subsequent arrhythmogenesis.
Transcriptomics of Biostimulation of Plants Under Abiotic Stress
Authors: González-Morales Susana , Solís-Gaona Susana , Valdés-Caballero Marin Virgilio , Juárez-Maldonado Antonio , Loredo-Treviño Araceli , Benavides-Mendoza Adalberto
Published: February 2021

Plant biostimulants are compounds, living microorganisms, or their constituent parts that alter plant development programs. The impact of biostimulants is manifested in several ways: via morphological, physiological, biochemical, epigenomic, proteomic, and transcriptomic changes. For each of these, a response and alteration occur, and these alterations in turn improve metabolic and adaptive performance in the environment. Many studies have been conducted on the effects of different biotic and abiotic stimulants on plants, including many crop species. However, as far as we know, there are no reviews available that describe the impact of biostimulants for a specific field such as transcriptomics, which is the objective of this review. For the commercial registration process of products for agricultural use, it is necessary to distinguish the specific impact of biostimulants from that of other legal categories of products used in agriculture, such as fertilizers and plant hormones. For the chemical or biological classification of biostimulants, the classification is seen as a complex issue, given the great diversity of compounds and organisms that cause biostimulation. However, with an approach focused on the impact on a particular field such as transcriptomics, it is perhaps possible to obtain a criterion that allows biostimulants to be grouped considering their effects on living systems, as well as the overlap of the impact on metabolism, physiology, and morphology occurring between fertilizers, hormones, and biostimulants.
Role of the NLRP3 Inflammasome: Insights Into Cancer Hallmarks
Authors: Lin Ting-Yi , Tsai Meng-Chun , Tu Wei , Yeh Hsin-Chih , Wang Shu-Chi , Huang Shu-Pin , Li Chia-Yang
Published: February 2021

In response to a variety of stresses, mammalian cells activate the inflammasome for targeted caspase-dependent pyroptosis. The research community has recently begun to deduce that the activation of inflammasome is instigated by several known oncogenic stresses and metabolic perturbations; nevertheless, the role of inflammasomes in the context of cancer biology is less understood. In manipulating the expression of inflammasome, researchers have found that NLRP3 serves as a deterministic player in conducting tumor fate decisions. Understanding the mechanistic underpinning of pro-tumorigenic and anti-tumorigenic pathways might elucidate novel therapeutic onco-targets, thereby providing new opportunities to manipulate inflammasome in augmenting the anti-tumorigenic activity to prevent tumor expansion and achieve metastatic control. Accordingly, this review aims to decode the complexity of NLRP3, whereby summarizing and clustering findings into cancer hallmarks and tissue contexts may expedite consensus and underscore the potential of the inflammasome in drug translation.
Alzheimer’s Risk Gene TREM2 Determines Functional Properties of New Type of Human iPSC-Derived Microglia
Authors: Reich Marvin , Paris Iñaki , Ebeling Martin , Dahm Nadine , Schweitzer Christophe , Reinhardt Dieter , Schmucki Roland , Prasad Megana , Köchl Fabian , Leist Marcel , Cowley Sally A. , Zhang Jitao David , Patsch Christoph , Gutbier Simon , Britschgi Markus
Published: February 2021

Microglia are key in the homeostatic well-being of the brain and microglial dysfunction has been implicated in neurodegenerative disorders such as Alzheimer’s disease (AD). Due to the many limitations to study microglia in situ or isolated for large scale drug discovery applications, there is a high need to develop robust and scalable human cellular models of microglia with reliable translatability to the disease. Here, we describe the generation of microglia-like cells from human induced pluripotent stem cells (iPSC) with distinct phenotypes for mechanistic studies in AD. We started out from an established differentiation protocol to generate primitive macrophage precursors mimicking the yolk sac ontogeny of microglia. Subsequently, we tested 36 differentiation conditions for the cells in monoculture where we exposed them to various combinations of media, morphogens, and extracellular matrices. The optimized protocol generated robustly ramified cells expressing key microglial markers. Bulk mRNA sequencing expression profiles revealed that compared to cells obtained in co-culture with neurons, microglia-like cells derived from a monoculture condition upregulate mRNA levels for Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), which is reminiscent to the previously described disease-associated microglia. TREM2 is a risk gene for AD and an important regulator of microglia. The regulatory function of TREM2 in these cells was confirmed by comparing wild type with isogenic TREM2 knock-out iPSC microglia. The TREM2-deficient cells presented with stronger increase in free cytosolic calcium upon stimulation with ATP and ADP, as well as stronger migration towards complement C5a, compared to TREM2 expressing cells. The functional differences were associated with gene expression modulation of key regulators of microglia. In conclusion, we have established and validated a work stream to generate functional human iPSC-derived microglia-like cells by applying a directed and neuronal co-culture independent differentiation towards functional phenotypes in the context of AD. These cells can now be applied to study AD-related disease settings and to perform compound screening and testing for drug discovery.
Bioinformatic Analysis of the Wound Peptidome Reveals Potential Biomarkers and Antimicrobial Peptides
Authors: Hartman Erik , Wallblom Karl , van der Plas Mariena J. A. , Petrlova Jitka , Cai Jun , Saleh Karim , Kjellström Sven , Schmidtchen Artur
Published: February 2021

Wound infection is a common and serious medical condition with an unmet need for improved diagnostic tools. A peptidomic approach, aided by mass spectrometry and bioinformatics, could provide novel means of identifying new peptide biomarkers for wound healing and infection assessment. Wound fluid is suitable for peptidomic analysis since it is both intimately tied to the wound environment and is readily available. In this study we investigate the peptidomes of wound fluids derived from surgical drainages following mastectomy and from wound dressings following facial skin grafting. By applying sorting algorithms and open source third party software to peptidomic label free tandem mass spectrometry data we provide an unbiased general methodology for analyzing and differentiating between peptidomes. We show that the wound fluid peptidomes of patients are highly individualized. However, differences emerge when grouping the patients depending on wound type. Furthermore, the abundance of peptides originating from documented antimicrobial regions of hemoglobin in infected wounds may contribute to an antimicrobial wound environment, as determined by in silico analysis. We validate our findings by compiling literature on peptide biomarkers and peptides of physiological significance and cross checking the results against our dataset, demonstrating that well-documented peptides of immunological significance are abundant in infected wounds, and originate from certain distinct regions in proteins such as hemoglobin and fibrinogen. Ultimately, we have demonstrated the power using sorting algorithms and open source software to help yield insights and visualize peptidomic data.
Immune Checkpoints: Novel Therapeutic Targets to Attenuate Sepsis-Induced Immunosuppression
Authors: McBride Margaret A. , Patil Tazeen K. , Bohannon Julia K. , Hernandez Antonio , Sherwood Edward R. , Patil Naeem K.
Published: February 2021

Sepsis is a leading cause of death in intensive care units and survivors develop prolonged immunosuppression and a high incidence of recurrent infections. No definitive therapy exists to treat sepsis and physicians rely on supportive care including antibiotics, intravenous fluids, and vasopressors. With the rising incidence of antibiotic resistant microbes, it is becoming increasingly critical to discover novel therapeutics. Sepsis-induced leukocyte dysfunction and immunosuppression is recognized as an important contributor towards increased morbidity and mortality. Pre-clinical and clinical studies show that specific cell surface inhibitory immune checkpoint receptors and ligands including PD-1, PD-L1, CTLA4, BTLA, TIM3, OX40, and 2B4 play important roles in the pathophysiology of sepsis by mediating a fine balance between host immune competency and immunosuppression. Pre-clinical studies targeting the inhibitory effects of these immune checkpoints have demonstrated reversal of leukocyte dysfunction and improved host resistance of infection. Measurement of immune checkpoint expression on peripheral blood leukocytes may serve as a means of stratifying patients to direct individualized therapy. This review focuses on advances in our understanding of the role of immune checkpoints in the host response to infections, and the potential clinical application of therapeutics targeting the inhibitory immune checkpoint pathways for the management of septic patients.
Balancing Model Complexity, Data Requirements, and Management Objectives in Developing Ecological Reference Points for Atlantic Menhaden
Authors: Drew Katie , Cieri Matthew , Schueller Amy M. , Buchheister Andre , Chagaris David , Nesslage Geneviève , McNamee Jason E. , Uphoff James H.
Published: February 2021

Atlantic menhaden is an important forage fish and the target of the largest fishery along the US East Coast by volume. Since 1999, managers at the Atlantic States Marine Fisheries Commission, stakeholders, and scientists have been interested in developing ecological reference points (ERPs) that account for menhaden’s role as a forage species. To accomplish this, we developed a suite of modeling approaches that incorporated predation on menhaden and changes in productivity over time and allowed for evaluation of trade-offs between menhaden harvest and ecosystem management objectives. These approaches ranged in complexity, from models with minimal data requirements and few assumptions to approaches with extensive data needs and detailed assumptions. This included a surplus production model with a time-varying intrinsic growth rate, a Steele-Henderson surplus production model, a multispecies statistical catch-at-age model, an Ecopath with Ecosim (EwE) model with a limited predator and prey field, and a full EwE model. We evaluated how each model could address managers’ objectives and compared outputs across the approaches, highlighting their strengths, weaknesses, and management utility. All models produced estimates of age-1 + biomass and exploitation rate that were similar in trend and magnitude to the single-species statistical catch-at-age model, especially in recent years. While the less complex models were relativity easy to implement and update, they lacked key elements needed to manage multiple species simultaneously. More complex models required a wider array of data and were more difficult to update within the current management time-frames, but produced a more useful framework for managers. Ultimately, an EwE model of intermediate complexity coupled with the existing single-species assessment model was recommended for use in management.