bluuebunny/crossref_metadata_2025 huggingface dataset:
An Online Platform for Community-Based Language Description and Documentation
Authors: Everson Rebecca , Honoré Wolf , Grimm Scott
Published: March 2021

We present two pieces of interlocking technology in development to facilitate community-based, collaborative language description and documentation: (i) a mobile app where speakers submit text, voice recordings and/or videos, and (ii) a community language portal that organizes submitted data and provides question/answer boards whereby community members can evaluate/supplement submissions.
The informal anthroponym Петръ Гоугнивыи. 3.
Authors:   National Aviation University, Mezhzherina H. V.
Published: March 2021

The article is devoted to finding out the motivational basis, reconstruction of reference connections, denotative features of an unofficial anthroponym Петръ Гоугнивыи available in the original and translated East Slavic written artifacts (the Lavrenty chronicle, «Chronicle of George Amartol», «Old Slavonic Kormchaia of 14 titles» etc.). The anthroponym belongs to two people — Patriarch Peter ІІІ of Alexandria V century (Πέτρος Μογγός) and the «chronicle» Roman heresiarch ІХ century. It is assumed that Peter ІІІ got an unofficial name among the Monophysites during his lifetime. It is proved that the transition from the assessment of a person by physical disabilities to religious and ethical assessment, from the meaning ‛who has a hoarse, vague voice’ to the meaning ‛heretic’ reflected in the internal form of the unofficial proprial name Μογγός and its translation equivalent Гоугнивыи. translation equivalent Гоугнивыи. The use of an informal anthroponym in written monuments after the thirteenth century has been traced in connection with reconstruction of denotative features of an unofficial anthroponym Петръ Гоугнивыи. A number of discussion issues were considered, including the origin of «Philosopher’s Speech», time of inclusion of the legend of Петръ Гоугнивыи in the chronicle, fact of existence of Pope ІХ century by name Петръ Гоугнивыи, ethnic roots of the heresiarch, etc. It was shown that Peter Huhnyvyy introduced into the Catholic faith a heretical teaching focused on pagan and Jewish dogmas. Denotation of second component in an unofficial name Петръ Гоугнивыи includes characteristics that appeared at rethinking the original semantics of Indo-European root *gou‑(n‑) and its continuants. Semantics of dissatisfaction, mockery, disrespect developed in East Slavic derivatives. The transition to cultural semantics has already taken place in a word-forming nest with a root ‑гоу(г)‑ at a time when the legend of Peter Huhnyvyy was included in the chronicle article * 988. The ethnocultural denotative components which are included in the content of the anthroponym Петръ Гоугнивыи, in its entirety coincide with the semantic structure of the word heretic. Combination of linguistic analysis with historical and cultural analysis, taking into account historical facts and information contained in apocryphal legends and scientific versions, gives reason to believe that the «chronicle» Peter Huhnyvyy was the real historical person.
Recent phraseological coinages of the COVID-19 period
Authors:   Ivan Franko National University of Lviv, Khoroz N. S.
Published: March 2021

The spread of COVID-19 worldwide has caused certain processes in almost every language. In particular, in the Russian language, there is a phenomenon of adapting well-known fixed phrases to extra-lingual conditions (namely to the life of the country in quarantine) through their various transformations. It is a range of the transformed fixed phrases thematically related to the topic of coronavirus that have become the subject matter of this article. They have been systematized: a) considering the types of transformations applied to them (cases of structural and semantic transformations (substitution of components of phraseological units, extension of their components using everyday words related to COVID-19, phraseological allusion, contamination), and cases of semantic transformations (change of the meaning of the idiom, extension of its valence and dephraseologisation) have been identified); b) considering the influence of transformations on the semantics of fixed phrases (denotative meaning of occasional figurative units have been either concretized, have acquired new semes, or have been partially or completely deformed; non-figurative fixed phrases implement the meaning which constitutes the sum of the meanings of their components, the connotative meaning of units of any type of semantic connection between the components is enhanced by creating a comic effect, which is achieved by transforming fixed phrases); c) considering the subject: in analysing transformed idioms, a hierarchical classification structure has been used: phraseosemantic series — variant-synonymous group — phraseosemantic field — phraseothematic field — phraseothematic group (the phraseothematic group ‟COVID-19 Pandemic”, the phraseothematic fields “COVID-19 Disease” and “Human Activity during the COVID-19 Pandemic” have been singled out, which, in turn, have been formed using 11 and 4 phraseosemantic fields, respectively, which have been combined on the basis of integral or differential features into numerous variant-synonymous groups and phraseological series). These fixed phrases constitute the latest occasional phraseological picture of the Russian world. Their fixation and study are important for understanding speech processes in synchrony, in their relationship to the extra-lingual situation.
A vibração focal na espasticidade de pacientes com patologias neurológicas: revisão
Authors: Pereira Tassiane Maria Alves , Nunes Nicolle dos Santos Moraes , Do Nascimento Jacqueline Stephanie Fernandes , Do Nascimento Janie Kelly Fernandes , Azizi Marcos Antônio Alves , Moreno Adalgiza Mafra , Orsini Marco , Silva Janaí­na de Moraes
Published: March 2021

Introdução: As injúrias neurológicas apresentam distúrbios de movimentos que prejudicam a funcionalidade e independência desses pacientes. A espasticidade é um dos distúrbios mais frequentes e acarreta complicações secundárias com interferência negativa nas funções fí­sicas e motoras desempenhadas na vida cotidiana. O objetivo do presente estudo foi revisar na literatura evidências que expõem o efeito da vibração focal na espasticidade de pacientes com injúrias neurológicas. Metodologia: Realizou-se uma busca nas bases e banco de dados Pubmed, PEDro, Scopus e Web of Science utilizando os descritores "focal vibration" AND "spasticity" estipulando critérios de inclusão e de qualidades metodológicas. No total cinco artigos foram incluí­dos e compuseram a revisão. Resultados: Os resultados evidenciaram melhoras significativas na redução da espasticidade e em parâmetros funcionais que influenciam na qualidade de vida destes pacientes. Conclusão: Conclui-se então que a vibração focal é uma intervenção eficaz na redução da espasticidade de pacientes com injúrias neurológicas. Palavras-chave: vibração focal, espasticidade, funcionalidade, fisioterapia.
Новації у митному законодавстві України
Authors: Несторишен І. В. , Туржанський В. А. , Бережнюк І. Г.
Published: March 2021

У статті узагальнено вітчизняну практику здійснення процедур постмитного контролю, а також обґрунтовано доцільність внесення змін до Митного кодексу України щодо запровадження інструментів постмитного контролю у вітчизняне митне законодавство. В основу дослідження покладено концепцію збалансування інтересів держави та суб’єктів зовнішньоекономічної діяльності щодо забезпечення національної безпеки та спрощення процедур митного контролю. Митний контроль після випуску є складовою частиною системи надання спрощень, який дозволяє забезпечити мінімальне втручання митних органів в зовнішньоекономічну діяльність бізнесу з високим ступенем довіри.

Одним з актуальних питань у сфері здійснення державної митної справи в Україні є наближення митного законодавства до положень міжнародних конвенцій та угод, а також в умовах реалізації подальших євроінтеграційних прагнень гармонізація вітчизняного інструментарію здійснення митного контролю із європейським. Зазначено, що 2016 р. в Європейському Союзі набув чинності ряд нормативних документів, які істотно змінили підходи до здійснення процедур митного контролю та порядок надання спрощень економічним операторам. Зокрема, Митним кодексом ЄС передбачено активне використання інструментів митного контролю після випуску (post-release control), який є одним із складових частин системи надання спрощень економічним операторам. В Україні, не зважаючи на передбачене нормативне підґрунтя контролю після випуску, ця форма митного контролю не працює повною мірою, а показники ефективності підрозділів митного аудиту Держмитслужби є низькими. Авторами проаналізовано нормативні документи ЄС, якими передбачено використання інструментів митного контролю після випуску в контексті внесення змін до Митного кодексу України, та узагальнено новації у вітчизняному митному законодавстві відповідно до положень митного законодавства ЄС.
Tratamento de Água Cinza em Unidade de Produção Agrícola Controlada associada a Hidrociclone
Authors: Costa Rubenia de Oliveira , Medeiros Altevir Paula de , Nascimento José Jefferson da Silva , Medronho Ricardo de Andrade , Silva Osvaldo Soares da , Brito Herllange Chaves de , Ferreira Aline Costa , Santos Neto Vicente Saraiva dos , Maracajá Patrício Borges , Bezerra Neto Francisco das Chagas
Published: March 2021

A água é um recurso determinante para o desenvolvimento urbano, industrial e agrícola, principalmente na região semiárida, em que é um fator escasso. Além do problema da quantidade de água disponível para a população, alguns fatores prejudicam ainda mais a sua disponibilidade, como o despejo de esgoto sem tratamento ou tratados inadequadamente, efluentes industriais e agrícolas e produtos químicos como, por exemplo, fertilizantes. Nessa esteira, pontua-se que a água cinza, em regiões semiáridas, tende a ser exacerbadamente utilizada, por ser uma alternativa viável e sustentável para o tratamento da água. Cabe destacar que os parâmetros analisados das águas cinza coletadas dos pontos de observação das unidades foram: Condutividade Elétrica (CE), pH, Turbidez e Oxigênio Dissolvido (OD). Assim, ante o exposto o presente artigo busca avaliar Unidades de Produção Agrícola Controlada/UPAC com e sem a presença de hidrociclone no processo de tratamento da água cinza gerada em uma lavanderia pública no município de Cabaceiras, no Estado da Paraíba, visando o reuso de água.
Aspectos associados ao tabagismo e os efeitos sobre a saúde
Authors: Cardoso Thais Carolina Alves , Rotondano Filho Adriano Ferro , Dias Laryssa Moura , Arruda Jalsi Tacon
Published: March 2021

O hábito de fumar – tabagismo, está associado ao desenvolvimento de uma série de doenças. É algo comum desde os primórdios da pré-história da humanidade. O presente estudo realizou uma revisão integrativa da literatura para reunir aspectos associados ao tabagismo e os efeitos sobre a saúde. Foi realizada uma revisão integrativa de literatura a partir de estudos originais foram obtidos nas bases de dados SciELO, Google Acadêmico e LILACS. O termo "cigarro" refere-se ao cigarro feito de tabaco, embora seja utilizado para designar outros produtos semelhantes. O tabagismo já não é mais sinônimo apenas do consumo de cigarros convencionais feitos de tabaco. Outros produtos como o tabaco orgânico utilizado para fazer o charuto, o narguilé e o cigarro eletrônico disputam lugar com os maços. Todos os derivados do tabaco, que podem ser usados nas formas de inalação (cigarro, charuto, cachimbo, narguilé, cigarro de palha, eletrônico), aspiração (rapé) e mastigação (fumo-de-rolo), são nocivos à saúde. É muito importante monitorar a iniciação do tabagismo, principalmente entre os jovens, por essa ser uma ação passível de prevenção.
Inovações em resina composta: uma revisão de literatura
Authors: Rodrigues Lucas Dantas , Costa Iury Alves , Rabelo Zidane Hurtado , Oliveira Lucas Lino de , Monteiro Rayanna Mayra Feitosa , Sá Henrique Cabral , Estellita Maria Clara Ayres , Lima Karlos Eduardo Rodrigues , Lemos Marcelo Victor Sidou , Fontes Natasha Muniz , Silva Raul Anderson Domingues Alves da , Isaias Pedro Henrique Chaves , Mendes Talita Arrais Daniel , Sales Ernanda Maria de Araújo
Published: March 2021

O presente estudo objetivou revisar a literatura acerca da incorporação de substâncias para aprimorar as propriedades mecânicas, químicas e ópticas dos compósitos. Para tanto, foi realizada uma busca na base de dados PubMed, utilizando o descritor “Composite Resins” combinado através do operador booleano AND com cada um dos seguintes descritores “Anti-bacterial Agents”, “Bulk Fill”, “Fillers” e “Photoinitiators”. Foram selecionados 11 artigos na língua inglesa. Existem resinas incorporadas por biovidro (BV) que reduzem a penetração de biofilme em espaços marginais dos compósitos. Estudos mostraram que a integração de metacrilatos e nanopartículas de fosfato de cálcio amorfo (NACP) favoreciam na ação antibacteriana, bem como na remineralização. Outro autor fundamentou o desenvolvimento de um compósito dentinário auto-reparável, bem como, a incorporação de dimetilaminohexadecil metacrilato de amônio quaternário (DMAHDM) que reduziu o crescimento de biofilme sem comprometer as propriedades mecânicas. Desse modo, constata-se a positiva e eficaz evolução dos compósitos resinosos favorecendo melhorias nas propriedades físicas e químicas. Entretanto, não há uma unanimidade de qual compósito garante suprimir todas as limitações.
Determinação do perfil fitoquímico e avaliação de atividades biológicas de extratos de folhas de Ilex brevicuspis Reissek. (Aquifoliaceae)
Authors: Mallmann Ana Paula , Santos Camila Vogt dos , Toledo Adrieli Gorlin , Lakoski Larissa Valéria , Bandeira Débora Marina , Corrêa Juliana Moço , Pinto Fabiana Gisele da Silva
Published: March 2021

O gênero Ilex compreende mais de 500 espécies sendo considerada uma fonte promissora para a extração de princípios ativos com diversas atividades biológicas. Diante desse foco, este trabalho utilizou folhas de Ilex brevicuspis Reissek para produção de extratos, objetivando a determinação fitoquímica, antioxidante, antibacteriana e acaricida sobre Dermanyssus gallinae (Degeer, 1778). As folhas foram coletadas, secas e trituradas em moinho, e seus extratos produzidos com diferentes solventes, etanol (EE), metanol (EM), acetato de etila (EAE) e água destilada (Eaq). As análises fitoquímicas revelaram três grupos de compostos: saponinas, esteroides e taninos. Os extratos apresentaram atividade inibitória e bactericida para cepas padrões (Gram-negativas e positivas) e para dez sorotipos de Salmonella spp. O extrato EM apresentou os melhores resultados de CIM para as cepas padrões, variando de 6,25 mg/mL a 50 mg/mL e para CBM de 6,25 mg/mL a 100 mg/mL. Para os sorotipos de Salmonella o extrato EE apresentou a melhor atividade antibacteriana, variando de 25 mg/mL a 50 mg/mL para CIM e 200 mg/mL para CBM. O extrato EM revelou elevada atividade acaricida de 94% e moderada capacidade antioxidante de 81,45%. Os ensaios demonstraram que os extratos EM e EE de I. brevicuspis representam um potencial alternativo para controle de bactérias e ácaros, demonstrando uma nova perspectiva para desenvolvimento de produtos naturais a partir de uma espécie nativa.
Evaluation of plasmatic levels of CK-MB and C-Reactive Protein in brachicephalic dogs who have narin stenosis before and after diode laser rhinoplasty
Authors: Mendes Junior Aguinaldo Francisco , Duarte Pâmela Cristina de Souza , Santos Gabriela Souza Leão Bezerra dos , Hotz Marina Ribeiro , Marques Juliana Letícia Rosseto , Almeida Vivian Gomes Ferreira de , Mothé Gabriele Barros , Soares Ana Maria Barros , Almosny Nádia Regina Pereira
Published: March 2021

To evaluate the protective effect of rhinoplasty with diode laser on the cardiovascular system and in the reduction of the inflammatory state, CK-MB and PCR measurements were performed before and 30 days after the surgical procedure. Rhinoplasty using the diode laser promoted a significant reduction in plasma CK-MB and PCR levels, 30 days after its completion. No association was found between the pre-surgical plasma concentration of CK-MB and CRP and the degree of stenosis of the nostrils, race, age, sex and weight of the animals. A significant reduction in CK-MB was observed in dogs with severe stenosis, French Bulldog, one year old and over four years old, male and between 10 and 20 kg. Animals with severe stenosis, of the Pug breed, weighing less than 10 kg and three years of age exhibited a significant decrease in serum CRP values ​​after surgery. As a result, the degree of stenosis of the nostrils, the breed, age, sex and weight of the animals did not influence the plasma concentration of NTpro-BNP, CK-MB and PCR in brachycephalic dogs. Rhinoplasty with diode laser has been shown to be effective in reducing the plasma concentration of the natriuretic peptide CK-MB and CRP in dogs with brachycephalic syndrome, showing that the procedure has a protective effect on the cardiovascular function of these animals and is also effective in reducing inflammatory biomarkers.
Proinflammatory status, genetics and atherosclerosis
Authors: Poledne R , Lorenzová A , Stávek P , Valenta Z , Hubáček J , Suchánek P , Piťha J
Published: March 2021

Over the last decade, C-reactive protein concentration analyzed
by the high sensitivity method (hsCRP) has been proven as a
marker of premature atherosclerosis. Concentration exceeding
2 mg/l represents an increased individual risk of myocardial
infarction and stroke but strict application of this borderline is
complicated by relations of CRP concentrations to other risk
factors of cardiovascular diseases. In a large 1 % representative
sample of the Czech population, a positive relation of hsCRP to
BMI, a waist circumference and triglyceride concentration was
documented. Substantial sex differences were found in its
relationship to age. Whereas it is continuously increasing in men,
this increase appears in women only after menopause. A
substantial decrease of body weight and visceral fat volume by
increased physical activity is accompanied by significant decrease
of hsCRP in young obese women. This decrease was not related
to a change of interleukin-6 concentration, although it is
supposed to regulate CRP production. CRP concentration is partly
under genetic control as a higher concentration in young siblings
of probands with proved coronary atherosclerosis was
documented. The participation of genes related to lipoprotein
metabolism (genes for apolipoprotein CI and apolipoprotein E)
influence hsCRP concentrations. We hypothesized that an
increased concentration of hsCRP represents a certain marker of
proinflammatory status related to central obesity and triglyceride
metabolism and it might be related to individual properties of
monocytes in atherogenesis.
End-organ damage in hypertensive transgenic Ren-2 rats: influence of early and late endothelin receptor blockade
Authors: Vernerová Z , Kujal P , Kramer HJ , Bäcker A , Červenka L , Vaněčková I
Published: March 2021

The rat strain transgenic for the murine Ren-2 renin gene (TGR)
is defined as a monogenic model of angiotensin II-dependent
hypertension with endogenous activation of the renin-angiotensin
system. Homozygous males TGR develop malignant hypertension
with a strong salt-sensitive component. These animals show
severe hypertension, proteinuria and high mortality.
Morphological changes of renal parenchyma correspond to
chronic ischemic glomerular changes. Heterozygous TGR develop
only mild hypertension and thus provide a more suitable model of
hypertension regarding to clinical studies. Within the renal
parenchyma, secondary focal segmental glomerulosclerosis
(FSGS) predominates. High-salt diet in heterozygous animals
induces transition from benign to malignant phase of
hypertension. In this case, ischemic glomerular changes are
superimposed on preexisting secondary FSGS. In the regression
model of hypertension (late-onset treatment) the effect of salt
intake is attenuated. In homozygous TGR, early selective ETA
receptor blockade decreased blood pressure and ameliorated
end-organ damage. Late selective ETA receptor blockade reduced
podocyte injury despite final severe hypertension. Survival rate
was markedly improved in both regimens with ETA selective
blockade, while there was only partial improvement with early
non-selective blockade. Both bosentan and atrasentan decreased
ET-1 levels in both regimens. In heterozygous TGR, early and
late ETA treatment substantially while ETA/ETB treatment partially
improved survival rate. Significant effect on BP was found with
early and late ETA blockade, while ETA/ETB blockade had no
effect. Bosentan and atrasentan similarly decreased ET-1 levels
on both regimens. In conclusion, selective ETA receptor blockade
is superior to nonselective ETA/ETB receptor blockade in
attenuating hypertension and end-organ damage. Its effect is
more pronounced when applied early in the life.
Fetal cardiology in the Czech Republic: current management of prenatally diagnosed congenital heart diseases and arrhythmias
Authors: Tomek V , Marek J , Jičínská H , Škovránek J
Published: March 2021

Reliable diagnosis of congenital heart defects and arrhythmias in
utero has been possible since the introduction of fetal
echocardiography. The nation-wide prenatal ultrasound screening
program in the Czech Republic enabled detection of cardiac
abnormities in 1/3 of patients born with any congenital heart
disease and up to 83 % of those with critical forms. Prenatal
frequency of individual heart anomalies significantly differed from
the postnatal frequency. Fetal isolated complete atrioventricular
block and supraventricular tachycardia may lead to heart failure
and are important causes of fetal mortality. The regression of
heart failure was achieved by a conversion to the sinus rhythm in
the supraventricular tachycardia and by increase of ventricular rate
in the complete atrioventricular block.
Anti-Allergy Potential of Averrhoa bilimbi Linn. Fruit Water Extract Shown by Its Suppressive Effect on the Degranulation of RBL-2H3 Cells
Authors: Santoso William Halim , Ishida Momoko , Nishi Kosuke , Sugahara Takuya , Putra Agus Budiawan Naro
Published: March 2021

Allergy rhinitis (AR), as reported by the World Allergy Organization (WAO), is one of the highest prevalence allergies affecting 10-30% of all adults and up to 40% of children. In Indonesia, current evidence showed that the prevalence of AR is increasing. Averrhoa bilimbi Linn. fruit (AF), or locally known as belimbing wuluh, has been scientifically proven to treat many diseases due to the abundant of polyphenol content which was shown to have the potential to treat allergies. Therefore, this study was aimed to investigate the anti-allergy potential of AF in vitro. The anti-allergy effect of Averrhoa bilimbi Linn. fruit water extract (AFWE) was examined using RBL-2H3 cells. At first, the cytotoxicity effect of AFWE was determined by WST-8 assay. The release of β-hexosaminidase by RBL-2H3 cells was also measured to evaluate degranulation suppression activity of AFWE. Lastly, calcium assay was employed to investigate the intracellular calcium concentration ([Ca­2+]i). Results demonstrated that AFWE does not show any cytotoxicity at any given concentration. In addition, AFWE at 1.25 mg/mL showed sufficient inhibitory effect towards degranulation by RBL-2H3 cells. Moreover, the degranulation-suppressing activity of AFWE was resulted from the inhibition of calcium-dependent signaling pathways. Unfortunately, the properties of active substances from AFWE have not been investigated. To conclude, this study indicated that AFWE has potential as an alternative treatment for allergic diseases.
El reto de aportar un carácter dinámico a las inspecciones de estructuras
Authors: Menéndez Corral Ana , Rodríguez González Alejandro
Published: March 2021

La operatividad y seguridad de las redes de transporte es un asunto de vital importancia para el bienestar económico y social de cualquier país. Dentro de dichas redes, no cabe duda de que los puentes constituyen puntos críticos por su especial vulnerabilidad y las consecuencias de todo tipo que conllevaría su hipotético fallo. Por ello, la evaluación de su salud estructural debe ser una cuestión primordial en todo sistema de gestión de puentes, y más teniendo en cuenta que muchos de ellos se encuentran próximos al fin de la vida útil para la que fueron proyectados. La evaluación de su estado de conservación se basa en la actualidad, de forma mayoritaria, en las inspecciones visuales. Este artículo se centra en las posibilidades que ofrecen los ensayos dinámicos, los avances en las monitorizaciones, comunicaciones y tratamiento de datos, para complementar y reforzar dichas inspecciones, eliminando la subjetividad y llegando, en tiempo real, a donde el ojo humano no puede llegar, de forma que los gestores de los puentes puedan decidir cómo, dónde y cuándo actuar de una manera más racional, objetiva y eficaz.
Optimizing Granulocyte Colony-Stimulating Factor Transcript for Enhanced Expression in Escherichia coli
Authors: Datta Sonal
Published: March 2021

The human granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor used to prevent and treat neutropenia. G-CSF stimulates the bone marrow to produce infection-fighting granulocytes. Food and Drug Administration of the United States approved G-CSF in 1991 and its PEGylated version in 2002 as a prophylactic and therapeutic measure against neutropenia. Recombinant human G-CSF is produced in surrogate host Escherichia coli and is PEGylated at N-terminal. Besides neutropenia, G-CSF is also used in bone marrow transplantation for the mobilization and maturation of peripheral blood stem cells. Considering the requirement of producing G-CSF therapeutic in large quantities, construct designing for high expression is critical for the biopharmaceutical and industrial application. Earlier studies have employed approaches such as codon optimization, use of strong promoters, employment of protein tags, secretion signals, optimization of protein folding, etc., for increasing expression and yield of therapeutic proteins. In this study, it was observed that mRNA transcribed from the native human cDNA of G-CSF and the codon-optimized variant leads to low protein expression in E. coli. To understand the underlying reasons, the mRNA secondary structure of the 5′ end of the G-CSF transcript was analyzed. This analysis revealed the presence of stable secondary structures at the 5′ end of the G-CSF transcript, arising from the native human gene and even from the codon-optimized sequence. These secondary structures were disrupted through translationally silent mutations within the first 24 nucleotides of the transcript without affecting the protein sequence. Interestingly, through this approach, the G-CSF protein expression was increased 60 folds as compared to native G-CSF construct. We believe that these findings create a roadmap for optimization of G-CSF transcript for enhanced expression in E. coli and could be employed to increase the expression of other therapeutic proteins.
Parameter-Dependency of Low-Intensity Vibration for Wound Healing in Diabetic Mice
Authors: Roberts Rita E. , Bilgen Onur , Kineman Rhonda D. , Koh Timothy J.
Published: March 2021

Chronic wounds in diabetic patients represent an escalating health problem, leading to significant morbidity and mortality. Our group previously reported that whole body low-intensity vibration (LIV) can improve angiogenesis and wound healing in diabetic mice. The purpose of the current study was to determine whether effects of LIV on wound healing are frequency and/or amplitude dependent. Wound healing was assessed in diabetic (db/db) mice exposed to one of four LIV protocols with different combinations of two acceleration magnitudes (0.3 and 0.6 g) and two frequencies (45 and 90 Hz) or in non-vibration sham controls. The low acceleration, low frequency protocol (0.3 g and 45 Hz) was the only one that improved wound healing, increasing angiogenesis and granulation tissue formation, leading to accelerated re-epithelialization and wound closure. Other protocols had little to no impact on healing with some evidence that 0.6 g accelerations negatively affected wound closure. The 0.3 g, 45 Hz protocol also increased levels of insulin-like growth factor-1 and tended to increase levels of vascular endothelial growth factor in wounds, but had no effect on levels of basic fibroblast growth factor or platelet derived growth factor-bb, indicating that this LIV protocol induces specific growth factors during wound healing. Our findings demonstrate parameter-dependent effects of LIV for improving wound healing that can be exploited for future mechanistic and therapeutic studies.
A New Zebrafish Model for Pseudoxanthoma Elasticum
Authors: Czimer Dávid , Porok Klaudia , Csete Dániel , Gyüre Zsolt , Lavró Viktória , Fülöp Krisztina , Chen Zelin , Gyergyák Hella , Tusnády Gábor E. , Burgess Shawn M. , Mócsai Attila , Váradi András , Varga Máté
Published: March 2021

Calcification of various tissues is a significant health issue associated with aging, cancer and autoimmune diseases. There are both environmental and genetic factors behind this phenomenon and understanding them is essential for the development of efficient therapeutic approaches. Pseudoxanthoma elasticum (PXE) is a rare genetic disease, a prototype for calcification disorders, resulting from the dysfunction of ABCC6, a transport protein found in the membranes of cells. It is identified by excess calcification in a variety of tissues (e.g., eyes, skin, arteries) and currently it has no cure, known treatments target the symptoms only. Preclinical studies of PXE have been successful in mice, proving the usefulness of animal models for the study of the disease. Here, we present a new zebrafish (Danio rerio) model for PXE. By resolving some ambiguous assemblies in the zebrafish genome, we show that there are two functional and one non-functional paralogs for ABCC6 in zebrafish (abcc6a, abcc6b.1, and abcc6b.2, respectively). We created single and double mutants for the functional paralogs and characterized their calcification defects with a combination of techniques. Zebrafish deficient in abcc6a show defects in their vertebral calcification and also display ectopic calcification foci in their soft tissues. Our results also suggest that the impairment of abcc6b.1 does not affect this biological process.
Activation of AMPK Promotes Maturation of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells
Authors: Ye Liang , Zhang Xinyuan , Zhou Qin , Tan Bin , Xu Hao , Yi Qin , Yan Liang , Xie Min , Zhang Yin , Tian Jie , Zhu Jing
Published: March 2021

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (hiPSC-CMs) are a promising cell source for disease modeling, myocardial regeneration, and drug assessment. However, hiPSC-CMs have certain immature fetal CM-like properties that are different from the characteristics of adult CMs in several aspects, including cellular structure, mitochondrial function, and metabolism, thus limiting their applications. Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) is an energy-sensing protein kinase involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in cardiomyocytes. This study investigated the effects of AMPK on the maturation of hiPSC-CMs. Activation of AMPK in hiPSC-CMs significantly increased the expression of CM-specific markers and resulted in a more mature myocardial structure compared to that in the control cells. We found that activation of AMPK improved mitochondrial oxidative phosphorylation (OxPhos) and the oxygen consumption rate (OCR). Additionally, our data demonstrated that activation of AMPK increased mitochondrial fusion to promote the maturation of mitochondrial structure and function. Overall, activation of AMPK is an effective approach to promote hiPSC-CMs maturation, which may enhance the utility of hiPSC-CMs in clinical applications.
Posttranslational Modifications in Conserved Transcription Factors: A Survey of the TALE-Homeodomain Superclass in Human and Mouse
Authors: Reichlmeir Marina , Elias Lena , Schulte Dorothea
Published: March 2021

Transcription factors (TFs) guide effector proteins like chromatin-modifying or -remodeling enzymes to distinct sites in the genome and thereby fulfill important early steps in translating the genome’s sequence information into the production of proteins or functional RNAs. TFs of the same family are often highly conserved in evolution, raising the question of how proteins with seemingly similar structure and DNA-binding properties can exert physiologically distinct functions or respond to context-specific extracellular cues. A good example is the TALE superclass of homeodomain-containing proteins. All TALE-homeodomain proteins share a characteristic, 63-amino acid long homeodomain and bind to similar sequence motifs. Yet, they frequently fulfill non-redundant functions even in domains of co-expression and are subject to regulation by different signaling pathways. Here we provide an overview of posttranslational modifications that are associated with murine and human TALE-homeodomain proteins and discuss their possible importance for the biology of these TFs.
Modulated Start-Up Mode of Cancer Cell Migration Through Spinophilin-Tubular Networks
Authors: Hwang Soyoung , Lee Peter Chang-Whan , Shin Dong Min , Hong Jeong Hee
Published: March 2021

Spinophilin (SPL) is a multifunctional actin-binding scaffolding protein. Although increased research on SPL in cancer biology has revealed a tumor suppressive role, its modulation in cancer biology, and oncological relevance remains elusive. Thus, we determined the role of SPL in the modulation of the junctional network and cellular migration in A549 lung cancer cell line. Knockdown of SPL promoted cancer cell invasion in agarose spot and scratch wound assays. Attenuation of SPL expression also enhanced invadopodia, as revealed by enhanced vinculin spots, and enhanced sodium bicarbonate cotransporter NBC activity without enhancing membranous expression of NBCn1. Disruption of the tubular structure with nocodazole treatment revealed enhanced SPL expression and reduced NBC activity and A549 migration. SPL-mediated junctional modulation and tubular stability affected bicarbonate transporter activity in A549 cells. The junctional modulatory function of SPL in start-up migration, such as remodeling of tight junctions, enhanced invadopodia, and increased NBC activity, revealed here would support fundamental research and the development of an initial target against lung cancer cell migration.
Loss-of-Function Variants in the SYNPO2L Gene Are Associated With Atrial Fibrillation
Authors: Clausen Alexander Guldmann , Vad Oliver Bundgaard , Andersen Julie Husted , Olesen Morten Salling
Published: March 2021

Multiple genome-wide association studies (GWAS) have identified numerous loci associated with atrial fibrillation (AF). However, the genes driving these associations and how they contribute to the AF pathogenesis remains poorly understood. To identify genes likely to be driving the observed association, we searched the FinnGen study consisting of 12,859 AF cases and 73,341 controls for rare genetic variants predicted to cause loss-of-function. A specific splice site variant was found in the SYNPO2L gene, located in an AF associated locus on chromosome 10. This variant was associated with an increased risk of AF with a relatively high odds ratio of 3.5 (p = 9.9 × 10−8). SYNPO2L is an important gene involved in the structural development and function of the cardiac myocyte and our findings thus support the recent suggestions that AF can present as atrial cardiomyopathy.
Older Adults’ Engagement in Senior University Lectures and the Effect of Individual Motivations
Authors: Ackermann Tobias Peter , Seifert Alexander
Published: March 2021

Among older adults, engagement in education can potentially have positive effects on cognition and psychological well-being and can prevent social isolation. The aim of this study is to investigate the role of individual motivations specific to older learners that underlie the frequency of participation at a senior university and how health or socioeconomic dimensions may affect the possibilities for participation. With data on participants from the senior university program at the University of Zurich (N = 811), we show that greater individual motivations regarding different aspects of learning have an effect on the frequency of lecture attendance, while other life circumstances do not. However, the findings show that when different forms of motivation are compared, instrumental motivation—meaning that the intention to use the gained knowledge now or in the future is responsible for the participant’s learning aspirations—is the only motivation that significantly increases lecture attendance. Hence, we conclude that to increase people’s engagement in this specific form of education in later life and to intensify lecture attendance, these programs should meet participants expectations.
Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
Authors: Sun Boju , Hayashi Misa , Kudo Maya , Wu Lili , Qin Lingling , Gao Ming , Liu Tonghua
Published: March 2021

Background

Pre-clinical research studies have shown that Madecassoside (MA) has favorable therapeutic effects on arthritis, acne, vitiligo and other diseases. However, the effects of MA on obesity have not yet been studied. This study mainly aimed to investigate the effects of MA in protecting against obesity and its underlying mechanism in reducing obesity.

Methods

Obese diabetic KKay/TaJcl mice model was adopted to the study. The body weight of all animals was recorded daily, and the blood glucose, blood lipid, and serum aminotransferase levels were examined, respectively. The expression of P-AMPK, SIRT1, P-LKB1, P-ACC, and P-HSL in abdominal fat, mesenteric fat, and epididymal fat was measured by western blotting, and the levels of PPARα, CPT1a, PGC-1α, UCP-1, Cidea, Cox7a1, and Cox8b were examined by real-time quantitative PCR (RT-qPCR).

Results

The results revealed that the body weight of the mice in MA group was significantly reduced, and the body mass index (BMI) showed significant difference between the two groups after 8 weeks of MA treatment. Further research revealed that it affected the mesenteric fat and epididymis fat by activating SIRT1/AMPK signaling pathway, and then promoted fatty acid oxidation of epididymal fat (PPARα ↑, CPT1a↑, and PGC-1α↑). Last but not the least, it also promoted the expression of UCP-1 and stimulated thermoregulatory genes (Cidea, Cox7a1, and Cox8b) in brown fat and mesenteric fat.

Conclusions

Taken together, these findings suggest that MA can inhibit the weight gain in obese diabetic mice, and reduce triglyceride levels, inhibit lipogenesis of mesenteric fat, promote epididymal fat lipolysis and fatty acid oxidation. Furthermore, MA treatment might promote mesenteric fat browning and activate mitochondrial function in brown fat as well as mesenteric fat.
Sperm DNA Methylation at Metabolism-Related Genes in Vegan Subjects
Authors: Franzago Marica , Sabovic Iva , Franchi Sara , De Santo Maria , Di Nisio Andrea , Luddi Alice , Piomboni Paola , Vitacolonna Ester , Stuppia Liborio , Foresta Carlo
Published: March 2021

Objective

To investigate if epigenome of sperm cells could be dynamically affected by nutrition.

Design and Methods

We assessed 40 healthy volunteers with different dietary habits and collected their demographic characteristics, as well as clinical and anthropometric parameters. We compared methylation profiles in sperm quantified by bisulfite pyrosequencing, at promoter-associated CpG sites of genes involved in metabolism including fat mass and obesity-associated (FTO) and melanocortin-4 receptor (MC4R) from six vegans and 34 omnivores. In addition, the FTO rs9939609 (T>A) was genotyped.

Results

Higher DNA methylation levels were detected in the sperm of vegan at FTO gene CpG1 (p=0.02), CpG2 (p=0.001), CpG3 (p=0.004), and CpG4 (p=0.003) sites and at MC4R-CpG2 site [p=0.016] as compared to sperm of omnivores. This association was not related to FTO genotype.

Conclusions

Although limited by the small number of investigated cases, our data provide insight into the role of diet on sperm DNA methylation in genes involved in metabolism.
Habitat Partitioning in the Marine Sector of Karst Subterranean Estuaries and Bermuda's Marine Caves: Benthic Foraminiferal Evidence
Authors: Cresswell Jacquelyn N. , van Hengstum Peter J.
Published: March 2021

Karst subterranean estuaries (KSEs) are created from the two- and three-way mixing of saline groundwater, rain, and oceanic water in the subsurface on carbonate landscapes, and this hydrographic framework promotes unique physical processes, biogeochemical cycling, and biological communities. Here we provide evidence that the source and quantity of particulate organic matter (POM) that is delivered to the benthos strongly correlates to benthic habitat partitioning in the oxygenated marine sectors of KSEs. A dataset of benthic foraminifera at 128 different locations from several large flooded cave systems in Bermuda were compiled and evaluated against common environmental characteristics (e.g., tidal exposure, substrate particle size, bulk organic matter, C:N, total organic carbon, and δ13Corg). Benthic areas receiving more carbon isotopically depleted organic matter sources (mean δ13Corg values < −23.2‰, C:N ratios >11), most likely from the terrestrial surface and some marine plankton, were dominated by Trochammina inflata, Bolivina spp., and Helenina anderseni. In contrast, benthic areas receiving more carbon isotopically enriched organic matter sources (mean δ13Corg values > −21.6‰, C:N ratios <10), most likely from marine plankton transported through marine cave openings cave from adjacent coastal waters, were dominated by Spirophthalmidium emaciatum, Spirillina vivipara, Patellina corrugata, and Rotaliella arctica. The benthic foraminifera most distal from any cave entrances were dominated by taxa also known from the deep-sea (e.g., Rotaliella, Spirophthalmidium) in sediment with the lowest bulk organic matter content (mean: 6%), or taxa that prefer hard substrates and are potentially living attached to cave walls (Patellina, Spirillina). While physical groundwater characteristics (e.g., salinity, dissolved oxygen) are expected drivers of benthic ecosystems in KSEs, these results suggest that POM source, quantity, and delivery mechanisms (e.g., groundwater-seawater circulation mechanisms, terrestrial flux) play an important role in benthic habitat partitioning and the spatial variability of biogeochemical cycles in the oxygenated marine sector of KSEs.
Seasonal and Spatial Detection of Pesticide Residues Under Various Weather Conditions of Agricultural Areas of the Kilombero Valley Ramsar Site, Tanzania
Authors: Materu Silvia F. , Heise Susanne , Urban Brigitte
Published: March 2021

This study was conducted in the Kilombero Valley Ramsar Site (KVRS), the largest low-altitude freshwater wetland in East Africa to: 1) determine pesticide contamination of soil, water, and sediment at different seasonal weather conditions 2) critically analyze the seasonal and spatial ecological impacts of pesticide contaminations under tropical weather conditions 3) estimate the potential environmental risks from pesticide exposure based on analytical data. Surface sediments, soil and water samples were collected from sugarcane, teak and rice plantations of the KVRS during the dry (January 2012) and the rainy (March–April 2013) seasons. Samples were screened for 97 different types of pesticide residues using and LC–MS and HPLC–MS. Physical-chemical properties of the sediment and soil samples and meteorological data were analyzed. 92% of soil and sediment samples had relatively low OM content (<5%) while 60% of samples had high clay content, indicating high cation exchange capacity that can bind pesticides to the soils. Field soil and air temperature ranging 28–35°C, total sunshine hours-208 h/month, photo radiation −764 MJ/m2, average precipitation 300 mm/month, wind speed >60 km/h, humidity >80% were recorded. Frequency of detection and concentration of pesticides residues depended on seasons. For the dry season sampling, glyphosate/AMPA (0.01–0.55 µg/g), and diuron (0.026–1.7 µg/g) were mostly detected in the sediment and soils. Monuron (1.28–3.9 µg/L) and propoxur (0.05–0.6 µg/L) were mostly detected in the rainy seasons (water and sediments). Glyphosate was above limit of detection in the dry season water samples indicating that its emission into the water system may have been directly through application. Maximum diuron concentrations in water were >30 times higher than the estimated predicted no-effect concentration (PNEC) value (0.054 µg/L) indicating a risk to aquatic community. Calculated pore water concentrations (0.992–0.081 µg/L), exceeded the estimated PNEC values during the dry season, indicating a risk to benthic organisms. Detection of pesticide is influenced by application, environmental factors and the timing of sampling. Further research is recommended to increase our knowledge on soil-water-sediment interactions in the tropics with regard to pesticides.
YWHAG Mutations Cause Childhood Myoclonic Epilepsy and Febrile Seizures: Molecular Sub-regional Effect and Mechanism
Authors: Ye Xing-Guang , Liu Zhi-Gang , Wang Jie , Dai Jie-Min , Qiao Pei-Xiu , Gao Ping-Ming , Liao Wei-Ping
Published: March 2021

YWHAG, which encodes an adapter protein 14-3-3γ, is highly expressed in the brain and regulates a diverse range of cell signaling pathways. Previously, eight YWHAG mutations have been identified in patients with epileptic encephalopathy (EE). In this study, using trios-based whole exome sequencing, we identified two novel YWHAG mutations in two unrelated families with childhood myoclonic epilepsy and/or febrile seizures (FS). The identified mutations included a heterozygous truncating mutation (c.124C>T/p.Arg42Ter) and a de novo missense mutation (c.373A>G/p.Lys125Glu). The two probands experienced daily myoclonic seizures that were recorded with ictal generalized polyspike-slow waves, but became seizure-free with simple valproate treatment. The other affected individuals presented FS. The truncating mutation was identified in the family with six individuals of mild phenotype, suggesting that YWHAG mutations of haploinsufficiency are relatively less pathogenic. Analysis on all missense mutations showed that nine mutations were located within 14-3-3γ binding groove and another mutation was located at residues critical for dimerization, indicating a molecular sub-regional effect. Mutation Arg132Cys, which was identified recurrently in five patients with EE, would have the strongest influence on binding affinity. 14-3-3γ dimers supports target proteins activity. Thus, a heterozygous missense mutation would lead to majority dimers being mutants; whereas a heterozygous truncating mutation would lead to only decreasing the number of wild-type dimer, being one of the explanations for phenotypical variation. This study suggests that YWHAG is potentially a candidate pathogenic gene of childhood myoclonic epilepsy and FS. The spectrum of epilepsy caused by YWHAG mutations potentially range from mild myoclonic epilepsy and FS to severe EE.