bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluasi Jumlah Limfosit Pasca Aplikasi Lendir Bekicot (Achatina fulica) pada Soket Tikus Wistar (Rattus norvegicus)
Authors: Riyani Nadya Jeihan , Pasaribu Robisnson , Mardiyantoro Fredy
Published: April 2021

Pendahuluan: Peradangan merupakan respon dasar terhadap adanya kerusakan jaringan atau luka pasca pencabutan gigi yang kemudian dilanjutkan dengan proses penyembuhan. Lendir bekicot dari spesies Achatina fulica diketahui memiliki kemampuan sebagai alternatif obat yang mempercepat proses penyembuhan luka. Tujuan Penelitian: penelitian ini bertujuan menguji pengaruh lendir bekicot (Achatina fulica) terhadap jumlah limfosit pada proses penyembuhan luka soket gigi pasca pencabutan gigi tikus wistar (Rattus norvegicus). Bahan dan Metode: Penelitian ini menggunakan bahan utama berupa lendir bekicot  yang diaplikasikan pada soket gigi tikus. Sampel dipilih menggunakan teknik Simple Random Sampling kemudian dibagi ke dalam dua kelompok, yaitu kelompok kontrol (K) dan perlakuan (P). Variabel yang diteliti pada penelitian ini adalah jumlah limfosit pada hari ketiga, kelima, dan ketujuh proses penyembuhan luka soket gigi tikus wistar yang diukur dari sediaan HPA dengan pengecatan Hematoxylin-Eosin. Hasil: Hasil penelitian menunjukan adanya perbedaan jumlah limfosit pada hari ketiga, kelima, dan ketujuh baik pada kelompok kontrol (K) maupun perlakuan (P). Dengan jumlah rerata limfosit pada kelompok kontrol adalah 5,48 ; 4,60 ; 64,48. Sedangkan hasil rerata limfosit kelompok perlakuan adalah : 11,6; 16,52; 10,80. Kesimpulan : penelitian ini menunjukkan bahwa lendir bekicot (Achatina fulica) berpengaruh pada jumlah limfosit pada proses penyembuhan luka soket gigi tikus wistar (Rattus norvegicus).
A Segurança Comunitária e a Pandemia de COVID-19 | Community Safety and the COVID-19 Pandemic
Authors: Correia Eduardo Pereira , Claro Ricardo
Published: April 2021

This article analyses the community safety paradigm in the light of the current pandemic crisis caused by COVID-19. In full evolution, the analysis presented considers the current security and civil protection needs, in particular the security aspects of community security. Through the development of strategies involving security forces and services, the community and citizens, the authors demonstrate the practical importance of security municipalisation through local administrative police, evolving into an important regionalization of security. Similarly, community policing and proximity strategies are observed in accordance with public security policies that point to greater political awareness in security problematization.
ДОЦІЛЬНІСТЬ ЗАПРОВАДЖЕННЯ СПРОЩЕНИХ ПРОЦЕДУР НЕПЛАТОСПРОМОЖНОСТІ У ЗАКОНОДАВСТВІ ПРО БАНКРУТСТВО
Authors: Донков С. В.
Published: April 2021

У статті розглянуті та проаналізовані поняття «спрощена судова процедура» та «спрощений порядок судового розгляду», досліджено становлення зазначених правових інститутів у цивільному, господарському процесуальних блоках законодавства, а також їх розвиток у законодавстві про неплатоспроможність та банкрутство. Разом з тим надані характеристики суб’єктів господарювання, відносно яких застосовуються зазначені процедури. Особливу увагу приділено правовим механізмам реалізації спрощених процедур банкрутства, зазначені запобіжники процесуальних зловживань учасниками процедур неплатоспроможності, надані пропозиції щодо запровадження спрощених порядків розгляду процедур банкрутства відсутніх боржників та підприємств-боржників з нульовими активами.
ПРОЦЕДУРА ВИКОНАННЯ СУДОВИХ РІШЕНЬ ТА ФРАУДАТОРНІ ПРАВОЧИНИ
Authors: Драган О. В.
Published: April 2021

У статті аналізується чинне законодавство України щодо процедури виконання судових рішень. Окреслено існуючі проблемні питання та зазначається такий проблемний момент, як фраудаторні правочини. Вказані правочини укладаються боржником з метою запобігання зверненню стягнення на майно. Це призводить до того, що боржниками майно реалізується поза межами виконавчого провадження і, як наслідок, судові рішення залишаються невиконаними. В українському законодавстві регулюються тільки в певних сферах та автором вказуються закони, якими безпосередньо їх регламентовано. У статті наводяться правові висновки Великої Палати Верховного Суду з цього питання. Запропоновано у разі виявлення випадків відчуження відповідачами майна для уникнення виконання судових рішень вжиття додаткових заходів шляхом звернення до суду з позовними заявами про визнання відповідних правочинів недійсними.
АНТИКРИЗОВЕ ОПОДАТКУВАННЯ ПІД ЧАС КАРАНТИНУ: ПРАВОВИЙ АНАЛІЗ
Authors: Мацелик Т. О. , Стріяшко Г. М.
Published: April 2021

Стаття присвячена науковому аналізу антикризового оподаткування під час карантину. Впровадження протиепідеміологічних заходів обмежувального характеру вимагають негайного реагування та здійснення значних змін у національній системі оподаткування, яка повинна якомога швидше підлаштуватись під ситуацію, яка склалася шляхом врахування останніх змін і доповнень до чинного законодавства.
ОРГАНІЗАЦІЯ ТА ПРАВОВЕ РЕГУЛЮВАННЯ КОНТРОЛЮ ЯКОСТІ НАФТОПРОДУКТІВ ПІД ЧАС ЇХ ЗБЕРІГАННЯ У ДЕРЖАВНОМУ РЕЗЕРВІ
Authors: Новицький А. М. , Дем’янчук Є. В.
Published: April 2021

У статті розглядається організація та правове регулювання контролю якості нафтопродуктів, що зберігаються у державному резерві. Найважливішою частиною забезпечення нафтопродуктами є система контролю їх якості та її стале функціонування. Застосуванню високоякісних нафтопродуктів повинні передувати роботи щодо забезпечення збереження їх якості та правильного зберігання на підприємствах, а також організації контролю якості нафтопродуктів, які постачаються до державного резерву.
Antimicrobial Resistance in Typhoidal Salmonella in Nepal: Surveillance for Enteric Fever, 2016-2019
Authors: Shrestha Rajeev , Adhikari Navin , Pradhan Sailesh , Amatya Ritu , Shrestha Basudha , Khadka Dhruba Kumar , Roy Renu , Pradhan Rojika , Tamrakar Dipesh
Published: April 2021

Background: Enteric fever (caused by Salmonella enterica) has been associated with poor hygiene and is endemic in the South-Asian countries. The increase in resistance to first line antimicrobials has been observed, while the emergence of multi/extremely drug resistance cases have been identified in several countries. The objective of this study is to analyze the current trend of antimicrobial resistance in Salmonella isolates in Nepal, and to identify the status of multi- and extremely- drug resistant isolates.Methods: We recruited individuals at study hospitals with suspected enteric fever between September 2016 and August 2019 and performed blood cultures. The Salmonella isolates were tested for antimicrobial susceptibility and the antimicrobial resistance trend was evaluated.Results: 1438 positive blood culture isolates were studied for antimicrobial resistance. 88% were culture positive for Salmonella Typhi and 12% for Salmonella Paratyphi. Multidrug resistant S. Typhi cases appeared mostly in December 2018 and January 2019, while there were no multidrug resistant S. Paratyphi cases. Also, extremely drug resistant S. Typhi cases were not observed during the study period. Conclusions: The Salmonella isolates were mostly susceptible to first-line antimicrobials, cephalosporins and others. Many fluoroquinolones non-susceptible Salmonella were obtained, nevertheless their overall trend seems to be declining. In addition, the S. Paratyphi total cases are reducing since September 2017. Among S. Typhi isolates, only few were multidrug resistant and there were no extremely drug resistant isolates. Keywords: Antimicrobial resistance; enteric fever; multi-drug resistant; Nepal; Salmonella; typhoid
Arqueología del grafiti. Estratos del lienzo urbano
Authors: Casado Víctor Almirón
Published: April 2021

¿Es la arqueología del grafiti un elemento consolidado? ¿podrían utilizarse ciertas perspectivas derivadas de la arqueología tradicional como método de análisis en el arte urbano?. Puesto que es un tema poco abordado, se presenta muy interesante traerlo a debate, analizando la posibilidad de precisar un método que favorezca su comprensión y estudio.
Fen Eğitiminde İşbirlikli Öğrenme Kuramı, Buluş Yoluyla Öğrenme Stratejisi ve Yapılandırmacı Yaklaşım Basamaklarının Akademik Başarı Üzerinde Etkisinin Karşılaştırılması
Authors: AVGIN Sakine Serap , UYGUN Büşra
Published: April 2021

Araştırmanın amacı, işbirlikli öğrenme kuramı, buluş yoluyla öğrenme stratejisi ve yapılandırmacı yaklaşım kuramı basamaklarının bireylerin akademik başarılarına etkisinin karşılaştırılmasıdır. Araştırma; ön test-son test modeline uygun Kahramanmaraş ilinde, MEB’e bağlı okullarda bulunan 7. sınıf öğrencileriyle yarı deneysel bir çalışma olarak yapılmıştır. Akademik başarıları birbirine yakın olan dört grup seçilmiş ve bu dört grup içinden üç deney ve bir kontrol grubu atanmıştır. Kontrol grubuna geleneksel öğretim yöntemi uygulanmıştır. Deney grupları olarak, işbirlikli öğrenme kuramı, buluş yoluyla öğrenme stratejisi ve yapılandırmacı yaklaşım basamaklarının uygulanacağı üç grup seçilmiştir. Çalışma her bir deney grubuna 4 haftalık süre boyunca uygulanmıştır. Uygulamaların öncesi ve sonrasında her iki gruba da Fen Bilgisi Başarı Testi ön-test ve son-test olarak uygulanmıştır. Veriler bağımsız t testi ile değerlendirilmiştir. Elde edilen verilere göre yapılandırmacı yaklaşım basamaklarının kullanıldığı deney grubu ile kontrol grubu arasındaki p anlamlılık değeri 0,24, buluş yoluyla öğrenme stratejisinin kullanıldığı deney grubu ile kontrol grubu arasındaki p anlamlılık değeri 0,002, işbirlikli öğrenme kuramının kullanıldığı deney grubu ile kontrol grubu arasındaki p anlamlılık değeri 0,001 olarak bulunmuştur. P anlamlılık değerleri p<0,005 olan deney ve kontrol grupları arasında anlamlı farklılık bulunmaktadır. Akademik başarıları ve p anlamlılık değerleri karşılaştırıldığında en fazla başarı işbirlikli öğrenme kuramı uygulanan grupta görülmüştür ve bu doğrultuda önerilerde bulunulmuştur.
Ortaokul Öğrencilerinin Fen Bilimleri ve Matematik Dersine Katılım Düzeylerinin Belirlenmesi ve Çeşitli Değişkenler Açısından İncelenmesi
Authors: FIRAT Selçuk , AÇIKGÜL FIRAT Esra
Published: April 2021

Son yıllarda oldukça popüler olan STEM entegrasyonunun etkili bir şekilde yürütülmesi aşamasında öğrenci katılımı önem arz etmektedir. Çünkü öğrencilerin derse aktif katılımları STEM başarılarında kilit rol oynamaktadır. Bu nedenle öğrencilerin fen bilimleri ve matematik derslerine katılımlarının belirlenmesi önem arz etmektedir. Buradan hareketle bu çalışma ile ortaokul öğrencilerinin fen bilimleri ve matematik derslerine katılımlarını belirlemek ve bazı değişkenler açısından incelemek amaçlanmıştır. Araştırma, nicel araştırma yöntemlerinden tekil tarama ve nedensel-karşılaştırma araştırması kullanılarak yürütülmüştür. Araştırmada veri toplama aracı olarak Fen Bilimleri ve Matematik Derslerine Katılım Ölçeği kullanılmıştır. Bu ölçek öğrenci katılımını; duyuşsal katılım, bilişsel katılım, davranışsal katılım ve sosyal katılım boyutlarında çok boyutlu olarak ölçmektedir. Araştırmadan elde edilen sonuçlara göre ortaokul öğrencilerinin fen bilimleri ve matematik derslerine katılım düzeylerinin yüksek olduğu belirlenmiştir. Ayrıca hem fen bilimleri hem de matematik derslerinde öğrencilerin tüm boyutlarda katılım düzeylerinde cinsiyet açısından kızların lehine anlamlı bir farklılık olduğu belirlenmiştir. Araştırmadan elde edilen diğer bir sonuç ise sosyal katılım dışında tüm katılım boyutlarında proje tasarlama konusunda kendilerini yeterli gören öğrencilerin anlamlı bir şekilde katılımlarının görmeyen öğrencilere göre yüksek olduğu belirlenmiştir. Araştırmadan elde edilen sonuçlar doğrultusunda önerilerde bulunulmuştur.
Аналіз парку військової автомобільної техніки, яка потребуватиме відновлення рухомими засобами технічно обслуговування та ремонту
Authors: Dachkovsky Vladimir , Kondratiuk Igor
Published: April 2021

У статті проведено аналіз парку військової автомобільної техніки, яка знаходиться на озброєнні військових частин (підрозділів) Збройних Сил України, яка потребуватиме технічного обслуговування та ремонту рухомими засобами технічно обслуговування та ремонту в польових умовах під час ведення бойових дій. Проведений аналіз військової автомобільної техніки свідчить, що більшість новітніх зразків, які знаходяться на озброєнні у військових частинах (підрозділах) Збройних Сил України перебувають на гарантійному терміні експлуатації від виробника, який підходить до завершення або уже завершився. За результатами аналізу встановлено, що більшість зразків автомобільної техніки оснащені новітніми базовими шасі закордонних виробників, дизельними двигунами екологічного класу Євро IV, сучасними системами забезпечення, електроустаткуванням та контрольно-вимірювальними приладами нового покоління. Разом з цим, проведений аналіз основних несправностей новітніх зразків військової автомобільної техніки показав, що зразки військової автомобільної техніки в основному виходили з ладу через низьку якість окремих деталей та складових одиниць, незадовільний стан сировини або порушення технологічного процесу тощо. Крім того, враховуючи потребу в проведенні технічного обслуговування та ремонту військової автомобільної техніки визначено невідповідності у можливостях існуючих на озброєнні рухомих засобів відновлення. Визначено, що в основі формування рухомих засобів технічного обслуговування та ремонту з урахуванням завдань, які покладаються на ремонтно-відновлювальні підрозділи повинні лежати три основних принципи: базовий, який полягає в розробленні уніфікованої базової платформи; мобільний, який полягає у забезпеченні можливості транспортування різними видами транспорту; блочно-модульний, який полягає у комплектуванні сучасними засобами діагностики та спеціальним обладнанням для виконання специфічних завдань з технічного обслуговування та ремонту військової автомобільної техніки на різних рівнях ієрархії.
Impactos no perfil epidemiológico da Dengue em meio a Pandemia da COVID-19 em Sergipe
Authors: Nascimento Crysvânia Santos , Correia João Paulo Siqueira , Temóteo Camila Conceição Santos , Campos Andre Luiz Baião
Published: April 2021

A dengue é uma patologia viral aguda, sistêmica, única e autolimitada em sua forma clássica, transmitida por artrópodes. Entretanto, o ano de 2020, foi marcado pela pandemia do novo Coronavírus (COVID-19) e, verificou-se uma diminuição nos casos de doenças notificadas causadas por arboviroses quando contrastado com o mesmo período do ano de 2019. O presente trabalho tem como proposta convidar os profissionais de saúde  e comunidade em geral à reflexão sobre a importância da notificação busca e assistência a dengue no estado de Sergipe em meio a pandemia do novo coronavírus, a fim de demonstrar os altos níveis de subnotificação e ausência da procura por assistência que podem causar impactos na qualidade de vida da população geral. Trata-se de um estudo observacional transversal, com abordagem analítica quantitativa, com dados coletados de 2019-2020 através da análise de Boletins Epidemiológicos e notificações do SINAN (Sistema de Agravos e Notificações) e SIM (Sistema de Informação de Mortalidade). Os dados obtidos mostraram que houve uma redução, comparando-se os anos 2019-2020, de 5164 casos notificados em 2019 para 959 casos (18,5 % do primeiro) em 2020, nas notificações nos casos de Dengue no período estudado da semana epidemiológica 12-30. As informações citadas mostraram que, provavelmente, os esforços direcionados a contenção da nova entidade emergente, COVID-19, dificultaram as notificações e os diagnósticos efetivos da patologia citada.
Prospecção científica e tecnológica do uso da vibração focal em comprometimentos motores em decorrência de patologias neurológicas
Authors: Pereira Tassiane Maria Alves , Siqueira Jéssica Inara de Brito , Nascimento Lucas da Silva , Almeida Cassio Costa , Orsini Marco , Silva Janaína de Moraes , Rocha Jefferson Almeida , Bastos Victor Hugo do Vale
Published: April 2021

O Brasil apresenta uma prevalência de 1,3 % deficientes físicos. No que tange os comprometimentos físicos relacionados a patologias neurológicas, estes geram incapacidade funcional em todo o mundo. Dessa forma, este trabalho teve como objetivo a realização da prospecção científica e tecnológica de pesquisas sobre uso da vibração focal associada a dispositivos móveis vestíveis em indivíduos com comprometimentos motores decorrentes de patologias neurológicas.  Na busca por patentes foram usadas as bases: Espacenet, INPI, USPTO e Web of Science; e os artigos nas bases: Scielo, Scopus, Science Diretc, Web of Science, Pubmed, de 1967 até 2020. Os resultados da busca por patentes no contexto mencionado foram negativos, e em relação aos artigos, obteve-se resultados significativos com 667 publicações no Science Diretc com pico de publicação no ano de 2018. Observou-se então, que novos estudos devem ser realizados para fomentar as propriedades e eficácia da vibração focal, e promover incentivos ao desenvolvimento e produções tecnológicas e científicas.
BAG2-Mediated Inhibition of CHIP Expression and Overexpression of MDM2 Contribute to the Initiation of Endometriosis by Modulating Estrogen Receptor Status
Authors: Chen Li-Juan , Hu Bin , Han Zhi-Qiang , Zhu Jian-Hua , Fan Xu , Chen Xue-Xing , Li Zi-Ping , Zhou Hao
Published: April 2021

Endometriosis is an estrogen-dependent gynecological disease primarily affecting women of childbearing age, which gives rise to pelvic pain calling for multiple operations, and sometimes leading to infertility. However, the etiology of endometriosis remains poorly understood. In this study we investigated the roles of two Ubiquitin E3 Ligases, namely hsc70-interacting protein (CHIP) and mouse double minute 2 (MDM2), in the abnormal estrogenic activity in endometriosis. We first collected endometrial tissues from 91 cases of endometriosis and 78 cases of uterine myomas. Next, we established a murine endometriosis model by ectopic endometrial tissue implantation. In other studies, we isolated human endometrial stromal cells (HESCs) were isolated from the endometrial tissues, and performed HA- or FLAG-immunoprecipitation assays and immunoblotting with an anti-ubiquitin antibody to test the interactions among BAG2, CHIP, MDM2, estrogen receptor α (ERα), and ERβ. The expression of ERα was downregulated while that of ERβ, BAG2, and MDM2 was upregulated in human endometriosis and in the mouse model. CHIP degraded ERβ instead of ERα via the ubiquitin-proteasome pathway, while BAG2 impaired the CHIP-mediated degradation of ERβ in cultured HESCs derived from human endometriosis. The degradation of ERα by MDM2 in cultured endometriosis-HESCs also occurred through the ubiquitin-proteasome pathway. Knockdown of both BAG2 and MDM2 alleviated the development of endometriosis in mice. Our findings suggest that the interference of BAG2 and MDM2 may have therapeutic effects in endometriosis. Understanding better the molecular mechanisms underlying the regulation of the abnormal estrogenic activity in endometriosis is crucial for the advancement of targeted therapeutic strategies.
Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta
Authors: Zhao Lu , Liu Dan , Ma Wei , Gu Hui , Wei Xiaowei , Luo Wenting , Yuan Zhengwei
Published: April 2021

Neural tube defects (NTDs) are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying molecular mechanisms remain elusive. Mitophagy is the best-known way of mitochondrial quality control. However, the role and regulation of mitophagy in NTDs have not yet been elucidated. In this study, we used an all-trans retinoic acid (ATRA)-induced rat model to investigate mitophagy and its underlying mechanism in spina bifida aperta (SBA). The results of western blot, immunofluorescence and RT-qPCR analyses indicated that mitophagy was impaired and Sirt1 was downregulated in SBA. Administration of resveratrol-a strong specific Sirt1 activator-activated Sirt1, thus attenuating autophagy suppression and ameliorating SBA. RNA-sequencing and bioinformatics analysis results indicated that transcriptional regulation played an important role in NTDs. A luciferase reporter assay was performed to demonstrate that the transcription factor Bhlhe40 directly bound to and negatively regulated Sirt1 expression. Further, we discovered that the Bhlhe40/Sirt1 axis regulated mitophagy in neural stem cells. Collectively, our results for the first time demonstrate that Bhlhe40/Sirt1 axis regulated mitophagy is implicated in ATRA-induced SBA. Our findings provide new insights into pathogenesis of NTDs and a basis for potential therapeutic targets for NTDs.
Neurorepair and Regeneration of the Brain: A Decade of Bioscaffolds and Engineered Microtissue
Authors: Zamproni Laura N. , Mundim Mayara T. V. V. , Porcionatto Marimelia A.
Published: April 2021

Graphical Abstract

Bioscaffolds potential applications in tissue engineering. Bioscaffolds can be used to grow stem cells and target their differentiationin vitro(upper, left)or be used as stem cell delivery route in a brain injury(upper, right). Bioscaffolds can also contain si/miRNAs that will modify locally neural cells gene expression(lower, left)or contain exosomes/growth factors for paracrine signaling such as stimulating neurogenesis and increase neural stem migration to injury area(lower, right). This cover has been designed using resources created by Vitaly Gorbachev fromFlaticon.com.
Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η
Authors: Liu Jiarui , Han Yang , Hu Shunfeng , Cai Yiqing , Yang Juan , Ren Shuai , Zhao Yi , Lu Tiange , Zhou Xiangxiang , Wang Xin
Published: April 2021

Exosomes, nanometer-sized membranous vesicles in body fluids, have emerged as promising non-invasive biomarkers for cancer diagnosis. However, the function of exosomes in diffuse large B-cell lymphoma (DLBCL) remains elusive. This study aimed to investigate the role of exosomal miR-107 in lymphomagenesis and explore its clinical significance. In this study, decreased exosomal miR-107, miR-375-3p, and upregulated exosomal miR-485-3p were detected in the plasma of DLBCL patients and showed potential diagnostic value. Downregulated miR-107 expression was associated with advanced Ann Arbor stage, high IPI score, LDH, and β2-MG level in DLBCL patients. Overexpression of miR-107 by miR-107 Agomir significantly abrogated cell proliferation, induced apoptosis, and inhibited cell invasion in vitro, and repressed tumor growth in vivo. Moreover, the downregulation of miR-107 went in the opposite direction. The target genes of miR-107 were mainly enriched in the PI3K-Akt, Hippo, and AMPK signaling pathways. Notably, upregulated 14-3-3η (YWHAH) was suppressed by miR-107 in DLBCL, suggesting that miR-107 may restrain tumorigenesis by targeting 14-3-3η. In summary, this study unveils the function of miR-107 in lymphomagenesis, highlighting its potential as a diagnostic and prognostic indicator and as a new therapeutic target in the management of DLBCL.
Systematic in silico Evaluation of Leishmania spp. Proteomes for Drug Discovery
Authors: dos Santos Vasconcelos Crhisllane Rafaele , Rezende Antonio Mauro
Published: April 2021

Leishmaniasis is a group of neglected infectious diseases, with approximately 1. 3 million new cases each year, for which the available therapies have serious limitations. Therefore, it is extremely important to apply efficient and low-cost methods capable of selecting the best therapeutic targets to speed up the development of new therapies against those diseases. Thus, we propose the use of integrated computational methods capable of evaluating the druggability of the predicted proteomes of Leishmania braziliensis and Leishmania infantum, species responsible for the different clinical manifestations of leishmaniasis in Brazil. The protein members of those proteomes were assessed based on their structural, chemical, and functional contexts applying methods that integrate data on molecular function, biological processes, subcellular localization, drug binding sites, druggability, and gene expression. These data were compared to those extracted from already known drug targets (BindingDB targets), which made it possible to evaluate Leishmania proteomes for their biological relevance and treatability. Through this methodology, we identified more than 100 proteins of each Leishmania species with druggability characteristics, and potential interaction with available drugs. Among those, 31 and 37 proteins of L. braziliensis and L. infantum, respectively, have never been tested as drug targets, and they have shown evidence of gene expression in the evolutionary stage of pharmacological interest. Also, some of those Leishmania targets showed an alignment similarity of <50% when compared to the human proteome, making these proteins pharmacologically attractive, as they present a reduced risk of side effects. The methodology used in this study also allowed the evaluation of opportunities for the repurposing of compounds as anti-leishmaniasis drugs, inferring potential interaction between Leishmania proteins and ~1,000 compounds, of which only 15 have already been tested as a treatment for leishmaniasis. Besides, a list of potential Leishmania targets to be tested using drugs described at BindingDB, such as the potential interaction of the DEAD box RNA helicase, TRYR, and PEPCK proteins with the Staurosporine compound, was made available to the public.
Quantification of Local Electric Field Changes at the Active Site of Cytochrome c Oxidase by Fourier Transform Infrared Spectroelectrochemical Titrations
Authors: Baserga Federico , Dragelj Jovan , Kozuch Jacek , Mohrmann Hendrik , Knapp Ernst-Walter , Stripp Sven T. , Heberle Joachim
Published: April 2021

Cytochrome c oxidase (CcO) is a transmembrane protein complex that reduces molecular oxygen to water while translocating protons across the mitochondrial membrane. Changes in the redox states of its cofactors trigger both O2 reduction and vectorial proton transfer, which includes a proton-loading site, yet unidentified. In this work, we exploited carbon monoxide (CO) as a vibrational Stark effect (VSE) probe at the binuclear center of CcO from Rhodobacter sphaeroides. The CO stretching frequency was monitored as a function of the electrical potential, using Fourier transform infrared (FTIR) absorption spectroelectrochemistry. We observed three different redox states (R4CO, R2CO, and O), determined their midpoint potential, and compared the resulting electric field to electrostatic calculations. A change in the local electric field strength of +2.9 MV/cm was derived, which was induced by the redox transition from R4CO to R2CO. We performed potential jump experiments to accumulate the R2CO and R4CO species and studied the FTIR difference spectra in the protein fingerprint region. The comparison of the experimental and computational results reveals that the key glutamic acid residue E286 is protonated in the observed states, and that its hydrogen-bonding environment is disturbed upon the redox transition of heme a3. Our experiments also suggest propionate A of heme a3 changing its protonation state in concert with the redox state of a second cofactor, heme a. This supports the role of propionic acid side chains as part of the proton-loading site.
Development and Preliminary Application of Multiplex Loop-Mediated Isothermal Amplification Coupled With Lateral Flow Biosensor for Detection of Mycobacterium tuberculosis Complex
Authors: Wang Xingyun , Wang Guirong , Wang Yacui , Quan Shuting , Qi Hui , Sun Lin , Shen Chen , Huang Hairong , Jiao Weiwei , Shen Adong
Published: April 2021

The aim of this study was to develop a simple and reliable method to detect Mycobacterium tuberculosis complex (MTBC) and verify its clinical application preliminarily. A loop-mediated isothermal amplification method coupled with lateral flow biosensor (LAMP-LFB) assay, was developed and evaluated for detection of MTBC. Two sets of primers, which targeted IS6110 and IS1081 sequences of MTBC, were designed for establishment of multiplex LAMP-LFB assay. The amplicons were labelled with biotin and fluorescein isothiocyanate (FITC) by adding FITC labelled primer and biotin-14-dATP and biotin-14-dCTP and could be visualized using LFB. The optimal reaction conditions of multiplex LAMP-LFB assay confirmed were 66°C for 50 min. The analytical sensitivity of multiplex LAMP-LFB is 10 fg of genomic templates using pure culture, and no cross-reactivity with other common bacteria and non-tuberculous mycobacteria strains was obtained. A total of 143 clinical samples collected from 100 TB patients (62 definite TB cases and 38 probable TB cases) and 43 non-TB patients were used for evaluating the feasibility of multiplex LAMP-LFB assay. The multiplex LAMP-LFB (82.0%, 82/100) showed higher sensitivity than culture (47.0%, 47/100, P < 0.001) and Xpert MTB/RIF (54.0%, 54/100, P < 0.001). Importantly, the multiplex LAMP-LFB assay detected additional 28 probable TB cases, which increased the percentage of definite TB cases from 62.0% (62/100) to 90.0% (90/100). The specificity of multiplex LAMP-LFB assay in patients without TB was 97.7% (42/43). Therefore, multiplex LAMP-LFB assay is a simple, reliable, and sensitive method for MTBC detection, especially in probable TB cases and resource limited settings.
Effects of Cardiotoxins on Cardiac Stem and Progenitor Cell Populations
Authors: Smith Andrew J.
Published: April 2021

As research and understanding of the cardiotoxic side-effects of anticancer therapy expands further and the affected patient population grows, notably the long-term survivors of childhood cancers, it is important to consider the full range of myocardial cell types affected. While the direct impacts of these toxins on cardiac myocytes constitute the most immediate damage, over the longer term, the myocardial ability to repair, or adapt to this damage becomes an ever greater component of the disease phenotype. One aspect is the potential for endogenous myocardial repair and renewal and how this may be limited by cardiotoxins depleting the cells that contribute to these processes. Clear evidence exists of new cardiomyocyte formation in adult human myocardium, along with the identification in the myocardium of endogenous stem/progenitor cell populations with pro-regenerative properties. Any effects of cardiotoxins on either of these processes will worsen long-term prognosis. While the role of cardiac stem/progenitor cells in cardiomyocyte renewal appears at best limited (although with stronger evidence of this process in response to diffuse cardiomyocyte loss), there are strong indications of a pro-regenerative function through the support of injured cell survival. A number of recent studies have identified detrimental impacts of anticancer therapies on cardiac stem/progenitor cells, with negative effects seen from both long-established chemotherapy agents such as, doxorubicin and from newer, less overtly cardiotoxic agents such as tyrosine kinase inhibitors. Damaging impacts are seen both directly, on cell numbers and viability, but also on these cells' ability to maintain the myocardium through generation of pro-survival secretome and differentiated cells. We here present a review of the identified impacts of cardiotoxins on cardiac stem and progenitor cells, considered in the context of the likely role played by these cells in the maintenance of myocardial tissue homeostasis.
Practices of Professional Learning Communities
Authors: Antinluoma Markku , Ilomäki Liisa , Toom Auli
Published: April 2021

Building professional learning communities (PLC) has become a widely recognized strategy for school development and for student achievement. Four Finnish comprehensive schools were identified as being ready to be PLCs in a previous quantitative study, and the purpose of this study was to investigate practices of PLCs in these schools. In this paper, we used data from qualitative multiple-case study, which investigated practices of leadership, culture, teacher collaboration, professional learning, and development. The results showed that the principals had played the main role in the progression of schools as PLCs. Principals were described as visionary leaders who had started positive progression, shared the leadership, and created commitment to common goals. The results indicated also that a change of leaders can have a positive effect. Decision-making processes were participative, inclusive, democratic, and collaborative, aiming for a satisfactory level of consensus. Relationships among staff were reported as being based on mutual trust and openness, and members were encouraged to express their opinions. Common responsibility of students, peer support, encouragement, and co-teaching were practiced. Co-teaching practices were identified as an effective form of collaborative work-embedded professional learning which is related to the core principles of professional learning communities. Structural conditions were reported as barriers to schools’ development as PLCs.
Teachers’ Perspectives on Achieving an Integrated Curricular Model of Primary STEM Education in Ireland: Authentic or Utopian Ideology?
Authors: Delahunty Thomas , Prendergast Mark , Ní Ríordáin Máire
Published: April 2021

Integrative science, technology, engineering and mathematics (STEM) education is heralded as a promising model for effective learning of 21st century STEM literacies and has been suggested as an approach that increases student motivation and engagement. In recent years Ireland has introduced policy with a renewed emphasis on integrated STEM education across all levels of schooling and paying particular attention to the early years and primary settings. The available international literature cites many concerns with potential barriers and failures to achieve authentic integration of the various STEM disciplines in educational contexts. An important determinant of the success of integrated STEM curricula are the backgrounds and attitudes of the individual teachers, as well as supports/experiences in designing and implementing an integrated curricular approach. In the Irish context, this is often in conflict with prescribed overloaded curricula and a subject focussed education system. Therefore, research is required into primary school teachers’ perspectives on achieving a truly integrated model of STEM education, particularly in the Irish context. This study employed a qualitative approach using semi-structured interviews with a sample of practicing teachers (N= 6) to gather perspectives on the potential and challenge of integrating STEM in their respective experiences. These teachers were enrolled in a practice orientated module on STEM education as part of their postgraduate studies. The data gathered was analysed to ascertain these teachers’ perspectives on the supports needed to overcome the challenges of integrating STEM subjects within their professional settings. Essentially, the findings of this study will discuss whether such an integrated STEM model is an authentic or utopian ideology.
The Role of O-GlcNAcylation in Immune Cell Activation
Authors: Qiang Amy , Slawson Chad , Fields Patrick E.
Published: April 2021

O-GlcNAcylation is a dynamic post-translational modification where the sugar, O-linked β-N-acetylglucosamine (O-GlcNAc) is added to or removed from various cytoplasmic, nuclear, and mitochondrial proteins. This modification is regulated by only two enzymes: O-GlcNAc transferase (OGT), which adds O-GlcNAc, and O-GlcNAcase (OGA), which removes the sugar from proteins. O-GlcNAcylation is integral to maintaining normal cellular function, especially in processes such as nutrient sensing, metabolism, transcription, and growth and development of the cell. Aberrant O-GlcNAcylation has been associated with a number of pathological conditions, including, neurodegenerative diseases, cancer, diabetes, and obesity. However, the role of O-GlcNAcylation in immune cell growth/proliferation, or other immune responses, is currently incompletely understood. In this review, we highlight the effects of O-GlcNAcylation on certain cells of the immune system, especially those involved in pro-inflammatory responses associated with diabetes and obesity.
ADP Induces Blood Glucose Through Direct and Indirect Mechanisms in Promotion of Hepatic Gluconeogenesis by Elevation of NADH
Authors: Cao Xinyu , Ye Xiaotong , Zhang Shuang , Wang Li , Xu Yanhong , Peng Shiqiao , Zhou Yang , Peng Yue , Li Junhua , Zhang Xiaoying , Han Xiao , Huang Wen-ying , Jia Weiping , Ye Jianping
Published: April 2021

Extracellular ADP, a derivative of ATP, interacts with the purinergic receptors in the cell membrane to regulate cellular activities. This signaling pathway remains unknown in the regulation of blood glucose in vivo. We investigated the acute activity of ADP in mice through a peritoneal injection. In the lean mice, in response to the ADP treatment, the blood glucose was elevated, and pyruvate tolerance was impaired. Hepatic gluconeogenesis was enhanced with elevated expression of glucogenic genes (G6pase and Pck1) in the liver. An elevation was observed in NADH, cAMP, AMP, GMP and citrate in the liver tissue in the targeted metabolomics assay. In the primary hepatocytes, ADP activated the cAMP/PKA/CREB signaling pathway, which was blocked by the antagonist (2211) of the ADP receptor P2Y13. In the circulation, gluconeogenic hormones including glucagon and corticosterone were elevated by ADP. Insulin and thyroid hormones (T3 and T4) were not altered in the blood. In the diet-induced obese (DIO) mice, NADH was elevated in the liver tissue to match the hepatic insulin resistance. Insulin resistance was intensified by ADP for further impairment in insulin tolerance. These data suggest that ADP induced the blood glucose through direct and indirect actions in liver. One of the potential pathways involves activation of the P2Y13/cAMP/PKA/CREB signaling pathway in hepatocytes and the indirect pathway may involve induction of the gluconeogenic hormones. NADH is a signal for gluconeogenesis in the liver of both DIO mice and lean mice.
The Effect of Technology Innovation on Corporate Sustainability in Chinese Renewable Energy Companies
Authors: Wang Pei , Zhang Zijin , Zeng Yeli , Yang Shucheng , Tang Xu
Published: April 2021

Technology innovation has become the main driving force of China’s economic growth. Sustainable development highlights the harmonious symbiosis of the economy and the ecological environment. Renewable energy companies characterized by technology-intensive and environmental friendliness are playing an increasingly important role in achieving economic development while alleviating environmental pressure. Therefore, this paper selects the A-share renewable energy listed companies in China between 2014 and 2019 as samples, using the fixed-effect model and the logit model to explore the effect of technology innovation on corporate sustainability. We find that technology innovation has a positive effect on both financial sustainability (FS) and social and environmental sustainability (SES). Due to the imbalance of regional social and environmental development and different degrees of emphasis placed on environmental and social responsibility, the positive impact of technology innovation on SES is heterogeneous between the east and the central and west regions. Moreover, as the strategic emerging industry, although the renewable energy industry is granted lots of subsidies from the government, the results show that when government subsidies exceed the threshold, the effect of technology innovation on FS is weakened. Government subsidies have a negative moderating effect on the relationship between innovation and SES. Furthermore, we subdivide government subsidies into government subsidies beforehand (GSB) and government subsidies afterwards (GSA). We reveal that the threshold effect of government subsidies mainly comes from GSA, while the moderating effect of government subsidies is caused by GSA and GSB. This paper is an expansion and enrichment of current studies on sustainable development and also puts forward feasible suggestions for the government to formulate precise and effective subsidy policies to stimulate technology innovation.
Dark Reduction Drives Evasion of Mercury From the Ocean
Authors: Lamborg Carl H. , Hansel Colleen M. , Bowman Katlin L. , Voelker Bettina M. , Marsico Ryan M. , Oldham Veronique E. , Swarr Gretchen J. , Zhang Tong , Ganguli Priya M.
Published: April 2021

Much of the surface water of the ocean is supersaturated in elemental mercury (Hg0) with respect to the atmosphere, leading to sea-to-air transfer or evasion. This flux is large, and nearly balances inputs from the atmosphere, rivers and hydrothermal vents. While the photochemical production of Hg0 from ionic and methylated mercury is reasonably well-studied and can produce Hg0 at fairly high rates, there is also abundant Hg0 in aphotic waters, indicating that other important formation pathways exist. Here, we present results of gross reduction rate measurements, depth profiles and diel cycling studies to argue that dark reduction of Hg2+ is also capable of sustaining Hg0 concentrations in the open ocean mixed layer. In locations where vertical mixing is deep enough relative to the vertical penetration of UV-B and photosynthetically active radiation (the principal forms of light involved in abiotic and biotic Hg photoreduction), dark reduction will contribute the majority of Hg0 produced in the surface ocean mixed layer. Our measurements and modeling suggest that these conditions are met nearly everywhere except at high latitudes during local summer. Furthermore, the residence time of Hg0 in the mixed layer with respect to evasion is longer than that of redox, a situation that allows dark reduction-oxidation to effectively set the steady-state ratio of Hg0 to Hg2+ in surface waters. The nature of these dark redox reactions in the ocean was not resolved by this study, but our experiments suggest a likely mechanism or mechanisms involving enzymes and/or important redox agents such as reactive oxygen species and manganese (III).
Temporal Non-stationarity of Path-Selection Movement Models and Connectivity: An Example of African Elephants in Kruger National Park
Authors: Kaszta Żaneta , Cushman Samuel A. , Slotow Rob
Published: April 2021

Effective conservation and land management require robust understanding of how landscape features spatially and temporally affect population distribution, abundance and connectivity. This is especially important for keystone species known to shape ecosystems, such as the African elephant (Loxodonta africana). This work investigates monthly patterns of elephant movement and connectivity in Kruger National Park (KNP; South Africa), and their temporal relationship with landscape features over a 12-month period associated with the occurrence of a severe drought. Based on elephant locations from GPS collars with a short acquisition interval, we explored the monthly patterns of spatial-autocorrelation of elephant movement using Mantel correlograms, and we developed scale-optimized monthly path-selection movement and resistant kernel connectivity models. Our results showed high variability in patterns of autocorrelation in elephant movements across individuals and months, with a preponderance of directional movement, which we believe is related to drought induced range shifts. We also found high non-stationarity of monthly movement and connectivity models; most models exhibited qualitative similarity in the general nature of the predicted ecological relationships, but large quantitative differences in predicted landscape resistance and connectivity across the year. This suggests high variation in space-utilization and temporal shifts of core habitat areas for elephants in KNP. Even during extreme drought, rainfall itself was not a strong driver of elephant movement; elephant movements, instead, were strongly driven by selection for green vegetation and areas near waterholes and small rivers. Our findings highlight a potentially serious problem in using movement models from a particular temporal snapshot to infer general landscape effects on movement. Conservation and management strategies focusing only on certain areas identified by temporarily idiosyncratic models might not be appropriate or efficient as a guide for allocating scarce resources for management or for understanding general ecological relationships.
Morphological Changes in the Mandibles Accompany the Defensive Behavior of Indiana Mite Biting Honey Bees Against Varroa Destructor
Authors: Smith Jada , Cleare Xaryn L. , Given Krispn , Li-Byarlay Hongmei
Published: April 2021

The honey bee (Apis mellifera) is the most important managed pollinator to sustainable agriculture and our ecosystem. Yet managed honey bee colonies in the United States experience 30–40% losses annually. Among the many biotic stressors, the parasitic mite Varroa destructor is considered one of the main causes of colony losses. Bees’ mite-biting behavior has been selected as a Varroa-tolerant or Varroa-resistant trait in the state of Indiana for more than a decade. A survey of damaged mites from the bottom of a colony can be used as an extended phenotype to evaluate the mite-biting behavior of a colony. In this study, on average, 37% of mites sampled from the breeding stocks of 59 colonies of mite biters in Indiana were damaged or mutilated, which is significantly higher than the 19% of damaged mites found in commercial colonies in the southern United States. Indiana mite biter colonies had a higher proportion of damaged mites, although among the damaged mites, the number of missing legs was not significantly higher. In addition, the morphology of pollen-forager worker bee mandibles was compared by X-ray microcomputed tomography for six parameters in two populations, and a difference was detected in one parameter. Our results provide scientific evidence that potentially explains the defensive mechanism against Varroa mites: structural changes in the worker bee mandibles.
Paralogs in the PKA Regulon Traveled Different Evolutionary Routes to Divergent Expression in Budding Yeast
Authors: Heineike Benjamin M. , El-Samad Hana
Published: April 2021

Functional divergence of duplicate genes, or paralogs, is an important driver of novelty in evolution. In the model yeast Saccharomyces cerevisiae, there are 547 paralog gene pairs that survive from an interspecies Whole Genome Hybridization (WGH) that occurred ~100MYA. In this work, we report that ~1/6th (110) of these WGH paralogs pairs (or ohnologs) are differentially expressed with a striking pattern upon Protein Kinase A (PKA) inhibition. One member of each pair in this group has low basal expression that increases upon PKA inhibition, while the other has moderate and unchanging expression. For these genes, expression of orthologs upon PKA inhibition in the non-WGH species Kluyveromyces lactis and for PKA-related stresses in other budding yeasts shows unchanging expression, suggesting that lack of responsiveness to PKA was likely the typical ancestral phenotype prior to duplication. Promoter sequence analysis across related budding yeast species further revealed that the subsequent emergence of PKA-dependence took different evolutionary routes. In some examples, regulation by PKA and differential expression appears to have arisen following the WGH, while in others, regulation by PKA appears to have arisen in one of the two parental lineages prior to the WGH. More broadly, our results illustrate the unique opportunities presented by a WGH event for generating functional divergence by bringing together two parental lineages with separately evolved regulation into one species. We propose that functional divergence of two ohnologs can be facilitated through such regulatory divergence.