bluuebunny/crossref_metadata_2025 huggingface dataset:
Propuesta de reintegración de productos autóctonos en la canasta básica: caso tortillas de zapallo
Authors: Ríos-Mariño Marcelo , Herrera-Caicedo Ana , Cajas-Cajas Viviana , Jijón-Argüello Washington
Published: March 2021

Las personas cada día están más preocupadas por su nutrición sin embargo, a la vez disponen de poco tiempo para la preparación de alimentos saludables para su consumo diario, es por eso que se ofrece un producto nuevo en el mercado siendo éste las Tortitas Kürbis que son tortillas de zapallo, el cual es un producto autóctono con alto nivel nutritivo y que ofrece un sin número de beneficios para la salud, entre ellos: ayuda a la digestión, aumenta el nivel de energía, previene la anemia, ayuda a la hipertensión y mejora el cuidado de la piel. La investigación de carácter descriptivo se enfoca en Parroquias Urbanas de la Administración Zonal Eugenio Espejo del D.M. de Quito, para la cual se utilizó la técnica de la encuesta. El estudio de mercado demuestra que existe una demanda insatisfecha frente a una oferta indirecta; además, se establece que el precio del paquete de 10 unidades más accesible para el consumidor potencial es de $ 1,50. Por otro lado, se hace un análisis de las fortalezas, debilidades, oportunidades y amenazas del cual se desprende la matriz de estrategias. Se concluye demostrando  la factibilidad comercial del producto y se plantea a futuro continuar con el estudio económico.
Improving Students’ Vocabulary Mastery Through Bingo Games
Authors: Rahmasari Brigitta Septarini
Published: March 2021

This research was aimed to improve the vocabulary mastery of students through Bingo Game. This research was an action research study. The place of the research was at SDK Petra Madiun, East Java, Indonesia. The subject of the research was fourth grade students of SDK Petra Madiun, consisting 30 students. It was done in two cycles. The researcher did some steps for each cycle. They were planning, action, observation, and reflection. The data were collected by using test, observation, and interview. Furthermore, the data were analyzed by using descriptive statistics. It was compared between the scores of pre test (before implementing Bingo game) and post test (after implementing Bingo game). The research findings showed that vocabulary mastery of most students improved after Bingo Game was used in the teaching and learning process. It was indicated by the increase of the mean of students’ vocabulary score in the pre-test and post-test (67.22 to 80.57). The students’ involvement and classroom interaction during the implementation of the game improved. It was showed by students’ enthusiasm during the game. They tried to be the first winner and raised their competitiveness among them. In addition, the implementation of Bingo Game and the complementary actions were successful to help the students memorize and understand new words easily. In conclusion, the students’ vocabulary mastery improved through the implementation of Bingo Game.
KORONAVİRÜS (COVID-19) SÜRECİNDE İLAHİYAT ALANINDA LİSANSÜSTÜ EĞİTİM GÖREN ÖĞRENCİLERİN UZAKTAN EĞİTİME BAKIŞLARI
Authors: GENÇ Muhammet Fatih , AY Mustafa Fatih , GÜMRÜKÇÜOĞLU Süleyman
Published: March 2021

Çalışmanın temel amacı İlahiyat alanında lisansüstü eğitim gören öğrencilerin Covid-19 pandemi sürecine ve bu süreçteki eğitim öğretim uygulamalarına ilişkin görüşlerini incelemektir. Çalışma karma yöntem araştırmalarından yakınsayan paralel desene uygun olarak tasarlanmıştır. Bu çerçevede anket yardımı ile nicel veriler toplanırken yarı yapılandırılmış mülakatlar ile de nitel veriler eş zamanlı olarak toplanmıştır. Çalışmanın verileri; Marmara, İstanbul, Kocaeli, Bursa Uludağ, Atatürk, Sivas Cumhuriyet, Recep Tayyip Erdoğan Üniversiteleri’nde İlahiyat alanında lisansüstü öğrenim gören 145 öğrenciden oluşan çalışma grubundan online olarak elde edilmiştir. Araştırmaya katılan öğrencilerin 56’sı erkek 89’u ise kadındır. Araştırmanın nitel boyutunda ise 6’sı kadın 5’i erkek 11 öğrenci ile yarı yapılandırılmış görüşme yapılmıştır. Bulgular çerçevesinde İlahiyat alanında lisansüstü öğrenimine devam eden öğrencilerin, uzaktan öğretimle ilgili genel olarak olumlu görüşler beyan ettiği görülmektedir. Pandemi nedeniyle uzaktan öğretime ani geçiş, öğrenci ve akademisyenleri hazırlıksız yakalamış olsa da öğrenci görüşleri çerçevesinde, kısa zamanda hem öğrenci hem de öğretim elemanlarının duruma adapte olduğu tespit edilmiştir.
TOPLUMSAL KALKINMA AMAÇLI YÜKSEK DİN ÖĞRETİMİ: İSMAİL HAKKI BALTACIOĞLU’NUN YAZILARINDAN HAREKETLE TÜRK DÜŞÜNCESİ DERGİSİNDE TOPLUM, DİN VE DİL İLİŞKİSİ
Authors: FURAT Ayşe Zişan
Published: March 2021

Cumhuriyet tarihi boyunca, özellikle de erken çok partili dönemde, yaşanan siyasi ve entelektüel dönüşümler, yüksek din öğretiminin amaçlarının da önemli ölçüde değişmesine neden olmuştur. Söz konusu değişimin önemli bir kesitini yansıtmayı amaçlayan bu makalede Peyami Safa’nın önderliğinde 1953-1960 yılları arasında süren, yayın hayatı boyunca dönemin tartışmalarını canlı bir şekilde yansıtan Türk Düşüncesi dergisi incelenmiştir. Dergi, din eğitiminin yeniden canlanışına sahne olan bu dönemde yüksek din öğretiminin amaçlarına toplumsal kalkınma odaklı bir bakış açısı sunan ilgi çekici bir kaynaktır. Yapılan tematik analiz doğrultusunda dergide yüksek din öğretiminin amaçlarına yönelik; doğru dinî bilginin üretilmesi, toplumun aydınlatılması ve Kur’an’ın Türkçeye çevirisi şeklinde üç temel temanın ön plana çıktığı tespit edilmiştir. Dergi yazarları arasında özellikle Baltacıoğlu tarafından öne çıkarılan bu temalar; yüksek din öğretiminin amaçlarının toplumsal kalkınma ekseninde yeniden tanımlandığını göstermektedir. İlahiyat fakültesi, kutsal metnin Türkçeye çevrilmesini sağlayarak toplumu oluşturan temel kurumlar arasında bulunan dinî kalkınmanın ve toplumsal kalkınmanın gerçekleştirilmesinde başat rol üstlenmektedir.
Using ensemble-mean climate scenarios for future crop yield projections: a stochastic weather generator approach
Authors: Ma D , Jing Q , Xu YP , Cannon AJ , Dong T , Semenov MA , Qian B
Published: March 2021

Using climate scenarios from only 1 or a small number of global climate models (GCMs) in climate change impact studies may lead to biased assessment due to large uncertainty in climate projections. Ensemble means in impact projections derived from a multi-GCM ensemble are often used as best estimates to reduce bias. However, it is often time consuming to run process-based models (e.g. hydrological and crop models) in climate change impact studies using numerous climate scenarios. It would be interesting to investigate if using a reduced number of climate scenarios could lead to a reasonable estimate of the ensemble mean. In this study, we generated a single ensemble-mean climate scenario (En-WG scenario) using ensemble means of the change factors derived from 20 GCMs included in CMIP5 to perturb the parameters in a weather generator, LARS-WG, for selected locations across Canada. We used En-WG scenarios to drive crop growth models in DSSAT ver. 4.7 to simulate crop yields for canola and spring wheat under RCP4.5 and RCP8.5 emission scenarios. We evaluated the potential of using the En-WG scenarios to simulate crop yields by comparing them with crop yields simulated with the LARS-WG generated climate scenarios based on each of the 20 GCMs (WG scenarios). Our results showed that simulated crop yields using the En-WG scenarios were often close to the ensemble means of simulated crop yields using the 20 WG scenarios with a high probability of outperforming simulations based on a randomly selected GCM. Further studies are required, as the results of the proposed approach may be influenced by selected crop types, crop models, weather generators, and GCM ensembles.
OLFACTORY GROOVE MENINGIOMAS – CLINICAL PRESENTATION, TREATMENT AND OUTCOMES
Authors: Cazac Tabita Larisa , Dărămuș Ioana Andreea , Dumitrescu B. C. , Toader C.
Published: March 2021

Olfactory groove meningiomas are benign tumors, which arise in the midline of the anterior cranial fossa, over the cribriform plate and frontosphenoid suture. They represent approximately 10 percent of all intracranial meningiomas, more likely to occur in women in the fifth and sixth decades of life. They often involve the area from the grista galli to the posterior planum sphenoidale, and can be either simetric, bilateral or unilateral based on their midline origin. We report the case of a 45-year-old man who presented with an episode of loss of consciousness, progressive mental disturbances, impairment of visual acuity, anosmia and headache. Gadolinium-enhanced T1-weighted MR images showed a well-defined, hyperintense mass, located in the anterior cranial fossa, measuring 45/50/61 mm, with homogenous enhancement and a broad dural attachment to the cribriform plate, from crista galli to the planum sphenoidale. Preoperative Angiography revealed tumor vascularization from anterior and posterior ethmoidal arteries, branches of ophthalmic artery and branches of external carotid artery. The olfactory groove meningioma was successfully resected using a bifrontal approach with frontal sinuses opened in order to avoid brain retraction. Cranialization with pericranium of frontal sinuses was performed at the end of surgical procedure. Improvement of visual acuity was noted, mental disturbances and seizures remitted, but cerebrospinal leakage occurred, resolved via recranialization of frontal sinuses and lumbar punctions. The last postoperative computer-tomography investigation showed total surgical removal with no recurrence or residual tumor. Total tumor removal must be performed with coagulation of its arachnoid attachments and resection of hyperostotic bone in order to avoid recurrence, but with least brain retraction.
THE MULTIDISCIPLINARY APPROACH IN A CASE OF PEDIATRIC EWING’S SARCOMA
Authors: Petrone Ana-Maria , Macadon Mădălina , Burnei Gh. , Gavriliu Ș. , Ghiță Raluca
Published: March 2021

Ewing's Sarcoma is a rare, malignant osseous tumor arising from undifferentiated cells originating from the neural crest; however it may also develop in the soft tissue. The initial evaluation of a patient who is suspected to be suffering from Ewing's Sarcoma entails taking a thorough medical history along with performing a detailed physical examination. Our patient was diagnosed with Ewing's Sarcoma upon seeking medical attention due to the sudden appearance of pain in his left hip. The medical staff conducted a series of investigations including X-rays, MRI, CT and 3D-CT scans of the inferior limb and pelvis in order to yield the diagnosis of Ewing's Sarcoma; however, the definitive diagnosis was confirmed only by the biopsy performed before the surgery for modular endoprotesation. The patient received preoperative chemotherapy (in order to reduce the tumor dimension) according to the EuroEwing 2008 Protocol. After the seventh course of chemotherapy, surgery was performed, consisting of in-block resection of the proximal left femur and hip joint, followed by the insertion of a modular femoral endoprosthesis. Postoperative follow-up, however necessitated another six courses of chemotherapy.
AFIKSASI DALAM KOLOM POLITIK DI KORAN JAWA POS EDISI JUMAT 1 NOVEMBER 2019
Authors: Ananda Firna Putri
Published: March 2021

Perubahan kata terdapat di berbagai sumber salah satunya di koran jawa pos,ternyata banyak kata yang mengalami perubahan kata seperti pada kolom Politik di koranJawa Pos edisi Jumat 1 November 2019, terdapat banyak kata yang mengalami perubahankata didalamnya. Kata-kata yang mengalami perubahan kata tersebut mengalami prosesafiksasi yang merupakan bagian dari proses morfemis dalam morfologi. Penelitian inimenganalisis proses afiksasi yang terdapat pada kolom Politik di koran Jawa Pos edisi Jumat1 November 2019. Didapatkan tiga proses perubahan kata yaitu prefiks, sufiks, dan konfiks,dari tujuh proses afiksasi. Ditemukan 20 prefiks, 7 sufiks, dan 20 konfiks. Afiksasimerupakan bentuk dasar yang mengalami proses pingimbuhan afiks dan menghasilkan katabaru. Proses afiksasi dibagi menjadi tujuh jenis yaitu prefiks, sufiks, infiks, konfiks,sirkumfiks, interfiks, dan transfiks. Prefiks merupakan bentuk dasar yang mendapatkanimbuhan afiks didepannya. Dalam bahasa indonesia prefiks sendiri dibedakan atas dua jenisyaitu prefiks asli dan prefiks serapan. Sufiks adalah bentuk dasar yang dibelakangnyadiimbuhkan afiks. Sufiks biasanya disebut akhiran atau imbuhan yang digabungkan di akhirkata. Keberadaan sufiks dapat ada beriringan dengan afiks-afiks yang lain. Dalam bahasaindonesia sufiks dibedakan menjadi dua jenis yaitu sufiks asli dan sufiks serapan.Sedangkan konfiks adalah bentuk dasar yang mendapat imbuhan afiks yang diletakkan dibagian awal dan bagian akhir. Ada dua hal yang sangat diperhatikan berkenaan dengankonfiks yang terdapat dalam bahasa Indonesia. Pertama, dalam menentukan apakah duabuah afiks (prefiks dan sufiks) termasuk konfiks atau tidak yaitu dengan cara mengetahuimakna gramatikal yang dihasilkan dari proses afiksasi secara konfiks. Sedangkan yangkedua, tentang konfiks me-/-kan dan me-/-i dalam bahasa indonesi di sebut sebagai konfiksatau bukan konfiks.
PRINSIP MAKSIM KEDERMAWANAN DALAM NOVEL HATI SUHITA KARYA KHILMA ANIS
Authors: A’idina Asfa , Fadli Rusli Ilham , Prihatin Yulianah
Published: March 2021

Penelitian ini bertujuan untuk mengetahui dan mendeskripsikan maksim kedermawanan dalam novel HatiSuhita karya Khilma Anis. Maksim kedermawanan termasuk dalam enam maksim kesantunan berahasayang didiutarakan oleh Leech yaitu maksim maksim kebijaksanaan, kedermawanan, pujian,kesederhanaan, pemufakatan dan kesimpatisan. Pendeskripsian maksim kedermawanan diperolehmelalui dialog antartokoh dalam novel Hati Suhita. Penelitian in menggunakan metode kualitatif, jadidata yang sudah didapatkan dideskripsikan. Teknik pengumpulan data yang dipakai dalam penelitian iniadalah teknik studi pustaka, teknik baca, dan teknik catat. Sedangkan teknik analisis data yangdipakai pada penelitian ini adalah teknik kajian isi. Berdasarkan hasil penelitian didapatkan bahwaterdapat 24 tuturan yang termasuk dalam maksim kedermawanan.
Effect of Differentiated Instruction and 5E Learning Cycle on Academic Achievement and Self-efficacy of Students in Physics Lesson
Authors:   Faculty of Education, Science Education Department, Ataturk University, Erzurum, Turkey, Salar Riza , Turgut Umit ,   Faculty of Education, Science Education Department, Ataturk University, Erzurum, Turkey
Published: March 2021

The learning characteristics of each student are different. Differentiated instruction considers individual differences, as such guides the learning journey rather than seeing these differences as a challenge. The purpose of this research was to compare the effects of differentiated instruction and 5E learning cycle in physics classes on the students' academic achievement and self-efficacy. We used the matching - pre-test/post-test - control group design to address the research questions. We conducted the study in three different schools, performed three experiments, and had three control groups. 162 10th grade students participated in the study. We used the ‘Electricity Prior Knowledge Test’, ‘Electricity Achievement Test’, and the ‘Physics Self-Efficacy Scale’ to collect data. SPSS version 20 software was used to analyse the obtained quantitative data. Independent samples t-test was used to determine whether there was a significant difference between the control and experimental group students’ level of prior knowledge regarding the subject of electricity. The analysis of covariance was used to determine whether there was a significant difference between the control and experimental group students’ course achievements after the implementation. Two-factor mixed-measures ANOVA was used to determine whether the experimental and control group students’ pre-test and post-test scores on self-efficacy differed. Based on the results, it can be concluded that differentiated instruction improved the academic achievement of the low- and mid-achieving students. When the self-efficacy scores of the students were analysed, no significant difference was found between the groups. Based on the results of the research, researchers or teachers who want to use differentiated teaching in their classrooms may be recommended to create level groups in the classroom.
Designing an experiment based on a script: Determining the critical thinking tendency and biological self-efficacy of prospective science teachers
Authors:   Science Education Department, Education Faculty, Burdur Mehmet Akif Ersoy University, Burdur-Turkey, Çeliker Huriye Deniş
Published: March 2021

The purpose of this research was to investigate the effect of problem-based scenarios method with experiments on the biology self-efficacy and critical thinking tendency of the prospective science teachers. In the study, pre-test and post-test experimental design without any control group was used. The participants of the research were 108 second-grade prospective science teachers in an university in the west of Turkey. Throughout twelve weeks, prospective teachers were given scenarios and they designed experiments based on these scenarios in the Biology Laboratory II course. The biology self-efficacy scale and critical thinking tendency scale were used as a pre-test and post-test. In the analysis of data, Wilcoxon Signed Rank Test for Paired Samples were used via SPSS-21. The findings showed that there was a statistically significant difference between biology self-efficacy scale’ pre-test and post-test of prospective teachers in favour of the post-test. There was also a statistically significant difference in critical thinking tendency scale in favour of the post-test. In the biology self-efficacy scale' sub-factors of learning levels and problem-solving, there was a statistically significant difference on behalf of the post-test. However, there was not a statistically significant difference between pre-test and post-test concerning the laboratory activity sub-factor of the biology self-efficacy scale. On behalf of post-tests, there was also a statistically significant difference in critical thinking tendency scale’s sub-factors as inquisitiveness, self-confidence, and systematicity. The results show that the problem-based scenario method with experiment certainly contributed to the biology self-efficacy and critical thinking tendency of pre-service science teachers. Based on these results it is recommended that the problem-based scenario method with experiment be used in the laboratory lessons of prospective teachers.
Teacher and Parent Perspectives on NGSS Alignment Following Teacher Professional Development
Authors:   Faculty of the Department of Medical Education, Western Michigan University Homer Stryker MD School of Medicine, Channell Adam , Cobern William ,   Faculty The Mallinson Institute for Science Education, Western Michigan University, Rudge David ,   Faculty The Mallinson Institute for Science Education, Western Michigan University and Faculty of the Department of Biological Sciences, Western Michigan University, Bentz Amy ,   Faculty The Mallinson Institute for Science Education, Western Michigan University and Faculty of the College of Education and Human Development, Western Michigan University
Published: March 2021

Abstract: This study examined United States K-12 science teacher interactions with parents during Next Generation Science Standards (NGSS) reform following teachers’ professional development (PD) participation, as well as parent accounts of understanding and support for NGSS. Fourteen teachers and fifteen parents completed an online surveys and phone interviews. Themes, based on coded data, were constructed to represent relationships between teachers and parents during NGSS classroom implementation post-PD. We found that parents were generally unaware of NGSS and not well-informed about the changes the new standards brought to their child’s science classrooms. Despite parents’ lack of NGSS understanding, parents generally gave positive feedback about teachers’ science instruction. However, parents expressed concern about their child’s ability to transition between grade levels and subjects, the lack of an aligned textbook and homework assignments, and confusion with how to help their children at home in preparation for assessments. The results of this study suggest that it is important for school districts to inform parents adequately about the new NGSS curriculum and its implementation. While this study took place in the United States and pertains to NGSS, the findings are broadly applicable to teacher development and communications with parents during standards reform, regardless of country.
Relationship between consciousness about environmental education concepts in secondary school chemistry curriculum and attitude of students towards environment
Authors:   Department of Science education, School of Science and Technology Education, Federal University of Technology, Minna Niger State, Nigeria., Osunji Olabode
Published: March 2021

The study aim to investigate the relationship between consciousness about environmental education concepts in senior secondary school chemistry curriculum and attitude of chemistry students towards the environment in Kwara state. The study deploys descriptive survey design. Using Simple random sampling and Stratified proportionate sampling techniques. A sample of four hundred (400) senior secondary school science students and 16 senior secondary schools was used for the study. Two structured Questionnaires with titles” Students Attitude to Environment Questionnaire (SAEQ) and Students Consciousness towards Environment Questionnaire (SCEQ)” were developed by the researcher. The validity coefficient of SAEQ and SCEQ was 0.801 and 0.765. These were obtained using Cronbach-alpha method. Four research questions and four null hypotheses guided the study. Data collected were analysis using mean standard deviation, one way ANOVA and Pearson Product moment correlation (PPMC). The findings from the study revealed that the student environmental consciousness influenced their attitude towards the environment and, that student’s continuous exhibition of attitude towards the environment is rooted on their inadequate consciousness or knowledge of the causes and effects of environmental problems, it was recommended that Ministry of Education updates the curriculum of Senior Secondary School managing Environmental Education (EE) content.
Insight Into Nanoliposomes as Smart Nanocarriers for Greening the Twenty-First Century Biomedical Settings
Authors: Aguilar-Pérez K. M. , Avilés-Castrillo J. I. , Medina Dora I. , Parra-Saldivar Roberto , Iqbal Hafiz M. N.
Published: March 2021

The necessity to develop more efficient, biocompatible, patient compliance, and safer treatments in biomedical settings is receiving special attention using nanotechnology as a potential platform to design new drug delivery systems (DDS). Despite the broad range of nanocarrier systems in drug delivery, lack of biocompatibility, poor penetration, low entrapment efficiency, and toxicity are significant challenges that remain to address. Such practices are even more demanding when bioactive agents are intended to be loaded on a nanocarrier system, especially for topical treatment purposes. For the aforesaid reasons, the search for more efficient nano-vesicular systems, such as nanoliposomes, with a high biocompatibility index and controlled releases has increased considerably in the past few decades. Owing to the stratum corneum layer barrier of the skin, the in-practice conventional/conformist drug delivery methods are inefficient, and the effect of the administered therapeutic cues is limited. The current advancement at the nanoscale has transformed the drug delivery sector. Nanoliposomes, as robust nanocarriers, are becoming popular for biomedical applications because of safety, patient compliance, and quick action. Herein, we reviewed state-of-the-art nanoliposomes as a smart and sophisticated drug delivery approach. Following a brief introduction, the drug delivery mechanism of nanoliposomes is discussed with suitable examples for the treatment of numerous diseases with a brief emphasis on fungal infections. The latter half of the work is focused on the applied perspective and clinical translation of nanoliposomes. Furthermore, a detailed overview of clinical applications and future perspectives has been included in this review.
Assessing the Quality of Knowledge for Adaptation–Experiences From Co-designing Climate Services in Sweden
Authors: André Karin , Järnberg Linn , Gerger Swartling Åsa , Berg Peter , Segersson David , Amorim Jorge H. , Strömbäck Lena
Published: March 2021

Adaptation to climate change is becoming more urgent, but the wealth of knowledge that informs adaptation planning and decision-making is not used to its full potential. Top-down approaches to knowledge production are identified as one important reason for the gap between science and practice and are criticized for not meeting the needs of intended users. In response to this challenge, there is a growing interest in the creation of user-oriented and actionable climate services to support adaptation. At the same time, recent research suggests that greater efforts are needed to evaluate the effectiveness of knowledge co-production processes and the best criteria by which to gauge the quality of knowledge outcomes, while also considering different stakeholder perspectives. This paper explores these issues through a critical assessment of the quality of knowledge for adaptation generated from a climate services co-design process in two case studies in Sweden. The study draws on experiences from a 5-year research collaboration in which natural and social science researchers, together with local stakeholders, co-designed climate services to support climate adaptation planning and decision-making. The well-established knowledge quality criteria of credibility, legitimacy, saliency, usability, and usefulness remain relevant, but are not sufficient to capture factors relating to whether and how the knowledge actually is applied by climate change adaptation planners and decision-makers. We observe that case-specific circumstances beyond the scope of the co-design process, including the decision-making context as well as non-tangible outcomes, also play crucial roles that should be accounted for in the knowledge assessment processes.
Digital Insights Into Nucleotide Metabolism and Antibiotic Treatment Failure
Authors: Lopatkin Allison J. , Yang Jason H.
Published: March 2021

Nucleotide metabolism plays a central role in bacterial physiology, producing the nucleic acids necessary for DNA replication and RNA transcription. Recent studies demonstrate that nucleotide metabolism also proactively contributes to antibiotic-induced lethality in bacterial pathogens and that disruptions to nucleotide metabolism contributes to antibiotic treatment failure in the clinic. As antimicrobial resistance continues to grow unchecked, new approaches are needed to study the molecular mechanisms responsible for antibiotic efficacy. Here we review emerging technologies poised to transform understanding into why antibiotics may fail in the clinic. We discuss how these technologies led to the discovery that nucleotide metabolism regulates antibiotic drug responses and why these are relevant to human infections. We highlight opportunities for how studies into nucleotide metabolism may enhance understanding of antibiotic failure mechanisms.
HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol
Authors: Hussain Imran , Deb Paromita , Chini Avisankar , Obaid Monira , Bhan Arunoday , Ansari Khairul I. , Mishra Bibhu P. , Bobzean Samara A. , Udden S. M. Nashir , Alluri Prasanna G. , Das Hriday K. , Brothers Robert Matthew , Perrotti Linda I. , Mandal Subhrangsu S.
Published: March 2021

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cellsin vitro. HOXA5 expression is also upregulatedin vivoin the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.
Multi ‘Omics Analysis of Intestinal Tissue in Ankylosing Spondylitis Identifies Alterations in the Tryptophan Metabolism Pathway
Authors: Berlinberg Adam J. , Regner Emilie H. , Stahly Andrew , Brar Ana , Reisz Julie A. , Gerich Mark E. , Fennimore Blair P. , Scott Frank I. , Freeman Alison E. , Kuhn Kristine A.
Published: March 2021

Intestinal microbial dysbiosis, intestinal inflammation, and Th17 immunity are all linked to the pathophysiology of spondyloarthritis (SpA); however, the mechanisms linking them remain unknown. One potential hypothesis suggests that the dysbiotic gut microbiome as a whole produces metabolites that influence human immune cells. To identify potential disease-relevant, microbiome-produced metabolites, we performed metabolomics screening and shotgun metagenomics on paired colon biopsies and fecal samples, respectively, from subjects with axial SpA (axSpA, N=21), Crohn’s disease (CD, N=27), and Crohn’s-axSpA overlap (CD-axSpA, N=12), as well as controls (HC, N=24). Using LC-MS based metabolomics of 4 non-inflamed pinch biopsies of the distal colon from subjects, we identified significant alterations in tryptophan pathway metabolites, including an expansion of indole-3-acetate (IAA) in axSpA and CD-axSpA compared to HC and CD and indole-3-acetaldehyde (I3Ald) in axSpA and CD-axSpA but not CD compared to HC, suggesting possible specificity to the development of axSpA. We then performed shotgun metagenomics of fecal samples to characterize gut microbial dysbiosis across these disease states. In spite of no significant differences in alpha-diversity among the 4 groups, our results confirmed differences in gene abundances of numerous enzymes involved in tryptophan metabolism. Specifically, gene abundance of indolepyruvate decarboxylase, which generates IAA and I3Ald, was significantly elevated in individuals with axSpA while gene abundances in HC demonstrated a propensity towards tryptophan synthesis. Such genetic changes were not observed in CD, again suggesting disease specificity for axSpA. Given the emerging role of tryptophan and its metabolites in immune function, altogether these data indicate that tryptophan metabolism into I3Ald and then IAA is one mechanism by which the gut microbiome potentially influences the development of axSpA.
Sex Hormones and Gender Influence the Expression of Markers of Regulatory T Cells in SLE Patients
Authors: Singh Ram P. , Bischoff David S.
Published: March 2021

Regulatory T cells have been implicated in the regulation and maintenance of immune homeostasis. Whether gender and sex hormones differentially influence the expression and function of regulatory T cell phenotype and their influence on FoxP3 expression remains obscure. We provide evidence in this study that the number and percent of human regulatory T cells (Tregs) expressing CD4+and CD8+are significantly reduced in healthy females compared to healthy males. In addition, both CD4+CD25+hiand CD8+CD25+hisubsets in healthy males have a 2-3 fold increase in FoxP3 mRNA expression compared to healthy females. Female SLE patients, compared to healthy women, have elevated plasma levels of estradiol and decreased levels of testosterone. Higher levels of testosterone correlate with higher expression of FoxP3 in CD4+CD25hiCD127lowputative Tregsin women with SLE. Incubation of CD4+regulatory T cells with 17β-estradiol at physiological levels generally decreased FoxP3 expression in females with SLE. These data suggest that females may be more susceptible than males to SLE and other autoimmune diseases in part because they have fewer Tregsand reduced FoxP3 expression within those cells due to normal E2 levels which suppress FoxP3 expression. In addition, low levels of plasma testosterone in women may further reduce the ability of the Tregsto express FoxP3. These data suggest that gender and sex hormones can influence susceptibility to SLE via effects on regulatory T cells and FoxP3 expression.
Interplay Between Sialic Acids, Siglec-E, and Neu1 Regulates MyD88- and TRIF-Dependent Pathways for TLR4-Activation During Leishmania donovani Infection
Authors: Karmakar Joyshree , Mandal Chitra
Published: March 2021

TLR4 activates two distinct signaling pathways involving adaptors MyD88 and TRIF to produce proinflammatory cytokines and type-I interferon respectively. How Leishmania donovani suppresses these pathways is not well studied. We earlier reported, TLR4 is hypersialylated due to reduced membrane-bound neuraminidase (Neu1) on infected-macrophages. We hypothesized that such enhanced sialoglycoconjugates on host cells may modulate the interactions with siglecs- which are the inhibitory receptors. Here, we examined the impact of such sialylation on overall TLR4 activation both in murine cell line J774A.1 and primary bone marrow derived macrophages (BMDM). Supporting this hypothesis, we demonstrated siglec-E engages hypersialylated TLR4 during infection. Such sialic acids-siglec-E interaction enhanced siglec-E phosphorylation that mediated its strong association with SHP1/SHP2 and also upregulated their phosphorylation in both types of macrophages. Pre-treatment of parasites and host cells with neuraminidase reduced SHP1/SHP2 phosphorylation and triggered TLR4 activation respectively through enhanced nuclear translocation of p-65. Moreover, a reciprocal interplay between Neu1 and siglec-E differentially regulates MyD88- and TRIF-pathways through sialic acids on TLR4 as their common substrate during infection. Correspondingly, Neu1 overexpression enhanced MyD88-signaling while still suppressing TRIF-activation. However, silencing siglec-E specifically activated TRIF-signaling. Pro-inflammatory cytokines corresponding to MyD88 and TRIF pathways were also upregulated respectively. Additionally, Neu1 overexpression or siglec-E silencing prevented TLR4 ubiquitination and subsequent degradation by Triad3A. Neu1-overexpression and siglec-E-silencing together followed by infection activated both MyD88 and TRIF-signaling through their enhanced TLR4-association. This elevated the MyD88-specific cytokines and TRIF-mediated IRF3 and IFN-β genes, thus upregulating the pro-inflammatory cytokines and nitric oxide levels and reduced anti-inflammatory cytokines. All these significantly inhibited parasite survival in macrophages thus demonstrating a previously unidentified dualistic regulation of TLR4signaling pathways activation through sialic acids by interplay of Neu1 and siglec-E during Leishmania infection.
Analysis of m6A-Related Signatures in the Tumor Immune Microenvironment and Identification of Clinical Prognostic Regulators in Adrenocortical Carcinoma
Authors: Jin Yi , Wang Zhanwang , He Dong , Zhu Yuxing , Hu Xueying , Gong Lian , Xiao Mengqing , Chen Xingyu , Cheng Yaxin , Cao Ke
Published: March 2021

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high rate of mortality and recurrence. N6-methyladenosine methylation (m6A) is the most common modification to affect cancer development, but to date, the potential role of m6A regulators in ACC prognosis is not well understood. In this study, we systematically analyzed 21 m6A regulators in ACC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. We identified three m6A modification patterns with different clinical outcomes and discovered a significant relationship between diverse m6A clusters and the tumor immune microenvironment (immune cell types and ESTIMATE algorithm). Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that the m6A clusters were strongly associated with immune infiltration in the ACC. Next, to further explore the m6A prognostic signatures in ACC, we implemented Lasso (Least Absolute Shrinkage and Selection Operator) Cox regression to establish an eight-m6A-regulator prognostic model in the TCGA dataset, and the results showed that the model-based high-risk group was closely correlated with poor overall survival (OS) compared with the low-risk group. Subsequently, we validated the key modifications in the GEO datasets and found that high HNRNPA2B1 expression resulted in poor OS and event-free survival (EFS) in ACC. Moreover, to further decipher the molecular mechanisms, we constructed a competing endogenous RNA (ceRNA) network based on HNRNPA2B1, which consists of 12 long noncoding RNAs (lncRNAs) and 1 microRNA (miRNA). In conclusion, our findings indicate the potential role of m6A modification in ACC, providing novel insights into ACC prognosis and guiding effective immunotherapy.
Longitudinal Assessment of Immune Responses to Repeated Annual Influenza Vaccination in a Human Cohort of Adults and Teenagers
Authors: Sung Meng-Hsuan , Shen Ye , Handel Andreas , Bahl Justin , Ross Ted M.
Published: March 2021

Background: The overall performance of a multiple component vaccine assessed by the vaccine-elicited immune responses across various strains in a repeated vaccination setting has not been well-studied, and the comparison between adults and teenagers is yet to be made.

Methods: A human cohort study was conducted at the University of Georgia, with 140 subjects (86 adults and 54 teenagers) repeatedly vaccinated in the 2017/2018 and 2018/2019 influenza seasons. Host information was prospectively collected, and serum samples were collected before and after vaccination in each season. The association between host factors and repeated measures of hemagglutination inhibition (HAI) composite scores was assessed by generalized linear models with generalized estimating equations.

Results: The mean HAI composite scores for the entire sample (t = 4.26, df = 139, p < 0.001) and the teenager group (t = 6.44, df = 53, p < 0.001) declined in the second season, while the changes in the adults were not statistically significant (t = −1.14, df = 85, p = 0.26). A mixture pattern of changes in both directions was observed in the adults when stratified by prior vaccination. In addition, the regression analysis suggested an interactive effect of age and BMI on the HAI composite scores in the overall population (beta = 0.005; 95% CI, 0.0008–0.01) and the adults (beta = 0.005; 95% CI, 0.0005–0.01).

Conclusions: Our study found distinct vaccine-elicited immune responses between adults and teenagers when both were repeatedly vaccinated in consecutive years. An interactive effect of age and BMI on the HAI composite scores were identified in the overall population and the adults.
Introducing the ArsR-Regulated Arsenic Stimulon
Authors: Rawle Rachel , Saley Tara C. , Kang Yoon-Suk , Wang Qian , Walk Seth , Bothner Brian , McDermott Timothy R.
Published: March 2021

The microbialarsoperon encodes the primary bacterial defense response to the environmental toxicant, arsenic. An important component of this operon is thearsRgene, which encodes ArsR, a member of the family of proteins categorized as DNA-binding transcriptional repressors. As currently documented, ArsR regulates its own expression as well as other genes in the samearsoperon. This study examined the roles of four ArsR proteins in the well-developed model Gram-negative bacteriumAgrobacterium tumefaciens5A. RNASeq was used to compare and characterize gene expression profiles in ± arsenite-treated cells of the wild-type strain and in four differentarsRmutants. We report that ArsR-controlled transcription regulation is truly global, extending well beyond the currentarsoperon model, and includes both repression as well as apparent activation effects. Many cellular functions are significantly influenced, including arsenic resistance, phosphate acquisition/metabolism, sugar transport, chemotaxis, copper tolerance, iron homeostasis, and many others. While there is evidence of some regulatory overlap, each ArsR exhibits its own regulatory profile. Furthermore, evidence of a regulatory hierarchy was observed; i.e. ArsR1 repressesarsR4, ArsR4 activatesarsR2, and ArsR2 repressesarsR3. Additionally and unexpectedly,aioB(arsenite oxidase small subunit) expression was shown to be under partial positive control by ArsR2 and ArsR4. Summarizing, this study demonstrates the regulatory portfolio of arsenite-activated ArsR proteins and includes essentially all major cellular functions. The broad bandwidth of arsenic effects on microbial metabolism assists in explaining and understanding the full impact of arsenic in natural ecosystems, including the mammalian gut.
Cell Death in Cyanobacteria: Current Understanding and Recommendations for a Consensus on Its Nomenclature
Authors: Aguilera Anabella , Klemenčič Marina , Sueldo Daniela J. , Rzymski Piotr , Giannuzzi Leda , Martin María Victoria
Published: March 2021

Cyanobacteria are globally widespread photosynthetic prokaryotes and are major contributors to global biogeochemical cycles. One of the most critical processes determining cyanobacterial eco-physiology is cellular death. Evidence supports the existence of controlled cellular demise in cyanobacteria, and various forms of cell death have been described as a response to biotic and abiotic stresses. However, cell death research in this phylogenetic group is a relatively young field and understanding of the underlying mechanisms and molecular machinery underpinning this fundamental process remains largely elusive. Furthermore, no systematic classification of modes of cell death has yet been established for cyanobacteria. In this work, we analyzed the state of knowledge in the field of cyanobacterial cell death. Based on that, we propose unified criterion for the definition of accidental, regulated, and programmed forms of cell death in cyanobacteria based on molecular, biochemical, and morphologic aspects following the directions of the Nomenclature Committee on Cell Death (NCCD). With this, we aim to provide a guide to standardize the nomenclature related to this topic in a precise and consistent manner, which will facilitate further ecological, evolutionary, and applied research in the field of cyanobacterial cell death.
Natural Transformation of Riemerella columbina and Its Determinants
Authors: Huang Li , Liu Mafeng , Zhu Dekang , Xie Li , Huang Mi , Xiang Chen , Biville Francis , Jia Renyong , Chen Shun , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Ou Xumin , Mao Sai , Gao Qun , Sun Di , Tian Bin , Wang Mingshu , Cheng Anchun
Published: March 2021

In a previous study, it was shown that Riemerella anatipestifer, a member of Flavobacteriaceae, is naturally competent. However, whether natural competence is universal in Flavobacteriaceae remains unknown. In this study, it was shown for the first time that Riemerella columbina was naturally competent in the laboratory condition; however, Flavobacterium johnsoniae was not naturally competent under the same conditions. The competence of R. columbina was maintained throughout the growth phases, and the transformation frequency was highest during the logarithmic phase. A competition assay revealed that R. columbina preferentially took up its own genomic DNA over heterologous DNA. The natural transformation frequency of R. columbina was significantly increased in GCB medium without peptone or phosphate. Furthermore, natural transformation of R. columbina was inhibited by 0.5 mM EDTA, but could be restored by the addition of CaCl2, MgCl2, ZnCl2, and MnCl2, suggesting that these divalent cations promote the natural transformation of R. columbina. Overall, this study revealed that natural competence is not universal in Flavobacteriaceae members and triggering of competence differs from species to species.
Epidemiological Study of Betacoronaviruses in Captive Malayan Pangolins
Authors: Li Linmiao , Wang Xiaohu , Hua Yan , Liu Ping , Zhou Jiabin , Chen Jing , An Fuyu , Hou Fanghui , Huang Wenzhong , Chen Jinping
Published: March 2021

The coronavirus disease 2019 (COVID-19) outbreak has significantly affected international public health safety. It has been reported that the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, could originate from bats and utilize the Malayan pangolin (Manis javanica) as an intermediate host. To gain further insights into the coronaviruses carried by pangolins, we investigated the occurrence of Betacoronavirus (β-CoV) infections in captive Malayan pangolins in the Guangdong province of China. We detected three β-CoV-positive M. javanica individuals with a positive rate of 6.98% and also detected β-CoV in two dead pangolins sampled in August 2019. The CoV carried by pangolins is a new β-CoV, which is genetically related to SARS-CoV-2. Furthermore, the expression of angiotensin-converting enzyme 2 (ACE2) was detected in eight organs of pangolins, with the highest ACE2 mRNA levels in the kidney, suggesting that these organs could be at a risk of β-CoV infection. These results enable us to better understand the status of β-CoV carried by Malayan pangolins, while providing a theoretical basis for better pangolin protection and viral control.
Ipsilateral Motor Evoked Potentials as a Measure of the Reticulospinal Tract in Age-Related Strength Changes
Authors: Maitland Stuart , Baker Stuart N.
Published: March 2021

Background: The reticulospinal tract (RST) is essential for balance, posture, and strength, all functions which falter with age. We hypothesized that age-related strength reductions might relate to differential changes in corticospinal and reticulospinal connectivity.

Methods: We divided 83 participants (age 20–84) into age groups <50 (n = 29) and ≥50 (n = 54) years; five of which had probable sarcopenia. Transcranial Magnetic Stimulation (TMS) was applied to the left cortex, inducing motor evoked potentials (MEPs) in the biceps muscles bilaterally. Contralateral (right, cMEPs) and ipsilateral (left, iMEPs) MEPs are carried by mainly corticospinal and reticulospinal pathways respectively; the iMEP/cMEP amplitude ratio (ICAR) therefore measured the relative importance of the two descending tracts. Grip strength was measured with a dynamometer and normalized for age and sex.

Results: We found valid iMEPs in 74 individuals (n = 44 aged ≥50, n = 29 < 50). Younger adults had a significant negative correlation between normalized grip strength and ICAR (r = −0.37, p = 0.045); surprisingly, in older adults, the correlation was also significant, but positive (r = 0.43, p = 0.0037).

Discussion: Older individuals who maintain or strengthen their RST are stronger than their peers. We speculate that reduced RST connectivity could predict those at risk of age-related muscle weakness; interventions that reinforce the RST could be a candidate for treatment or prevention of sarcopenia.