bluuebunny/crossref_metadata_2025 huggingface dataset:
LEARNING PROGRESSIONS IN LOWER-SECONDARY SCHOOL SCIENCE EDUCATION IN JAPAN
Authors: Kinoshita Hiroyoshi , Utani Ryosuke
Published: October 2021

This research examined whether incorporating learning progress (LPs) in teaching can help Japanese lower-secondary school students systemically understand science concepts. A teaching plan incorporating the learning progressions (LPs) concept was developed. Next, a lesson was conducted for 36 third-year students of a public lower-secondary school in Japan (Hiroshima Prefecture) from the unit of “Ions and Atoms.” Then, the portfolios used in the class and the assessment questions after the class were analyzed. The results show that some students understood the concepts systemically at the grade level indicated by the LPs; however, some students did not. The results of this study suggest the following: (1) teachers should examine the appropriate teaching methods in the target unit and incorporate teaching to allow students to engage with what they are learning; (2) students should understand the lower-level concepts related to the target unit based on LPs, and if the level of understanding is insufficient, teachers should incorporate time to review and reconstruct the concepts.
Keywords: lower-secondary school science, scientific concepts, learning progressions (LPs), systemic learning
Development of Inquiry-Based Mechanics Teaching Materials to Train Critical Thinking Skills for FKIP Physics Students, Universitas Pattimura Ambon
Authors: Heppy Sapulete  , Fryan Sopacua
Published: October 2021

This research is to produce inquiry-based mechanics teaching materials to train critical thinking skills of Physics FKIP students, Pattimura University, Ambon. The research design used the Kemp model (1994) and the learning process was packaged in an inquiry setting with a total sample size of 26 students in the 2020/2021 school year. The data collected were in the form of teaching material validation data, critical thinking skills test instrument validation data, critical thinking skills data, and student response data. The data analysis techniques used include: qualitative descriptive analysis including: the results of validation of teaching materials, the results of instrument validation tests of critical thinking skills, the results of critical thinking skills, and the results of student responses. The results showed that: 1) the validity of the student teaching materials developed was categorized as valid; 2) the validity of the developed critical thinking skills test instrument was categorized as valid; 3) in the percentage of critical thinking skills there is an increase in value from pretest to posttest by more than 40%; 4) Student responses to teaching materials and the implementation of learning are very positive and the lowest percentage is obtained, namely 85% satisfaction with a very good assessment. Based on the results, it can be concluded that the development of inquiry-based mechanics teaching materials can train critical thinking skills of Physics FKIP students, Pattimura University, Ambon.
COVID-19 Australia: Epidemiology Report 51: Reporting period ending 26 September 2021
Authors:   COVID-19 National Incident Room Surveillance Team
Published: October 2021

This is the fifty-first epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 23:59 Australian Eastern Standard Time [AEST] 26 September 2021. It includes data on COVID-19 cases diagnosed in Australia.
Fluorescent properties anionic derivative of thioflavin T
Authors: Maskevich Alexander A.
Published: October 2021

We have investigated the spectral properties of a new benzothiazole dye – a thioflavin T derivative – 3-sulfopropyl-5-methoxy-2-[3-(3,5-diethyl-2-benzothiazolidene)-1-propienyl]-benzothiazolium (Th-C11). Based on quantum-chemical calculations, it is shown that the molecule in the ground state has a flat structure. In an excited state, the minimum energy corresponds to a twisted conformation, in which the aromatic fragments are arranged orthogonally. Since the twisted state is non-fluorescent, the transition to this state (torsion relaxation) is a quenching process. Th-C11 dye exhibits the properties of a fluorescent molecular rotor. As a result of experimental studies, it was found that torsion relaxation of molecular fragments is the main process that determines the strong dependence of the quantum yield and the duration of fluorescence decay on the viscosity of the solvent. A characteristic feature of this dye is the sensitivity of the fluorescence parameters – the quantum yield, the decay duration and the position of the spectrum not only to the viscosity, but also to the polarity of the medium. The paper also explains the dependence of the position of the absorption and fluorescence spectra on the polarity and viscosity of the solvent as a result of the manifestation of the processes of torsion and solvation relaxation of the chromophore and solvent molecules.
Reconsidering Public Space: The Case of Turkish Associations in France
Authors: Kiran Alia
Published: October 2021

This article examines how immigrant culture in modern-day France is communicated through Turkish associations as a medium of the public space. Through interviews with members of various types of cultural associations, I explore how public and private space dictate how culture and identity are understood within the French context. To better explain their goals and how they fit into larger French "cultural" discussion, I develop a simple typology of these cultural associations as "localizing" or "orientalizing" immigrant culture. Pointing to the space between these categories, I show the need for the immigrant experience to be recognized as part of French history in these public spaces in order to directly confront the issue of "neo-racism."
Toward a Rose Forever in Bloom: Translations of Yunus Emre, a 13th Century Anatolian Sufi
Authors: Genc Ekrem
Published: October 2021

Toward a Rose Forever in Bloom is a translation project aimed at creating a sample framework through which Sufi poetry can be understood in its traditional and Islamic context. I outline my translation methodology, as well as the resources that I used in making my translations, such as a new dictionary dedicated solely to the works of Yunus Emre as well as a recent critical edition of his original works, neither of which were available to previous English translators. Through my annotated translations sampled from six overarching themes found in the works of Yunus Emre, a 13th century Anatolian Sufi, an analysis of the legends surrounding his biography, and a discussion of the historical context, I portray Sufism as a path within mainstream Islam, in contrast to modern perceptions and varying translation methods that suggest otherwise.
UM ESTUDO SOBRE OS SISTEMAS LINEARES SOB A ÓTICA DOS REGISTROS DE REPRESENTAÇÃO SEMIÓTICA
Authors: Santos Gabrielle Nunes dos , Grützmann Thaís Philipsen , Soares Maria Arlita da Silveira
Published: October 2021

A presente pesquisa visa investigar como acadêmicos resolvem atividades que envolvam transformações cognitivas de tratamento e conversão, e quais são os registros mobilizados por eles, assim como, elencando quais os métodos escolhidos para a resolução dos sistemas lineares. Para atender o objetivo o texto discorre sobre a teoria dos Registros de Representação Semiótica, aporte teórico da pesquisa. Trata-se de uma pesquisa de caráter qualitativo definida como um estudo de caso. Os participantes dessa pesquisa são acadêmicos dos cursos de Licenciatura em Matemática, Bacharelado e Licenciatura em Física e Ciências Econômicas, que estavam matriculados nas disciplinas de Álgebra Linear I e II no segundo semestre de 2018. Os dados foram produzidos a partir de duas das atividades envolvendo o conteúdo já mencionado. Na análise referente aos Registros de Representação Semiótica as resoluções dos acadêmicos evidenciaram os registros de representação em língua natural, algébrica, matricial e, por último, a gráfica, nesta ordem. Ao analisar os métodos apresentados para a resolução de Sistemas Lineares, identificou-se que em ambas as turmas os métodos escolhidos em maioria foram Substituição e Escalonamento/Eliminação Gaussiana.
ELEMENTOS ASSOCIADOS À RETENÇÃO EM CÁLCULO I: A PERSPECTIVA DE ESTUDANTES DO CURSO DE FÍSICA DA UNIVERSIDADE FEDERAL DO ESPÍRITO SANTO
Authors: Guio Thaisa Carneiro da Cunha , Barcellos Leandro da Silva
Published: October 2021

Neste trabalho, foram analisados fatores que influenciaram a retenção na disciplina de Cálculo I de acordo com a perspectiva de estudantes/ex-estudantes da graduação em Física da Universidade Federal do Espírito Santo. Para tanto, realizamos um estudo qualitativo e do tipo exploratório, no qual os dados foram produzidos e coletados por meio de um questionário misto, no segundo semestre de 2019. O processo analítico ancorou-se na Análise de Conteúdo, e buscou interpretar percepções e vivências relativas às retenções. Com um total de 27 (vinte e sete) estudantes participantes no questionário, os fatores mais mencionados foram: a base matemática insuficiente, o nível de exigência das aulas e/ou avaliações, transtornos psicológicos e/ou problemas de saúde, bem como a postura e didática do(a) docente em sala de aula. Apesar de nossos resultados permitirem o estabelecimento de relações entre esses e outros dos diversos fatores apontados pelos(as) alunos(as), eles corroboram o fato de que a retenção em Cálculo I constitui um problema estritamente multifacetado e complexo.
ENSINANDO MATEMÁTICA FINANCEIRA COM TECNOLOGIAS: UMA EXPERIÊNCIA UTILIZANDO LABORATÓRIO ROTACIONAL EM TEMPOS DE ENSINO REMOTO
Authors: Souza Lázaro Rômulo de , Soares Edivanha Bezerra da Silva , Oliveira Glaydson Francisco Barros de
Published: October 2021

Em tempos de pandemia, o ensino remoto foi a tônica das práticas escolares, os professores precisaram se reinventar e, no ensino de Matemática, isso não foi exceção. Nesse sentido, o presente artigo objetiva apresentar uma experiência realizada em uma aula de Matemática Financeira na Educação Básica, em que foi utilizada uma adaptação do modelo de Ensino Híbrido Laboratório Rotacional, como estratégia de ensino. Amparado no paradigma qualitativo, realizamos um pré-teste com a finalidade de identificar o nível de entendimento dos estudantes com relação à temática a ser abordada, fundamental para a organização e execução da presente proposta de ensino através de streaming livre, proporcionando um ambiente colaborativo e interativo, no qual o estudante é o centro na construção do conhecimento. Através da aplicação, percebeu-se que houve melhoria na aprendizagem dos estudantes referente aos conteúdos: porcentagem, juros simples e juros compostos, evidenciada durante as etapas da proposta. Entendemos que os dados apresentados, contribuem para o debate quanto à utilização da tecnologia em tempos de ensino remoto e de ensino presencial
Immune-Related LncRNAs Affect the Prognosis of Osteosarcoma, Which Are Related to the Tumor Immune Microenvironment
Authors: Huang Qingshan , Lin Yilin , Chen Chenglong , Lou Jingbing , Ren Tingting , Huang Yi , Zhang Hongliang , Yu Yiyang , Guo Yu , Wang Wei , Wang Boyang , Niu Jianfang , Xu Jiuhui , Guo Lei , Guo Wei
Published: October 2021

Background: Abnormal expression of lncRNA is closely related to the occurrence and metastasis of osteosarcoma. The tumor immune microenvironment (TIM) is considered to be an important factor affecting the prognosis and treatment of osteosarcoma. This study aims to explore the effect of immune-related lncRNAs (IRLs) on the prognosis of osteosarcoma and its relationship with the TIM.

Methods: Ninety-five osteosarcoma samples from the TARGET database were included. Iterative LASSO regression and multivariate Cox regression analysis were used to screen the IRLs signature with the optimal AUC. The predict function was used to calculate the risk score and divide osteosarcoma into a high-risk group and low-risk group based on the optimal cut-off value of the risk score. The lncRNAs in IRLs signature that affect metastasis were screened for in vitro validation. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were used to evaluate the role of TIM in the influence of IRLs on osteosarcoma prognosis.

Results: Ten IRLs constituted the IRLs signature, with an AUC of 0.96. The recurrence and metastasis rates of osteosarcoma in the high-risk group were higher than those in the low-risk group. In vitro experiments showed that knockdown of lncRNA (AC006033.2) could increase the proliferation, migration, and invasion of osteosarcoma. ssGSEA and ESTIMATE results showed that the immune cell content and immune score in the low-risk group were generally higher than those in the high-risk group. In addition, the expression levels of immune escape-related genes were higher in the high-risk group.

Conclusion: The IRLs signature is a reliable biomarker for the prognosis of osteosarcoma, and they alter the prognosis of osteosarcoma. In addition, IRLs signature and patient prognosis may be related to TIM in osteosarcoma. The higher the content of immune cells in the TIM of osteosarcoma, the lower the risk score of patients and the better the prognosis. The higher the expression of immune escape-related genes, the lower the risk score of patients and the better the prognosis.
Crosstalk Between the Tumor Microenvironment and Cancer Cells: A Promising Predictive Biomarker for Immune Checkpoint Inhibitors
Authors: Li Xiaoying , Yang Yueyao , Huang Qian , Deng Yu , Guo Fukun , Wang Gang , Liu Ming
Published: October 2021

Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer treatment and are emerging as promising curative treatments in different type of cancers. However, only a small proportion of patients have benefited from ICIs and there is an urgent need to find robust biomarkers for individualized immunotherapy and to explore the causes of immunotherapy resistance. In this article, we review the roles of immune cells in the tumor microenvironment (TME) and discuss the effects of ICIs on these cell populations. We discuss the potential of the functional interaction between the TME and cancer cells as a predictive biomarker for ICIs. Furthermore, we outline the potential personalized strategies to improve the effectiveness of ICIs with precision.
Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators
Authors: Olson Keith M. , Traynor John R. , Alt Andrew
Published: October 2021

Allosteric modulators (AMs) of G-protein coupled receptors (GPCRs) are desirable drug targets because they can produce fewer on-target side effects, improved selectivity, and better biological specificity (e.g., biased signaling or probe dependence) than orthosteric drugs. An underappreciated source for identifying AM leads are peptides and proteins—many of which were evolutionarily selected as AMs—derived from endogenous protein-protein interactions (e.g., transducer/accessory proteins), intramolecular receptor contacts (e.g., pepducins or extracellular domains), endogenous peptides, and exogenous libraries (e.g., nanobodies or conotoxins). Peptides offer distinct advantages over small molecules, including high affinity, good tolerability, and good bioactivity, and specific disadvantages, including relatively poor metabolic stability and bioavailability. Peptidomimetics are molecules that combine the advantages of both peptides and small molecules by mimicking the peptide’s chemical features responsible for bioactivity while improving its druggability. This review 1) discusses sources and strategies to identify peptide/peptidomimetic AMs, 2) overviews strategies to convert a peptide lead into more drug-like “peptidomimetic,” and 3) critically analyzes the advantages, disadvantages, and future directions of peptidomimetic AMs. While small molecules will and should play a vital role in AM drug discovery, peptidomimetics can complement and even exceed the advantages of small molecules, depending on the target, site, lead, and associated factors.
Efficacy and Safety of High-Power Short-Duration Radiofrequency Catheter Ablation of Atrial Fibrillation
Authors: Park Je-Wook , Yang Song-Yi , Kim Min , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: October 2021

Introduction: Whereas, high-power short-duration (HPSD) radiofrequency (RF) ablation is generally used in atrial fibrillation (AF) catheter ablation (CA), its efficacy, safety, and influence on autonomic function have not been well established in a large population. This study compared HPSD-AFCA and conventional power (ConvP)-AFCA in propensity score matched-population.

Methods: In 3,045 consecutive patients who underwent AFCA, this study included 1,260 patients (73.9% male, 59 ± 10 years old, 58.2% paroxysmal type) after propensity score matching: 315 in 50~60W HPSD group vs. 945 in the ConvP group. This study investigated the procedural factors, complication rate, rhythm status, and 3-month heart rate variability (HRV) between the two groups and subgroups.

Results: Procedure time was considerably short in the HPSD group (135 min in HPSD vs. 181 min in ConvP, p < 0.001) compared to ConvP group, but there was no significant difference in the complication rate (2.9% in HPSD vs. 3.7% in ConvP, p = 0.477) and the 3-month HRV between the two groups. At the one-year follow-up, there was no significant difference in rhythm outcomes between the two groups (Overall, Log-rank p = 0.885; anti-arrhythmic drug free, Log-rank p = 0.673). These efficacy and safety outcomes were consistently similar irrespective of the AF type or ablation lesion set. The Cox regression analysis showed that the left atrium volume index estimated by computed tomography (HR 1.01 [1.00–1.02]), p = 0.003) and extra-pulmonary vein triggers (HR 1.59 [1.03–2.44], p = 0.036) were independently associated with one-year clinical recurrence, whereas the HPSD ablation was not (HR 1.03 [0.73–1.44], p = 0.887).

Conclusion: HPSD-AFCA notably reduced the procedure time with similar rhythm outcomes, complication rate, and influence on autonomic function as ConvP-AFCA, irrespective of the AF type or ablation lesion set.
Discordance Between Glucose Levels Measured in Interstitial Fluid vs in Venous Plasma After Oral Glucose Administration: A Post-Hoc Analysis From the Randomised Controlled PRE-D Trial
Authors: Færch Kristine , Amadid Hanan , Bruhn Lea , Clemmensen Kim Katrine Bjerring , Hulman Adam , Ried-Larsen Mathias , Blond Martin Bæk , Jørgensen Marit Eika , Vistisen Dorte
Published: October 2021

Aims

The oral glucose tolerance test (OGTT) is together with haemoglobin A1c (HbA1c) gold standard for diagnosing prediabetes and diabetes. The objective of this study was to assess the concordance between glucose values obtained from venous plasma versus interstitial fluid after oral glucose administration in 120 individuals with prediabetes and overweight/obesity.

Methods

120 adults with prediabetes defined by HbA1c 39-47 mmol/mol and overweight or obesity who participated in the randomised controlled PRE-D trial were included in the study. Venous plasma glucose concentrations were measured at 0, 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT) performed on three different occasions within a 26 weeks period. During the OGTT, the participants wore a CGM device (IPro2, Medtronic), which assessed glucose concentrations every five minutes.

Results

A total of 306 OGTTs with simultaneous CGM measurements were obtained. Except in fasting, the CGM glucose values were below the OGTT values throughout the OGTT period with mean (SD) differences of 0.2 (0.7) mmol/L at time 0 min, -1.1 (1.3) at 30 min, -1.4 (1.8) at 60 min, and -0.5 (1.1) at 120 min). For measurements at 0 and 120 min, there was a proportional bias with an increasing mean difference between CGM and OGTT values with increasing mean of the two measurements.

Conclusions

Due to poor agreement between the OGTT and CGM with wide 95% limits of agreement and proportional bias at 0 and 120 min, the potential for assessing glucose tolerance in prediabetes using CGM is questionable.
Toward an Understanding of Physical and Biological Properties of Corn-Based Whole Stillage, Thin Stillage, and Condensed Distillers Solubles and Changes Thereof During Storage
Authors: Rosentrater Kurt A. , Yang Lu
Published: October 2021

The production of bio-based ethanol has been one of the fastest growing industries in the United States during the past decade. Thus, wider exploration of ethanol coproduct uses is necessary in the ethanol plant. Currently, process steams such as whole stillage, thin stillage, and syrup are processed into distiller dried grains with solubles and fed to livestock. The storability of whole stillage, thin stillage, and syrup influences the economic and energetic balances of fuel ethanol production. However, there are few investigations of the shelf life for these products or how to measure these quantities. The objectives of this research were to test physical and biological properties of whole stillage, thin stillage, and syrup and determine storability and allowable shelf life for these materials as influenced by storage temperature levels. Using standard laboratory methods, several properties were determined, including moisture content, water activity, thermal properties (conductivity, resistivity, volumetric heat capacity, and diffusivity), color, mold development, and CO2 production. Also, the separation processes due to settling were observed over 72 h. The thin stillage and whole stillage had relative high average moisture contents of 92% (w.b.) and 87% (w.b.), respectively, and a mean water activity of 0.99; the high water content marked samples easily susceptible to rapid spoilage. Time had a significant effect (p < 0.05) on properties of coproducts. Both thin stillage and whole stillage samples got mold growth after 5 days incubation at 32°C. Thin stillage had the greatest separation rate in the settling experiment. However, syrup had a relative low average moisture content of 62% and an average water activity of 0.92. No mold growth and settling separation happened in syrup samples. There was no evidence showing that a linear relationship exists between Hunter L*, a* and b*, and mold growth. The Solvita® test showed that high-temperature treatment caused high CO2 production in all samples. The exponential models described the relationship between storage time (from 0 to 5 days at 25 and 35°C) and CO2 concentration for the three coproducts. This study is a first step to explore opportunities for utilizing valuable components from these coproducts. Follow-up study should work on separation processes to concentrate the valuable components of these coproducts. Exploring the potential value of ethanol coproducts could maintain and improve the profitability of the ethanol industry.
Reducing Hinge Flexibility of CAR-T Cells Prolongs Survival In Vivo With Low Cytokines Release
Authors: Zhang Ang , Sun Yao , Du Jie , Dong Yansheng , Pang Honggang , Ma Lei , Si Shaoyan , Zhang Zhong , He Mingyi , Yue Yang , Zhang Xiaoli , Zhao Weichao , Pi Jianjun , Chang Mindong , Wang Quanjun , Zhang Yikun
Published: October 2021

Chimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in B cell malignancies. However, high tumor burden limits clinical efficacy and increases the risk of cytokine release syndrome and neurotoxicity, which is associated with over-activation of the CAR-T cells. The hinge domain plays an important role in the function of CAR-T cells. We hypothesized that deletion of glycine, an amino acid with good flexibility, may reduce the flexibility of the hinge region, thereby mitigating CAR-T cell over-activation. This study involved generating a novel CAR by deletion of two consecutive glycine residues in the CD8 hinge domain of second-generation (2nd) CAR, thereafter named 2nd-GG CAR. The 2nd-GG CAR-T cells showed similar efficacy of CAR expression but lower hinge flexibility, and its protein affinity to CD19 protein was lower than that of 2nd CAR-T cells. Compared to the 2nd CAR-T cells, 2nd-GG CAR-T cells reduced proinflammatory cytokine secretion without diminishing the specific cytotoxicity toward tumor cells in vitro. Furthermore, 2nd-GG CAR-T cells prolonged overall survival in an immunodeficient mouse model bearing NALM-6 when tumor burden was high. This study demonstrated that a lower-flexibility of CD8α hinge improved survival under high tumor burden and reduced proinflammatory cytokines in preclinical studies. While there is potential for improved safety and efficacy, yet this needs validation with clinical trials.
Autophagy Induced by Palmitic Acid Regulates Neutrophil Adhesion Through the Granule-Dependent Degradation of αMβ2 Integrin in Dairy Cows With Fatty Liver
Authors: Peng Zhicheng , Zhao Chenxu , Du Xiliang , Yang Yuchen , Li Yunfei , Song Yuxiang , Fang Baochen , Zhang Yuming , Qin Xia , Zhang Yuanyuan , Li Xiaobing , Wang Zhe , Li Xinwei , Liu Guowen
Published: October 2021

β2 integrins are critical for neutrophil firm adhesion, trans-endothelial migration, and the recruitment to the inflamed tissue. Autophagy is implicated in cell migration and tumor metastasis through facilitating the turnover of β1 integrins; however, whether autophagy is able to control neutrophil migration by promoting the degradation of β2 integrins is unexplored. Here, we show that high blood levels of palmitic acid (PA) strongly triggered neutrophil autophagy activation, leading to adhesion deficiency in dairy cows with fatty liver. The three neutrophil granule subtypes, namely, azurophil granules (AGs), specific granules (SGs), and gelatinase granules (GGs), were engulfed by the autophagosomes for degradation, resulting in an increased vacuolation in fatty liver dairy cow neutrophils. Importantly, the adhesion-associated molecules CD11b and CD18 distributed on AGs, SGs, and GGs were degraded with the three granule subtypes by autophagy. Moreover, FGA, Hsc70, and TRIM21 mediated the degradation of cytosolic oxidized–ubiquitinated CD11b and CD18. Collectively, our results demonstrate that high blood PA triggers neutrophil autophagy-dependent vacuolation and granule-dependent adhesion deficiency, decreasing neutrophil mobility, and impairing the innate immune system of dairy cow with fatty liver. This theory extends the category of autophagy in maintaining granule homeostasis and provides a novel strategy to improve the immune of dairy cows with metabolic disease.
Metabolic Engineering of Non-carotenoid-Producing Yeast Yarrowia lipolytica for the Biosynthesis of Zeaxanthin
Authors: Xie Yuxiao , Chen Shulin , Xiong Xiaochao
Published: October 2021

Zeaxanthin is vital to human health; thus, its production has received much attention, and it is also an essential precursor for the biosynthesis of other critical carotenoids such as astaxanthin and crocetin. Yarrowia lipolytica is one of the most intensively studied non-conventional yeasts and has been genetically engineered as a cell factory to produce carotenoids such as lycopene and β-carotene. However, zeaxanthin production by Y. lipolytica has not been well investigated. To fill this gap, β-carotene biosynthesis pathway has been first constructed in this study by the expression of genes, including crtE, crtB, crtI, and carRP. Three crtZ genes encoding β-carotene hydroxylase from different organisms were individually introduced into β-carotene-producing Y. lipolytica to evaluate their performance for producing zeaxanthin. The expression of crtZ from the bacterium Pantoea ananatis (formerly Erwinia uredovora, Eu-crtZ) resulted in the highest zeaxanthin titer and content on the basis of dry cell weight (DCW). After verifying the function of Eu-crtZ for producing zeaxanthin, the high-copy-number integration into the ribosomal DNA of Y. lipolytica led to a 4.02-fold increase in the titer of zeaxanthin and a 721% increase in the content of zeaxanthin. The highest zeaxanthin titer achieved 21.98 ± 1.80 mg/L by the strain grown on a yeast extract peptone dextrose (YPD)–rich medium. In contrast, the highest content of DCW reached 3.20 ± 0.11 mg/g using a synthetic yeast nitrogen base (YNB) medium to culture the cells. Over 18.0 g/L of citric acid was detected in the supernatant of the YPD medium at the end of cultivation. Furthermore, the zeaxanthin-producing strains still accumulated a large amount of lycopene and β-carotene. The results demonstrated the potential of a cell factory for zeaxanthin biosynthesis and opened up an avenue to engineer this host for the overproduction of carotenoids.
Promoting Extracellular Electron Transfer of Shewanella oneidensis MR-1 by Optimizing the Periplasmic Cytochrome c Network
Authors: Sun Weining , Lin Zhufan , Yu Qingzi , Cheng Shaoan , Gao Haichun
Published: October 2021

The low efficiency of extracellular electron transfer (EET) is a major bottleneck for Shewanella oneidensis MR-1 acting as an electroactive biocatalyst in bioelectrochemical systems. Although it is well established that a periplasmic c-type cytochrome (c-Cyt) network plays a critical role in regulating EET efficiency, the understanding of the network in terms of structure and electron transfer activity is obscure and partial. In this work, we attempted to systematically investigate the impacts of the network components on EET in their absence and overproduction individually in microbial fuel cell (MFC). We found that overexpression of c-Cyt CctA leads to accelerated electron transfer between CymA and the Mtr system, which function as the primary quinol oxidase and the outer-membrane (OM) electron hub in EET. In contrast, NapB, FccA, and TsdB in excess severely impaired EET, reducing EET capacity in MFC by more than 50%. Based on the results from both strategies, a series of engineered strains lacking FccA, NapB, and TsdB in combination while overproducing CctA were tested for a maximally optimized c-Cyt network. A strain depleted of all NapB, FccA, and TsdB with CctA overproduction achieved the highest maximum power density in MFCs (436.5 mW/m2), ∼3.62-fold higher than that of wild type (WT). By revealing that optimization of periplasmic c-Cyt composition is a practical strategy for improving EET efficiency, our work underscores the importance in understanding physiological and electrochemical characteristics of c-Cyts involved in EET.
Mapping of a Subgingival Dual-Species Biofilm Model Using Confocal Raman Microscopy
Authors: Kriem Lukas Simon , Wright Kevin , Ccahuana-Vasquez Renzo Alberto , Rupp Steffen
Published: October 2021

Techniques for continuously monitoring the formation of subgingival biofilm, in relation to the determination of species and their accumulation over time in gingivitis and periodontitis, are limited. In recent years, advancements in the field of optical spectroscopic techniques have provided an alternative for analyzing three-dimensional microbiological structures, replacing the traditional destructive or biofilm staining techniques. In this work, we have demonstrated that the use of confocal Raman spectroscopy coupled with multivariate analysis provides an approach to spatially differentiate bacteria in an in vitro model simulating a subgingival dual-species biofilm. The present study establishes a workflow to evaluate and differentiate bacterial species in a dual-species in vitro biofilm model, using confocal Raman microscopy (CRM). Biofilm models of Actinomyces denticolens and Streptococcus oralis were cultured using the “Zürich in vitro model” and were analyzed using CRM. Cluster analysis was used to spatially differentiate and map the biofilm model over a specified area. To confirm the clustering of species in the cultured biofilm, confocal laser scanning microscopy (CLSM) was coupled with fluorescent in vitro hybridization (FISH). Additionally, dense bacteria interface area (DBIA) samples, as an imitation of the clusters in a biofilm, were used to test the developed multivariate differentiation model. This confirmed model was successfully used to differentiate species in a dual-species biofilm and is comparable to morphology. The results show that the developed workflow was able to identify main clusters of bacteria based on spectral “fingerprint region” information from CRM. Using this workflow, we have demonstrated that CRM can spatially analyze two-species in vitro biofilms, therefore providing an alternative technique to map oral multi-species biofilm models.
Weighted Integration of Duration Information Across Visual and Auditory Modality Is Influenced by Modality-Specific Attention
Authors: Yoshimatsu Hiroshi , Yotsumoto Yuko
Published: October 2021

We constantly integrate multiple types of information from different sensory modalities. Generally, such integration is influenced by the modality that we attend to. However, for duration perception, it has been shown that when duration information from visual and auditory modalities is integrated, the perceived duration of the visual stimulus leaned toward the duration of the auditory stimulus, irrespective of which modality was attended. In these studies, auditory dominance was assessed using visual and auditory stimuli with different durations whose timing of onset and offset would affect perception. In the present study, we aimed to investigate the effect of attention on duration integration using visual and auditory stimuli of the same duration. Since the duration of a visual flicker and auditory flutter tends to be perceived as longer than and shorter than its physical duration, respectively, we used the 10 Hz visual flicker and auditory flutter with the same onset and offset timings but different perceived durations. The participants were asked to attend either visual, auditory, or both modalities. Contrary to the attention-independent auditory dominance reported in previous studies, we found that the perceived duration of the simultaneous flicker and flutter presentation depended on which modality the participants attended. To further investigate the process of duration integration of the two modalities, we applied Bayesian hierarchical modeling, which enabled us to define a flexible model in which the multisensory duration is represented by the weighted average of each sensory modality. In addition, to examine whether auditory dominance results from the higher reliability of auditory stimuli, we applied another models to consider the stimulus reliability. These behavioral and modeling results suggest the following: (1) the perceived duration of visual and auditory stimuli is influenced by which modality the participants attended to when we control for the confounding effect of onset–offset timing of stimuli, and (2) the increase of the weight by attention affects the duration integration, even when the effect of stimulus reliability is controlled. Our models can be extended to investigate the neural basis and effects of other sensory modalities in duration integration.
An Efficacy and Feasibility Analysis of Chinese Patent Medicine Combined With Letrozole in the Treatment of Women With Ovulation Disorders: A Network Meta-Analysis
Authors: Zhu Jing-Yan , Liu Jian , Cao Xiao-Jing , Wang Xiao-Yun
Published: October 2021

Objective: To compare the efficacy of various listed Chinese patent medicines combined with letrozole in the treatment of ovulation disorders using network meta-analysis (NMA). Methods: We conducted a systematic literature search in PubMed, Cochrane Central Register of Controlled Trials, Embase, Chinese Biomedical Literature, China National Knowledge Infrastructure, Wanfang, and VIP Information databases up to June 2020. Randomized controlled trials reporting Chinese patent medicine combined with letrozole for ovulation disorders were included. The Stata 13 and WinBUGS1.43 software were used for data analysis. Results: A total of 24 randomized controlled trials were included, involving 2,318 patients. The results showed that when compared with patients using only letrozole, the ovulation rate was higher in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, Fufang Xuanju capsules, or Dingkun Dan, and Fufan Xuanju capsules showed the greatest improvement; the pregnancy rate was higher in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, or Dingkun Dan; and the endometrial thickness on the day of follicular maturity was greater in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, Fufang Xuanju capsules, Bailing capsules, or Dingkun Dan. In terms of the sequencing of NMA results, Fufang Xuanju capsules combined with letrozole gave the best results in improving the ovulation rate and increasing the endometrial thickness, while Dingkun Dan combined with letrozole achieved the best results for improving the pregnancy rate. Conclusion: Letrozole combined with Chinese patent medicine is more effective than letrozole alone in the treatment of ovulation disorders. Fufang Xuanju capsules is good at improving the ovulation rate and increasing the endometrial thickness. Dingkun Dan is good at improving the pregnancy rate. The appropriate choice of treatment should be made according to the actual clinical situation. This study is registered with the International Prospective Register of Systematic Reviews (CRD42020200603).
Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity
Authors: Kuwabara Yuki , Salavatian Siamak , Howard-Quijano Kimberly , Yamaguchi Tomoki , Lundquist Eevanna , Mahajan Aman
Published: October 2021

Introduction: Sympathetic hyperactivity is strongly associated with ventricular arrhythmias and sudden cardiac death. Neuromodulation provides therapeutic options for ventricular arrhythmias by modulating cardiospinal reflexes and reducing sympathetic output at the level of the spinal cord. Dorsal root ganglion stimulation (DRGS) is a recent neuromodulatory approach; however, its role in reducing ventricular arrhythmias has not been evaluated. The aim of this study was to determine if DRGS can reduce cardiac sympathoexcitation and the indices for ventricular arrhythmogenicity induced by programmed ventricular extrastimulation. We evaluated the efficacy of thoracic DRGS at both low (20 Hz) and high (1 kHz) stimulation frequencies.

Methods: Cardiac sympathoexcitation was induced in Yorkshire pigs (n = 8) with ventricular extrastimulation (S1/S2 pacing), before and after DRGS. A DRG-stimulating catheter was placed at the left T2 spinal level, and animals were randomized to receive low-frequency (20 Hz and 0.4 ms) or high-frequency (1 kHz and 0.03 ms) DRGS for 30 min. High-fidelity cardiac electrophysiological recordings were performed with an epicardial electrode array measuring the indices of ventricular arrhythmogenicity—activation recovery intervals (ARIs), electrical restitution curve (Smax), and Tpeak–Tend interval (Tp-Te interval).

Results: Dorsal root ganglion stimulation, at both 20 Hz and 1 kHz, decreased S1/S2 pacing-induced ARI shortening (20 Hz DRGS −21±7 ms, Control −50±9 ms, P = 0.007; 1 kHz DRGS −13 ± 2 ms, Control −46 ± 8 ms, P = 0.001). DRGS also reduced arrhythmogenicity as measured by a decrease in Smax (20 Hz DRGS 0.5 ± 0.07, Control 0.7 ± 0.04, P = 0.006; 1 kHz DRGS 0.5 ± 0.04, Control 0.7 ± 0.03, P = 0.007), and a decrease in Tp-Te interval/QTc (20 Hz DRGS 2.7 ± 0.13, Control 3.3 ± 0.12, P = 0.001; 1 kHz DRGS 2.8 ± 0.08, Control; 3.1 ± 0.03, P = 0.007).

Conclusions: In a porcine model, we show that thoracic DRGS decreased cardiac sympathoexcitation and indices associated with ventricular arrhythmogenicity during programmed ventricular extrastimulation. In addition, we demonstrate that both low-frequency and high-frequency DRGS can be effective neuromodulatory approaches for reducing cardiac excitability during sympathetic hyperactivity.
Disruption of the Serine/Threonine Kinase Akt Gene Affects Ovarian Development and Fecundity in the Cigarette Beetle, Lasioderma serricorne
Authors: Xu Kang-Kang , Yan Yi , Yan Shu-Yan , Xia Peng-Liang , Yang Wen-Jia , Li Can , Yang Hong
Published: October 2021

Serine/threonine kinase Akt, an important component of the insulin signaling pathway, plays an essential role in many physiological processes. In this study, we identified and characterized an Akt gene (designated LsAkt) from the cigarette beetle, Lasioderma serricorne. LsAkt contains a 1614 bp open reading frame encoding a 537 amino acid protein that possesses a conserved pleckstrin homology domain and a serine/threonine kinase domain. The expression of LsAkt was high in pupal stages and peaked in day-4 female pupae. In adult tissues, LsAkt was highly expressed in the thorax, ovary, and midgut. The expression of LsAkt was induced by methoprene or bovine insulin in vivo, but significantly decreased by 20-hydroxyecdysone. RNA interference-mediated knockdown of LsAkt resulted in severely blocked ovarian development and reduced fecundity and hatchability. The vitellogenin (Vg) content and juvenile hormone (JH) titers of LsAkt-depletion beetles were decreased, and expressions of Vg and four JH signaling and biosynthetic genes were significantly decreased. Silencing of LsAkt reduced the amounts of glucose, glycogen, and trehalose in female adults and affected the expressions of seven key carbohydrate metabolic genes. Taken together, it is inferred that Akt implicates in L. serricorne reproduction by modification of Vg synthesis, juvenile hormone production and carbohydrate metabolism.
Two Carbohydrate-Based Natural Extracts Stimulate in vitro Pollen Germination and Pollen Tube Growth of Tomato Under Cold Temperatures
Authors: Laggoun Ferdousse , Ali Nusrat , Tourneur Sabine , Prudent Grégoire , Gügi Bruno , Kiefer-Meyer Marie-Christine , Mareck Alain , Cruz Florence , Yvin Jean-Claude , Nguema-Ona Eric , Mollet Jean-Claude , Jamois Frank , Lehner Arnaud
Published: October 2021

To date, it is widely accepted by the scientific community that many agricultural regions will experience more extreme temperature fluctuations. These stresses will undoubtedly impact crop production, particularly fruit and seed yields. In fact, pollination is considered as one of the most temperature-sensitive phases of plant development and until now, except for the time-consuming and costly processes of genetic breeding, there is no immediate alternative to address this issue. In this work, we used a multidisciplinary approach using physiological, biochemical, and molecular techniques for studying the effects of two carbohydrate-based natural activators on in vitro tomato pollen germination and pollen tube growth cultured in vitro under cold conditions. Under mild and strong cold temperatures, these two carbohydrate-based compounds significantly enhanced pollen germination and pollen tube growth. The two biostimulants did not induce significant changes in the classical molecular markers implicated in pollen tube growth. Neither the number of callose plugs nor the CALLOSE SYNTHASE genes expression were significantly different between the control and the biostimulated pollen tubes when pollens were cultivated under cold conditions. PECTIN METHYLESTERASE (PME) activities were also similar but a basic PME isoform was not produced or inactive in pollen grown at 8°C. Nevertheless, NADPH oxidase (RBOH) gene expression was correlated with a higher number of viable pollen tubes in biostimulated pollen tubes compared to the control. Our results showed that the two carbohydrate-based products were able to reduce in vitro the effect of cold temperatures on tomato pollen tube growth and at least for one of them to modulate reactive oxygen species production.
Enviromic Assembly Increases Accuracy and Reduces Costs of the Genomic Prediction for Yield Plasticity in Maize
Authors: Costa-Neto Germano , Crossa Jose , Fritsche-Neto Roberto
Published: October 2021

Quantitative genetics states that phenotypic variation is a consequence of the interaction between genetic and environmental factors. Predictive breeding is based on this statement, and because of this, ways of modeling genetic effects are still evolving. At the same time, the same refinement must be used for processing environmental information. Here, we present an “enviromic assembly approach,” which includes using ecophysiology knowledge in shaping environmental relatedness into whole-genome predictions (GP) for plant breeding (referred to as enviromic-aided genomic prediction, E-GP). We propose that the quality of an environment is defined by the core of environmental typologies and their frequencies, which describe different zones of plant adaptation. From this, we derived markers of environmental similarity cost-effectively. Combined with the traditional additive and non-additive effects, this approach may better represent the putative phenotypic variation observed across diverse growing conditions (i.e., phenotypic plasticity). Then, we designed optimized multi-environment trials coupling genetic algorithms, enviromic assembly, and genomic kinships capable of providingin-silicorealization of the genotype-environment combinations that must be phenotyped in the field. As proof of concept, we highlighted two E-GP applications: (1) managing the lack of phenotypic information in training accurate GP models across diverse environments and (2) guiding an early screening for yield plasticity exerting optimized phenotyping efforts. Our approach was tested using two tropical maize sets, two types of enviromics assembly, six experimental network sizes, and two types of optimized training set across environments. We observed that E-GP outperforms benchmark GP in all scenarios, especially when considering smaller training sets. The representativeness of genotype-environment combinations is more critical than the size of multi-environment trials (METs). The conventional genomic best-unbiased prediction (GBLUP) is inefficient in predicting the quality of a yet-to-be-seen environment, while enviromic assembly enabled it by increasing the accuracy of yield plasticity predictions. Furthermore, we discussed theoretical backgrounds underlying how intrinsic envirotype-phenotype covariances within the phenotypic records can impact the accuracy of GP. The E-GP is an efficient approach to better use environmental databases to deliver climate-smart solutions, reduce field costs, and anticipate future scenarios.
The Relationship Between (sub)national Identity, Citizenship Conceptions, and Perceived Ethnic Threat in Flanders and Wallonia for the Period 1995–2020: A Measurement Invariance Testing Strategy
Authors: Billiet Jaak , Meeusen Cecil , Abts Koen
Published: October 2021

This article examines the relationship between (sub)national identity and attitudes towards immigrants in the multinational context of Belgium. We extend our previous studies by analysing a longer time period (1995–2020) and by making a strong case for the idea that measurement invariance testing and theoretical meaningfulness are closely intertwined. To examine whether and how the relationship between (sub)national identity and perceived ethnic threat has changed over time and between regions, we first test for metric invariance of the latent concepts. Using data from the Belgian National Election Studies, we illustrate that evaluating invariance of measurements is a necessary condition for comparative research, but also that measurement equivalence testing should be considered as an empirical guide showing researchers where substantial conclusions should potentially be revisited and theoretical validity rethought. Next, we verify whether the relationship between (sub)national identity and perceptions of ethnic threat across subnational units can be attributed to different conceptions of community membership -in terms of ethnic and/or civic citizenship conceptions- in Flanders and Wallonia. While we expected that a strong identification with Flanders would primarily be related to an ethnic citizenship representation, and as a result, stronger feelings of threat towards immigrants; we expected that a strong identification with Wallonia would primarily be related to a civic representation of the nation and therefore lower feelings of threat. Thanks to our thorough invariance testing strategy, the conceptualisation and measurement of (sub)national identity had to be adjusted in Wallonia, and the hypotheses had to be qualified.