bluuebunny/crossref_metadata_2025 huggingface dataset:
Alunos com deficiência intelectual: O trabalho pedagógico e o ensino das ciências
Authors: Andrade Joanna Angélica Melo de , Silva Elizamar Ciríaco da , Pagan Alice Alexandre
Published: May 2021

A Educação tem buscado adequar seu papel às atuais demandas da sociedade, dentre elas, a promoção de igualdade e oportunidades de aprendizagem. No sentido de iniciar uma compreensão desse processo, este trabalho buscou descrever e analisar concepções e práticas de algumas professoras, do município de Aracaju-SE, que ensinam ciências, sobre o processo de inclusão do aluno com deficiência intelectual (DI) nas salas de aula de ensino regular. A pesquisa foi realizada em seis escolas de Aracaju, a partir da aplicação de 16 questionários a professoras do Ensino Fundamental I e II. Os dados foram interpretados a partir do método da Análise de Conteúdo Bardin (2016). Os resultados revelaram que a intelectual é a mais expressiva das deficiências no município, no entanto, as professoras consultadas não se consideram capacitadas para atender os alunos DI em classes regulares, dado que este despreparo é advindo, segundo elas, tanto de deficiências na formação inicial quanto da formação continuada, o que requer modificações na atual conjuntura da educação e do currículo de formação dos professores de ciências. Para que a Educação Inclusiva seja potencializada sugere-se que os professores sejam capacitados a utilizarem metodologias focadas no estudante, de maneira que todos os alunos e alunas possam desenvolver seu potencial a partir da construção de um pensamento científico, baseado na curiosidade e na ação de interação com o meio a qual eles estão inseridos.
Papel das intervenções educativas relacionado aos riscos ocupacionais para os profissionais de enfermagem
Authors: Farias Jucirema Rodrigues , Chermont Aurimery Gomes , Savino Neto Silvestre , Silva Junior Paulo Cesar Beckman da , Farias Jucenira Rodrigues , Flexa Raissa dos Santos
Published: May 2021

Objetivo: Descrever quais os riscos ocupacionais encontrados no ambiente laboral da enfermagem de acordo com as literaturas, bem como identificar o papel das intervenções educacionais em saúde relacionado aos riscos ocupacionais. Método: revisão integrativa, cujo os critérios de elegibilidade dos artigos foram corresponder aos descritores associados: Profissionais de Enfermagem, Tecnologia Biomédica, Riscos Ocupacionais, Enfermagem do Trabalho e estar disponível eletronicamente nas bases de dados: BVS, LILACS, Medline/PUBMED, SCIELO e na BDENF, com ano de publicação referente a 2015 a 2020. Resultados: foram selecionados 16 publicações para análise, com predomínio de autores brasileiros enfermeiros, dos quais observou-se a preocupação do Profissional da área quanto a redução e controle dos riscos ocupacionais para com a sua equipe, nos diferentes ambientes de trabalho, sendo encontrado estudos em sua maioria em hospitais seguido por unidades básicas de saúde, utilizando a educação continuada e permanente como ferramenta para minimizar os riscos ocupacionais. Considerações Finais: o profissional de enfermagem compondo a equipe de saúde é o profissional mais exposto aos riscos ocupacionais nos diversos ambientes de prestação de serviços de saúde. Riscos como biológicos, químicos, físicos, ergonômicos e psicossociais.
Influência do substrato dos telhados verdes na redução do escoamento superficial quando submetido às condições climáticas da Região Metropolitana do Recife
Authors: Barros Camila Barrêtto Rique de , Soares Willames de Albuquerque , Holanda Marco Aurelio Calixto Ribeiro de
Published: May 2021

O processo de urbanização acarreta a diminuição de áreas permeáveis, gerando uma redução na taxa de infiltração e consequente aumento do escoamento das águas pluviais, intensificando a frequência e a magnitude dos alagamentos. Contudo, o uso de telhados verdes vem se mostrando uma prática eficiente na redução e retardo desse escoamento. Nesse sentido, buscou-se identificar a classe textural ótima para o substrato de um telhado verde submetido às condições climáticas da Região Metropolitana do Recife (RMR). Para isso, realizou-se a calibração e validação do modelo Hydrus-1D com uso do volume drenado por um protótipo de telhado verde. Em seguida foram feitas simulações do fluxo de água no solo com diferentes classes texturais. Após a validação foi verificada uma boa eficiência do modelo na representação dos valores observados. Por fim, as classes texturais que apresentaram as maiores capacidades de retenção média foram a franca arenosa, franca, franco siltosa e silte. Com isso, para região estudada, o substrato do telhado verde deve ser composto por uma dessas categorias de solo. Na falta das mesmas, devem ser empregadas a areia, areia franca, franco argilo siltosa ou franco argilosa.
Análise da produção científica sobre a tecnologia e a inovação no agronegócio
Authors: Santos Isabel Cristina dos , Silveira Glaucia Bambirra , Silva Renato Emanuel Gomes da
Published: May 2021

O estudo visa apresentar a literatura mais recente sobre o tema inovação e tecnologia aplicadas ao agronegócio. O trabalho consistiu em realizar uma análise dos artigos científicos publicados no banco de dados da Web of Science no período de 2016 a 2020. Trata-se de uma pesquisa exploratória, de abordagem quantitativa, com a utilização da Teoria do Enfoque Meta-analítico Consolidado, que proporciona uma abordagem integradora de revisão da literatura. Os resultados apontaram que 2.427 artigos científicos, nacionais e internacionais, em vários idiomas e em diversas áreas do conhecimento, adotaram abordagem simultânea dos descritores inovação, tecnologia e agronegócio, no período de 2016 a 2020. Dentre esses estudos, destacam-se 104 artigos elaborados por pesquisadores brasileiros. A Empresa Brasileira de Pesquisa Agropecuária, Universidade de São Paulo e a Universidade Estadual Paulista foram as instituições brasileiras que mais se destacaram nas produções acadêmicas, apresentando trabalhos compartilhados com organizações brasileiras e estrangeiras, o que contribuiu para a difusão do conhecimento no tema inovação e tecnologia no agronegócio.
Modeling trophic webs in freshwater fishpond systems using Ecopath: towards better polyculture management
Authors: Aubin J , Baizeau V , Jaeger C , Roucaute M , Gamito S
Published: May 2021

Freshwater pond polyculture faces many challenges in Europe. Appropriate tools must be developed to better understand and manage trophic interactions in pond ecosystems. The objective of our study was to understand the trophic interactions and make inference on the fish diet in common carp polyculture through a combination of experiments and trophic web modeling. We conducted an experiment in small fishponds of common carp polyculture reared with roach and perch and used Ecopath with Ecosim software to characterize the food web. Two replicates of 3 treatments were performed: a semi-extensive pond with low fish density and no formulated feed, an intensive pond with twice the fish density and formulated feed and an intensive pond coupled with a planted lagoon. Ten trophic groups were defined to describe the food web. The modeling procedure enabled us to estimate the diets of each trophic group. The fish diet in fed and non-fed treatments differed greatly since the carp fed mainly on formulated feed when available. The roach exhibited trophic plasticity by adapting their diet to the available resources. The benthic macroinvertebrates and zooplankton were preyed upon intensively; they became the limiting factors for fish production and depended on phytoplankton availability. Detritus and phytoplankton were the main sources of nutrients in all treatments but were not used efficiently. These results provide several insights for improving polyculture. In particular, they promote better management of zooplankton and macroinvertebrates as food sources for target species and a better balance in fish assemblages for more efficient use of resources.
Lomba Kreativitas Tanaman Hidroponik sebagai Strategi dalam Mewujudkan Kampung Hijau di RW 09 Kelurahan Kebon Pala Kota Administrasi Jakarta Timur
Authors: Ulinata Ulinata , Dianty Grace Putri , Hasugian Ajeng ED , Kidingallo Enrique K
Published: May 2021

Untuk dapat mewujudkan kampung hijau secara perlahan dan mencapai kondisi masyarakat yang hidup sehat terutama pada masa Pandemik COVID 19, serta meningkatkan ketahanan pangan bagi masyarakat yang memiliki keterbatasan lahan, maka hidroponik merupakan pilihan yang tepat. 

         Program Studi Arsitektur Fakultas Teknik UKI melalui program Pengabdian Pada Masyarakat melakukan kegiatan Green Action 22 Lomba Kreativitas Tanaman Hidroponik sebagai Strategi dalam Mewujudkan Kampung Hijau di RW 09 Kelurahan Kebon Pala Kota Administrasi Jakarta Timur 2020.

Metode yang dilakukan adalah mengadakan lomba kreasi tanaman hidroponik untuk menggiatkan kembali kegiatan berkreasi menanam khususnya hidroponik sehingga perlahan akan dapat meningkatkan ketahanan pangan dan mewujudkan kampung hijau di kelurahan Kebon Pala tersebut.

 Prosesnya menyiapkan alat dan bahan yang akan dipergunakan pada saat lomba berupa stereofoam, dua botol nutrisi AB mix, pembolong, selang, netpot, airator, flanel potong, rockwool, benih selada, samhong, TDS, nampan, gelas ukur yang dibagikan kepada para peserta lomba. Waktu perlombaan sekitar 5-6 minggu. Hasilnya adalah pada saat pengumuman pemenang, peserta wajib menunjukkan hasil panen yang sudah dikemas. Kategori pemenang berdasarkan empat kriteria diantaranya tingkat kerapian alat dan media tanam, perkembangan benih, bobot panen yang dihasilkan kemasannya. Selain hadiah, para peserta juga memperoleh edukasi mengenai hidroponik.
Peran Pelatihan Ketahanan dan Motivasi bagi Peningkatan Kinerja Guru Honorer di Kabupaten Bandung Barat
Authors: Bob Foster  , Fitriani Reyta  , Susan Purnama  , Bernadetha Nadeak  , Elfrida Sormin
Published: May 2021

Untuk mencipakan siswa yang berkualitas salah satunya dengan meningkatkan ketahanan seorang guru. Ketahanan guru dalam menghadapi kondisi sulit perlu menjadi perhatian pimpinan sekolah dalam upaya peningkatan kualitas pendidikan, dengan asumsi ketahanan akan meningkatkan kinerja guru dan menentukan pencapaian tujuan pendidikan. Selain ketahanan guru motivasi dari pihak sekolah juga memiliki peranan penting. Jika motivasi sekolah rendah, maka akan berakibat buruk pada kinerja guru. Dengan adanya fenomena tersebut, terdapat kemungkinan penurunan kinerja guru honorer. Keberhasilan sekolah dalam memperbaiki kinerja guru dapat dipengaruhi pada pemberian pelatihan bagi peningkatan kualitas sumber daya guru dalam bekerja salah satunya pelatihan bagi ketahanan guru dalam mengatasi rintangan mengajar dan menhadapi kondisi sulit. Penelitian kuantitatif ini adalah hasil pengembangan pengabdian kepada masyarakat yang dilakukan oleh akademisi dari fakultas ekonomi dan bisnis Universitas Informatika dan Bisnis Bandung, dengan tujuan menguji pengaruh pelatihan ketahanan guru dan pemberian motivasi terhadap peningkatan kinerja pada 100 (seratus) guru honorer di Kabupaten Bandung Barat. Hipotesis diuji dengan analisis data Partial Least Square (PLS). Hasil menunjukkan bahwa pelatihan ketahanan diri meningkatkan kinerja guru  sedangkan motivasi tidak beperan meningkatkan kinerja guru honorer di Kabupaten Bandung Barat.
Bir Politik Anlatı Olarak Ahmet Kaya Şarkıları: Açık Yaranın Sesi (İlkay Kara)
Authors: KIZILKAYA Zeynep Zelal
Published: May 2021

Bir Politik Anlatı Olarak Ahmet Kaya Şarkıları: Açık Yaranın Sesi (İlkay Kara)
G Protein-Coupled Receptor Kinase 2 (GRK2) Regulates T Cell Response in a Murine Model of House Dust Mite-Induced Asthma
Authors: Kammala Ananth K. , Yang Canchai , Panettieri Reynold A. , Das Rupali , Subramanian Hariharan
Published: May 2021

G protein-coupled receptor kinase 2 (GRK2) is an adapter protein that modulates G protein-coupled receptor (GPCR) signaling. It also regulates the functions and activity of other intracellular proteins in many cell types. Accordingly, GRK2 is thought to contribute to disease progression by a variety of mechanisms related to its multifunctional roles. Indeed, GRK2 levels are enhanced in patient samples as well as in preclinical models of several diseases. We have previously shown that GRK2 regulates mast cell functions, and thereby contributes to exacerbated inflammation during allergic reactions. In the current study, we observed that GRK2 levels are enhanced in the lungs of human asthma patients and in mice sensitized to house dust mite extract (HDME) allergen. Consistent with these findings, interleukin (IL)-4 and IL-13 levels were reduced in the lungs of GRK2+/− mice in a HMDE mouse model of asthma. Because Th2 cells are the major source of these cytokines during asthma, we determined the role of GRK2 in regulating T cell-specific responses in our HMDE mouse model. We observed a significant reduction of airway hyperresponsiveness (AHR), lung eosinophil and lymphocyte counts, serum IgE, Th2 cytokines (IL-4 and IL-13), goblet cell hyperplasia and mucus production in mice that had reduced GRK2 expression specifically in T cells. Collectively, our studies reveal an important role for GRK2 in regulating T cell response during asthma pathogenesis and further elucidation of the mechanisms through which GRK2 modulates airway inflammation will lead to the development of new therapeutic strategies for asthma.
hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression
Authors: Gong Chunli , Yang Huan , Wang Sumin , Liu Jiao , Li Zhibin , Hu Yiyang , Chen Yang , Huang Yu , Luo Qiang , Wu Yuyun , Liu En , Xiao Yufeng
Published: May 2021

High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2-related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Here, we showed that hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. We further found that hTERT increases NRF2 expression at both the mRNA and protein levels. Our data also revealed that hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability. Using DNA pull-down/MS analysis, we found that hTERT can recruit YBX1 to upregulate NRF2 promoter activity. We also found that hTERT/YBX1 may localize to the P2 region of the NRF2 promoter. Taken together, our results demonstrate that hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter. These results provide a new theoretical basis for CRC treatment.
Information Entropy as Quantifier of Potential Predictability in the Tropical Indo-Pacific Basin
Authors: Ikuyajolu Olawale J. , Falasca Fabrizio , Bracco Annalisa
Published: May 2021

Global warming is posed to modify the modes of variability that control much of the climate predictability at seasonal to interannual scales. The quantification of changes in climate predictability over any given amount of time, however, remains challenging. Here we build upon recent advances in non-linear dynamical systems theory and introduce the climate community to an information entropy quantifier based on recurrence. The entropy, or complexity of a system is associated with microstates that recur over time in the time-series that define the system, and therefore to its predictability potential. A computationally fast method to evaluate the entropy is applied to the investigation of the information entropy of sea surface temperature in the tropical Pacific and Indian Oceans, focusing on boreal fall. In this season the predictability of the basins is controlled by two regularly varying non-linear oscillations, the El Niño-Southern Oscillation and the Indian Ocean Dipole. We compute and compare the entropy in simulations from the CMIP5 catalog from the historical period and RCP8.5 scenario, and in reanalysis datasets. Discrepancies are found between the models and the reanalysis, and no robust changes in predictability can be identified in future projections. The Indian Ocean and the equatorial Pacific emerge as troublesome areas where the modeled entropy differs the most from that of the reanalysis in many models. A brief investigation of the source of the bias points to a poor representation of the ocean mean state and basins' connectivity at the Indonesian Throughflow.
Characteristics of Ang-(1–7)/Mas-Mediated Amelioration of Joint Inflammation and Cardiac Complications in Mice With Collagen-Induced Arthritis
Authors: Wang Zhongjie , Huang Wenhan , Ren Feifeng , Luo Lei , Zhou Jun , Huang Dongmei , Jiang Mei , Du Huaan , Fan Jinqi , Tang Lin
Published: May 2021

Objectives

Rheumatoid arthritis (RA) is a disabling disease with a high incidence that is regularly accompanied by cardiovascular complications. Several studies have suggested that renin–angiotensin–aldosterone system (RAAS) is closely associated with RA. The aim of this study was to investigate the mechanisms underlying Angiotensin-(1–7) [Ang-(1–7)] and its Mas receptor agonist (AVE0991) on joint inflammation and cardiac complications in a collagen-induced arthritis (CIA) model.

Methods

Collagen type II was injected into DBA/1 mice to construct an arthritis model. CIA mice were treated with Ang-(1–7) (2.0 mg/kg intraperitoneally) and AVE0991 (3.0 mg/kg intraperitoneally). The serum levels of inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 β, IL-6, and C-reactive protein (CRP)] were determined by ELISA. The mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways in joint tissues and the transforming growth factor (TGF)-β/Smad pathway and levels of α-Smooth muscle action (SMA) and β-myosin heavy chain (MHC) protein expression in cardiac tissues were assessed by western blots. The levels of TGF-β/Smad pathway, α-SMA, and β-MHC RNA in cardiac tissues were analyzed by real time-PCR. The levels of receptor activator of nuclear factor kappa ligand (RANKL) and promoting matrix metalloproteinase (MMP)-3 expression in the ankle joints were detected by immunohistochemistry and real time-PCR.

Results

Ang-(1–7) and AVE0991 reduced the levels of inflammatory cytokines and inhibited the MAPKs and NF-κB signaling pathways in ankle joint tissues, reduced RANKL and MMP3 expression, and ameliorated local joint inflammation and bone destruction compared with the control group. In addition, Ang-(1–7) and AVE0991 attenuated the TGF-β/Smad signaling pathway, reduced the levels of α-SMA and β-MHC expression, and diminished inflammatory cell infiltration into the myocardial interstitium and myocardial interstitial fibrosis in the hearts of CIA mice.

Conclusions

Ang-(1–7) alleviated joint damage caused by inflammation likely through the attenuation of NF-κB and MAPK pathways and ameliorated inflammation-induced cardiac fibrosis and activation of the TGF-β/Smad pathway. Moreover, Ang-(1–7) was likely mediated through the Mas receptor. This study provides theoretical evidence for exploring novel clinical therapeutic approaches for RA and its cardiac complications.
Effects of Sediment Characteristics on Carbon Dioxide Fluxes Based on Interacting Factors in Unvegetated Tidal Flats
Authors: Lin Wei-Jen , Chiu Ming-Chih , Lin Chiao-Wen , Lin Hsing-Juh
Published: May 2021

The contribution of unvegetated tidal flats to global net primary production is comparable to that of some vegetated coastal habitats. However, compared to carbon flux regulating factors in vegetated habitats, those in unvegetated tidal flats are not well understood, particularly in terms of their cause-effect relationships. Maximum gross primary production (GPPm), net primary production (NPP) and total respiration (TR) during emersion at noon when the irradiance level was at the saturation level for photosynthesis in nine unvegetated tidal flats across the Taiwan Strait in tropical and subtropical regions were determined in winter and summer from 2011 to 2016 to examine the direct and indirect relationships between sediment characteristics and carbon fluxes by using structural equation models (SEM). Most of the GPPm and NPP values were higher in winter than in summer. Conversely, the TR values were higher in summer than in winter. The NPP values at some sites shifted to negative values in summer, indicating the sites were carbon sources. The values of GPPm, TR and NPP for the tidal flats all increased significantly with increasing sediment mud content. The SEM results showed that the sediment mud content directly increased GPPm or indirectly increased GPPm via a compositional shift in benthic microalgae. The sediment mud content also directly increased TR or indirectly increased TR via increased organic matter content. The contribution of benthic microalgal and macrofaunal biomass to TR was relatively minor. This result suggests that primary production was stimulated mainly by the organic matter content rather than by increased microalgal biomass. With the integrated SEM framework, our results showed mechanistic evidence of how sediment mud content acted as a critical factor regulating carbon fluxes in unvegetated tidal flats.
Viral RNA in City Wastewater as a Key Indicator of COVID-19 Recrudescence and Containment Measures Effectiveness
Authors: Wurtz Nathalie , Lacoste Alexandre , Jardot Priscilla , Delache Alain , Fontaine Xavier , Verlande Maxime , Annessi Alexandre , Giraud-Gatineau Audrey , Chaudet Hervé , Fournier Pierre-Edouard , Augier Patrick , La Scola Bernard
Published: May 2021

In recent years, and more specifically at the beginning of the COVID-19 crisis, wastewater surveillance has been proposed as a tool to monitor the epidemiology of human viral infections. In the present work, from July to December 2020, the number of copies of SARS-CoV-2 RNA in Marseille’s wastewater was correlated with the number of new positive cases diagnosed in our Institute of Infectious Disease, which tested about 20% of the city’s population. Number of positive cases and number of copies of SARS-CoV-2 RNA in wastewater were significantly correlated (p = 0.013). During the great epidemic peak, from October to December 2020, the curves of virus in the sewers and the curves of positive diagnoses were perfectly superposed. During the summer period, the superposition of curves was less evident as subject to many confounding factors that were discussed. We also tried to correlate the effect of viral circulation in wastewater with containment measures, probably the most unbiased correlation on their potential inflection effect of epidemic curves. Not only is this correlation not obvious, but it also clearly appears that the drop in cases as well as the drop in the viral load in the sewers occur before the containment measures. In fact, this suggests that there are factors that initiate the end of the epidemic peak independently of the containment measure. These factors will therefore need to be explored more deeply in the future.
Comprehensive Proteomic Analysis of Lysine Acetylation in Nicotiana benthamiana After Sensing CWMV Infection
Authors: Yuan Bowen , Liu Tingting , Cheng Ye , Gao Shiqi , Li Linzhi , Cai Linna , Yang Jian , Chen Jianping , Zhong Kaili
Published: May 2021

Protein lysine acetylation (Kac) is an important post-translational modification mechanism in eukaryotes that is involved in cellular regulation. To investigate the role of Kac in virus-infected plants, we characterized the lysine acetylome of Nicotiana benthamiana plants with or without a Chinese wheat mosaic virus (CWMV) infection. We identified 4,803 acetylated lysine sites on 1,964 proteins. A comparison of the acetylation levels of the CWMV-infected group with those of the uninfected group revealed that 747 sites were upregulated on 422 proteins, including chloroplast localization proteins and histone H3, and 150 sites were downregulated on 102 proteins. Nineteen conserved motifs were extracted and 51 percent of the acetylated proteins located on chloroplast. Nineteen Kac sites were located on histone proteins, including 10 Kac sites on histone 3. Bioinformatics analysis results indicated that lysine acetylation occurs on a large number of proteins involved in biological processes, especially photosynthesis. Furthermore, we found that the acetylation level of chloroplast proteins, histone 3 and some metabolic pathway-related proteins were significantly higher in CWMV-infected plants than in uninfected plants. In summary, our results reveal the regulatory roles of Kac in response to CWMV infection.
Layer-Skipping Connections Improve the Effectiveness of Equilibrium Propagation on Layered Networks
Authors: Gammell Jimmy , Buckley Sonia , Nam Sae Woo , McCaughan Adam N.
Published: May 2021

Equilibrium propagation is a learning framework that marks a step forward in the search for a biologically-plausible implementation of deep learning, and could be implemented efficiently in neuromorphic hardware. Previous applications of this framework to layered networks encountered a vanishing gradient problem that has not yet been solved in a simple, biologically-plausible way. In this paper, we demonstrate that the vanishing gradient problem can be mitigated by replacing some of a layered network's connections with random layer-skipping connections in a manner inspired by small-world networks. This approach would be convenient to implement in neuromorphic hardware, and is biologically-plausible.
Therapy of Pediatric-Onset Multiple Sclerosis: State of the Art, Challenges, and Opportunities
Authors: Margoni Monica , Rinaldi Francesca , Perini Paola , Gallo Paolo
Published: May 2021

Treatment of pediatric-onset multiple sclerosis (POMS) has been tailored after observational studies and data obtained from clinical trials in adult-onset multiple sclerosis (AOMS) patients. There are an increasing number of new therapeutic agents for AOMS, and many will be formally studied for use also in POMS. However, there are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss the current state of the art of POMS therapy and will focus on the newer therapies (oral and infusion disease-modifying drugs) and on those still currently under investigation.
Single-Nucleus Chromatin Accessibility Landscape Reveals Diversity in Regulatory Regions Across Distinct Adult Rat Cortex
Authors: Yu Yeya , Wei Xiaoyu , Deng Qiuting , Lan Qing , Guo Yiping , Han Lei , Yuan Yue , Fan Peng , Wu Peiying , Shangguan Shuncheng , Liu Yang , Lai Yiwei , Volpe Giacomo , Esteban Miguel A. , Liu Chuanyu , Hou Yong , Liu Longqi
Published: May 2021

Rats have been widely used as an experimental organism in psychological, pharmacological, and behavioral studies by modeling human diseases such as neurological disorders. It is critical to identify and characterize cell fate determinants and their regulatory mechanisms in single-cell resolutions across rat brain regions. Here, we applied droplet-based single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) to systematically profile the single-cell chromatin accessibility across four dissected brain areas in adult Sprague–Dawley (SD) rats with a total of 59,023 single nuclei and identified 16 distinct cell types. Interestingly, we found that different cortex regions exhibit diversity in both cellular compositions and gene regulatory regions. Several cell-type-specific transcription factors (TFs), including SPI1, KLF4, KLF6, and NEUROD2, have been shown to play important roles during the pathogenesis of various neurological diseases, such as Alzheimer’s disease (AD), astrocytic gliomas, autism spectrum disorder (ASD), and intellectual disabilities. Therefore, our single-nucleus atlas of rat cortex could serve as an invaluable resource for dissecting the regulatory mechanisms underlying diverse cortex cell fates and further revealing the regulatory networks of neuropathogenesis.
The Prognosis of Single Hormone Receptor-Positive Breast Cancer Stratified by HER2 Status
Authors: Zhao Hengqiang , Gong Yiping
Published: May 2021

Single estrogen receptor (ER)+ and progesterone receptor (PR)+ tumors account for about10% of all breast cancers. However, the prognosis of these single hormone receptor-positive (HR+) tumor remains unclear. We aimed to investigate the characteristics of single HR+ breast tumors according to HER2 status in order to improve the treatment of patients with single HR+. Patients from the SEER program (2010-2016) were divided into ER+PR-, ER-PR+, ER+PR+ and ER-PR- molecular subtypes stratified by HER2 status. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared by Kaplan–Meier curves after propensity score matching (PSM). A total of 203,406 patients were enrolled. Single ER+ and PR+ tumors account for 11.9% of the total population. For HER2- subtype, patients with ER+PR- (n = 16906 pairs) and ER-PR+ (n = 1395 pairs) had worse prognoses than those with ER+PR+ with hazard ratio (HR) and 95% confidence interval (CI) of 1.52 (1.41-1.64) and 2.25 (1.76-2.88) for OS; and 1.94 (1.76-2.14) and 2.57 (1.94-3.40) for BCSS, respectively; ER+PR- showed a better prognosis than ER-PR+ (n = 1394 pairs) and ER-PR- (n = 9626 pairs) with HR (95% CI) of 1.32 (1.06-1.65) and 1.44 (1.33-1.55) for OS, and 1.32 (1.03-1.69) and 1.46 (1.34-1.60) for BCSS, respectively; ER-PR+ had a similar prognosis relative to ER-PR- (n = 1395 pairs) after PSM. For HER2+ subtype, patients with ER-PR+, ER+PR-, and ER-PR- had similar OS and BCSS; ER+PR+ showed a similar prognosis compare with ER-PR+ (n = 535 pairs), but had better OS and BCSS than ER+PR- (n = 5376 pairs) and ER-PR- (n = 8143 pairs) after PSM. In addition, ER+PR+HER2+ showed similar OS and better BCSS compared with ER+PR+HER2- after PSM. In conclusion, single PR+ patients experienced poorer prognoses than single ER+ patients, and may be treated as ER-PR- patients in HER2- subtype. In HER2+ patients, both single ER+ and single PR+ cases showed similar prognoses compared with ER-PR- cases, and may be treated as ER-PR- patients.
CircHECTD1 Regulates Cell Proliferation and Migration by the miR-320-5p/SLC2A1 Axis in Glioblastoma Multiform
Authors: Li Wen , Wang Shanshan , Shan Boquan , Cheng Xiang , He Hui , Qin Jianbing , Tang Yi , Zhao Heyan , Tian Meiling , Zhang Xinhua , Jin Guohua
Published: May 2021

Glioblastoma multiform (GBM) is the most common and malignant primary brain cancer in adults, and thus, novel potential therapeutic targets for diagnosis and treatment are urgently needed. Circular RNAs (circRNAs) are a class of widespread and diverse endogenous RNAs that have been suggested as potential critical mediators during progression of various tumors. In this study, we investigated the involvement of circHECTD1 in GBM progression. CircHECTD1 Lentivirus, miR-320-5p mimic, and SLC2A1 Lentivirus were transduced into cancer cells independently or together. circHECTD1, miR-320-5p, and SLC2A1 level were detected by qRT-PCR. Western blot and qRT-PCR were applied to measure the expression of SLC2A1, CyclinD1, CDK2, and PCNA. Flow cytometry, EdU, colony formation, Transwell and wound-healing assays were conducted to assess cell proliferation and migration. Luciferase reporter assays were performed to determine the effect of miR-320-5p on circHECTD1 or SLC2A1. Xenograft experiments were implemented to evaluate tumor growth in vivo. CircHECTD1 expression led to the promotion of proliferation and migration of GBM cells. In addition, circHECTD1 acted as a ceRNA to interact with miR-320-5p, which targeted the solute carrier family 2 member 1 (SLC2A1). In vivo experiments also revealed that circHECTD1 promoted tumor growth. Collectively, our findings showed that the circHECTD1-miR-320-5p-SLC2A1 regulatory pathway promoted the progression of GBM, suggesting that circHECTD1 may be a therapeutic target for GBM.
PD-1-Positive Tumor-Associated Macrophages Define Poor Clinical Outcomes in Patients With Muscle Invasive Bladder Cancer Through Potential CD68/PD-1 Complex Interactions
Authors: Jiang Li-Ren , Zhang Ning , Chen Si-Teng , He Jin , Liu Yong-Hua , Han Ya-Qin , Shi Xiao-Qin , Yang Ji-Ji , Mu Dong-Yun , Fu Guo-Hui , Gao Feng
Published: May 2021

Tumor-associated macrophages (TAMs) regulate tumor immunity. Previous studies have shown that the programmed cell death protein 1 (PD-1)-positive TAMs have an M2 macrophage phenotype. CD68 is a biomarker of TAMs and is considered to be a poor prognostic marker of several malignancies. Our results show that PD-1-positive TAMs can be a negative survival indicator in patients with muscle-invasive bladder cancer (MIBC), and that the mechanistic effects could result due to a combination of PD-1 and CD68 activity. We analyzed 22 immune cell types using data from 402 patients with MIBC from the TCGA database, and found that a high immune score and M2 TAMs were strongly associated with poor clinical outcomes in patients with MIBC. Further, we analyzed resected samples from 120 patients with MIBC and found that individuals with PD-1-positive TAMs showed a reduction in 5-year overall survival and disease-free survival. Additionally, PD-1-positive TAMs showed a significant association with higher programmed death-ligand 1 (PD-L1) expression, the Ki67 index, the pT stage and fewer CD8-positive T cells. Through the co-immunoprecipitation (co-IP) assay of THP-1 derived macrophages, we found that CD68 can bind to PD-1. The binding of CD68 and PD-1 can induce M2 polarization of THP-1 derived macrophages and promote cancer growth. The anti-CD68 treatment combined with peripheral blood mononuclear cells (PBMC) showed obvious synergy effects on inhibiting the proliferation of T24 cells. Together, these results indicate for the first time that CD68/PD-1 may be a novel target for the prognosis of patients with MIBC.
Procalcitonin in Preterm Neonates: A Different Threshold and Prolonged Interpretation
Authors: Bianco Blandine , François-Garret Bérengère , Butin Marine , Dalmasso Cyril , Casagrande Florence , Mokhtari Mostafa , Eleni Dit Trolli Sergio
Published: May 2021

Objectives: To evaluate the positive threshold of PCT for neonates of <32 weeks of gestation for the diagnosis of early-onset sepsis and to determine if the level of PCT collected within 6 h of life could be used.

Design: Retrospective and bicentric study from May 2016 to April 2018.

Setting: Two groups were established, neonates evaluated for PCT at birth (CordPCT) and within 6 h of life (delPCT).

Patients: Two hundred and sixty neonates of <32 weeks of gestation born in Nice and South Paris (Bicêtre) University Hospitals, had been evaluated for PCT level.

Main Outcomes Measures: The value of the PCT positive threshold was determined for the total population and each groups thanks ROC curves.

Results: The threshold level of PCT for the total population was 0.98 ng/mL. The threshold value of cordPCT group was 1.00 vs. 0.98 ng/mL for delPCT group. The area under the Receiver Operating Characteristics curve for PCT sampled in delPCT group was significantly higher than in cordPCT group (0.94 compared to 0.75).

Conclusions: The threshold level of PCT was higher in this cohort of neonates of <32 weeks of gestation compared to the value generally described for term neonates. The secondary sampling PCT level seems to be usable in screening algorithm for early-onset neonatal sepsis.
Update on the Molecular Genetics of Timothy Syndrome
Authors: Bauer Rosemary , Timothy Katherine W. , Golden Andy
Published: May 2021

Timothy Syndrome (TS) (OMIM #601005) is a rare autosomal dominant syndrome caused by variants in CACNA1C, which encodes the α1C subunit of the voltage-gated calcium channel Cav1.2. TS is classically caused by only a few different genetic changes and characterized by prolonged QT interval, syndactyly, and neurodevelopmental delay; however, the number of identified TS-causing variants is growing, and the resulting symptom profiles are incredibly complex and variable. Here, we aim to review the genetic and clinical findings of all published case reports of TS to date. We discuss multiple possible mechanisms for the variability seen in clinical features across these cases, including mosaicism, genetic background, isoform complexity of CACNA1C and differential expression of transcripts, and biophysical changes in mutant CACNA1C channels. Finally, we propose future research directions such as variant validation, in vivo modeling, and natural history characterization.
Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats
Authors: Baranowska Iwona , Gawrys Olga , Roszkowska-Chojecka Malwina M. , Badzynska Bozena , Tymecka Dagmara , Olszynski Krzysztof H. , Kompanowska-Jezierska Elzbieta
Published: May 2021

The contribution of chymase, one of the enzymes responsible for angiotensin II generation in non-ACE pathway, remains unclear in the development of hypertension. The aim of the study was to investigate chymase inhibition as potential antihypertensive therapy in spontaneously hypertensive rats (SHR). To block chymase we employed chymostatin, a commercial inhibitor, and new analogues of rapeseed-derived peptides, VWIS and RIY. These simple and easy to obtain peptides not only block chymase, but also possess weak activity to inhibit ACE. This is a first attempt to evaluate the impact of chronic administration of selected inhibitors on blood pressure of SHR in two phases of hypertension. Male SHR (6 or 16 weeks old) were treated daily for two weeks with chymostatin (CH; 2 mg/kg/day), the peptides VWIS (12.5 mg/kg/day) or RIY (7.5 mg/kg/day); control groups received chymostatin solvent (0.15% DMSO in saline) or peptide solvent (saline). The substances were administered intravenously to conscious animals via a chronically cannulated femoral vein. Systolic blood pressure (SBP) was measured by telemetry. Metabolic parameters were measured weekly, and tissue samples were harvested after two weeks of treatment. None of the administered chymase inhibitors affected the development of hypertension in young rats. Only RIY exhibited beneficial properties when administered in the established phase of hypertension: SBP decreased from 165 ± 10 to 157 ± 7 mmHg while the excretion of nitric oxide metabolites increased significantly. The glomerulosclerosis index was lower after RIY treatment in both age groups (significant only in young rats 0.29 ± 0.05 vs 0.48 ± 0.04 in the control group; p < 0.05). Hence, it seems that peptide RIY exhibits some positive effect on renal morphology. The results obtained suggest that the peptide RIY may be a useful tool in the treatment of hypertension, especially in cases when ACE inhibitors are not effective.
Identification and Evaluation of Suitable Reference Genes for RT-qPCR Analysis in Hippodamia variegata (Coleoptera: Coccinellidae) Under Different Biotic and Abiotic Conditions
Authors: Xie Jiaoxin , Liu Tinghui , Khashaveh Adel , Yi Chaoqun , Liu Xiaoxu , Zhang Yongjun
Published: May 2021

Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) is an accurate and convenient technique for quantifying expression levels of the target genes. Selection of the appropriate reference gene is of the vital importance for RT-qPCR analysis. Hippodamia variegata is one of the most important predatory natural enemies of aphids. Recently, transcriptome and genome sequencings of H. variegata facilitate the gene functional studies. However, there has been rare investigation on the detection of stably expressed reference genes in H. variegata. In the current study, by using five analytical tools (Delta Ct, geNorm, NormFinder, BestKeeper, and RefFinder), eight candidate reference genes, namely, Actin, EF1α, RPL7, RPL18, RPS23, Tubulin-α, Tubulin-β, and TufA, were evaluated under four experimental conditions including developmental stages, tissues, temperatures, and diets. As a result, a specific set of reference genes were recommended for each experimental condition. These findings will help to improve the accuracy and reliability of RT-qPCR data, and lay a foundation for further exploration on the gene function of H. variegata.
Genome-Wide Identification of Tannase Genes and Their Function of Wound Response and Astringent Substances Accumulation in Juglandaceae
Authors: Wang Jianhua , Wang Ketao , Lyu Shiheng , Huang Jianqin , Huang Chunying , Xing Yulin , Wang Yige , Xu Yifan , Li Peipei , Hong Junyan , Xi Jianwei , Si Xiaolin , Ye Hongyu , Li Yan
Published: May 2021

Tannins are important polyphenol compounds with different component proportions in different plant species. The plants in the Juglandaceae are rich in tannins, including condensed tannins and hydrolyzable tannins. In this study, we identified seven tannase genes (TAs) responsible for the tannin metabolism from walnut, pecan, and Chinese hickory, and three nut tree species in the Juglandaceae, which were divided into two groups. The phylogenetic and sequence analysis showed that TA genes and neighboring clade genes (TA-like genes) had similar sequences compared with other carboxylesterase genes, which may be the origin of TA genes produced by tandem repeat. TA genes also indicated higher expressions in leaf than other tissues and were quickly up-regulated at 3 h after leaf injury. During the development of the seed coat, the expression of the synthesis-related gene GGTs and the hydrolase gene TAs was continuously decreased, resulting in the decrease of tannin content in the dry sample of the seed coat of Chinese hickory. However, due to the reduction in water content during the ripening process, the tannin content in fresh sample increased, so the astringent taste was obvious at the mature stage. In addition, the CcGGTs’ expression was higher than CiGGTs in the initiation of development, but CcTAs continued to be down-regulated while CiTA2a and CiTA2b were up-regulated, which may bring about the significant differences in tannin content and astringent taste between Chinese hickory and pecan. These results suggested the crucial role of TAs in wound stress of leaves and astringent ingredient accumulation in seed coats of two nut tree species in the Juglandaceae.
Horizontally Acquired nrDNAs Persist in Low Amounts in Host Hordeum Genomes and Evolve Independently of Native nrDNA
Authors: Krak Karol , Caklová Petra , Kopecký David , Blattner Frank R. , Mahelka Václav
Published: May 2021

Nuclear ribosomal DNA (nrDNA) has displayed extraordinary dynamics during the evolution of plant species. However, the patterns and evolutionary significance of nrDNA array expansion or contraction are still relatively unknown. Moreover, only little is known of the fate of minority nrDNA copies acquired between species via horizontal transfer. The barley genus Hordeum (Poaceae) represents a good model for such a study, as species of section Stenostachys acquired nrDNA via horizontal transfer from at least five different panicoid genera, causing long-term co-existence of native (Hordeum-like) and non-native (panicoid) nrDNAs. Using quantitative PCR, we investigated copy number variation (CNV) of nrDNA in the diploid representatives of the genus Hordeum. We estimated the copy number of the foreign, as well as of the native ITS types (ribotypes), and followed the pattern of their CNV in relation to the genus’ phylogeny, species’ genomes size and the number of nrDNA loci. For the native ribotype, we encountered an almost 19-fold variation in the mean copy number among the taxa analysed, ranging from 1689 copies (per 2C content) in H. patagonicum subsp. mustersii to 31342 copies in H. murinum subsp. glaucum. The copy numbers did not correlate with any of the genus’ phylogeny, the species’ genome size or the number of nrDNA loci. The CNV was high within the recognised groups (up to 13.2 × in the American I-genome species) as well as between accessions of the same species (up to 4×). Foreign ribotypes represent only a small fraction of the total number of nrDNA copies. Their copy numbers ranged from single units to tens and rarely hundreds of copies. They amounted, on average, to between 0.1% (Setaria ribotype) and 1.9% (Euclasta ribotype) of total nrDNA. None of the foreign ribotypes showed significant differences with respect to phylogenetic groups recognised within the sect. Stenostachys. Overall, no correlation was found between copy numbers of native and foreign nrDNAs suggesting the sequestration and independent evolution of native and non-native nrDNA arrays. Therefore, foreign nrDNA in Hordeum likely poses a dead-end by-product of horizontal gene transfer events.
Rationalizing Inconsistent Consumer Behavior. Understanding Pathways That Lead to Negative Spillover of Pro-environmental Behaviors in Daily Life
Authors: Dreijerink Lieke , Handgraaf Michel , Antonides Gerrit
Published: May 2021

Ideally, pro-environmental consumer behavior leads to a lower impact on the environment. However, due to negative behavioral spillovers environmentally friendly behavior could lead to an overall higher environmental impact if subsequent environmentally unfriendly behavior occurs. In this exploratory interview study we focused on two pathways leading to negative spillover: a psychological path (perceived effort, moral licensing) and an economic path (rebound effects). We wanted to gain insight into people’s motivations to behave environmentally unfriendly and to explore people’s level of awareness of both pathways. Our results indicate that pro-environmental behaviors that are associated with higher effort are performed less frequently, and that when people do not perform these behaviors they associate them with higher effort levels. When people perceive behaviors as more effortful they increasingly seem to use arguments to motivate and rationalize why performing the behavior is difficult or impossible. Moreover, we found that although some people can imagine that moral licensing and rebound effects could occur and can provide examples from their own lives, most people assess these concepts as not rational. People seem unaware of the relation between a first pro-environmental behavior (PEB) and a subsequent behavior, and therefore inconsistencies in behavior go unnoticed. As people are good at rationalizing why they do not perform specific PEBs, they in general feel satisfied with their own pro-environmental actions. In order to discourage negative spillovers, we describe a number of approaches and research ideas aimed at taking away the grounds for rationalization.
Neuroimaging and DNA Methylation: An Innovative Approach to Study the Effects of Early Life Stress on Developmental Plasticity
Authors: Mariani Wigley Isabella Lucia Chiara , Mascheroni Eleonora , Peruzzo Denis , Giorda Roberto , Bonichini Sabrina , Montirosso Rosario
Published: May 2021

DNA methylation plays a key role in neural cell fate and provides a molecular link between early life stress and later-life behavioral phenotypes. Here, studies that combine neuroimaging methods and DNA methylation analysis in pediatric population with a history of adverse experiences were systematically reviewed focusing on: targeted genes and neural correlates; statistical models used to examine the link between DNA methylation and neuroimaging data also considering early life stress and behavioral outcomes. We identified 8 studies that report associations between DNA methylation and brain structure/functions in infants, school age children and adolescents faced with early life stress condition (e.g., preterm birth, childhood maltreatment, low socioeconomic status, and less-than optimal caregiving). Results showed that several genes were investigated (e.g., OXTR, SLC6A4, FKBP5, and BDNF) and different neuroimaging techniques were performed (MRI and f-NIRS). Statistical model used ranged from correlational to more complex moderated mediation models. Most of the studies (n = 5) considered DNA methylation and neural correlates as mediators in the relationship between early life stress and behavioral phenotypes. Understanding what role DNA methylation and neural correlates play in interaction with early life stress and behavioral outcomes is crucial to promote theory-driven studies as the future direction of this research fields.