bluuebunny/crossref_metadata_2025 huggingface dataset:
Impactos na saúde da mulher mãe cuidadora de criança com câncer
Authors: Pinheiro Izabela da Silva , Guerra Beatriz Cristina de Oliveira , Silva Leila Rangel da , Pacheco Patrícia Quintans Cundines , Monnerat Isabela da Costa , Teixeira Selma Villas Boas , Macedo Eliza Cristina , Veras Regina Claudia
Published: January 2021

Objetivo: mapear as produções científicas quanto aos impactos para a saúde da mulher mãe cuidadora de criança/adolescente com câncer. Método: revisão integrativa da literatura, realizada nas bases informatizadas da Biblioteca Virtual de Saúde (BVS) em maio de 2020. A questão da pesquisa foi “Quais os impactos na saúde da mulher mãe cuidadora de criança/adolescente com câncer?”. Resultados: Foram encontrados 46 artigos investigando a saúde da mulher-mãe cuidadora de criança com câncer e com a aplicação dos critérios de inclusão e exclusão foram selecionados 8 estudos. As mulheres-mães são as principais cuidadoras, o que acarreta na sobrecarga materna e no adoecimento expresso nas áreas: física, financeira, social, de informação, moral e emocional. Conclusão: A saúde da mãe-cuidadora é bastante afetada, sendo o adoecimento emocional o aspecto mais significativo. Essa é uma área de investigação ainda nova no cenário da enfermagem que precisa continuar avançando. Novas pesquisas precisam ser realizadas, em busca de um melhor entendimento acerca das necessidades dessa população.
Ocorrência de sangramento gengival na primeira infância em clínica integrada infantil de uma instituição de ensino superior
Authors: Silva Maísa Sales Oliveira e , Costa Bianca Maria de Melo , Cardoso Lucas Santana , Costa Bianne Maria de Melo , Torres Bianca Oliveira , Trinta Roberta Remiliana Silva
Published: January 2021

O estudo teve como objetivo verificar a prevalência de sangramento gengival em crianças na primeira infância em uma clínica infantil de Odontologia, visando salientar a importância da promoção a saúde bucal e buscando subsidiar os profissionais de Odontologia a diagnosticar e ajudar a prevenir a gengivite em crianças. Trata-se de um estudo transversal, descritivo e quantitativo, realizado nas dependências da Clínica-Escola de Odontologia do Centro Universitário de João Pessoa (UNIPÊ). A amostra foi obtida, de forma não probabilística por conveniência, sendo constituída de 100 prontuários de crianças de 3 a 6 anos. As informações foram registradas em uma ficha para tratamento estatístico dos dados. Em relação ao sexo, 53% das crianças eram do sexo masculino e 47% feminino. A ocorrência do sangramento gengival em crianças da primeira infância foi observada em 63% da amostra e 37% não apresentaram nenhum sangramento gengival. Em 49% das crianças obteve-se o escore do Índice de Sangramento Gengival (ISG) entre 1 a 10 %; em 11% obteve-se o escore do ISG entre 11 a 25 % e apenas 3% obteve o escore do ISG entre 26 e 50%. Em relação a presença de biofilme, as crianças de cinco e seis anos apresentaram uma porcentagem maior do Índice de Higiene Bucal (IHB), assim como ISG. Concluiu-se que a ocorrência do sangramento gengival nas crianças da primeira infância desta pesquisa foi elevada (63%), não tendo sua ocorrência influenciada pelo sexo, mas associada ao aumento de idade. A presença do sangramento mostrou-se associada ao acúmulo do biofilme.
Estrategias y materiales didácticos digitales para estudiantes en educación infantil con diversidad de aprendizaje
Authors: Pinos Karina Maribel Castillo , Velazco Derling Jose Mendoza
Published: January 2021

El estudio llevado a cabo tuvo como finalidad determinar la relación de las acciones estratégicas y materiales didácticos digitales implementados pos los facilitadores o docentes sobre el aprendizaje de los alumnos de 3 a 6 años con diversidad de aprendizaje en la ciudad de Azogues. En este caso, el enfoque del estudio fue cuantitativo y de tipo descriptivo correlacional de Pearson, mientras que el diseño aplicado fue de tipo no experimental transeccional. Se trabajó con una población compuesta de 12 alumnos con discapacidad intelectual, considerando la aplicación de la ficha de observación, para lo cual se diseñaron dos formatos de preguntas direccionadas a evaluar cada una de las variables estudiadas. Los resultados de la correlación de Pearson demostraron que las estrategias y materiales didácticos (EMD) están relacionas favorablemente en un orden de 0.639 con el aprendizaje en los niños con diversidad de aprendizaje (ADI); en cuyo caso se identificó que la correlación es significativa en el nivel 0,05 bilateral. No obstante, con base a la discusión realizada se determinó que las estrategias y materiales didácticos digitales empleados deben ser aplicadas de manera más eficiente para obtener mejores resultados a nivel de aprendizaje, principalmente en el caso de los estudiantes que presentan mayor grado de diversidad de aprendizaje, puesto que de acuerdo con la investigación muestran mayores dificultades de aprendizaje.
Diagnóstico socioeconômico de pequenos agricultores da comunidade Tracateua, Município de Moju, Pará, Brasil
Authors: Silva Sávia Poliana da , Viégas Ismael de Jesus Matos , Nogueira Ana Karlla Magalhães , Lima Silvia Kalini dos Santos de , Silva Dioclea Almeida Seabra , Viégas Socorro de Fátima Souza da Silva
Published: January 2021

A agricultura familiar é fundamental para o desenvolvimento econômico sustentável do espaço rural (Lima & Wilkinson, 2002), tendo grande importância na absorção da mão-de-obra, na geração de empregos e na produção alimentar, nutricional e produtiva local, territorial dos povos rurais e urbanos (Gomes, 2017). Os trabalhos desenvolvidos nas comunidades agrárias brasileiras são de importância fundamental para a economia do país, essencialmente, na contemporaneidade, para as pequenas comunidades rurais. Partindo deste ponto, estabeleceu-se como objetivo desse trabalho identificar e avaliar as características socioeconômicas e o perfil dos agricultores na comunidade Tracateua, localizada no município de Moju (PA). O estudo foi desenvolvido na comunidade Tracateua, município de Moju, Estado do Pará, que está localizada no ramal da Embrapa, no km 30 da PA 150, situado a aproximadamente 38 km da sede do município (Moju) e 295 km da cidade de Belém. Na comunidade de Tracateua, município de Moju, não há reserva de mão de obra para dedicar à agricultura familiar. Os produtos mais produzidos na comunidade são a mandioca, o milho, o feijão, o arroz e o maracujá, sendo a mandioca o principal produto, vendido na forma de farinha. Quanto à relação entre as variáveis estudadas, a correlação entre elas pode ser considerada média. Os principais fatores socioeconômicos que mais se destacam são: a relação do tempo na comunidade com a renda mensal da família, outras rendas, tamanho da propriedade, escolaridade do chefe da família e área de cultivo e a Idade do chefe da família influencia o número de filhos.
Estatística Descritiva utilizando o software LibreOffice Calc: experimento com um cubo virtual
Authors: Pontes Edel Alexandre Silva , Pontes Edel Guilherme Silva
Published: January 2021

Diante do advento do computador vem se discutindo em diversos congressos de educação, ciência e tecnologia novas alternativas no processo de ensino e aprendizagem eficiente de matemática. Professor e alunos interagem plenamente na busca de soluções para essa transformação educacional visando gerar modelos que valorizem o pensamento crítico, criativo e inovador. O uso das Tecnologias da Informação e Comunicação – TICs no meio escolar tem ocasionado mudanças drásticas na forma de ensinar e na forma de aprender matemática. Este artigo objetivou apresentar uma sugestão de uma aula motivacional, para alunos do ensino fundamental, utilizando medidas estatísticas descritivas no software LibreOffice Calc. Alguns questionamentos serão apresentados que venham por em dúvida a verdadeira eficiência de uma aula motivacional de Estatística na Educação Básica utilizando o Software LibreOffice Calc Espera-se que propostas educacionais como essa sejam fundamentais para aproximar a escola tradicional do mundo tecnológico.
O impacto da maquiagem nas emoções e na percepção de beleza
Authors: Nuevo Patrícia de Souza , Crestani Sandra , Ribas João Luiz Coelho
Published: January 2021

A imagem pessoal é um fator chave na comunicação e socialização dos indivíduos e exerce uma influência positiva na autoestima quando está alinhada com uma autoimagem positiva. Diante disso, o objetivo desta revisão da literatura é explorar os efeitos da maquiagem na atividade cerebral e na neurobiologia das emoções. A maquiagem é um dispositivo usado diariamente por várias pessoas, e seu uso pode ser considerado uma prática difundida e antiga que fortalece a autoestima de muitas mulheres ao proporcionar-lhes uma sensação de segurança que valoriza a imagem de si mesmas. Pode-se inferir que, uma vez que a maquiagem serve para realçar a beleza de alguém (e tendo em vista que a beleza é um conceito abrangente), ela pode estar intimamente relacionada às emoções. Uma série de estudos tem como objetivo explorar a nossa percepção de alguém que usa maquiagem, e como isso afeta nossa compreensão, bem como os procedimentos envolvidos em sua aplicação e seus possíveis efeitos. Em particular, pode ser destacada a relação entre a composição, a autoestima, as emoções e as células cerebrais que estão envolvidas nas emoções e a forma como se expressam.
Correlation between total air pollutant emissions and incidence of type 1 diabetes in the Russian Federation
Authors: Choi Hoon Sung , Kim Jin Taek , Seo Ji-Young , Linkov Faina , Shubnikov Evgeniy , Lee Hong Kyu
Published: January 2021

Background: Exposure to air pollution (gaseous pollutants and/or particulate matter) has been associated with the incidence, prevalence, and mortality of type 1 diabetes (T1D).Purpose: To examine the quantitative relationship between air pollutant emissions and the incidence of T1D.Methods: We examined the association between the incidence of T1D and type 2 diabetes (T2D) in 2017 as well as that of T1D in patients younger than 15 years in 2016 with “emissions of air-polluting substances from stationary and mobile sources by regions of the Russian Federation in 2016” as reported by the Federal Diabetes Register of Russia downloaded from the Russian government website (http://www.mnr.gov.ru/docs/gosudarstvennye_doklady/o_sostoyanii_i_ob_okhrane_okruzhayushchey_sredy_rossiyskoy_federatsii/).Results: The incidence of T1D across all ages in each region of the Russian Federation correlated with the total air pollutants emitted in the region each year (r=0.278, P=0.013). The incidence of T2D was also correlated with the amount of air pollutants (r=0.234, P=0.037) and the incidence of T1D (r=0.600, P<0.001) in each country. Similarly, the incidence of T1D in patients younger than 15 years correlated with the total air pollutants emitted each year in each region (r=0.300, P=0.011).Conclusion: The quantitative relationship between the total air pollutants emitted and the incidence of T1D and T2D in the Russian Federation suggests that air pollution contributes to the development of T1D and T2D.
Prehistory of Košice – settlement in the Neolithic
Authors: Kaminská Ľubomíra
Published: January 2021

This article presents the results of archaeological excavations at the sites Košice-Galgovec I-III and Červený rak on the southeastern edge of Košice in 1997–2001 indicated several stages of settlement and their dating. AMS 14C dates for the Tiszadob group were 6260±35 BP, 5330–5140 calBC; for the early stage of the Bükk culture they were 6310±40-35 BP, 5285±42 calBC. Assessment of residential, farming and settlement features was carried out, and numerous remains of pottery and lithic industry were classified with regard to contemporary sites in the Košická kotlina basin and in northeastern Hungary. The researchers evaluated the settlement in the microregion of Košice from the beginning of the Eastern Linear Pottery culture – the Proto-Linear stage – to the Barca III group and the Tiszadob group and the subsequent settlement during the Bükk culture period.
Physical Exercise-Induced Cardiovascular Adjustments Are
Modulated by Muscarinic Cholinoceptors within the Ventromedial
Hypothalamic Nucleus
Authors: Wanner S P , Guimarães J B , Pires W , La Guardia R B , Haibara A S , Marubayashi U , Coimbra C C , Lima N R V
Published: January 2021

The effects of blocking ventromedial hypothalamic nucleus (VMH)
muscarinic cholinoceptors on cardiovascular responses were
investigated in running rats. Animals were anesthetized with
pentobarbital sodium and fitted with bilateral cannulae into the
VMH. After recovering from surgery, the rats were familiarized to
running on a treadmill. The animals then had a polyethylene
catheter implanted into the left carotid artery to measure blood
pressure. Tail skin temperature (Ttail), heart rate, and systolic,
diastolic and mean arterial pressure were measured after
bilateral injections of 0.2 μl of 5 × 10−9
mol methylatropine or
0.15 M NaCl solution into the hypothalamus. Cholinergic blockade
of the VMH reduced time to fatigue by 31% and modified the
temporal profile of cardiovascular and Ttail adjustments without
altering their maximal responses. Mean arterial pressure peak
was achieved earlier in methylatropine-treated rats, which also
showed a 2-min delay in induction of tail skin vasodilation,
suggesting a higher sympathetic tonus to peripheral vessels. In
conclusion, muscarinic cholinoceptors within the VMH are
involved in a neuronal pathway that controls exercise-induced
cardiovascular adjustments. Furthermore, blocking of cholinergic
transmission increases sympathetic outflow during the initial
minutes of exercise, and this higher sympathetic activity may be
responsible for the decreased performance.
ABOUT DISCUSSION QUESTIONS OF DRUG DISEASE DIAGNOSTICS AS AN INTERDISCIPLINARY PROBLEM
Authors:   SE «Institute of Dermatology and Venereology of NAMS of Ukraine», Soloshenko E.M.
Published: January 2021

The objective of the study – to detect drug sensitization in patients with diffuse dermatoses and complicated allergic anamnesis and to analyze drug spectrum. Materials and methods. 195 patients with drug disease and diffuse dermatoses followed by complicated allergic anamnesis were observed. Drug sensitization was detected by ultrasonic test, agglomeration reaction of leucocytes and rate of erythrocyte sedimentation in the presence of drug. Results. There were detected 23.60% of patients with drug disease, 12.30% with eczema, 11.30% with food toxidermy, 13.80% with psoriasis, 12.80% with atopic dermatitis, 26.20% with other dermatoses. Drug sensitization was detected in 70.80% patients with eczema, 22.70% with food toxidermy, 44.40% with psoriasis, 72.0% with atopic dermatitis, 60.80% with other dermatoses. The most frequently detected sensitization was registered to such drugs as antibiotics (24.60%), cardiovascular (17.40%) and hypotensive (15.40%) medicines, local anaesthetics and analgetics (15.90%), anti-inflammatory (12.30%) medicines, vitamins (13.80%), gastrointestinal medicines (11.30%), corticosteroids (5.10%) and antihistamines (4.10%). Conclusions. 1. Drug sensitization was most frequently detected in patients with eczema, atopic dermatitis and psoriasis. 2. Drug disease was caused in patients with diffuse dermatoses by polysensitization to such drugs as antibiotics (24.60%), cardiovascular (17.40%) and hypotensive (15.40%) medicines, local anaesthetics and analgetics (15.90%), anti-inflammatory medicines (12.30%), vitamins (13.80%), gastrointestinal medicines (11.30%), corticosteroids (5.10%) and antihistamines (4.10%). 3. Drug disease is an interdisciplinary problem because it was detected to the different groups of drugs in patients with diffuse dermatoses both by dermatovenerologists and doctors of all specialties
CHRONIC PRURITUS IN CHILD’S SKIN DISEASES
Authors:   Shupyk National Medical Academy of Postgraduate Education, Kaliuzhna L.D.
Published: January 2021

The article presents modern information on the clinical use and safety of the first-generation H1-antihistamine – dimetindene maleate. Pruritus (itch) mediators act both peripherally (histamine, proteases) and centrally (opioids) and has several mechanisms. Pruritus is the dominant symptom of skin diseases; almost all inflamamatory skin diseases can have associated pruritus. Doctors have focused on the almost one dermatosis with signs of itching – atopic dermatitis. At the same time, the range of diseases, both dermatological and systemic, accompanied by itching, is much wider.
Task Based Learning (TBL) in EFL Classroom: from theory to practice
Authors: Sholeh Muhammad Badrus , Nur Sahril , Salija Kisman
Published: January 2021

Task-Based Learning (TBL) is one of the contemporary approaches, which has attracted a great deal of study in recent decades. It is a language education approach that offers students the opportunity to use authentic target language use by tasks. Task-Based Learning drives skill-based teaching and learning, engages students in the learning process, motivates and enhances student imagination. This paper focuses on some fundamental aspects of TBL in literature: (1) the task-based learning definition, (2) the task-based learning characteristics, (3) the task-based learning framework, (4) the task-based learning benefits, and (5) a proposed task-based learning practice for EFL learners. The paper gives useful suggestions to EFL teachers who have similar teaching strategies to help students meet such learning goals in their classrooms and continue positive TBL patterns in teaching and learning.
Developing a Tooth in situ Organ Culture Model for Dental and Periodontal Regeneration Research
Authors: El-Gendy Reem , Junaid Sarah , Lam Stephen K. L. , Elson Karen M. , Tipper Joanne L. , Hall Richard M. , Ingham Eileen , Kirkham Jennifer
Published: January 2021

In this study we have realized the need for an organ culture tooth in situ model to simulate the tooth structure especially the tooth attachment apparatus. The importance of such a model is to open avenues for investigating regeneration of the complex tooth and tooth attachment tissues and to reduce the need for experimental animals in investigating dental materials and treatments in the future. The aim of this study was to develop a porcine tooth in situ organ culture model and a novel bioreactor suitable for future studies of periodontal regeneration, including application of appropriate physiological loading. The Objectives of this study was to establish tissue viability, maintenance of tissue structure, and model sterility after 1 and 4 days of culture. To model diffusion characteristics within the organ culture system and design and develop a bioreactor that allows tooth loading and simulation of the chewing cycle.

Methods: Twenty-one porcine first molars were dissected aseptically in situ within their bony sockets. Twelve were used to optimize sterility and determine tissue viability. The remainder were used in a 4-day organ culture study in basal medium. Sterility was determined for medium samples and swabs taken from all tissue components, using standard aerobic and anaerobic microbiological cultures. Tissue viability was determined at days 1 and 4 using an XTT assay and Glucose consumption assays. Maintenance of structure was confirmed using histology and histomorphometric analysis. Diffusion characteristics were investigated using micro-CT combined with finite element modeling. A suitable bioreactor was designed to permit longer term culture with application of mechanical loading to the tooth in situ.

Result: XTT and Glucose consumption assays confirmed viability throughout the culture period for all tissues investigated. Histological and histomorphometric analysis confirmed maintenance of tissue structure. Clear microbiological cultures indicated maintenance of sterility within the organ culture system. The novel bioreactor showed no evidence of medium contamination after 4 days of culture. Finite element modeling indicated nutrient availability to the periodontium.

Conclusion: A whole tooth in situ organ culture system was successfully maintained over 4 days in vitro.
Performance of AnMBR in Treatment of Post-consumer Food Waste: Effect of Hydraulic Retention Time and Organic Loading Rate on Biogas Production and Membrane Fouling
Authors: Ariunbaatar Javkhlan , Bair Robert , Ozcan Onur , Ravishankar Harish , Esposito Giovanni , Lens Piet N. L. , Yeh Daniel H.
Published: January 2021

Anaerobic digestion of food waste (FW) is typically limited to large reactors due to high hydraulic retention times (HRTs). Technologies such as anaerobic membrane reactors (AnMBRs) can perform anaerobic digestion at lower HRTs while maintaining high chemical oxygen demand (COD) removal efficiencies. This study evaluated the effect of HRT and organic loading rate (OLR) on the stability and performance of a side-stream AnMBR in treating diluted fresh food waste (FW). The reactor was fed with synthetic FW at an influent concentration of 8.24 (± 0.12) g COD/L. The OLR was increased by reducing the HRT from 20 to 1 d. The AnMBR obtained an overall removal efficiency of >97 and >98% of the influent COD and total suspended solids (TSS), respectively, throughout the course of operation. The biological process was able to convert 76% of the influent COD into biogas with 70% methane content, while the cake layer formed on the membrane gave an additional COD removal of 7%. Total ammoniacal nitrogen (TAN) and total nitrogen (TN) concentrations were found to be higher in the bioreactor than in the influent, and average overall removal efficiencies of 17.3 (± 5) and 61.5 (± 3)% of TAN and TN, respectively, were observed with respect to the bioreactor concentrations after 2 weeks. Total phosphorus (TP) had an average removal efficiency of 40.39 (± 5)% with respect to the influent. Membrane fouling was observed when the HRT was decreased from 7 to 5 d and was alleviated through backwashing. This study suggests that the side-stream AnMBR can be used to successfully reduce the typical HRT of wet anaerobic food waste (solids content 7%) digesters from 20 days to 1 day, while maintaining a high COD removal efficiency and biogas production.
Characterization of the Biodistribution of a Silica Vesicle Nanovaccine Carrying a Rhipicephalus (Boophilus) microplus Protective Antigen With in vivo Live Animal Imaging
Authors: Mody Karishma T. , Zhang Bing , Li Xun , Fletcher Nicholas L. , Akhter Dewan T. , Jarrett Sandy , Zhang Jun , Yu Chengzhong , Thurecht Kristofer J. , Mahony Timothy J. , Mitter Neena
Published: January 2021

Development of veterinary subunit vaccines comes with a spectrum of challenges, such as the choice of adjuvant, antigen delivery vehicle, and optimization of dosing strategy. Over the years, our laboratory has largely focused on investigating silica vesicles (SVs) for developing effective veterinary vaccines for multiple targets. Rhipicephalus microplus (cattle tick) are known to have a high impact on cattle health and the livestock industry in the tropical and subtropical regions. Development of vaccine using Bm86 antigen against R. microplus has emerged as an attractive alternative to control ticks. In this study, we have investigated the biodistribution of SV in a live animal model, as well as further explored the SV ability for vaccine development. Rhodamine-labeled SV-140-C18 (Rho-SV-140-C18) vesicles were used to adsorb the Cy5-labeled R. microplus Bm86 antigen (Cy5-Bm86) to enable detection and characterization of the biodistribution of SV as well as antigen in vivo in a small animal model for up to 28 days using optical fluorescence imaging. We tracked the in vivo biodistribution of SVs and Bm86 antigen at different timepoints (days 3, 8, 13, and 28) in BALB/c mice. The biodistribution analysis by live imaging as well as by measuring the fluorescent intensity of harvested organs over the duration of the experiment (28 days) showed greater accumulation of SVs at the site of injection. The Bm86 antigen biodistribution was traced in lymph nodes, kidney, and liver, contributing to our understanding how this delivery platform successfully elicits antibody responses in the groups administered antigen in combination with SV. Selected tissues (skin, lymph nodes, spleen, kidney, liver, and lungs) were examined for any cellular abnormalities by histological analysis. No adverse effect or any other abnormalities were observed in the tissues.
Single-Molecule, Super-Resolution, and Functional Analysis of G Protein-Coupled Receptor Behavior Within the T Cell Immunological Synapse
Authors: Felce James H. , Parolini Lucia , Sezgin Erdinc , Céspedes Pablo F. , Korobchevskaya Kseniya , Jones Mathew , Peng Yanchun , Dong Tao , Fritzsche Marco , Aarts Dirk , Frater John , Dustin Michael L.
Published: January 2021

A central process in immunity is the activation of T cells through interaction of T cell receptors (TCRs) with agonistic peptide-major histocompatibility complexes (pMHC) on the surface of antigen presenting cells (APCs). TCR-pMHC binding triggers the formation of an extensive contact between the two cells termed the immunological synapse, which acts as a platform for integration of multiple signals determining cellular outcomes, including those from multiple co-stimulatory/inhibitory receptors. Contributors to this include a number of chemokine receptors, notably CXC-chemokine receptor 4 (CXCR4), and other members of the G protein-coupled receptor (GPCR) family. Although best characterized as mediators of ligand-dependent chemotaxis, some chemokine receptors are also recruited to the synapse and contribute to signaling in the absence of ligation. How these and other GPCRs integrate within the dynamic structure of the synapse is unknown, as is how their normally migratory Gαi-coupled signaling is terminated upon recruitment. Here, we report the spatiotemporal organization of several GPCRs, focusing on CXCR4, and the G protein Gαi2 within the synapse of primary human CD4+T cells on supported lipid bilayers, using standard- and super-resolution fluorescence microscopy. We find that CXCR4 undergoes orchestrated phases of reorganization, culminating in recruitment to the TCR-enriched center. This appears to be dependent on CXCR4 ubiquitination, and does not involve stable interactions with TCR microclusters, as viewed at the nanoscale. Disruption of this process by mutation impairs CXCR4 contributions to cellular activation. Gαi2 undergoes active exclusion from the synapse, partitioning from centrally-accumulated CXCR4. Using a CRISPR-Cas9 knockout screen, we identify several diverse GPCRs with contributions to T cell activation, most significantly the sphingosine-1-phosphate receptor S1PR1, and the oxysterol receptor GPR183. These, and other GPCRs, undergo organization similar to CXCR4; including initial exclusion, centripetal transport, and lack of receptor-TCR interactions. These constitute the first observations of GPCR dynamics within the synapse, and give insights into how these receptors may contribute to T cell activation. The observation of broad GPCR contributions to T cell activation also opens the possibility that modulating GPCR expression in response to cell status or environment may directly regulate responsiveness to pMHC.
Mechanochemical Control of Symmetry Breaking in the Caenorhabditis elegans Zygote
Authors: Gan Wan Jun , Motegi Fumio
Published: January 2021

Cell polarity is the asymmetric organization of cellular components along defined axes. A key requirement for polarization is the ability of the cell to break symmetry and achieve a spatially biased organization. Despite different triggering cues in various systems, symmetry breaking (SB) usually relies on mechanochemical modulation of the actin cytoskeleton, which allows for advected movement and reorganization of cellular components. Here, the mechanisms underlying SB inCaenorhabditis eleganszygote, one of the most popular models to study cell polarity, are reviewed. A zygote initiates SB through the centrosome, which modulates mechanics of the cell cortex to establish advective flow of cortical proteins including the actin cytoskeleton and partitioning defective (PAR) proteins. The chemical signaling underlying centrosomal control of the Aurora A kinase–mediated cascade to convert the organization of the contractile actomyosin network from an apolar to polar state is also discussed.
HIF-1α/BNIP3-Mediated Autophagy Contributes to the Luteinization of Granulosa Cells During the Formation of Corpus Luteum
Authors: Tang Zonghao , Zhang Zhenghong , Lin Qingqiang , Xu Renfeng , Chen Jiajie , Wang Yuhua , Zhang Yan , Tang Yedong , Shi Congjian , Liu Yiping , Yang Hongqin , Wang Zhengchao
Published: January 2021

During the luteinization after ovulation in mammalian ovary, the containing cells undergo an energy consuming function re-determination process to differentiate into luteal cells under avascular environment. Previous evidences have delineated the contribution of autophagy to the cell differentiation and the catabolic homeostasis in various types of mammalian cells, whereas few interest had been focused on the involvement of autophagy in the luteinization of granulosa cells during the formation of early corpus luteum. Herein, the present study investigated that expression and contribution of autophagy during granulosa cell luteinization and early luteal development through in vivo and in vitro experiments. The results clearly demonstrated that HIF-1α/BNIP3-mediated autophagy plays a vital role in the luteinization of granulosa cells during the early luteal formation in vivo and in vitro. In the neonatal corpus luteum, HIF-1α up-regulated BNIP3 expressions, which contributed to the autophagic initiation by disrupting beclin1 from Bcl-2/beclin1 complex and protected cells from apoptosis by curbing the skew of mitochondria balance under avascular niche. Notably, Inhibition of HIF-1α activity by echinomycin enhanced the levels of cytoplasmic cytochrome c and cell apoptosis in the nascent corpus luteum. These findings revealed that HIF-1α/BNIP3-mediated autophagy enabled the process of granulosa cell luteinization and protected the granulosa-lutein cells from further apoptosis under hypoxia niche. To our knowledge, the present study firstly clarified that HIF-1α/BNIP3-mediated autophagy contributes to the luteinization of granulosa cells during the formation of pregnant corpus luteum, which will help us further understanding the luteal biology and provide us new clues for the treatment of luteal insufficiency.
Vascular Adhesion Protein-1 Determines the Cellular Properties of Endometrial Pericytes
Authors: Gharanei Seley , Fishwick Katherine , Peter Durairaj Ruban , Jin Tianrong , Siamantouras Eleftherios , Liu Kuo-Kang , Straube Anne , Lucas Emma S. , Weston Christopher J. , Rantakari Pia , Salmi Marko , Jalkanen Sirpa , Brosens Jan J. , Tan Bee Kang
Published: January 2021

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule and a primary amine oxidase involved in immune cell trafficking. Leukocyte extravasation into tissues is mediated by adhesion molecules expressed on endothelial cells and pericytes. Pericytes play a major role in the angiogenesis and vascularization of cycling endometrium. However, the functional properties of pericytes in the human endometrium are not known. Here we show that pericytes surrounding the spiral arterioles in midluteal human endometrium constitutively express VAP-1. We first characterize these pericytes and demonstrate that knockdown of VAP-1 perturbed their biophysical properties and compromised their contractile, migratory, adhesive and clonogenic capacities. Furthermore, we show that loss of VAP-1 disrupts pericyte-uterine natural killer cell interactions in vitro. Taken together, the data not only reveal that endometrial pericytes represent a cell population with distinct biophysical and functional properties but also suggest a pivotal role for VAP-1 in regulating the recruitment of innate immune cells in human endometrium. We posit that VAP-1 could serve as a potential biomarker for pregnancy pathologies caused by a compromised perivascular environment prior to conception.
Identification of Genome Sequences of Polyphosphate-Accumulating Organisms by Machine Learning
Authors: Liu Bohan , Nan Jun , Zu Xuehui , Zhang Xinhui , Xiao Qiliang
Published: January 2021

In the field of sewage treatment, the identification of polyphosphate-accumulating organisms (PAOs) usually relies on biological experiments. However, biological experiments are not only complicated and time-consuming, but also costly. In recent years, machine learning has been widely used in many fields, but it is seldom used in the water treatment. The present work presented a high accuracy support vector machine (SVM) algorithm to realize the rapid identification and prediction of PAOs. We obtained 6,318 genome sequences of microorganisms from the publicly available microbial genome database for comparative analysis (MBGD). Minimap2 was used to compare the genomes of the obtained microorganisms in pairs, and read the overlap. The SVM model was established using the similarity of the genome sequences. In this SVM model, the average accuracy is 0.9628 ± 0.019 with 10-fold cross-validation. By predicting 2,652 microorganisms, 22 potential PAOs were obtained. Through the analysis of the predicted potential PAOs, most of them could be indirectly verified their phosphorus removal characteristics from previous reports. The SVM model we built shows high prediction accuracy and good stability.
Identification of a Novel RAMA/RON3 Rhoptry Protein Complex in Plasmodium falciparum Merozoites
Authors: Ito Daisuke , Chen Jun-Hu , Takashima Eizo , Hasegawa Tomoyuki , Otsuki Hitoshi , Takeo Satoru , Thongkukiatkul Amporn , Han Eun-Taek , Tsuboi Takafumi
Published: January 2021

Malaria causes a half a million deaths annually. The parasite intraerythrocytic lifecycle in the human bloodstream is the major cause of morbidity and mortality. Apical organelles of merozoite stage parasites are involved in the invasion of erythrocytes. A limited number of apical organellar proteins have been identified and characterized for their roles during erythrocyte invasion or subsequent intraerythrocytic parasite development. To expand the repertoire of identified apical organellar proteins we generated a panel of monoclonal antibodies against Plasmodium falciparum schizont-rich parasites and screened the antibodies using immunofluorescence assays. Out of 164 hybridoma lines, 12 clones produced monoclonal antibodies yielding punctate immunofluorescence staining patterns in individual merozoites in late schizonts, suggesting recognition of merozoite apical organelles. Five of the monoclonal antibodies were used to immuno-affinity purify their target antigens and these antigens were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two known apical organelle protein complexes were identified, the high-molecular mass rhoptry protein complex (PfRhopH1/Clags, PfRhopH2, and PfRhopH3) and the low-molecular mass rhoptry protein complex (rhoptry-associated proteins complex, PfRAP1, and PfRAP2). A novel complex was additionally identified by immunoprecipitation, composed of rhoptry-associated membrane antigen (PfRAMA) and rhoptry neck protein 3 (PfRON3) of P. falciparum. We further identified a region spanning amino acids Q221-E481 within the PfRAMA that may associate with PfRON3 in immature schizonts. Further investigation will be required as to whether PfRAMA and PfRON3 interact directly or indirectly.
Thrombosis and Coagulopathy in COVID-19: Current Understanding and Implications for Antithrombotic Treatment in Patients Treated With Percutaneous Coronary Intervention
Authors: Liu Hangkuan , Wang Zhijia , Sun Haonan , Teng Tianming , Li Yongle , Zhou Xin , Yang Qing
Published: January 2021

Coronavirus disease 2019 (COVID-19), a respiratory syndrome, is a global pandemic. Therefore, there is an urgent need to explore mechanisms implicated in the pathogenesis of the disease. Clinical and autopsy studies show a complex chain of events preceding COVID-19-related death. The disease is characterized by endothelial dysfunction, platelet activation, thrombosis, coagulopathy, and multiple organ failure. Globally, millions of patients with coronary heart disease undergo percutaneous coronary intervention (PCI) each year. These patients undergo high-intensity antithrombotic therapy during hospitalization and dual antiplatelet therapy (DAPT) for at least 6 months post PCI. COVID-19 is characterized by changes in platelet counts. Treatment of ischemic events that occur during stent implantation is associated with bleeding complications in patients following PCI complicated by COVID-19. This review summarizes recent progress in activation status and levels of COVID-19-related platelet changes. These findings will provide information on the effectiveness of antithrombotic therapy for the management of platelet changes in COVID-19 patients.
Deformation Pattern of the Northern Sector of the Malta Escarpment (Offshore SE Sicily, Italy): Fault Dimension, Slip Prediction, and Seismotectonic Implications
Authors: Gambino Salvatore , Barreca Giovanni , Gross Felix , Monaco Carmelo , Krastel Sebastian , Gutscher Marc-André
Published: January 2021

Marine seismic reflection data coupled with on-land structural measurements improve our knowledge about the active deformation pattern of the northern sector of the Malta Escarpment, a bathymetric and structural discontinuity in the near-offshore of Eastern Sicily. As favourably oriented to be reactivated within the Neogene Africa–Europe convergence, it is believed that the Malta Escarpment has a significant role in the recent seismotectonic framework of the Western Ionian Basin and the Hyblean foreland domain of SE Sicily, where some of the largest and most destructive Mediterranean earthquakes are located according to available historical catalogs. Offshore seismic data along with bathymetric grids illuminate the shallow subseafloor setting and allow more accurate mapping of the seafloor expression of previously identified faults in the area. The seismic interpretation and the near-fault sediment pattern analysis provide constraints on fault 3D geometries as well as on their through-time tectonic activity, suggesting also that part of the observed deformation may have been caused by nontectonic processes. Identified faults form currently an E-dipping, roughly N–S trending, and 60 km-long extensional belt deforming the seafloor with a significant displacement amount in the Ionian offshore between Catania and Siracusa. 3-dimensional parameters of faults were then used to derive expected magnitudes and their reactivation propensity. Empirical scaling relationships and forward methods point to a high seismic potential for the detected fault as well as predict the fault slip behavior according to the field-derived differential stress. This combined analysis along with faults displacement measurements pointed out how the longest and most continuous fault could be capable of generating M > 7 seismic events, putting forward strong seismotectonic implications for the adjacent and densely populated Hyblean Plateau. The expected magnitude and the estimated recurrence time interval are compatible with those inferred for large historical earthquakes in the area even if other offshore seismic sources cannot be ruled out.
Regulation of the EGFR Pathway by HSP90 Is Involved in the Pathogenesis of Cushing’s Disease
Authors: Shen Yue , Ji Chenxing , Jian Xuemin , Zhou Juan , Zhang Qilin , Qiao Nidan , Zhang Yichao , Shou Xuefei , Zhou Xiang , Ma Zengyi
Published: January 2021

Purpose

To investigate the role of heat-shock protein Hsp90 in adrenocorticotropic hormone (ACTH)-secreting cells, and to explore the potential clinical application of an inhibitor of Hsp90, 17-N-allylamino-17-demethoxygeldanamycin(17-AAG) in corticotropinomas [also known as “Cushing’s disease” (CD)].

Methods

Culture of mouse pituitary tumor [AtT-20/D16v-F2 (ATCC® CRL-1795™)] cells and human pituitary ACTH-secreting tumor cells were employed. Hepatocellular carcinoma cell line (HLE) was used to evaluate EGFR inhibition by 17-AAG. Cell viability was evaluated using a commercial kit. The ACTH level was measured by a radioimmunoassay. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to measure expression of proopiomelanocortin (POMC) mRNA. Western blotting was done to measure protein levels.

Results

17-AAG suppressed the viability and proliferation, and promoted the apoptosis, of AtT-20/D16v-F2 cells. 17-AAG suppressed the synthesis and secretion of ACTH in AtT-20/D16v-F2 cells and down-regulated POMC transcription. 17-AAG acted in a similar pattern upon treatment with human pituitary ACTH-secreting tumor cells. Inhibition by 17-AAG was stronger in human pituitary ACTH-secreting tumor cells carrying the ubiquitin-specific protease-8 (USP8) mutant in comparison with cells carrying wild-type USP8.

Conclusions

The HSP90 inhibitor 17-AAG reduced the viability and secretory function of human pituitary ACTH-secreting tumor cells, and tumor cells carrying the USP8 mutant were more sensitive to 17-AAG than tumor cells carrying wild-type USP8. 17-AAG could be a potential treatment option for CD.
A High-Resolution Digital Elevation Model in Combination With Water Table Depth and Continuous Soil Redox Potential Measurements Explain Soil Respiration and Soil Carbon Stocks at the ICOS Site Sorø
Authors: Callesen Ingeborg , Brændholt Andreas , Schrumpf Marion , Vesterdal Lars , Magnussen Andreas , Vorenhout Michel , Larsen Klaus Steenberg
Published: January 2021

Quantification of activity data and emission factors for carbon (C) in inland wetland mineral soils (IWMS) lack suitable low cost indicators for key soil C processes in temperate forests. In a beech (Fagus sylvatica L.) forest near Sorø, Denmark, SOC stocks and the risk of losing pre-drainage legacy SOC were studied using a digital elevation model (0.4 m resolution), redox potential and soil respiration measurements. The results were compared with a digitized legacy soil map used in the national GHG reporting to UNFCCC. In upland, flat and sloping terrain, an aerobic soil environment (Eh > 400 mV) prevailed throughout most of the year, but in a peat-filled topographic depression (TD) anaerobic conditions (Eh < 400 mV) fully or sporadically occurred in the growing season, controlled by the ditching-affected water table. The relief included SOC rich TDs making up 18.9% of the area based on the “Filled sink” algorithm (Saga GIS). In contrast, the peat cover on the legacy soil map was 8.2%. Furthermore, the mapped peat polygons were offset from the TDs defined by the DEM. The SOC stocks at 0–40 cm depth outside TDs (least squares mean 8.4 ± sem 0.3 kg C m−2) were significantly lower than within TDs (11.9 ± sem 0.5 kg C m−2). Average annual soil respiration increased linearly with the SOC stock by 0.06 kg C per kg SOC up to a SOC stock of 11 kg C m−2 to 20 cm depth, and a SOC loss of 0.23 ± se 0.10 kg C m−2 yr−1 was indicated inside the TD areas, close to the IPCC estimate of 0.26 kg C m−2 yr−1 for drained organic soils under forest. Our results show that continuous sensor-based monitoring of redox potential and shallow water tables linked with high-resolution DEMs offer the possibility to estimate the spatial extent of inland wetland mineral soils and their status as aerobic or anaerobic as indicated by iron rods with higher accuracy than previously. This underpins the potential use of such data for activity data mapping in Tier 3 greenhouse gas reporting.
The Susceptibility and Potential Functions of the LBX1 Gene in Adolescent Idiopathic Scoliosis
Authors: Luo Ming , Zhang Yuxiao , Huang Shishu , Song Yueming
Published: January 2021

Genome-wide association studies have identified many susceptibility genes for adolescent idiopathic scoliosis (AIS). However, most of the results are hard to be replicated in multi-ethnic populations. LBX1 is the most promising candidate gene in the etiology of AIS. We aimed to appraise the literature for the association of LBX1 gene polymorphisms with susceptibility and curve progression in AIS. We also reviewed the function of the LBX1 gene in muscle progenitor cell migration and neuronal determination processes. Three susceptibility loci (rs11190870, rs625039, and rs11598564) near the LBX1 gene, as well as another susceptibility locus (rs678741), related to LBX1 regulation, have been successfully verified to have robust associations with AIS in multi-ethnic populations. The LBX1 gene plays an essential role in regulating the migration and proliferation of muscle precursor cells, and it is known to play a role in neuronal determination processes, especially for the fate of somatosensory relay neurons. The LBX1 gene is the most promising candidate gene in AIS susceptibility due to its position and possible functions in muscle progenitor cell migration and neuronal determination processes. The causality between susceptibility loci related to the LBX1 gene and the pathogenesis of AIS deserves to be explored with further integrated genome-wide and epigenome-wide association studies.
Synthetic Cationic Autoantigen Mimics Glatiramer Acetate Persistence at the Site of Injection and Is Efficacious Against Experimental Autoimmune Encephalomyelitis
Authors: Song Jimmy Y. , Griffin J. Daniel , Larson Nicholas R. , Christopher Matthew A. , Middaugh C. Russell , Berkland Cory J.
Published: January 2021

A synthetic peptide, K-PLP, consisting of 11-unit poly-lysine (K11) linked via polyethylene glycol (PEG) to proteolipid protein epitope (PLP) was synthesized, characterized, and evaluated for efficacy in ameliorating experimental autoimmune encephalomyelitis (EAE) induced by PLP. K-PLP was designed to mimic the cationic nature of the relapsing-remitting multiple sclerosis treatment, glatiramer acetate (GA). With a pI of ~10, GA is able to form visible aggregates at the site of injection via electrostatic interactions with the anionic extracellular matrix. Aggregation further facilitates the retention of GA at the site of injection and draining lymph nodes, which may contribute to its mechanism of action. K-PLP with a pI of ~11, was found to form visible aggregates in the presence of glycosaminoglycans and persist at the injection site and draining lymph nodes in vivo, similar to GA. Additionally, EAE mice treated with K-PLP showed significant inhibition of clinical symptoms compared to free poly-lysine and to PLP, which are the components of K-PLP. The ability of the poly-lysine motif to retain PLP at the injection site, which increased the local exposure of PLP to immune cells may be an important factor affecting drug efficacy.