bluuebunny/crossref_metadata_2025 huggingface dataset:
Needs Assessment of Blended Learning Based Islamic Education on Higher Islamic Education Samarinda
Authors: Setiawan Agus
Published: June 2021

This research aims to determine the potential and needs of lecturers and students in PAI learning which will be applied with the blended learning strategy. This research is a descriptive research with triangulation method and data sources. Data was collected through preliminary observations, analysis of students condition got from survey results (google form online) to 21 students from 4 faculties and several study programs, and interviews (lecturers and students). As for the data analysis used by adopting models from Miles, Huberman and Saldana, namely with three steps: data reduction, data display and withdrawal of conclusion data. The results of the study state that the potential and needs based on need assessment at  IAIN Samarinda are: 1) the blended learning model is indispensable for the current technological development conditions at IAIN Samarinda, and on the achievements of KKNI in implementing learning with ICT, 2) survey results through google online form states that the analysis of student needs for innovative and interesting learning is 100% and student opinions about the learning needs of blended learning at IAIN Samarinda is 81%. 3) the expectations of this assessment need are: a) the blended learning model should have been implemented at  university by looking at technological developments, b) the need for a complete module on blended learning (including RPS, learning devices, e-learning and evaluation) so that the implementation can be achieved, c) pedagogical socialization of blended learning to lecturers and students, d) facilities and infrastructure, e) and policies regarding the implementation of blended learning.The implication of this research could be a reference for other researchers to develop blended learning  model in higher education.
Stochastic Stability and Analytical Solution with Homotopy Perturbation Method of Multicompartment Non-Linear Epidemic Model with Saturated Rate
Authors: Chahrazed Laid
Published: June 2021

In this work, we consider a nonlinear epidemic model with a saturated incidence rate. we consider a population of size N(t) at time t, this population is divided into six subclasses, with N(t)=S(t)+I(t)+I₁(t)+I₂(t)+I₃(t)+Q(t). Where S(t), I(t), I₁(t), I₂(t), I₃(t), and Q(t) denote the sizes of the population susceptible to disease, infectious members, and quarantine members, respectively. We have made the following contributions: 1. The local stabilities of the infection-free equilibrium and endemic equilibrium are; analyzed, respectively. The stability of a disease-free equilibrium and the existence of other nontrivial equilibria can be determined by the ratio called the basic reproductive number. 2. We find the analytical solution of the nonlinear epidemic model by Homotopy perturbation method. 3. Finally the stochastic stabilities. The study of its sections are justified with theorems and demonstrations under certain conditions. In this work, we have used the different references cited in different studies in the three sections already mentioned.
Job Selection Priorities of Accounting and Finance Graduates: An Empirical Evidence from Pakistan
Authors: Anjum Sadia
Published: June 2021

This study aims to evaluate the impact of six independent variables namely; professional growth, financial earnings, organizational repute, job environment, job security, and interest in the subject on one dependent variable i.e. job selection priorities of accounting and finance graduates in the perspective of Pakistan. The data of the study comprises 900 responses from final year graduates of 15 universities of Pakistan. The study used a structured questionnaire technique consisting of three parts (Part I= Demographic Characteristics, Part II and Part III= Assessment information of independent and dependent variables respectively) with 28 close-ended questions. Each item of the questionnaire was assessed using a 5-point Likert scale. The study employed demographic analysis, scale analysis, and inferential analysis. The empirical findings evidenced a positive correlation of all independent variables with dependent variables whereas no correlation was found among independent variables, and only three independent variables have a significant impact on the dependent variable of the study.
Effect of Static and Dynamic Stretching Warm-Up Methods on Agility, Speed and Leg Power Performance in School Level Netball Players
Authors: Gamlath H.G.J.H Gnanawardena , W.M.N.S Wijethunga  , S. Weerasinghe
Published: June 2021

A warm-up helps the individuals to prepare themselves for strenuous workouts. The warm-up is generally executed before participation in any physical activity or sports. The objective of the study was to investigate the effects of sequencing lower-body static and dynamic stretching combinations on agility, speed, and leg power of school-level female Netball players. Three different stretching protocols were performed: (a) Static Stretching combined with Dynamic Stretching (SS+DS), (b) Dynamic Stretching combined with Static Stretching (DS+SS), and (c) Dynamic Stretching combined with Dynamic Stretching (DS+DS). A control warm-up condition without stretching was implemented with a prior aerobic warm-up followed by dynamic activities. Dependent variables included a 30-m Sprint, Agility run, and jump tests to measure speed, agility, and leg power performance. The level of significance was set at 5% for statistical analysis. The method used for statistical analysis was two-way ANOVA. There was no significant impact of stretching protocols on agility (p=0.257), speed (p=0.106), and leg power (p=0.902) of school-level female netball athletes. The results of the analysis allow the authors to retain the hypothesis that a sequence of static and dynamic stretching combinations does not significantly affect the agility, speed, and leg power of school-level female netball athletes.
CAMPANHA “IPTU PREMIADO” E SEU IMPACTO NA ARRECADAÇÃO NO MUNICÍPIO DE PEJUÇARA
Authors: Castro Luiz , ´Porciuncula Luciana , Bueno Carla
Published: June 2021

A arrecadação municipal é relevante para o desenvolvimento dos municípios, em que dentre os diversos impostos, ressalta-se o Imposto Predial e Territorial Urbano (IPTU), o qual é um tributo que serve como instrumento de planejamento e gestão urbana. Para tanto, a pesquisa teve como objetivo avaliar o resultado da campanha “IPTU Premiado” na inadimplência dos contribuintes do IPTU no município de Pejuçara/RS. Em relação a metodologia, trata-se de uma pesquisa qualitativa e quantitativa, descritiva, bibliográfica, documental e estudo de caso único, na qual foi feita entrevista semiestruturada e análise de documentos. Os resultados evidenciaram que, devido à realização da campanha “IPTU Premiado”, o município obteve redução no índice de inadimplência, o que contribui com seu desenvolvimento, posto que, quanto maior for a arrecadação, maior serão os benefícios para a população. Portanto, destaca-se a importância de que o município desenvolva estratégias que garantam uma administração eficiente, em vista de maior crescimento.
ANÁLISE DA INCIDÊNCIA DO IMPOSTO DE RENDA: um estudo multicaso das particularidades na atividade rural
Authors: Nunes Osmar Manoel , Montardo Schumacher Kelem , Wohlenberg Janaína
Published: June 2021

O Imposto de Renda (IR) é um tributo compulsório que incide de forma progressiva e direta sobre os rendimentos de pessoas físicas e jurídicas. Conhecer a destinação dos recursos patrimoniais se torna indispensável para a gestão financeira, além de contribuir para o levantamento das receitas, despesas e custos inerentes a atividade realizada, necessários para a elaboração da declaração do IR. Este artigo buscou analisar a forma como ocorre a incidência do IR de produtores rurais que exercem atividade no município de Dom Pedrito/RS. Foram analisadas as particularidades de elaboração dos cálculos do IR pelo resultado, em que são contabilizadas as receitas e despesas no exercício fiscal, e pelo limite de 20% sobre a receita bruta total. A pesquisa de múltiplos casos, com caráter exploratório, contou com uma análise documental da declaração de oito produtores locais. Foram identificados o porte dos produtores e das propriedades, com base na receita e nos módulos fiscais, as principais deduções consideradas ao meio agropecuário e a forma correta de contabilizar a existência de prejuízo proveniente do exercício atual ou anterior, identificando a alternativa menos onerosa de tributação ao produtor rural.
Les intellectuels de gauche. Critique et consensus dans la Suisse d’après-guerre (1945-1968)
Authors: Buclin Hadrien
Published: June 2021

Les intellectuels de gauche s’intéresse à l’engagement des intellectuels progressistes dans la vie politique suisse, de la fin de la Seconde Guerre mondiale au fameux cycle de contestation de 1968, une période souvent délaissée par la recherche historique. Revenant sur l’action politique de personnalités, parfois oubliées, qui ont préparé le terrain à la contestation des années 1970, ce livre permet aussi de mieux comprendre le conservatisme helvétique de l’époque de la guerre froide et la manière dont l’establishment a marginalisé, voire réprimé, des personnalités jugées trop critiques. Alors que la recherche historique en Suisse est souvent fragmentée, en raison du plurilinguisme et du fédéralisme, ce livre propose une véritable histoire nationale, impliquant aussi bien la partie alémanique que francophone du pays, sur une période couvrant un quart de siècle, tout en replaçant la vie politique et intellectuelle helvétique en perspective européenne et internationale. Il restitue enfin dans toute leur complexité la diversité des courants et sensibilités au sein de la gauche et leur évolution.
浅谈小型电力排灌站技术更新改造
Authors: 黄 伟
Published: June 2021

以舒城县境内电力排灌站为例，对农村小型电力排灌站技术更新改造进行了重点分析，提出有关技术更新改造方面的技术措施和组织管理方面建议。文章中讨论的电力排灌站有别于机电排灌站，机电排灌站包含电力排灌站，电力排灌站主要动力来自电力资源。
浅析农田水利灌溉渠道工程运行维护及管理
Authors: 王 春海
Published: June 2021

在社会快速发展的带动下，我国各个领域的发展都取得了良好的成绩，就现如今我国农田水利灌溉渠道管理和维护工作实际情况来说，人们对于人性化管理工作提出了更高的要求，要想切实的对农业生产行业的稳步健康发展给予良好的保证，那么还应切实综合各方面实际情况和需要来设计考核和奖惩机制，结合实际规范标准以及专门的管理制度来为各项工作的有序开展给予辅助。利用有效的方式方法来对农田水利灌溉工程加以高水平的维护和管理，这样就能够切实的延长水利工程的使用寿命，并且也可以增强水利工程的综合性能。但是当前我国农田水利灌溉渠道工程维护机制还存在诸多的问题，这样必然的会对各项工作的实施造成严重的影响，对于上述问题我们应当将国外先进管理理念加以合理的运用，从而对实际问题进行解决，为整个行业的稳步健康发展创造良好的基础。
大数据角度下水利工程质量风险管理的方法
Authors: 裘 明华
Published: June 2021

最近这几年来，我们国家在经济领域当中取得了很大的进步和发展，我们国家的各行各业都迎来了前所未有的繁荣发展和机遇挑战在当下这个大数据背景之下，水利工程在开展质量风险管理的时候，也发生了很大的变化，在这种情况之下，我们必须要对水利工程质量风险管理提出更加严格的要求，只有这样才能够更好的保证水利工程建设的质量。
全面推行河长制打好河湖管理牌
Authors: 汪 五洲
Published: June 2021

河湖长制作为我国河湖治理与保护领域中的一项重大制度创新，从根本上解决了以往的“九龙治水”与“碎片化”问题。但是，作为一种新的制度，河湖长制也存在固有的缺陷与不足。河湖长制在推进过程中，需要正确处理好流域整体与流域内部、政府与市场、权利与责任、补偿主体与补偿客体、政府监管与社会监管之间的关系，建立健全长效机制。推行河湖长制，使人民群众对“清新空气、干净饮水、安全食品、优美环境”的要求，有了初步“获得感”。
KOMPOSISI KARAWITAN ISMUNING CAHYA: INTERPRETASI KEESAAN TUHAN MELALUI TOKOH SEMAR
Authors: Sugiyanto Danis , Setiawan Sigit
Published: June 2021

This work is entitled "Ismuning Cahya", is a work of contemporary Javanese gamelan music composition with the theme "the form of the Oneness of God” represented by the wayang character, Semar. The purpose of the creation of this works is to prove the existence of contemporary music (gamelan), as a reference for gamelan students who are interested in creating works of art (music). The output of this artistic research work is in the form of works (both live and/ or audio documentation) and scientific works which contain the process of developing the works "Ismuning Cahya". From there, it is hoped that this work will be able to become a model for the creation of works of art, especially the creation of contemporary gamelan.
Dietary plasticity of two coastal dolphin species in the Benguela upwelling ecosystem
Authors: Caputo M , Elwen S , Gridley T , Kohler SA , Roux JP , Froneman PW , Kiszka JJ
Published: June 2021

Defining the trophic relationships of marine predators and their dietary preferences is essential in understanding their role and importance in ecosystems. Here we used stable isotope analysis of skin samples (δ15N values reflecting trophic level and δ13C values reflecting foraging habitat) to investigate resource partitioning and spatial differences of the feeding ecology of dusky dolphins Lagenorhynchus obscurus and Heaviside’s dolphins Cephalorhynchus heavisidii from 2 coastal study sites separated by 400 km along the coast of central (Walvis Bay) and southern (Lüderitz) Namibia in the Benguela upwelling ecosystem. Overall, isotopic niches of both predators were significantly different, indicating partitioning of resources and foraging habitats. Despite their smaller body size, Heaviside’s dolphins fed at a significantly higher trophic level than dusky dolphins. Stable isotope mixing models revealed that both species fed on high trophic level prey (i.e. large Merluccius spp., large Sufflogobius bibarbatus, and Trachurus t. capensis) at Walvis Bay. The diet of both dolphin species included smaller pelagic fish and squid at Lüderitz. Spatial differences highlight that Heaviside’s and dusky dolphins may exhibit dietary plasticity driven by prey availability, and that they likely form distinct population segments. Important prey for both dolphin species, specifically Merluccius spp. and T. t. capensis, are the main target of trawl fisheries in the Benguela upwelling ecosystem, highlighting potential resource overlap between dolphins and fisheries.
COVID-19 and the ‘Myriad’: A Comparative Assessment of Emergency Responses from Europe and South America
Authors: Barker Kim , Uribe-Jongbloed Enrique , Scholz Tobias
Published: June 2021

The COVID-19 pandemic has highlighted – across intricate borders, different geographies, and legal jurisdictions – that there is only so much that can be done in the way of governance to tackle the challenge posed by a virus. The pandemic is a global problem, one which has affected almost every country in significant and seldom-felt ways. Governments have been forced to react, to respond with emergency measures, temporary rules and legislation, and impose restrictions on freedoms. It has brought to the fore a range of responses, locally, regionally, nationally, and internationally. What is particularly evident across the unfolding of the pandemic is the divergent approaches in introducing governance measures to control behaviour, to share data and information, and to report on the pandemic while holding decision-makers to account.

Much of the reporting of government reactions to the pandemic has focussed on emergency restrictions, lockdowns, the suspension of ‘normal’ gatherings, public health data, and tracing apps. Each of these is bundled up with concerns over the interferences with freedoms, a lack of scrutiny and holding to account of governance bodies and lawmakers, and privacy concerns. The new ways of working, governing, and communicating emergency rules is a COVID-19 legacy for governments, but is it one that will shift our expectations? The balance between fundamental freedoms has been – to an extent – pitted against the public health agenda and the nature of the emergency response by governments across the world, but particularly in Germany, the UK, and South America.

This article explores the nature of the government responses through emergency measures (and restrictions) and tracing programmes in three countries: Germany, the United Kingdom, and Colombia. The assessment – and comparison – of three countries, across two diverse regions – offers a unique discussion from the perspective of pandemic responses to the COVID-19 emergency. The pandemic itself provides an opportunity to compare countries, governance responses, and legalities that may not otherwise be possible. The myriad of responses seen throughout the pandemic offers a unique opportunity for comparative discussion – this paper provides that discussion, but in so doing, assesses whether it is possible to recommend a ‘one size fits all’ approach to governance emergencies.
Histone Arginine Methyltransferase CARM1-Mediated H3R26me2 Is Essential for Morula-to-Blastocyst Transition in Pigs
Authors: Cao Zubing , Tong Xu , Yin Huiqun , Zhou Naru , Zhang Xiangdong , Zhang Mengya , Wang Xin , Liu Qiuchen , Yan Yelian , Ma Yangyang , Yu Tong , Li Yunsheng , Zhang Yunhai
Published: June 2021

Coactivator-associated arginine methyltransferase 1 (CARM1) is involved in both establishment of first pluripotent lineage and pluripotency maintenance of embryonic stem cells (ESCs) in mice. However, the histone substrates and role of CARM1 in early embryonic development remain largely unknown. Here, we show that CARM1 specifically catalyzes H3R26me2 to promote porcine blastocyst formation. The putative histone substrates of CARM1, including H3R2me2, H3R17me2, and H3R26me2, are present in pig early embryos. The changes of CARM1 mRNA during early embryogenesis parallel that of H3R26me2. Functional studies using a combinational approach of chemical inhibition and RNA interference (RNAi) showed that catalytic activity inhibition of CARM1 protein or knockdown (KD) of CARM1 mRNA did not alter the levels of both H3R2me2 and H3R17me2, but significantly reduced H3R26me2 levels in porcine embryos. Furthermore, CARM1 inhibition or KD did not affect embryo development to the 2-cell, 4-cell, 8-cell, and morula stages, but severely compromised blastocyst development. CARM1 knocked down embryos that developed to the blastocyst stage had fewer total cells, inner cell mass (ICM), and trophectoderm (TE) cells. Mechanistically, single embryo RNA-sequencing analysis revealed that CARM1 KD altered the transcriptome characterized by downregulation of key genes associated with Hippo and PI3K-AKT signaling pathways. Taken together, these results demonstrate that CARM1 specifically catalyzes H3R26me2 in porcine embryos and participates in blastocyst development.
Reference Intervals for Serum Thyroid-Stimulating Hormone Based on a Recent Nationwide Cross-Sectional Study and Meta-Analysis
Authors: Wang Xichang , Li Yongze , Zhai Xiaodan , Wang Haoyu , Zhang Fan , Gao Xiaotong , Liu Shengyu , Teng Weiping , Shan Zhongyan
Published: June 2021

Objective

The aim of our study was to compare the reference intervals (RIs) [median (2.5th-97.5th percentiles)] for thyroid-stimulating hormone (TSH) between subgroups stratified by ethnicity and iodine status in a global context.

Design and Methods

Primary data were derived from a recently published cross-sectional study in mainland China. Secondary data were obtained from online databases. The RIs for TSH were calculated in the reference population according to the National Academy of Clinical Biochemistry (NACB) standard and in the disease-free population. A meta-analysis of ethnicity- and iodine status-specific TSH RIs was performed.

Results

The primary data showed that the TSH RI (mU/L) in the disease-free population was 2.33 (0.67, 7.87), which is wider than the published RI [2.28 (0.74, 7.04)] in the reference population. The meta-analysis showed that whether in the reference or disease-free population, the RIs in Yellows were much higher than those in Caucasians. In the reference population, the median and 2.5th percentile in the iodine-sufficient subgroup were both lower than the iodine-deficient or more-than-adequate subgroup, while the 97.5th percentile showed a positive trend with increasing sufficiency of iodine. However, in the disease-free population, the iodine-sufficient subgroup had a lower median and 97.5th percentile but higher 2.5th percentile than the iodine-deficient subgroup.

Conclusion

Yellows have a higher TSH RI than Caucasians. In the reference population, both the median and 2.5th percentile TSH in the iodine-sufficient population were the lowest among the different iodine status subgroups, while the 97.5th percentile of TSH showed an upward trend with increasing iodine sufficiency.
Vγ9Vδ2 T Cells Concurrently Kill Cancer Cells and Cross-Present Tumor Antigens
Authors: Holmen Olofsson Gitte , Idorn Manja , Carnaz Simões Ana Micaela , Aehnlich Pia , Skadborg Signe Koggersbøl , Noessner Elfriede , Debets Reno , Moser Bernhard , Met Özcan , thor Straten Per
Published: June 2021

The human Vγ9Vδ2 T cell is a unique cell type that holds great potential in immunotherapy of cancer. In particular, the therapeutic potential of this cell type in adoptive cell therapy (ACT) has gained interest. In this regard optimization of in vitro expansion methods and functional characterization is desirable. We show that Vγ9Vδ2 T cells, expanded in vitro with zoledronic acid (Zometa or ZOL) and Interleukin-2 (IL-2), are efficient cancer cell killers with a trend towards increased killing efficacy after prolonged expansion time. Thus, Vγ9Vδ2 T cells expanded for 25 days in vitro killed prostate cancer cells more efficiently than Vγ9Vδ2 T cells expanded for 9 days. These data are supported by phenotype characteristics, showing increased expression of CD56 and NKG2D over time, reaching above 90% positive cells after 25 days of expansion. At the early stage of expansion, we demonstrate that Vγ9Vδ2 T cells are capable of cross-presenting tumor antigens. In this regard, our data show that Vγ9Vδ2 T cells can take up tumor-associated antigens (TAA) gp100, MART-1 and MAGE-A3 - either as long peptide or recombinant protein – and then present TAA-derived peptides on the cell surface in the context of HLA class I molecules, demonstrated by their recognition as targets by peptide-specific CD8 T cells. Importantly, we show that cross-presentation is impaired by the proteasome inhibitor lactacystin. In conclusion, our data indicate that Vγ9Vδ2 T cells are broadly tumor-specific killers with the additional ability to cross-present MHC class I-restricted peptides, thereby inducing or supporting tumor-specific αβTCR CD8 T cell responses. The dual functionality is dynamic during in vitro expansion, yet, both functions are of interest to explore in ACT for cancer therapy.
Association of Polymorphisms in T-Cell Activation Costimulatory/Inhibitory Signal Genes With Allograft Kidney Rejection Risk
Authors: Santiago Jose Luis , Sánchez-Pérez Luis , Pérez-Flores Isabel , de la Higuera Maria Angeles Moreno , Romero Natividad Calvo , Querol-García Javier , Urcelay Elena , Sánchez-Fructuoso Ana Isabel
Published: June 2021

The genes CD28, CD86 and CTLA-4 conform the costimulatory (CD28-CD86) or inhibitory (CTLA-4-CD86) signal in T-cell activation. T-cell immune response has a critical role in allograft rejection, and single nucleotide polymorphisms (SNPs) located in these genes have been widely analyzed with controversial results. We analyzed a group of SNPs located in the three genes: CD28: rs3116496; CD86: rs1129055; and CTLA-4: rs231775 and rs3087243 in a cohort of 632 consecutively recruited kidney transplanted subjects. All polymorphisms were genotyped by TaqMan chemistry and the diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. The analyses showed a statistically significant protective effect to T cell-mediated rejection (TCMR) in carriers of the CTLA-4 rs3087243*G allele, especially in patients with TCMR Banff ≥2 in the overall cohort and in patients without thymoglobulin induction therapy. Both associations were corroborated as independent factors in the multivariate analysis. Interestingly, associations with rejection were not found for any SNP in patients with thymoglobulin induction therapy. As expected, considering the major role of these genes in T-cell activation, no effect was observed for antibody-mediated rejection (ABMR). In conclusion, the SNP rs3087243 located in the CTLA-4 gene may be considered a useful independent biomarker for TCMR risk especially for severe TCMR in patients who did no received thymoglobulin induction therapy.
Measuring the Impact of Targeting FcRn-Mediated IgG Recycling on Donor-Specific Alloantibodies in a Sensitized NHP Model
Authors: Manook Miriam , Flores Walter J. , Schmitz Robin , Fitch Zachary , Yoon Janghoon , Bae Yeeun , Shaw Brian , Kirk Allan , Harnois Melissa , Permar Sallie , Farris Alton B. , Magnani Diogo M. , Kwun Jean , Knechtle Stuart
Published: June 2021

Background

In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA.

Methods

Six (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG, were measured, in addition to IgM and protective immunity. Subsequently, 60mg/kg IV was given in the setting of kidney transplantation from skin graft donors. Kidney transplant recipients received RhATG, and tacrolimus, MMF, and steroid for maintenance immunosuppression.

Results

Circulating total IgG was reduced from a baseline 100% on D0 to 32.0% (mean, SD ± 10.6) on d4 post infusion (p<0.05), while using a DSA assay. T-cell flow cross match (TFXM) was reduced to 40.6±12.5% of baseline, and B-cell FXCM to 52.2±19.3%. Circulating total IgM and DSA IgM were unaffected by treatment. Pathogen-specific antibodies (anti-gB and anti-tetanus toxin IgG) were significantly reduced for 14d post infusion. Post-transplant, circulating IgG responded to anti-FcRn mAb treatment, but DSA increased rapidly.

Conclusion

Targeting the FcRn-mediated recycling of IgG is an effective means of lowering circulating donor-specific IgG in the sensitized recipient, although in the setting of organ transplantation mechanisms of rapid antibody rise post-transplant remains unaffected.
Targeted Expression of Myelin Autoantigen in the Periphery Induces Antigen-Specific T and B Cell Tolerance and Ameliorates Autoimmune Disease
Authors: Na Shin-Young , Krishnamoorthy Gurumoorthy
Published: June 2021

There is a great interest in developing antigen-specific therapeutic approaches for the treatment of autoimmune diseases without compromising normal immune function. The key challenges are to control all antigen-specific lymphocyte populations that contribute to pathogenic inflammatory processes and to provide long-term protection from disease relapses. Here, we show that myelin oligodendrocyte glycoprotein (MOG)-specific tolerance can be established by ectopic expression of MOG in the immune organs. Using transgenic mice expressing MOG-specific CD4, CD8, and B cell receptors, we show that MOG expression in the bone marrow cells results in impaired development of MOG-specific lymphocytes. Ectopic MOG expression has also resulted in long-lasting protection from MOG-induced autoimmunity. This finding raises hope that transplantation of autoantigen-expressing bone marrow cells as a therapeutic strategy for specific autoantigen-driven autoimmune diseases.
Interaction of Type 1 Porcine Reproductive and Respiratory Syndrome Virus With In Vitro Derived Conventional Dendritic Cells
Authors: Li Yanli , Mateu Enric
Published: June 2021

The present study delineates the interaction of a typical PRRSV1.1 isolate 3267 (moderate virulence) with in vitro derived pig conventional dendritic cells, cDC1, cDC2, and a CD14+ population (designated as CD14+ DCs). cDC1 and cDC2 were not susceptible to 3267 infection, but a fraction of CD14+ DCs were infected. After exposure to the virus, all three DC types remained immature as determined by no increase of maturation molecules (MHC-I, MHC-II, CD80/86, CCR7), no release of cytokines, no modification of antigen presentation abilities, and no alteration of endocytic/phagocytic capabilities. However, when infected MARC-145 cells were used as a source of viral antigens, cDC2 and CD14+ DCs showed a significant increase in the expression of maturation molecules and substantial release of cytokines, notably IL-12/IL-23p40 (by both DC types) and IL-10 (by CD14+ DCs). To address the impact of PRRSV1 3267 on TLR3- and TLR7-mediated activation, cDC1, cDC2, and CD14+ DCs were inoculated by the virus (live or UV-inactivated) for 6 h prior to or simultaneously with the addition of poly I:C (TLR3 ligand) or gardiquimod (TLR7 ligand; not used for cDC1). Compared with using TLR ligand alone, combination with the virus did not result in any alteration to the maturation markers on all DC types but changed the cytokine response to either TLR3 or TLR7 ligand. Pre-exposure of cDC2 or CD14+ DCs to the live virus resulted in an increased production of IFN-α upon poly I:C stimulation, while pre-exposure to UV-inactivated virus tended to enhance the release of IL-10 upon gardiquimod stimulation. Simultaneous addition of the live virus and the TLR ligand either had no effect (mainly in cDC2) or impaired most of the cytokine release after gardiquimod stimulation (in CD14+ DCs). When used as antigen presenting cells, cDC2 pre-inoculated by the live virus before addition of gardiquimod impaired the proliferation of CD4–CD8– T cells. In the case of CD14+ DCs, pre-exposure to the live virus or simultaneously added with TLR3 or TLR7 ligand largely decreased the proliferation of CD4–CD8+ and CD4–CD8+ T-cell subsets. For cDC1, no significant changes were observed in cytokine responses or T-cell proliferation after poly I:C stimulation. Of note, cDC1 had a short life during in vitro culturing, for which the results obtained might be biased. Overall, exposure to PRRSV1 did not induce maturation of cDC1, cDC2, or CD14+ DCs, but modified TLR3 and TLR7-associated responses (except for cDC1), which may affect the development of adaptive immunity during PRRSV1 infection. Moreover, the sensing of infected cells was different from that of the free virus.
Stabilization of Hypoxia-Inducible Factor Promotes Antimicrobial Activity of Human Macrophages Against Mycobacterium tuberculosis
Authors: Zenk Sebastian F. , Hauck Sebastian , Mayer Daniel , Grieshober Mark , Stenger Steffen
Published: June 2021

Hypoxia-inducible factor (HIF) is a key oxygen sensor that controls gene expression patterns to adapt cellular metabolism to hypoxia. Pharmacological inhibition of prolyl-hydroxylases stabilizes HIFs and mimics hypoxia, leading to increased expression of more than 300 genes. Whether the genetic program initialized by HIFs affects immune responses against microbial pathogens, is not well studied. Recently we showed that hypoxia enhances antimicrobial activity againstMycobacterium tuberculosis(Mtb) in human macrophages. The objective of this study was to evaluate whether the oxygen sensor HIF is involved in hypoxia-mediated antimycobacterial activity. Treatment ofMtb-infected macrophages with the prolyl-hydroxylase inhibitor Molidustat reduced the release of TNFα and IL-10, two key cytokines involved in the immune response in tuberculosis. Molidustat also interferes with the p38 MAP kinase pathway. HIF-stabilization by Molidustat also induced the upregulation of the Vitamin D receptor and human β defensin 2, which define an antimicrobial effector pathway in human macrophages. Consequently, these immunological effects resulted in reduced proliferation of virulentMtbin human macrophages. Therefore, HIFs may be attractive new candidates for host-directed therapies against infectious diseases caused by intracellular bacteria, including tuberculosis.
Marseilleviruses: An Update in 2021
Authors: Sahmi-Bounsiar Dehia , Rolland Clara , Aherfi Sarah , Boudjemaa Hadjer , Levasseur Anthony , La Scola Bernard , Colson Philippe
Published: June 2021

The family Marseilleviridae was the second family of giant viruses that was described in 2013, after the family Mimiviridae. Marseillevirus marseillevirus, isolated in 2007 by coculture on Acanthamoeba polyphaga, is the prototype member of this family. Afterward, the worldwide distribution of marseilleviruses was revealed through their isolation from samples of various types and sources. Thus, 62 were isolated from environmental water, one from soil, one from a dipteran, one from mussels, and two from asymptomatic humans, which led to the description of 67 marseillevirus isolates, including 21 by the IHU Méditerranée Infection in France. Recently, five marseillevirus genomes were assembled from deep sea sediment in Norway. Isolated marseilleviruses have ≈250 nm long icosahedral capsids and 348–404 kilobase long mosaic genomes that encode 386–545 predicted proteins. Comparative genomic analyses indicate that the family Marseilleviridae includes five lineages and possesses a pangenome composed of 3,082 clusters of genes. The detection of marseilleviruses in both symptomatic and asymptomatic humans in stool, blood, and lymph nodes, and an up-to-30-day persistence of marseillevirus in rats and mice, raise questions concerning their possible clinical significance that are still under investigation.
A nadA Mutation Confers Nicotinic Acid Auxotrophy in Pro-carcinogenic Intestinal Escherichia coli NC101
Authors: Lopez Lacey R. , Barlogio Cassandra J. , Broberg Christopher A. , Wang Jeremy , Arthur Janelle C.
Published: June 2021

Inflammatory bowel diseases (IBDs) and inflammation-associated colorectal cancer (CRC) are linked to blooms of adherent-invasiveEscherichia coli(AIEC) in the intestinal microbiota. AIEC are functionally defined by their ability to adhere/invade epithelial cells and survive/replicate within macrophages. Changes in micronutrient availability can alter AIEC physiology and interactions with host cells. Thus, culturing AIEC for mechanistic investigations often involves precise nutrient formulation. We observed that the pro-inflammatory and pro-carcinogenic AIEC strain NC101 failed to grow in minimal media (MM). We hypothesized that NC101 was unable to synthesize a vital micronutrient normally found in the host gut. Through nutrient supplementation studies, we identified that NC101 is a nicotinic acid (NA) auxotroph. NA auxotrophy was not observed in the other non-toxigenicE. colior AIEC strains we tested. Sequencing revealed NC101 has a missense mutation innadA, a gene encoding quinolinate synthase A that is important forde novonicotinamide adenine dinucleotide (NAD) biosynthesis. Correcting the identifiednadApoint mutation restored NC101 prototrophy without impacting AIEC function, including motility and AIEC-defining survival in macrophages. Our findings, along with the generation of a prototrophic NC101 strain, will greatly enhance the ability to performin vitrofunctional studies that are needed for mechanistic investigations on the role of intestinalE. coliin digestive disease.
SARS-CoV-2-Host Chimeric RNA-Sequencing Reads Do Not Necessarily Arise From Virus Integration Into the Host DNA
Authors: Kazachenka Anastasiya , Kassiotis George
Published: June 2021

The human genome bears evidence of extensive invasion by retroviruses and other retroelements, as well as by diverse RNA and DNA viruses. High frequency of somatic integration of the RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the DNA of infected cells was recently suggested, based on a number of observations. One key observation was the presence of chimeric RNA-sequencing (RNA-seq) reads between SARS-CoV-2 RNA and RNA transcribed from human host DNA. Here, we examined the possible origin specifically of human-SARS-CoV-2 chimeric reads in RNA-seq libraries and provide alternative explanations for their origin. Chimeric reads were frequently detected also between SARS-CoV-2 RNA and RNA transcribed from mitochondrial DNA or episomal adenoviral DNA present in transfected cell lines, which was unlikely the result of SARS-CoV-2 integration. Furthermore, chimeric reads between SARS-CoV-2 RNA and RNA transcribed from nuclear DNA were highly enriched for host exonic, rather than intronic or intergenic sequences and often involved the same, highly expressed host genes. Although these findings do not rule out SARS-CoV-2 somatic integration, they nevertheless suggest that human-SARS-CoV-2 chimeric reads found in RNA-seq data may arise during library preparation and do not necessarily signify SARS-CoV-2 reverse transcription, integration in to host DNA and further transcription.
The Therapeutic Effects of Whole-Body Vibration in Patients With Fibromyalgia. A Randomized Controlled Trial
Authors: Mingorance José A. , Montoya Pedro , Miranda José G. Vivas , Riquelme Inmaculada
Published: June 2021

Fibromyalgia is a chronic pain disease with few effective therapeutic options. We evaluated the efficacy of a 12-weeks therapy program that involves the use of whole body vibration in patients with fibromyalgia. The experimental group (N = 20 patients) participated in a neuromuscular training with a rotational whole body vibration platform for 12 weeks. The control group (N = 20 patients) received no physiotherapy treatment. The following variables were assessed before, after and 3 months after the therapy program: Fibromyalgia impact questionnaire, pain intensity, quality of life, sensitivity measurements (pressure pain thresholds, vibration thresholds), motor function tasks (Berg scale, 6-min walk test, isometric back muscle strength), and static and dynamic balance. We found improvements in the indexes of functional disability, static equilibrium and vibration sensitivity and a reduction of pain sensitivity. Our results showed that the intervention group improved almost all parameters immediately after the therapy program, in contrast to the control group that showed no changes. These improvements were not maintained in the follow-up. The whole body vibration therapy can be an effective therapy in patients with fibromyalgia and it can improve symptomatology and quality of life in these patients.
Three-Dimensional Culture of Ameloblast-Originated HAT-7 Cells for Functional Modeling of Defective Tooth Enamel Formation
Authors: Földes Anna , Sang-Ngoen Thanyaporn , Kádár Kristóf , Rácz Róbert , Zsembery Ákos , DenBesten Pamela , Steward Martin C. , Varga Gábor
Published: June 2021

Background: Amelogenesis, the formation of dental enamel, is well understood at the histomorphological level but the underlying molecular mechanisms are poorly characterized. Ameloblasts secrete enamel matrix proteins and Ca2+, and also regulate extracellular pH as the formation of hydroxyapatite crystals generates large quantities of protons. Genetic or environmental impairment of transport and regulatory processes (e.g. dental fluorosis) leads to the development of enamel defects such as hypomineralization.

Aims: Our aims were to optimize the culture conditions for the three-dimensional growth of ameloblast-derived HAT-7 cells and to test the effects of fluoride exposure on HAT-7 spheroid formation.

Methods: To generate 3D HAT-7 structures, cells were dispersed and plated within a Matrigel extracellular matrix scaffold and incubated in three different culture media. Spheroid formation was then monitored over a two-week period. Ion transporter and tight-junction protein expression was investigated by RT-qPCR. Intracellular Ca2+ and pH changes were measured by microfluorometry using the fluorescent dyes fura-2 and BCECF.

Results: A combination of Hepato-STIM epithelial cell differentiation medium and Matrigel induced the expansion and formation of 3D HAT-7 spheroids. The cells retained their epithelial cell morphology and continued to express both ameloblast-specific and ion transport-specific marker genes. Furthermore, like two-dimensional HAT-7 monolayers, the HAT-7 spheroids were able to regulate their intracellular pH and to show intracellular calcium responses to extracellular stimulation. Finally, we demonstrated that HAT-7 spheroids may serve as a disease model for studying the effects of fluoride exposure during amelogenesis.

Conclusion: In conclusion, HAT-7 cells cultivated within a Matrigel extracellular matrix form three-dimensional, multi-cellular, spheroidal structures that retain their functional capacity for pH regulation and intracellular Ca2+ signaling. This new 3D model will allow us to gain a better understanding of the molecular mechanisms involved in amelogenesis, not only in health but also in disorders of enamel formation, such as those resulting from fluoride exposure.
The Role of Temperature Variability on Seasonal Electricity Demand in the Southern US
Authors: Cawthorne Dylan , de Queiroz Anderson Rodrigo , Eshraghi Hadi , Sankarasubramanian Arumugam , DeCarolis Joseph F.
Published: June 2021

The reliable and affordable supply of energy through interconnected systems represent a critical infrastructure challenge. Seasonal and interannual variability in climate variables—primarily precipitation and temperature—can increase the vulnerability of such systems during climate extremes. The objective of this study is to understand and quantify the role of temperature variability on electricity consumption over representative areas of the Southern United States. We consider two states, Tennessee and Texas, which represent different climate regimes and have limited electricity trade with adjacent regions. Results from regression tests indicate that regional population growth explains most of the variability in electricity demand at decadal time scales, whereas temperature explains 44–67% of the electricity demand variability at seasonal time scales. Seasonal temperature forecasts from general circulation models are also used to develop season-ahead power demand forecasts. Results suggest that the use of climate forecasts can potentially help to project future residential electricity demand at the monthly time scale.

Capsule Summary: Seasonal temperature forecasts from GCMs can potentially help in predicting season-ahead residential power demand forecasts for states in the Southern US.
The Reaction of Winter Oilseed Rape to Different Foliar Fertilization with Macro- and Micronutrients
Authors: Jarecki Wacław
Published: June 2021

Foliar fertilization provides cultivated plants with the necessary nutrients during the growing season. The conducted field experiment was aimed at comparing the effectiveness of different variants of foliar fertilization applied in the cultivation of winter oilseed rape (Brassica napus L.), cultivar ‘ES Cesario’. The experimental factors were: A (control), B (YaraVita Brassitrel Pro), C (YaraVita Brassitrel Pro and YaraVita Thiotrac), D (YaraVita Brassitrel Pro and YaraVita Bortrac), E (YaraVita Brassitrel Pro and YaraVita Bortrac and YaraVita Thiotrac) and F (YaraVita Thiotrac). Weather conditions were variable over the years of the study and had a modifying effect on most of the tested parameters. Intensive foliar fertilization (variants D and E) resulted in a significant increase in the number of pods per plant, seed and fat yields, and SPAD (soil plant analysis development) and LAI (leaf area index) indices compared to the control. The protein yield was the highest after fertilizer applications in variants C and E. The use of YaraVita Thiotrac alone (variant F) did not provide the expected results. Foliar fertilizers applied in variant D increased Gs (leaf stomatal conductance) measurements and fat content in seeds but decreased TSW and seed protein content. It was shown that intensive foliar fertilization (variants D and E) increased seed boron content compared to YaraVita Thiotrac fertilization and the control. Fat and protein yields were strongly positively correlated with seed yield (r = 0.93 and r = 0.71, respectively). The best economic effect was obtained after applying foliar fertilization in variants D and E; therefore, they can be recommended for agricultural practice.
Understanding the Temporal Variability of Rainfall for Estimating Agro-Climatic Onset of Cropping Season over South Interior Karnataka, India
Authors: Sanjeevaiah Shivaramu Huchahanumegowdanapalya , Rudrappa Kodandarama Shettygowdanadoddi , Lakshminarasappa Mohankumar Thavakadahalli , Huggi Lingaraj , Hanumanthaiah Manjunatha Melekote , Venkatappa Sowmya Dadireddihalli , Lingegowda Nagesha , Sreeman Sheshshayee M.
Published: June 2021

Annual, seasonal and intra-seasonal variations in rainfall affect crop production from land preparation to the realization of potential crop yield in a region. Particularly, the onset of the rainy season is most crucial for determining the sowing period. Statistical analysis (Modified Mann-Kendall aka MMK-test for trend and likelihood ratio test for shifting pattern) of 60 years rainfall of south interior Karnataka (SIK) inferred the presence of temporal variability in rainfall. There was a monotonic increase in rainfall of February, March, April, June and August months (a positive sign of MM-K (tau) value), with a negligible rate of change (Sen’s slope towards zero). Upon seasonal analysis, there was a significant increase in winter, pre-monsoon and monsoonal rainfall as compared to post-monsoonal rainfall (higher Sen’s slope for pre-monsoon), indicating a need for agronomic interventions for estimating an effective date of sowing for reducing risks of crop production. Further, the agro-climatic onset of cropping season was estimated by considering soil–crop–water relations. Earlier onset of cropping season was estimated based on thresholds of soil–crop–water relations, which highlights sowing of crops in advance (May 1st fortnight) instead of late (June 1st fortnight) to avoid crop losses due to early-season drought.
Prognostic Value of Ki67 and Other Clinical and Histopathological Factors in Canine Apocrine Gland Anal Sac Adenocarcinoma
Authors: Morello Emanuela Maria , Cino Marzia , Giacobino Davide , Nicoletti Arturo , Iussich Selina , Buracco Paolo , Martano Marina
Published: June 2021

Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.