bluuebunny/crossref_metadata_2025 huggingface dataset:
Felnőtt tanulók Hajdú-Bihar megye szakképzési centrumaiban
Authors: Erdei Gábor , Teperics Károly
Published: January 2021

A szakképzés a rendszerváltozás óta jelentős átalakulásokat mutató oktatási ágazat, amely átalakulási folyamatnak egyik fontos lépese valósult meg 2015-ben, a centrumok létrejöttével. Az új rendszerben és működési struktúrában a felnőttoktatás a szakpolitika pioritásává vált. Kvantitatív kutatásunkban Hajdú-Bihar megye két centrumának tagintézményeiben tanuló felnőtteket vizsgáltuk (1002 válaszadó), így az empirikus munka andragógiai aspektussal is rendelkezik. A kutatási kérdések az intézmény- és szakmaválasztási motivációk; a tanulás folyamata, tanulási nehézségek; a munkaerő-piaci kilátások; és az oktatás értékelése kérdésköreire fókuszáltak.Vocational training has been an education sector that has undergone significant transformations since the change of regime, which was an important step in the transformation process in 2015, with the establishment of the centers. In the new system and operational structure, adult learning has become a policy priority. In our quantitative research, we examined adults studying in the member institutions of the two centers of Hajdú-Bihar county (1002 respondents), so the empirical work also has an andragogical aspect. Research questions include institutional and career choice motivations; the process of learning, learning difficulties; labor market prospects; and focused on issues of education evaluation.
建筑工程绿色节能施工技术研究
Authors: 程 远腾
Published: January 2021

建筑工程建设需要消耗大量的资源，采用多种技术，在实际建设中容易对周围的环境产生不良影响，甚至污染当地的环境，这不符合我国绿色节能发展要求，为此，企业需要加强绿色节能施工理念的贯彻落实，加强节能材料的应用，将传统施工管理理念改进创新，将绿色节能技术的使用价值充分发挥出来，确保工程建设效果，提升节能环保性能。
老龄化背景下综合体公共建筑设计方案探讨
Authors: 徐 树平
Published: January 2021

在社会老龄化发展背景下，建筑设计需综合考虑老年群体的特点及需求，选择合适地理位置，实施合理空间规划，优化设计建筑细节。基于此，文章以清远艺术中心建筑方案设计为例，从综合建筑总体设计与细节设计入手，论述老龄化背景下综合体公共建筑的设计方案，总结综合体公共建筑设计方案关爱老年人的要点，汇总经验以供参考。
绿色施工管理理念下的土建施工管理创新策略
Authors: 李 健
Published: January 2021

近年来，在社会快速发展的带动下，使得民众的思想意识发生了巨大的变化，人们对生活环境提出了更高的要求，这样就推动了我国建筑工程行业的发展。在这种发展形势下，建筑工程行业不但为民众提供了大量的就业岗位，并且也为社会经济水平的提升创造了良好的基础。在当前可持续发展理念的带动下，人们对于绿色生态理念越发的重视，将绿色施工管理理念运用到土建工程施工管理工作之中，能够有效的提升建筑工程环保效果，提高各类资源的利用效率。鉴于此，这篇文章主要针对绿色施工管理理念在建筑施工管理创新中的运用展开全面深入的研究分析，希望能够对我国建筑工程行业的持续稳定发展有所帮助。
电力工程中输电线路施工技术及管理
Authors: 刘 大立
Published: January 2021

目前我国社会的发展进程势头正猛，现如今只有不断革新现有的技术水平才能够提升施工企业自身的竞争实力。改革开放以后，人们的生活质量已经发生了质的飞跃，日常生活中用电的情况非常普遍。在整个电力系统之中，输电线路属于其中较为重要的一个部分，所以输电线路施工工作对施工技术要求相对较高，因为整个工程涉及到工作量较多，具有一定的复杂性，并且在实际操作过程中极易受到外界多方面因素的影响，所以施工工作人员务必要加以重点关注，切实的落实输电线路施工技术管理工作，这样才能从根本上对电力工程施工质量加以保障，推动电力工程建设工作能够得以有序的开展。
水利水电工程水库大坝混凝土的施工技术研究
Authors: 欧阳 云虎 , 束 帮文 , 李 书嘉 , 王 璇 , 姚 荣盛
Published: January 2021

随着我国经济水平的不断提高，水利水电工程项目建设的不断发展，建设水利水电工程的规模和要求也逐渐提高。目前，由于我国水利水电工程整体施工体系较为落后，水利水电工程施工质量逐渐降低。本篇文章中，对水利水电工程水库大坝混凝土的施工技术进行研究。
如何做好水利水电工程施工建设管理工作
Authors: 花 建彬 , 殷 荣军 , 夏 崇徽 , 王 洪楼 , 苏 海燕
Published: January 2021

水利水电工程项目的施工建设对于保障我国农业发展、调节水资源利用情况等起到了重要的作用。水利水电工程项目建设质量的优劣直接关系到其作用的大小，因此在项目建设过程中要做好管理工作，保障项目质量。因为水利水电工程项目建设地的施工环境较为恶劣，涉及到的专业较多，管理工作就显得尤为重要。结合工作实际，简要分析当前水利水电工程项目施工建设管理工作中存在的问题，并指出具体的管理对策。
工程监理在水利工程施工质量管理中的作用
Authors: 刘 德荣
Published: January 2021

改革开放以后我国的经济得到了快速的发展，而水利工程作为一项基础设施工程，在社会发展中有着重要的作用，水利工程的建设和经济的发展，人民的生活也都有着密切的关系，受到了社会各界的广泛关注。经过多年的发展我国的水利工程建设也取得了很大的进步，不过在管理方面却有些问题，影响了其作用的发挥，下面我们就对这些问题进行了分析，提出了一些相应的解决方案，希望能够有助于提升水利建设管理的水平，促进水利工程的发展。
变电站遥视技术在电力系统自动化中的应用
Authors: 徐 梁
Published: January 2021

近年来，在多方面利好因素的影响下，使得我国科学技术水平的得到了显著的提升，从而有效的促进了变电站遥视技术的良好发展，将这项技术切实的引用导诸多领域之中，起到了非常重要的影响作用。社会的飞速发展，使得各个领域以及民众的生活对电力能源的需求不断增加，要想能够生产出足够的电力能源，那么最为重要的就是需要不断提升生产技术的水平，管理工作人员需要从企业各方面实际情况入手，来对电力生产系统加以优化完善，切实合理的引用变电站遥视技术，能够对完善电力系统自动化体系起到积极的影响作用。
电力企业改革下电力市场营销策略
Authors: 高 源
Published: January 2021

在社会快速发展的带动下，使得各个领域都得到了全面的发展进步，无论是社会发展还是民众生活水平的提升对于电力能源的需求量都在不断的增加，这样就对电力企业运营生产工作提出了更高的要求。因为受到电力市场飞速发展的影响，使得以往老旧落后的电力营销观念已经无法满足电力企业的发展需要了，所以电力营销工作务必要进行适当的调整。就现如今实际情况来看，我国电力企业改革工作正处在稳步发展阶段，怎样针对当下电力市场营销工作中所存在的各种问题加以切实的解决，推动电力企业的持续健康发展是各个电力企业改革工作中的重点。
水环境监测机构出具检测报告容易出现的问题及原因分析
Authors: 祝 宾红
Published: January 2021

水环境检测报告是准确、及时反映水环境现状及发展趋势的有效证明，盖有计量认证标识的水环境检测报告可用于水环境产品质量评价、成果及司法鉴定，具有相应法律效力，对水环境管理与保护、污染与控制以及政府决策等具有重要的作用。本文对水环境监测机构出具对外出具检测报告时容易出现一些问题以及产生的原因进行深入分析和探讨，以达到促进水环境检测机构规范化运行的目的。
浅议水利工程的灌溉管理
Authors: 白 占军
Published: January 2021

近年来，我国社会经济发展十分迅猛，从而使得社会发展对水利资源的需求量不断的增加，再加上我国水资源储备量较少，所以对我国水资源的调控工作提出了更高的要求。为了从根本上保证能够为农业生产提供充足的水源，我国在各个地区建造了大量的水利工程，要想将这些水利工程的作用充分的发挥出来，那么我们需要从水利灌溉入手来实施管理工作。但是就当下我国水利灌溉管理工作的各方面情况来说，因为受到多方面因素的影响，所以造成了水利灌溉的效率和效果较差的情况，鉴于此这篇文章主要针对水利工程灌溉管理工作展开全面深入的分析研究，希望能够对我国社会和谐稳定发展起到积极的促进作用。
The Transit of Civilization: Methodological and Prognostic Aspects
Authors: Neklessa Alexander Ivanovich
Published: January 2021

The article is based on the report “The Transit of Civilizations: Methodological and Prognostic Aspects of Civilizational Competition”. It is devoted to the analysis of methodological and prognostic aspects of diachronic civilizational competition in the process of the current transformation of Modernity into the new historical state, defined as Postmodernity. Methodological and prognostic aspects of this historical transit are analyzed. The general aim of the study is to observe effective strategies for behavior while in situations of complexity, volatility, uncertainty and ambiguity. Different methods of orientation, action and management in post-war period are described and the possibility of their further transformation up to the next epistemological revolution is discussed. There is also an attempt to present certain analytical tools. Civilization is a dynamic concept, a social analogue of evolution. The globalization of modernity is accompanied by post-modern individuation, the antipode of industrial culture and mass society. The process of splitting of political structures, genesis of technical and anthropological complexity, creation of cloud structures – all this distorts the modern World Order. System approach is usually used to study complexities, while view of the future is based on a combination of transdisciplinary analysis, global context and long-term perspective. New methodological approach is produced for replacing the globality with fractality, long-term prognostics with non-linear dynamics, and transdisciplinary generalizations with uniqueness. The article also analyzes the latest generation of methodologies that possibly will allow us to make decisions and effectively act in this complex environment full of wicked situations and processes as well as non-classical approaches, such as the mode of action based on the analysis of deep codes of evolution, the art of non-classical operative, synergetic behavior, phenomen of serendipity etc. Research of the innovative methodological and predictive tools is an imperative for sustainable development, taking into account the upcoming turbulence of the social environment.
The Compamy’s Power Growth Model System
Authors: Danilin Vacheslav I.
Published: January 2021

When calculating the company's business plan, in many cases there is a problem of lack of resources to fully meet the demand for the company's products. In article (Danilin, 2019) the system of models of coordination of decisions between the leading divisions of the company was offered: production department, sales department, department of, financial department. However, the production department was presented in this article only by one model, and technological services were absent. In this article more detailed system of models for production department when calculating the production program is offered, and agreeing on the decision with model of technological service. The calculation of the production program (the company's capacity) and its growth is possible due to several areas: a) the development by the technology departments of short-term projects aimed at the implementation of resource consumption standards; b) the development by technology departments of additional production methods for manufacturing products or services, along with the main; c) additional acquisition of resources through investment; d) outsourcing of domestic semi-finished products. There were special models for each area that would reduce the level of increase in the company's ability to meet the demand for its production. The purpose of the article was to show an opportunity to create a model system out of them, allowing them to maximize the capacity of the production company within the framework of the existing investment opportunities. The scientific novelty is to develop the meta-historical basis for the sequence of implementation of individual models and to harmonize them with each other to solve the problem. The example shows that the use of these directions in a certain sequence allows to increase the power of the company and as close as possible to 100% of the satisfaction of demand.
Stress Testing as a Banking Risk Assessment Tool: A Review of International Practice, Methods and Methodology
Authors: Bidzhoyan Davit S.
Published: January 2021

Stress testing is a broad research area, at the interference of many disciplines (finance, banking, econometrics, macroeconomics, microeconomics, mathematical analysis etc.), and is of interest to both theoretical scientists and practitioners. The usefulness of this approach became evident after the financial crisis of 2007–2009, which prompted many researchers to develop and constantly improve stress-testing methodologies, using which it is possible to accurately forecast the behavior of banks and the financial sector in crisis periods. It allows banks to assess the scale of losses and timely take the necessary measures to strengthen the financial condition. Today, economic science has the biggest arsenal of stress testing methods that allow us to assess potential losses in crisis periods that correspond to extreme but plausible events. The stress testing methodologies cover all-important types of risks (credit, interest rate risk, liquidity risk etc.), as well as specific risks. The presence of a huge number of stress testing methods guarantees its versatility and depth, which could be explained by the attempt using this methods to create a behavior model of banks, which are quite complex in structure and functionality. The purpose of this study is to provide a concise, but at the same time comprehensive classification of stress testing methods, as well as a review of the current approaches to stress testing or to solving its various aspects (for example, developing stress scenarios) presented by scientists, international organizations, central banks and other interested parties. This paper is an introduction to the vast field of analytics – stress testing, and is oriented to banking and financial analysts, macroeconomists who want either to familiarize themselves with stress testing as a tool for assessing banking risks, or to systematize all the accumulated knowledge in this area in order to better understand economic processes.
A inclusão de crianças com deficiências no contexto escolar a partir dos recursos da comunicação suplementar e alternativa
Authors: Morais Nadja Maria de Menezes , Lima Jôse Pessoa de , Silva Regina Celi Delfino da , Jesus Tássia Souza de , Gabriel Rosenice de Lima , Mamedes Rosilene Felix
Published: January 2021

O presente estudo objetivou analisar, refletir e discutir sobre a importância de conhecermos um pouco mais a respeito da temática de Comunicação Suplementar e Alternativa e como ela pode contribuir para o desenvolvimento dos alunos que não possuem a fala funcional. Estamos em pleno século XXI, mas ainda carecemos muito de informações e conhecimento sobre como trabalhar na escola com estes recursos em sala de aula. Para a metodologia, optamos em realizar uma discussão teórica e metodológica a partir do recorte de dois recursos adaptados na comunicação alternativa abordados pelos autores Manzini e Deliberato. Tais recursos foram encontrados no portal de aporte técnicos para auxiliar a comunicação alternativa por meio de equipamento e material pedagógico especial na educação, na capacitação e na recreação da pessoa com deficiência física, além de termos escolhido a autora Mantoan por entendermos que ela traz um conceito mais amplo sobre a Educação Inclusiva e sua contribuição nos espaços escolares, entre outros teóricos que versam sobre o assunto.
Feminization of hawksbill turtle hatchlings in the twenty-first century at an important regional nesting aggregation
Authors: Chatting M , Hamza S , Al-Khayat J , Smyth D , Husrevoglu S , Marshall CD
Published: January 2021

Projected climate change is forecasted to have significant effects on biological systems worldwide. Marine turtles in particular may be vulnerable, as the sex of their offspring is determined by their incubating temperature, termed temperature-dependent sex determination. This study aimed to estimate historical, and forecast future, primary sex ratios of hawksbill turtleEretmochelys imbricatahatchlings at an important nesting ground in northeastern Qatar. Incubation temperatures from the Arabian/Persian Gulf were measured over 2 nesting seasons. Climate data from same period were regressed with nest temperatures to estimate incubation temperatures and hatchling sex ratios for the site from 1993 to 2100. Future hatchling sex ratios were estimated for 2 climate forecasts, one mid-range (SSP245) and one extreme (SSP585). Historical climate data showed female-biased sex ratios of 73.2 ± 12.1% from 1993 to 2017. Female biases from 2018 to 2100 averaged 85.7% ± 6.7% under the mid-range scenario and 87.9% ± 5.4% under the high-range scenario. In addition, predicted female hatchling production was >90% from 2054 and 2052 for SSP245 and SSP585, respectively. These results show that hawksbill primary sex ratios in Qatar are at risk of significant feminization by the year 2100 and that hawksbill turtle incubation temperatures in an extreme, understudied environment are already comparable to those predicted in tropical rookeries during the latter half of the 21stcentury. These results can help conservationists predict primary sex ratios for hawksbill turtles in the region in the face of 21st-century climate change.
Habitat use and selection patterns inform habitat conservation priorities of an endangered large carnivore in southern Europe
Authors: de Gabriel Hernando M , Karamanlidis AA , Grivas K , Krambokoukis L , Papakostas G , Beecham J
Published: January 2021

Understanding the habitat use and selection patterns of endangered species is essential in developing management measures that will protect critical habitat and mitigate human-wildlife conflicts. This understanding is particularly important in areas with high anthropogenic pressures. To understand the ecological role of various habitat types in the conservation of an endangered large carnivore in southern Europe, with its distinct environmental conditions and predominantly anthropogenic landscapes, we studied 18 GPS-collared brown bears Ursus arctos in Greece. We examined the use and selection of habitats according to age and sex categories and behavioral status during 5 ecologically defined seasons. Areas with rough terrain were identified as important refuge areas and were used by all bears in late hyperphagia and emergence. All bears used areas closer to human-related habitat features during the night. Habitat selection was positive for areas with rough terrain and naturalized (i.e. abandoned or not intensive) crops and areas close to water courses, while high-altitude areas and roads were avoided. The selection or avoidance of other habitats varied across bear categories and between stationary and moving behavior. We recommend that the results of the study be used to develop guidelines for species conservation and allow for prioritizing management actions that will promote the conservation of bears in Greece. In particular, the habitat use patterns provide information on how to limit interactions between humans and bears in space and/or time, while the habitat selection patterns indicate suitable habitats that should be protected/improved based on their importance and ecological role for the species.
Factors influencing readmission among Thais with myocardial infarction
Authors: Polsook Rapin , Aungsuroch Yupin
Published: January 2021

Background: Readmission among patients with myocardial infarction is costly, and it has become a marker of quality of care. Therefore, factors related to readmission warrant examination.
Objective: This study aimed at examining factors influencing readmission in Thai with myocardial infarction.
Methods: This was a cross-sectional study with 200 participants randomly selected from five regional hospitals in Thailand. All research tools used indicated acceptable validity and reliability. Linear Structural Relationship version 8.72 was used for the data analysis.
Results: The findings showed that the hypothesized model with social support, depression, symptom severity, comorbidity, and quality of life could explain 4% (R2 = 0.04) of the variance in readmission (c2 = 1.39, df = 2, p < 0.50, c2/df = 0.69, GIF = 1.00, RMSEA = 0.00, SRMR = 0.01, and AGFI = 0.98). Symptom severity was the most influential factor that had a positive and direct effect on the readmission rate (0.06, p < 0.05).
Conclusions: These findings serve as an input to decrease readmission in patients with myocardial infarction by reducing the symptom severity and comorbidity and promoting a better quality of life.
The Adipose Microenvironment Dysregulates the Mammary Myoepithelial Cells and Could Participate to the Progression of Breast Cancer
Authors: Delort Laetitia , Cholet Juliette , Decombat Caroline , Vermerie Marion , Dumontet Charles , Castelli Florence A. , Fenaille François , Auxenfans Céline , Rossary Adrien , Caldefie-Chezet Florence
Published: January 2021

Breast cancer is the most common cancer among women worldwide. Overweight and obesity are now recognized as established risk factors for this pathology in postmenopausal women. These conditions are also believed to be responsible for higher recurrence and mortality rates. Reciprocal interactions have been described between adipose and cancer cells. An adipose microenvironment favors a greater proliferation of cancer cells, their invasion and even resistance to anti-cancer treatments. In addition, the chronic low-grade inflammation observed in obese individuals is believed to amplify these processes. Among the cell types present in the breast, myoepithelial cells (MECs), located at the interface of the epithelial cells and the stroma, are considered “tumor suppressor” cells. During the transition from ductal carcinomain situto invasive cancer, disorganization or even the disappearance of MECs is observed, thereby enhancing the ability of the cancer cells to migrate. As the adipose microenvironment is now considered as a central actor in the progression of breast cancer, our objective was to evaluate if it could be involved in MEC functional modifications, leading to the transition ofin situto invasive carcinoma, particularly in obese patients. Through a co-culture model, we investigated the impact of human adipose stem cells from women of normal weight and obese women, differentiated or not into mature adipocytes, on the functionality of the MECs by measuring changes in viability, apoptosis, gene, and miRNA expressions. We found that adipose cells (precursors and differentiated adipocytes) could decrease the viability of the MECs, regardless of the original BMI. The adipose cells could also disrupt the expression of the genes involved in the maintenance of the extracellular matrix and to amplify the expression of leptin and inflammatory markers. miR-122-5p and miR-132-3p could also be considered as targets for adipose cells. The metabolite analyses revealed specific profiles that may be involved in the growth of neoplastic cells. All of these perturbations could thus be responsible for the loss of tumor suppressor status of MECs and promote the transition fromin situto invasive carcinoma.
Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct Gjb2-Related Hereditary Deafness Models
Authors: Xu Kai , Chen Sen , Xie Le , Qiu Yue , Bai Xue , Liu Xiao-Zhou , Zhang Hui-Min , Wang Xiao-Hui , Jin Yuan , Sun Yu , Kong Wei-Jia
Published: January 2021

The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. GJB2, encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice.
Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis
Authors: Zheng Dandan , Zhu Yu , Shen Yili , Xiao Sisi , Yang Lehe , Xiang Youqun , Dai Xuanxuan , Hu Wanle , Zhou Bin , Liu Zhiguo , Zhao Haiyang , Zhao Chengguang , Huang Xiaoying , Wang Liangxing
Published: January 2021

Background

Colorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC.

Methods

Cell function tests were performed to observe the inhibitory effect of cynaropicrin on human CRC cells (RKO, HCT116, and DLD-1). Expression levels of LIFR, P-STAT3, P-STAT4, and apoptotic proteins were detected by Western blotting. Immunoprecipitation confirmed the presence of LIFR/STAT3/STAT4 complex. Cell immunofluorescence assay was used to observe the subcellular localization of STAT3 and STAT4. In vivo efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice.

Results

Cynaropicrin significantly reduced the survival ability of human CRC cells and promoted apoptosis in a dose-dependent manner. Western blotting results suggested that the antitumor effects of cynaropicrin might be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus. Cynaropicrin also suppressed tumor growth in the xenograft model.

Conclusion

The results showed that cynaropicrin exerted a strong inhibitory effect on CRC in vitro and in vivo. Our study concluded that cynaropicrin has potential application prospects in the field of anti-CRC therapy.
Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Origin, Polarization, Function, and Reprogramming
Authors: Yang Sen , Liu Qiaofei , Liao Quan
Published: January 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy. PDAC is only cured by surgical resection in its early stage, but there remains a relatively high possibility of recurrence. The development of PDAC is closely associated with the tumor microenvironment. Tumor-associated macrophages (TAMs) are one of the most abundant immune cell populations in the pancreatic tumor stroma. TAMs are inclined to M2 deviation in the tumor microenvironment, which promotes and supports tumor behaviors, including tumorigenesis, immune escape, metastasis, and chemotherapeutic resistance. Herein, we comprehensively reviewed the latest researches on the origin, polarization, functions, and reprogramming of TAMs in PDAC.
Peroxisomal Metabolite and Cofactor Transport in Humans
Authors: Chornyi Serhii , IJlst Lodewijk , van Roermund Carlo W. T. , Wanders Ronald J. A. , Waterham Hans R.
Published: January 2021

Peroxisomes are membrane-bound organelles involved in many metabolic pathways and essential for human health. They harbor a large number of enzymes involved in the different pathways, thus requiring transport of substrates, products and cofactors involved across the peroxisomal membrane. Although much progress has been made in understanding the permeability properties of peroxisomes, there are still important gaps in our knowledge about the peroxisomal transport of metabolites and cofactors. In this review, we discuss the different modes of transport of metabolites and essential cofactors, including CoA, NAD+, NADP+, FAD, FMN, ATP, heme, pyridoxal phosphate, and thiamine pyrophosphate across the peroxisomal membrane. This transport can be mediated by non-selective pore-forming proteins, selective transport proteins, membrane contact sites between organelles, and co-import of cofactors with proteins. We also discuss modes of transport mediated by shuttle systems described for NAD+/NADH and NADP+/NADPH. We mainly focus on current knowledge on human peroxisomal metabolite and cofactor transport, but also include knowledge from studies in plants, yeast, fruit fly, zebrafish, and mice, which has been exemplary in understanding peroxisomal transport mechanisms in general.
Rocking the Boat: The Decisive Roles of Rho Kinases During Oocyte, Blastocyst, and Stem Cell Development
Authors: Saadeldin Islam M. , Tukur Hammed A. , Aljumaah Riyadh S. , Sindi Ramya A.
Published: January 2021

The rho-associated coiled-coil-containing proteins (ROCKs or rho kinase) are effectors of the small rho-GTPase rhoA, which acts as a signaling molecule to regulate a variety of cellular processes, including cell proliferation, adhesion, polarity, cytokinesis, and survival. Owing to the multifunctionality of these kinases, an increasing number of studies focus on understanding the pleiotropic effects of the ROCK signaling pathway in the coordination and control of growth (proliferation, initiation, and progression), development (morphology and differentiation), and survival in many cell types. There is growing evidence that ROCKs actively phosphorylate several actin-binding proteins and intermediate filament proteins during oocyte cytokinesis, the preimplantation embryos as well as the stem cell development and differentiation. In this review, we focus on the participation of ROCK proteins in oocyte maturation, blastocyst formation, and stem cell development with a special focus on the selective targeting of ROCK isoforms, ROCK1, and ROCK2. The selective switching of cell fate through ROCK inhibition would provide a novel paradigm for in vitro oocyte maturation, experimental embryology, and clinical applications.
Tales of the ER-Golgi Frontier: Drosophila-Centric Considerations on Tango1 Function
Authors: Feng Zhi , Yang Ke , Pastor-Pareja José C.
Published: January 2021

In the secretory pathway, the transfer of cargo from the ER to the Golgi involves dozens of proteins that localize at specific regions of the ER called ER exit sites (ERES), where cargos are concentrated preceding vesicular transport to the Golgi. Despite many years of research, we are missing crucial details of how this highly dynamic ER-Golgi interface is defined, maintained and functions. Mechanisms allowing secretion of large cargos such as the very abundant collagens are also poorly understood. In this context, Tango1, discovered in the fruit fly Drosophila and widely conserved in animal evolution, has received a lot of attention in recent years. Tango1, an ERES-localized transmembrane protein, is the single fly member of the MIA/cTAGE family, consisting in humans of TANGO1 and at least 14 different related proteins. After its discovery in flies, a specific role of human TANGO1 in mediating secretion of collagens was reported. However, multiple studies in Drosophila have demonstrated that Tango1 is required for secretion of all cargos. At all ERES, through self-interaction and interactions with other proteins, Tango1 aids ERES maintenance and tethering of post-ER membranes. In this review, we discuss discoveries on Drosophila Tango1 and put them in relation with research on human MIA/cTAGE proteins. In doing so, we aim to offer an integrated view of Tango1 function and the nature of ER-Golgi transport from an evolutionary perspective.
Closing the Gap: Mechanisms of Epithelial Fusion During Optic Fissure Closure
Authors: Chan Brian Ho Ching , Moosajee Mariya , Rainger Joe
Published: January 2021

A key embryonic process that occurs early in ocular development is optic fissure closure (OFC). This fusion process closes the ventral optic fissure and completes the circumferential continuity of the 3-dimensional eye. It is defined by the coming together and fusion of opposing neuroepithelia along the entire proximal-distal axis of the ventral optic cup, involving future neural retina, retinal pigment epithelium (RPE), optic nerve, ciliary body, and iris. Once these have occurred, cells within the fused seam differentiate into components of the functioning visual system. Correct development and progression of OFC, and the continued integrity of the fused margin along this axis, are important for the overall structure of the eye. Failure of OFC results in ocular coloboma—a significant cause of childhood visual impairment that can be associated with several complex ocular phenotypes including microphthalmia and anterior segment dysgenesis. Despite a large number of genes identified, the exact pathways that definitively mediate fusion have not yet been found, reflecting both the biological complexity and genetic heterogeneity of the process. This review will highlight how recent developmental studies have become focused specifically on the epithelial fusion aspects of OFC, applying a range of model organisms (spanning fish, avian, and mammalian species) and utilizing emerging high-resolution live-imaging technologies, transgenic fluorescent models, and unbiased transcriptomic analyses of segmentally-dissected fissure tissue. Key aspects of the fusion process are discussed, including basement membrane dynamics, unique cell behaviors, and the identities and fates of the cells that mediate fusion. These will be set in the context of what is now known, and how these point the way to new avenues of research.
Recent Advances in Molecular Diagnostics of Fungal Plant Pathogens: A Mini Review
Authors: Hariharan Ganeshamoorthy , Prasannath Kandeeparoopan
Published: January 2021

Phytopathogenic fungal species can cause enormous losses in quantity and quality of crop yields and this is a major economic issue in the global agricultural sector. Precise and rapid detection and identification of plant infecting fungi are essential to facilitate effective management of disease. DNA-based methods have become popular methods for accurate plant disease diagnostics. Recent developments in standard and variant polymerase chain reaction (PCR) assays including nested, multiplex, quantitative, bio and magnetic-capture hybridization PCR techniques, post and isothermal amplification methods, DNA and RNA based probe development, and next-generation sequencing provide novel tools in molecular diagnostics in fungal detection and differentiation fields. These molecular based detection techniques are effective in detecting symptomatic and asymptomatic diseases of both culturable and unculturable fungal pathogens in sole and co-infections. Even though the molecular diagnostic approaches have expanded substantially in the recent past, there is a long way to go in the development and application of molecular diagnostics in plant diseases. Molecular techniques used in plant disease diagnostics need to be more reliable, faster, and easier than conventional methods. Now the challenges are with scientists to develop practical techniques to be used for molecular diagnostics of plant diseases. Recent advancement in the improvement and application of molecular methods for diagnosing the widespread and emerging plant pathogenic fungi are discussed in this review.
Frequent Pet Contact as Risk Factor for Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis
Authors: Grehn Claudia , Eschenhagen Patience , Temming Svenja , Düesberg Uta , Neumann Konrad , Schwarz Carsten
Published: January 2021

Aspergillus fumigatus (Af) frequently colonizes the respiratory tract of patients with cystic fibrosis (CF). Af is associated with loss of pulmonary function and allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity fungal lung disease. Environmental factors have impact on CF patients’ lung function variation. The aim of this nationwide questionnaire survey was to investigate the amount of CF patients with frequent pet contact including pet species and to examine the potential impact of frequent pet contact on the occurrence of Af colonization and ABPA diagnosis in these patients. The survey was carried out in 31 German CF centers in 2018. A total of 1232 who completed the surveys were included, and statistical analysis was performed by chi-squared test. Within the study cohort 49.8% of subjects (n = 614; CF patients < 18years: 49.4%, n = 234; ≥ 18years: 50.1%, n = 380) reported frequent contact to pets, of which 60.7% reported frequent contact to dogs, 42.3% to cats and other animals. Of those with frequent pet contact, 71.8% (n = 441) had contact to one pet or more pets from the same family. Af colonization was not significantly associated with frequent pet contact. ABPA diagnosis was documented in 16.7% (n = 206) of all included CF patients and was significantly associated with frequent pet contact (18.9%, n = 116, p = 0.042), confirming previous single center examinations. Particularly, patients with frequent contact to dogs showed an increased ABPA prevalence of 21.3%. Frequent pet contact might be a risk factor for ABPA. CF patients who are sensitized to Af should be informed about the increased risk to develop an ABPA by frequent pet contact. Patients with recurrent onset of ABPA should be evaluated in terms of frequent pet contact.
Burkitt Lymphomas Evolve to Escape Dependencies on Epstein-Barr Virus
Authors: Hutcheson Rebecca L. , Chakravorty Adityarup , Sugden Bill
Published: January 2021

Epstein–Barr Virus (EBV) can transform B cells and contributes to the development of Burkitt lymphoma and other cancers. Through decades of study, we now recognize that many of the viral genes required to transform cells are not expressed in EBV-positive Burkitt lymphoma (BL) tumors, likely due to the immune pressure exerted on infected cells. This recognition has led to the hypothesis that the loss of expression of these viral genes must be compensated through some mechanisms. Recent progress in genome-wide mutational analysis of tumors provides a wealth of data about the cellular mutations found in EBV-positive BLs. Here, we review common cellular mutations found in these tumors and consider how they may compensate for the viral genes that are no longer expressed. Understanding these mutations and how they may substitute for EBV’s genes and contribute to lymphomagenesis can serve as a launchpad for more mechanistic studies, which will help us navigate the sea of genomic data available today, and direct the discoveries necessary to improve the treatment of EBV-positive BLs.
Case Report: Emergency CABG Following Failure of PTCA in a COVID-19 Patient
Authors: Romiti Silvia , Totaro Marco , Laderchi Amalia , Peruzzi Mariangela , Vinciguerra Mattia , Greco Ernesto
Published: January 2021

The coronavirus disease 2019 (COVID-19) pandemic outbreak, caused by severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) is affecting people worldwide representing a public health emergency. The effect of concomitant COVID-19 on patients who underwent cardiac surgery using cardiopulmonary bypass (CPB) is still undefined. Both SARS-Cov-2 infection and CPB can develop a cytokines storm and haemostatic disarrangements leading to acute respiratory distress syndrome (ARDS) and post-perfusion lung syndrome, respectively. SARS-Cov-2 infection may trigger and exacerbate post-inflammatory state after CPB resulting in higher risk of post-surgical adverse outcomes. International guidelines lack to provide standard management protocols for pre-operative COVID-19 patients requiring non-deferrable cardiac surgery intervention. We present a report of a successful coronary artery bypass grafting (CABG) emergency operation in a COVID-19 patient, who presented unstable angina and coronary artery dissection during cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA).
Complement-Dependent Activity of CD20-Specific IgG Correlates With Bivalent Antigen Binding and C1q Binding Strength
Authors: Bondza Sina , Marosan Anita , Kara Sibel , Lösing Josephine , Peipp Matthias , Nimmerjahn Falk , Buijs Jos , Lux Anja
Published: January 2021

Monoclonal antibodies directed against the CD20 surface antigen on B cells are widely used in the therapy of B cell malignancies. Upon administration, the antibodies bind to CD20 expressing B cells and induce their depletion via cell- and complement-dependent cytotoxicity or by induction of direct cell killing. The three antibodies currently most often used in the clinic are Rituximab (RTX), Ofatumumab (OFA) and Obinutuzumab (OBI). Even though these antibodies are all of the human IgG1 subclass, they have previously been described to vary considerably in the effector functions involved in therapeutic B cell depletion, especially in regards to complement activation. Whereas OFA is known to strongly induce complement-dependent cytotoxicity, OBI is described to be far less efficient. In contrast, the role of complement in RTX-induced B cell depletion is still under debate. Some of this dissent might come from the use of different in vitro systems for characterization of antibody effector functions. We therefore set out to systematically compare antibody as well as C1q binding and complement-activation by RTX, OFA and OBI on human B cell lines that differ in expression levels of CD20 and complement-regulatory proteins as well as human primary B cells. Applying real-time interaction analysis, we show that the overall strength of C1q binding to live target cells coated with antibodies positively correlated with the degree of bivalent binding for the antibodies to CD20. Kinetic analysis revealed that C1q exhibits two binding modes with distinct affinities and binding stabilities, with exact numbers varying both between antibodies and cell lines. Furthermore, complement-dependent cell killing by RTX and OBI was highly cell-line dependent, whereas the superior complement-dependent cytotoxicity by OFA was independent of the target B cells. All three antibodies were able to initiate deposition of C3b on the B cell surface, although to varying extent. This suggests that complement activation occurs but might not necessarily lead to induction of complement-dependent cytotoxicity. This activation could, however, initiate complement-dependent phagocytosis as an alternative mechanism of therapeutic B cell depletion.
A Deep Insight of Spermatogenesis and Hormone Levels of Aqua-Cultured Turbot (Scophthalmus maximus)
Authors: Liu Yifan , Liu Qinghua , Xu Shihong , Wang Yanfeng , Feng Chengcheng , Zhao Chunyan , Song Zongcheng , Li Jun
Published: January 2021

Turbot (Scophthalmus maximus) is an important marine fish both in Europe and North China. Although there are plenty of studies on the reproduction of turbot, the complete cytological process of spermatogenesis remains unclear. In this study, we investigated the submicroscopic structure of total 23 types of male germ cells throughout the breeding season, with a relatively complete process of the primary spermatocytes. We found that the spermatid tail formed early at Spermatid II, and there were at least 16 spherical mitochondria in the spermatozoa. The hepatosomatic index (HSI) and gonadosomatic index (GSI) both peaked during the breeding season. Preliminary analysis showed that the vitality of mature sperm was negatively correlated with the proportion of sperm deformity. The serum 3,5,3′-triiodothyronine (T3), 5-hydroxytryptamine (5-HT), testosterone (T), 17α,20β-Dihydroxy-4-pregnen-3-one (17α,20β-DHP), and 17β-estradiol (E2) all increased during the maturity period, with the change of T content most noticeable. Whereas in the testis, an overall high level of 11-ketotestosterone (11-KT) was more remarkable. The expression and localization of androgen receptor (AR) mRNA showed that the AR was highly expressed at the stages of II (15 – 70 g), with a slight rebound at the mature stages [IV(2200 g) to V(2500 g)], whose change was ahead to the changes of T and 11-KT. Fluorescence in situ hybridization (FISH) analysis showed that the AR mainly distributed in but not limited to Sertoli cells. This study represents the most complete overview of the reproductive cycle and spermatogenesis of turbot, which provides an important reference for the reproduction research and the guidance of flatfish breeding.
Genomic and Functional Characterization of Enterococcus faecalis Isolates Recovered From the International Space Station and Their Potential for Pathogenicity
Authors: Bryan Noelle C. , Lebreton Francois , Gilmore Michael , Ruvkun Gary , Zuber Maria T. , Carr Christopher E.
Published: January 2021

Enterococcus faecalis is a multidrug resistant, opportunistic human pathogen and a leading cause of hospital acquired infections. Recently, isolates have been recovered from the air and surfaces onboard the International Space Station (ISS). Pangenomic and functional analyses were carried out to assess their potential impact on astronaut health. Genomes of each ISS isolate, and both clinical and commensal reference strains, were evaluated for their core and unique gene content, acquired antibiotic resistance genes, phage, plasmid content, and virulence traits. In order to determine their potential survival when outside of the human host, isolates were also challenged with three weeks of desiccation at 30% relative humidity. Finally, pathogenicity of the ISS strains was evaluated in the model organism Caenorhabditis elegans. At the culmination of this study, there were no defining signatures that separated known pathogenic strains from the more commensal phenotypes using the currently available resources. As a result, the current reliance on database information alone must be shifted to experimentally evaluated genotypic and phenotypic characteristics of clinically relevant microorganisms.
Fungal and Bacterial Diversity Patterns of Two Diversity Levels Retrieved From a Late Decaying Fagus sylvatica Under Two Temperature Regimes
Authors: Muszynski Sarah , Maurer Florian , Henjes Sina , Horn Marcus A. , Noll Matthias
Published: January 2021

Environmental fluctuations are a common occurrence in an ecosystem, which have an impact on organismic diversity and associated ecosystem services. The aim of this study was to investigate how a natural and a species richness-reduced wood decaying community diversity were capable of decomposing Fagus sylvatica dead wood under a constant and a fluctuating temperature regime. Therefore, microcosms with both diversity levels (natural and species richness-reduced) were prepared and incubated for 8 weeks under both temperature regimes. Relative wood mass loss, wood pH, carbon dioxide, and methane emissions, as well as fungal and bacterial community compositions in terms of Simpson‘s diversity, richness and evenness were investigated. Community interaction patterns and co-occurrence networks were calculated. Community composition was affected by temperature regime and natural diversity caused significantly higher mass loss than richness-reduced diversity. In contrast, richness-reduced diversity increased wood pH. The bacterial community composition was less affected by richness reduction and temperature regimes than the fungal community composition. Microbial interaction patterns showed more mutual exclusions in richness-reduced compared to natural diversity as the reduction mainly reduced abundant fungal species and disintegrated previous interaction patterns. Microbial communities reassembled in richness-reduced diversity with a focus on nitrate reducing and dinitrogen-fixing bacteria as connectors in the network, indicating their high relevance to reestablish ecosystem functions. Therefore, a stochastic richness reduction was followed by functional trait based reassembly to recover previous ecosystem productivity.
Overcoming Challenges to Make Bacteriophage Therapy Standard Clinical Treatment Practice for Cystic Fibrosis
Authors: Ng Renee N. , Tai Anna S. , Chang Barbara J. , Stick Stephen M. , Kicic Anthony
Published: January 2021

Individuals with cystic fibrosis (CF) are given antimicrobials as prophylaxis against bacterial lung infection, which contributes to the growing emergence of multidrug resistant (MDR) pathogens isolated. Pathogens such as Pseudomonas aeruginosa that are commonly isolated from individuals with CF are armed with an arsenal of protective and virulence mechanisms, complicating eradication and treatment strategies. While translation of phage therapy into standard care for CF has been explored, challenges such as the lack of an appropriate animal model demonstrating safety in vivo exist. In this review, we have discussed and provided some insights in the use of primary airway epithelial cells to represent the mucoenvironment of the CF lungs to demonstrate safety and efficacy of phage therapy. The combination of phage therapy and antimicrobials is gaining attention and has the potential to delay the onset of MDR infections. It is evident that efforts to translate phage therapy into standard clinical practice have gained traction in the past 5 years. Ultimately, collaboration, transparency in data publications and standardized policies are needed for clinical translation.
Comparative Genomics of Leuconostoc carnosum
Authors: Candeliere Francesco , Raimondi Stefano , Spampinato Gloria , Tay Moon Yue Feng , Amaretti Alberto , Schlundt Joergen , Rossi Maddalena
Published: January 2021

Leuconostoc carnosum is a known colonizer of meat-related food matrices. It reaches remarkably high loads during the shelf life in packaged meat products and plays a role in spoilage, although preservative effects have been proposed for some strains. In this study, the draft genomes of 17 strains of L. carnosum (i.e., all the strains that have been sequenced so far) were compared to decipher their metabolic and functional potential and to determine their role in food transformations. Genome comparison and pathway reconstruction indicated that L. carnosum is a compact group of closely related heterofermentative bacteria sharing most of the metabolic features. Adaptation to a nitrogen-rich environment, such as meat, is evidenced by 23 peptidase genes identified in the core genome and by the autotrophy for nitrogen compounds including several amino acids, vitamins, and cofactors. Genes encoding the decarboxylases yielding biogenic amines were not present. All the strains harbored 1–4 of 32 different plasmids, bearing functions associated to proteins hydrolysis, transport of amino acids and oligopeptides, exopolysaccharides, and various resistances (e.g., to environmental stresses, bacteriophages, and heavy metals). Functions associated to bacteriocin synthesis, secretion, and immunity were also found in plasmids. While genes for lactococcin were found in most plasmids, only three harbored the genes for leucocin B, a class IIa antilisterial bacteriocin. Determinants of antibiotic resistances were absent in both plasmids and chromosomes.