bluuebunny/crossref_metadata_2025 huggingface dataset:
THE IMPACT OF FINANCIAL INSTRUMENTS ON BUSINESS DEVELOPMENT
Authors: Tanklevska Nataliya
Published: February 2022

The article identifies theoretical approaches to the formation of a set of financial instruments that directly affect the development of enterprises. Objective and subjective factors that affect the dynamics and efficiency of financial instruments are identified. The expediency of using financial forecasting as one of the financial methods, which allows to predict the development of economic processes in the future, as well as financial planning. If financial forecasting is a strategy for developing state finances in a certain perspective, then financial planning is tactical ways to achieve this perspective. Emphasis is placed on the need to apply the budgeting system in financial planning, especially in the context of market relations and financial turbulence. It is determined that financial control is a necessary condition for uninterrupted, efficient and gradual business development. The classification of types, forms and methods of financial control is given. Peculiarities of financial regulation of activity of business entities are determined, the basic principles of the liberal concept and the concept of state regulation are considered. The main instrument of socio-economic development as a managed process in a market economy is the economic and legal mechanism of state regulation, which includes both the system of privileges and subsidiary financial means of development, as well as a set of regulations and measures aimed at limiting certain unsatisfactory consequences of economic activity. Moreover, the financial levers of influence on the development of business structures are given. Only the complex application of all financial instruments can ensure the qualitative development of business entities. Among all financial levers, a special place is occupied by taxes and fees, through which the state mobilizes funds to perform its functions, as well as affects and encourages entrepreneurial activity, promotes investment activity etc. In a market economy, the use of administrative methods of influence is too limited, and therefore the main emphasis in the regulation of the economy is on taxation and financial stimulation of business structures development. Issues of ensuring the financial stability of business entities, strengthening their financial security, as well as identifying factors that affect the state and development of enterprise financing may be topics for further research.
Effective Digital Marketing Strategies Used by MSMEs in NCR Under New Normal
Authors: Santos Ohle Nychail , Santos Ma. Sophia , Dragas Chelzy Divine , Posadas Marie Abigail
Published: February 2022

The changes in our daily lives, or, which have been called the "new normal," have an implication in the shifting of tradition to online business activities. This study aims to explore how effective search engine marketing, content marketing, influential marketing, social media marketing, and email marketing as strategies in digital marketing used by different MSMEs operating in NCR under the new normal and if these strategies can give a long-term gain in businesses. The study was conducted through a survey questionnaire by MSMEs owners in NCR. The study results found that Social Media Marketing is very effective as a Digital Marketing strategy and has a significantly low positive relationship with Digital Content and Influencer Marketing. The study will contribute to identifying the effectiveness of digital marketing strategies that will benefit the businesses under the new normal in terms of increasing their sales and in the future, as people get accustomed to the activities under the new normal.
Motivation Level of Filipino Young Learners in L2 Learning on Online Distance Learning: Language Acquisition: Level of Motivation, Online Distance Learning, Second Language, Research
Authors: ESCABILLAS VERONICA , Ilustre Ramil G.
Published: February 2022

This journal article is a conflation of qualitative, quantitative exploration, papers and review papers published over the last decade. A brief overview of the level of motivation is provided, supported by the literature review. Hence, accumulated stylish practices in motivating learners in learning a second language will be presented. These exploration findings are anticipated to contribute to the sweats in the teaching and literacy area, particularly in acknowledging the level of motivation of the young Filipino learners in learning the second language. This journal used a grounded theory design to synthesize the motivation level of Filipino young learners in L2 Learning on Online Distance Learning. The journal article intends to offer styles to be suitable to enhance tutoring learning English as a second language to encourage pupils in their literacy manner and maintain their motivation consistently.
EL PATRIMONIO ARTESANAL: LOS SOMBREROS DE PAJA TOQUILLA
Authors: Aguilar-García María Leonor
Published: February 2022

En este artículo se aborda el tema del patrimonio cultural y artesanal, distinguiéndolo entre el material e inmaterial; además se destaca la importancia que tiene la conservación del mismo como parte de nuestra cultura e identidad, que es cabalmente lo que singulariza e individualiza a las culturas en el actual mundo globalizado. Dentro del patrimonio artesanal se aborda el tejido de sombreros de paja toquilla, artesanía que fuera declarada como Patrimonio Inmaterial por parte de la UNESCO en diciembre de 2012, y que es considerada como la artesanía másimportante del Ecuador y la más representativa de las provincia de Manabí, Azuay y Cañar.

Palabras clave: Patrimonio cultural y artesanal, patrimonio inmaterial, sombrero de paja toquilla, tejido.

AbstractIn this article the issue of cultural and craft heritage is addressed, distinguishing between material and immaterial; also the importance of its conservation as part of our culture and identity,which is fully what distinguishes and individualizes cultures in today’s globalized world stands. Inside the craft heritage weaving straw hats, crafts was declared Intangible Heritage by UNESCO in December 2012, and is considered the most important craft of Ecuador also the most representative handicrafts of the Provinces of Manabi, Azuay and Canar.Keywords: cultural and craft heritage, intangible heritage, toquilla straw hats, fabric.
DIGNIDADE DA PESSOA HUMANA E A RESERVA DO POSSÍVEL NAS AÇÕES DE MEDICAMENTOS
Authors: Silva Igor Lins
Published: February 2022

O presente artigo analisou a relação entre o princípio da dignidade da pessoa humana e o instrumento da reserva do possível nas ações de medicamentos, tendo em vista que pela precariedade do sistema público de saúde e da escassez de recursos públicos, muitos cidadãos se utilizam de meios judiciais invocando o mínimo existencial para obter medicamentos não fornecidos pelo Estado, ocasionando um grande impacto no orçamento público. Para tal objetivo, foi feita uma análise do direito à saúde nas Constituições Brasileiras, seguido de um estudo mais aprofundado do princípio da dignidade da pessoa humana, do mínimo existencial e da reserva do possível. Foi realizada uma pesquisa jurisprudencial perante os Tribunais Superiores com o fito de buscar os julgados mais recentes sobre o tema. Aderiu-se uma metodologia com abordagem dedutiva e método de procedimento monográfico. A coleta de dados utilizada foi a de documentação indireta, por meio de livros e jurisprudências dos tribunais superiores. Concluiu-se que enquanto não houver maior diálogo entre os Poderes, o mínimo existencial e a reserva do possível sempre serão utilizados como um meio de tentar mascarar os diversos problemas de gestão do Poder Público.
Palavras-chave: Reserva do possível; Dignidade da pessoa humana; Medicamentos; Saúde; Estado.
ABSTRACT
This article analyze the relationship between the principle of the dignity of the human person and the instrument of reserving the possible in the drug lawsuits, bearing in mind that due to the precariousness of the public health system and the scarcity of public resources, many citizens use judicial means invoking the minimum existencial to obtain medicines not supplied by the State, causing a great impact on the public budget. For this purpose, an analysis of the right to health in the Brazilian Constitutions was made, followed by a more in-depth study of the principle of human dignity, the minimum existential and the reserve of the possible. A jurisprudence survey from the Superior Courts in order to seek the most recent judgments on the subject. A methodology with a deductive approach and a monographic procedure method was used. The data collection used was indirect documentation, through books and jurisprudence from the Superior Courts. It was concluded that as long as there is no dialogue between the Powers, the minimum existencial and the reserve of the possible will always be used as a means of trying to mask the various management problems of the Public Power.
Keywords: Reserve of possible; Dignity of the human person; Drugs; Public health system; State.
PANDEMIA E ECONOMIA:
Authors: Tostes Yhon
Published: February 2022

O artigo discorre sobre a necessidade de um maior diálogo interdisciplinar entre Direito e Economia, especialmente agora quando vivemos uma Pandemia do Coronavírus COVID-19. Apresentaremos o tema na área de contratos bancários e os fundamentos da análise econômica do direito, bem como, a utilização da nova lei de declaração de direitos de liberdade econômica e de livre mercado nas decisões judiciais no Brasil.
ACESSO À CULTURA COMO A FUNÇÃO SOCIAL DOS DIREITOS AUTORAIS
Authors: De Andrade Barbosa Santos de Mesquita Alessandra , Biolcati Rodrigues Alessandra , Afonso de Mesquita Evandro , Rodrigues José Luis
Published: February 2022

O presente trabalho encara a problemática da relevância do acesso à cultura como elemento decorrente da função social dos direitos autorais, suas relações e seus efeitos sobre os limites da proteção. Destaca-se a relevância e importância do direito de acesso à cultura por meio de uma análise e apresentadas as normas jurídicas e fatos sociais que regulam e informam tanto os direitos culturais, em particular o direito de acesso às obras protegidas pelas normas autorais. Ao final conclui-se pela existência de elementos sociais e instrumentos jurídicos para uma efetiva concretização do direito de acesso à cultura, e pela necessidade de uma mudança na forma como são concebidas, interpretadas e aplicadas as normas jurídicas em questão.
Pembuatan Virgin Coconut Oil (VCO) Dengan Metode Enzimatis Dan Fermentasi
Authors: Dwi Sutanto Teja Dwi , Ratnawati Devi , HP Agus Martono
Published: February 2022

Virgin coconut oil (VCO) is coconut oil that contains medium chain fatty acids (MCFA) which are easily broken down by the body in very high amounts. Besides that, VCO also has very high antioxidant content such as tocopherol and beta-carotene. This PPM activity aims to provide VCO Making Training with the Enzymatic Method with pineapple fruit extract and fermentation with baker's yeast in the community of RT 12 RW 03 Pematang Governor Village, Muara Bangkahulu District, Bengkulu City. The activity began with a lecture followed by a discussion and practice of making VCO with enzymatic and fermentation methods. The results of observations in the field indicate that the target community of this PPM activity is very enthusiastic to take part in this activity because they feel they have gained additional new knowledge about how to make VCO which can complement their knowledge of the known VCO making technique, namely the fishing method. With the knowledge of making VCO taught in this activity, the target community will be able to have alternative methods for making VCO other than what has been known so far with easily obtained equipment. Keywords:   VCO; MCFA; antivirus; enzymatic; Fermentation
Creating a Multivariate-Multifunctional Database for Weed Control to Support Organic Mixed Vegetable Production
Authors: Ashqer Yaqeen Salatneh
Published: February 2022

The organic sector has become one of the fastest-growing agricultural movements in the United States. Weed management is one of the most significant challenges for organic vegetable growers since weed interference reduces crop yield and quality. This paper aims to share an innovative method to design, develop, and implement a multivariate- multifunctional database to help small-scale organic mixed vegetable farms to prevent the spread of weeds from the seeding stage of production. We monitored different types of vegetables in spring 2019 that were produced on a 0.5- acre plot in a small urban farm in Guilford County, North Carolina. We documented the environmental and climatic factors for all vegetables. The database we collected incorporates numbers of records, description of conditions, and photo images of vegetable and weed growth. The expected contribution of this study is to determine or calculate.
Iodine Nutrition Knowledge of Food Handlers: A Capricorn and Waterberg District Study, Limpopo Province, South Africa
Authors: Solomon Mabapa Ngoako
Published: February 2022

Given the public health importance of eliminating iodine deficiency and its consequences, one can assume that consumers are informed and educated about iodine nutrition and iodine deficiency disorders such as impaired mental function, goitre, hypothyroidism, cretinism, retarded physical development and even child mortality [1]. Salt fortification was an intervention initiated by the government to address iodine deficiency disorders but the community has limited information on the salt fortification and its benefits [2]. Intensive implementation activities of monitoring and evaluation of salt fortification have revealed the limited knowledge of how to translate efficacious interventions into effective programs with relevant mechanisms for program monitoring, quality assurance, and impact evaluation to the beneficiaries of the programme [3].
Suitability Evaluation of Urban Soils underline by Asu River Parent Material forCassava Manihotesculenta and Bambara groundnut (Vignasubterranea (L.) Verdc) Production in Ebonyi, Southeastern Nigeria
Authors: Emenyonu Chris
Published: February 2022

Cassava and Bambara groundnut are commonly consumed crops in Nigeria. Cassava is a tuber crop of utmost importance in Nigeria and increasing the production of cassava will enhance food security because cassava is consumed widely in Nigeria and Bambara groundnut is the third most important legume after groundnut (Arachishypogaea) and cowpea (Vignaunguiculata) in Africa. Soil suitability evaluation of some urban soils derived from Asu river group in Ebonyi rainforest agroecological zone of South eastern Nigeria was undertaken to define the fitness of the soil for production of River for Cassava (Manihotesculenta and Bambara groundnut (Vignasubterranea (L.) Verdc). The FAO guideline for land evaluation was used. Results obtained showed that sand content ranged from 481.85 – 669.6 g kg-1, silt content ranged from 192.8 – 330.27 g kg-1 while clay content ranged from 137.6-258.35 g kg-1. Bulk density ranged from 1.43- 1.44 gcm-3 and textural class ranged from sandyloam to sandy clay loam. PH varied from very strongly acidic (4.37) to moderately acidic (5.79). Organic matter ranged from 5.08-7.94 g kg-1. Soils were low in available phosphorus with values ranging from 7.60-10.34 g kg-1 and total nitrogen ranged from 0.30 to 0.85 g kg-1. Suitability evaluation showed that all the sites studied were currently not suitable (N1) for cassava production when the pH requirement for cassava was matched with pH of the study area. These urban soils were also currently not suitable (N1) for Bambara groundnut production due to limitation of rainfall and total nitrogen. Therefore, this study recommends liming of soil of the study area to encourage cultivation and promote sustainable cassava production and in the cassava of bambara groundnut, since rainfall of the area is not suitable for its production, there is no need to embark on its cultivation except in alternative irrigation pattern is to be used.
Fauna and Ecological Groups of Mollusks in Reservoirs of Uzbekistan
Authors: Boimurodov Kh. , Aliev B. , Jabbarova T. , Suyarov S. , Jalilov F. , Mirzamurodov О.
Published: February 2022

In the Chimkurgan reservoir there are 11 species and 2 subspecies belonging to 4 families. 11 species of mollusks belonging to 6 families were found in the Qoratepa reservoir. 5 species of Corbicula cor, C. fliminalis, C. purpurea, Corbiculina tibetensis and C. ferghanensis distributed in the Chimkurgan reservoir are eurybiont species and 9 species are Sinanondonta gibba, S. orbicularis, S. puerorum, Colletopterum ponderosum volgense, Euglesa bactrianum, C. syreum sogdianum, Odhneripisidium sogdianum were found to be stenobiont species. Corbiculina tibetensis and C. ferghanensis in the Qoratepa Reservoir have been studied as common eurybiont species, while the remaining species are stenobiont species.
Bombast and Sesquipedalian Words: Translation, Mistranslation, and the Epigraph to The Waste Land
Authors: Clemens Ruth Alison
Published: February 2022

The epigraph to T. S. Eliot's long poem The Waste Land (1922) is one of the most well-known paratexts of twentieth-century literature. However, as previous scholars have noted, the popularized English translation from the Ancient Greek of Petronius’ Satyricon contains a small but significant mistranslation: the Cumaean Sibyl is not actually hanging in a cage. This essay unearths another meaning in Ancient Greek of the ampulla in which the poet oracle is trapped: bombast. Using a Deleuzean new-materialist reading of text and paratext, this article proposes how the new meanings of the ampulla reconfigure both the significance of the original mistranslation and also the position of the poem itself, with its bombastic networks of allusions and paratextual complexities.
PERAN MEDIA MASSA DALAM POLITIK LUAR NEGERI: KASUS DI INDONESIA
Authors: Setiawan Asep
Published: February 2022

As a country embraces democratic values in its political system, mass media has an increasing role in influencing government policy making including foreign policy making. Study on mass media relations with foreign policy making has developed to level conceptual even theoretical framework in mass communication study. This article shows that theoretical and analytical approaches toward media and foreign policy decision making have at least seven analytical frameworks. Those tools of analysis are CNN Effect, the Indexing Hypothesis, Media – Policy Interaction Model, Positioning Theory Agenda – Setting Theory, Propaganda Model dan Manufacturing Consent. In Indonesia, study on relations between media and foreign policy has not been developed. But there is prominent case in foreign policy change of Indonesia regarding Iranian nuclear issue in United Nations Security Council.
KAWASAN EKONOMI KHUSUS (KEK) MANDALIKA DALAM IMPLEMENTASI KONSEP PARIWISATA BERBASIS ECOTOURISM: PELUANG DAN TANTANGAN
Authors: Nala Estriani Heavy
Published: February 2022

This article analyzes the concept of ecotourism as an alternative to the eco-friendly tourism sector. The tourism sector becomes one of the strategic sectors in increasing the country's economic growth. The multiplier effect of tourism industry makes this sector continue to increase significantly. Indonesia sets this sector as core leading sector. The government's seriousness in working on tourism destinations, realized by forming Special Economic Zone (KEK) of tourism, one of which is KEK Mandalika. However, in the midst of mass tourism development, the concern over environmental issues has come under scrutiny. Tourism industry demanded to also pay attention to the environmental damages caused by the development of the tourism industry. This research further finds that KEK Mandalika uses the ecotourism concept in response to the demands for the tourism industry to be sustainable and started to put more concern over environmental issues. The application of ecotourism in several sectors in KEK Mandalika is done because ecotourism is called to be an alternative for the development of eco-friendly tourism sector. However, a number of challenges arise on how ecotourism should not only involves a small part of the entourage or elite party, and still put forward the environmental aspect amid the demands of a rapidly growing tourism market.
DAMPAK BANTUAN INDONESIA TERHADAP NEGARA ANGGOTA KERJA SAMA SELATAN-SELATAN DI KAWASAN ASIA
Authors: Ahmad Rizaldi Ayu Rachmawaty,A Ade Rachmaliani
Published: February 2022

South South Cooperation (SSC) is a form of development cooperation between developing countries based on the principle of solidarity, equality (mutual opportunity) and the principle of mutual benefit. Indonesia is one of the member countries of Cooperation which is active as a foreign aid provider for SSC partner countries. So far, the available discussions have only focused on the benefits of South South Cooperation (SSC) on Indonesia's national interests. This journal examines from another perspective on the impact of Indonesia's foreign assistance on the development of member states of South South Cooperation. The research method used was descriptive qualitative with a focus on providing assistance in the Asian region. Foreign aid provided by Indonesia focuses more on training and community empowerment programs. Indonesia also provided financial assistance but the value was no greater than non-financial assistance worth US $ 60 million. In addition, Indonesia's foreign aid for conflict countries in Asia includes educational, economic, health and social programs that aim to help and alleviate the suffering of people in the midst of conflict. The impact of the provision of non-financial assistance is that people in developing countries in Asia get new knowledge, skills and information to be implemented in their countries and increase community empowerment so that they are not increasingly dependent on foreign financial assistance.
Strategi Diplomasi Kemanusiaan Pemerintah Indonesia Dalam Kasus Krisis Kemanusiaan Yang Dialami Etnis Rohingya Di Myanmar Tahun 201
Authors: Fernando Ersento Maraden Sitorus Ardli Johan Kusuma
Published: February 2022

This research wants to look at the humanitarian diplomacy strategy by the Indonesian government to provide humanitarian assistance to the Rohingya ethnic groups (especially those still in Myanmar in 2017). Myanmar's military and also the majority of people in Rakhine who are Buddhists have committed acts of violence and seized the human rights of the Rohingya ethnic group which is an ethnic minority in Rakhine who are Muslim. The issue attracted the attention of the international community, including Indonesia. This study uses a qualitative method, with a descriptive analytic approach, where data are collected by literature study. The findings of this study are: the Indonesian government has used several humanitarian diplomacy strategies, including: conducting a diplomatic approach between the Indonesian government and the Myanmar government (with due regard to the ASEAN Way), collaborating with the United Nations (offering formula 4+1 as a form of implementation of the recommendations from Advisory Commission Report for Rakhine), involved civilians to channel aid to the Rohingya ethnic group in Myanmar (forming AKIM consisting of 11 humanitarian agencies). The strategy succeeded in breaking through the blockade carried out by the Myanmar government as an effort to block humanitarian assistance provided by the international community.
Global Maritime Fulcrum Optimization In Maintaining Indonesian Maritime Sovereignty
Authors: Ida Susilowati, Muhammad Sholeh Nur Rohim Yunus
Published: February 2022

The regulation of International maritime law has become a long-standing discussion in International life. It is not surprising if many international conventions were born as a result of agreements between countries. The main trigger for the occurrence of sea conflicts is the potential for extraordinary marine wealth that can be exploited by the International community. Therefore, the regulation of sea law is vital in order to maintain discipline and world peace and in addition to protecting the sovereignty of each country. This research uses a qualitative research method with a descriptive analysis approach.
Urgensi City Branding Dalam Paradiplomasi : Studi Kasus Kabupaten Serang
Authors: Rizkiya Ayu Maulida Rizky Hikmawan
Published: February 2022

In the era of globalization, regions is required to increase their capacity to meet the needs of the society. Unfortunately not all regions have advantages in their efforts to fulfill the welfare of its people. There are regions that do not have a significant level of income so the economic growth relatively slow. This situation need to be overcome by the local government by implementing specific strategies that are expected to be an alternative to increase the regional income. One of the strategy that can be taken by the local government is to carry out some cooperation with another actors from outside the country. The cooperation is expected to bring investment which can bring positive results for regional development, including the welfare of the people. However, before carrying out foreign cooperation, the local government must be able to form a regional branding which is expected to be a unique value for foreign parties to work together. In this article we try to provide input for the local government of Kabupaten Serang to form a special branding for the region. Through this research, we hope to help Kabupaten Serang to design strategic foreign cooperation and by the end produce many benefits for the society
Removal of Environmental Nanoparticles Increases Protein Synthesis and Energy Production in Healthy Humans
Authors: Antuña Eduardo , Carlos Bermejo-Millo Juan , Caso-Onzain Enrique , Caso-Peláez Enrique , Potes Yaiza , Coto-Montes Ana
Published: February 2022

Currently, industrial activity causes the environmental release of nanoparticles that have multiple adverse effects on population health. There is a clear correlation between the increase in particulate air pollution and the increases in mortality and morbidity rates in both adults and children, which demonstrates the toxic effects of these particles. However, the effect of particle removal on healthy individuals is unknown. Thus, in this preliminary study, we showed, for the first time, how the filtering equipment that we used significantly reduced a large amount of nanoparticles in a minimum time and induced a reduction of oxidative damage in healthy individuals of both sexes after 25, 50 and 100 days of exposure. These effects led to increased protein synthesis and enhanced mitochondrial efficiency, thus resulting in a highly significant triggering of ATP synthesis. These results not only provide insight into the chronic effects that environmental nanoparticles have on individuals prior to the development of pathologies but also demonstrate a system capable of reversing nanoparticle toxicity and allowing cellular energy recovery.
Sensory Systems and Transcriptional Regulation in Escherichia coli
Authors: Femerling Georgette , Gama-Castro Socorro , Lara Paloma , Ledezma-Tejeida Daniela , Tierrafría Víctor H. , Muñiz-Rascado Luis , Bonavides-Martínez César , Collado-Vides Julio
Published: February 2022

In free-living bacteria, the ability to regulate gene expression is at the core of adapting and interacting with the environment. For these systems to have a logic, a signal must trigger a genetic change that helps the cell to deal with what implies its presence in the environment; briefly, the response is expected to include a feedback to the signal. Thus, it makes sense to think of genetic sensory mechanisms of gene regulation. Escherichia coli K-12 is the bacterium model for which the largest number of regulatory systems and its sensing capabilities have been studied in detail at the molecular level. In this special issue focused on biomolecular sensing systems, we offer an overview of the transcriptional regulatory corpus of knowledge for E. coli that has been gathered in our database, RegulonDB, from the perspective of sensing regulatory systems. Thus, we start with the beginning of the information flux, which is the signal’s chemical or physical elements detected by the cell as changes in the environment; these signals are internally transduced to transcription factors and alter their conformation. Signals transduced to effectors bind allosterically to transcription factors, and this defines the dominant sensing mechanism in E. coli. We offer an updated list of the repertoire of known allosteric effectors, as well as a list of the currently known different mechanisms of this sensing capability. Our previous definition of elementary genetic sensory-response units, GENSOR units for short, that integrate signals, transport, gene regulation, and the biochemical response of the regulated gene products of a given transcriptional factor fit perfectly with the purpose of this overview. We summarize the functional heterogeneity of their response, based on our updated collection of GENSORs, and we use them to identify the expected feedback as part of their response. Finally, we address the question of multiple sensing in the regulatory network of E. coli. This overview introduces the architecture of sensing and regulation of native components in E.coli K-12, which might be a source of inspiration to bioengineering applications.
Gasdermin-E Mediated Pyroptosis—A Novel Mechanism Regulating Migration, Invasion and Release of Inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-like Synoviocytes
Authors: Wu Tao , Zhang Xue-Pei , Zhang Qian , Zou Yao-Yao , Ma Jian-Da , Chen Le-Feng , Zou Yao-Wei , Xue Ji-Meng , Ma Ruo-Fan , Chen Zhong , Dai Lie
Published: February 2022

Synovium fibroblast-like synoviocytes (FLSs) are important participants in the pathogenesis of synovitis and joint destruction in rheumatoid arthritis (RA). Pyroptosis is a pro-inflammatory and cell lytic programmed cell death mechanism mediated by gasdermin (GSDM) family proteins. In this study, we demonstrated the increased expression of GSDME and increased levels of GSDME-mediated pyroptosis in RA synovial tissues. In vitro, stimulation with TNF-α plus hypoxia mimicking the inflammatory and hypoxic environment in RA synovium induced GSDME-mediated pyroptosis in RA-FLSs in combination with the promotion of migration and invasion abilities and the release of inflammatory cytokines (IL-6, IL-8). Moreover, knockdown of GSDME significantly inhibited the proliferation rate, migration/invasion effects and cytokines released through the reduction of GSDME-mediated pyroptosis. The immunohistochemistry results showed that RA patients with high GSDME N-terminal (GSDME-NT) expression, which is the active form of GSDME, showed higher IL-6 expression in both lining and sublining layer of synovium than that in patients with low GSDME-NT expression, osteoarthritis and non-inflammatory orthopedic arthropathies. Our findings revealed a novel mechanism regulating cell proliferation, migration, invasion and inflammatory cytokines release during the process of GSDME mediated pyroptosis in RA.
Sterol Metabolism Differentially Contributes to Maintenance and Exit of Quiescence
Authors: Peselj Carlotta , Ebrahimi Mahsa , Broeskamp Filomena , Prokisch Simon , Habernig Lukas , Alvarez-Guerra Irene , Kohler Verena , Vögtle F.-Nora , Büttner Sabrina
Published: February 2022

Nutrient starvation initiates cell cycle exit and entry into quiescence, a reversible, non-proliferative state characterized by stress tolerance, longevity and large-scale remodeling of subcellular structures. Depending on the nature of the depleted nutrient, yeast cells are assumed to enter heterogeneous quiescent states with unique but mostly unexplored characteristics. Here, we show that storage and consumption of neutral lipids in lipid droplets (LDs) differentially impacts the regulation of quiescence driven by glucose or phosphate starvation. Upon prolonged glucose exhaustion, LDs were degraded in the vacuole via Atg1-dependent lipophagy. In contrast, yeast cells entering quiescence due to phosphate exhaustion massively over-accumulated LDs that clustered at the vacuolar surface but were not engulfed via lipophagy. Excessive LD biogenesis required contact formation between the endoplasmic reticulum and the vacuole at nucleus-vacuole junctions and was accompanied by a shift of the cellular lipid profile from membrane towards storage lipids, driven by a transcriptional upregulation of enzymes generating neutral lipids, in particular sterol esters. Importantly, sterol ester biogenesis was critical for long-term survival of phosphate-exhausted cells and supported rapid quiescence exit upon nutrient replenishment, but was dispensable for survival and regrowth of glucose-exhausted cells. Instead, these cells relied on de novo synthesis of sterols and fatty acids for quiescence exit and regrowth. Phosphate-exhausted cells efficiently mobilized storage lipids to support several rounds of cell division even in presence of inhibitors of fatty acid and sterol biosynthesis. In sum, our results show that neutral lipid biosynthesis and mobilization to support quiescence maintenance and exit is tailored to the respective nutrient scarcity.
Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies
Authors: Ma Xue , Gao Hua-Jie , Zhang Qing , Yang Meng-Ge , Bi Zhua-Jin , Ji Su-Qiong , Li Yue , Xu Li , Bu Bi-Tao
Published: February 2022

Objectives: Endoplasmic reticulum (ER) stress plays pivotal roles in the regulation of skeletal muscle damage and dysfunction in multiple disease conditions. We postulate the activation of ER stress in idiopathic inflammatory myopathies (IIM).

Methods: Thirty-seven patients with immune-mediated necrotizing myopathy (IMNM), 21 patients with dermatomyositis (DM), 6 patients with anti-synthetase syndrome (ASS), and 10 controls were enrolled. The expression of ER stress-induced autophagy pathway was detected using histological sections, Western blot, and real-time quantitative Polymerase Chain Reaction.

Results: ER stress-induced autophagy pathway was activated in biopsied muscle of patients with IMNM, DM, and ASS. The ER chaperone protein, glucose-regulated protein 78 (GRP78)/BiP expression in skeletal muscle correlated with autophagy, myofiber atrophy, myonecrosis, myoregeneration, and disease activity in IMNM.

Conclusion: ER stress was involved in patients with IIM and correlates with disease activity in IMNM. ER stress response may be responsible for skeletal muscle damage and repair in IIM.
Gα12 and Gα13: Versatility in Physiology and Pathology
Authors: Guo Paipai , Tai Yu , Wang Manman , Sun Hanfei , Zhang Lingling , Wei Wei , Xiang Yang K. , Wang Qingtong
Published: February 2022

G protein-coupled receptors (GPCRs), as the largest family of receptors in the human body, are involved in the pathological mechanisms of many diseases. Heterotrimeric G proteins represent the main molecular switch and receive cell surface signals from activated GPCRs. Growing evidence suggests that Gα12 subfamily (Gα12/13)-mediated signaling plays a crucial role in cellular function and various pathological processes. The current research on the physiological and pathological function of Gα12/13 is constantly expanding, Changes in the expression levels of Gα12/13 have been found in a wide range of human diseases. However, the mechanistic research on Gα12/13 is scattered. This review briefly describes the structural sequences of the Gα12/13 isoforms and introduces the coupling of GPCRs and non-GPCRs to Gα12/13. The effects of Gα12/13 on RhoA and other signaling pathways and their roles in cell proliferation, migration, and immune cell function, are discussed. Finally, we focus on the pathological impacts of Gα12/13 in cancer, inflammation, metabolic diseases, fibrotic diseases, and circulatory disorders are brought to focus.
The Molecular Pathways of Pyroptosis in Atherosclerosis
Authors: Song Dan , Li Manman , Yu Xue , Wang Yuqin , Fan Jiaying , Yang Wei , Yang Liming , Li Hong
Published: February 2022

Atherosclerosis (AS) is a chronic inflammatory disease seriously endangering human health, whose occurrence and development is related to many factors. Pyroptosis is a recently identified novel programmed cell death associated with an inflammatory response and involved in the formation and progression of AS by activating different signaling pathways. Protein modifications of the sirtuin family and microRNAs (miRNAs) can directly or indirectly affect pyroptosis-related molecules. It is important to link atherosclerosis, thermogenesis and molecular modifications. This article will systematically review the molecular pathways of pyroptosis in AS, which can provide a new perspective for AS prevention and treatment.
Identification of Bipotential Blood Cell/Nephrocyte Progenitors in Drosophila: Another Route for Generating Blood Progenitors
Authors: Morin-Poulard Ismaël , Destalminil-Letourneau Manon , Bataillé Laetitia , Frendo Jean-Louis , Lebreton Gaëlle , Vanzo Nathalie , Crozatier Michèle
Published: February 2022

The Drosophila lymph gland is the larval hematopoietic organ and is aligned along the anterior part of the cardiovascular system, composed of cardiac cells, that form the cardiac tube and its associated pericardial cells or nephrocytes. By the end of embryogenesis the lymph gland is composed of a single pair of lobes. Two additional pairs of posterior lobes develop during larval development to contribute to the mature lymph gland. In this study we describe the ontogeny of lymph gland posterior lobes during larval development and identify the genetic basis of the process. By lineage tracing we show here that each posterior lobe originates from three embryonic pericardial cells, thus establishing a bivalent blood cell/nephrocyte potential for a subset of embryonic pericardial cells. The posterior lobes of L3 larvae posterior lobes are composed of heterogeneous blood progenitors and their diversity is progressively built during larval development. We further establish that in larvae, homeotic genes and the transcription factor Klf15 regulate the choice between blood cell and nephrocyte fates. Our data underline the sequential production of blood cell progenitors during larval development.
Exploring Effects of C. elegans Protective Natural Microbiota on Host Physiology
Authors: Kissoyan Kohar Annie B. , Peters Lena , Giez Christoph , Michels Jan , Pees Barbara , Hamerich Inga K. , Schulenburg Hinrich , Dierking Katja
Published: February 2022

The Caenorhabditis elegans natural microbiota was described only recently. Thus, our understanding of its effects on nematode physiology is still in its infancy. We previously showed that the C. elegans natural microbiota isolates Pseudomonas lurida MYb11 and P. fluorescens MYb115 protect the worm against pathogens such as Bacillus thuringiensis (Bt). However, the overall effects of the protective microbiota on worm physiology are incompletely understood. Here, we investigated how MYb11 and MYb115 affect C. elegans lifespan, fertility, and intestinal colonization. We further studied the capacity of MYb11 and MYb115 to protect the worm against purified Bt toxins. We show that while MYb115 and MYb11 affect reproductive timing and increase early reproduction only MYb11 reduces worm lifespan. Moreover, MYb11 aggravates killing upon toxin exposure. We conclude that MYb11 has a pathogenic potential in some contexts. This work thus highlights that certain C. elegans microbiota members can be beneficial and costly to the host in a context-dependent manner, blurring the line between good and bad.
Epigenetic Manipulation of Psychiatric Behavioral Disorders Induced by Toxoplasma gondii
Authors: Yin Kun , Xu Chao , Zhao Guihua , Xie Huanhuan
Published: February 2022

Toxoplasma gondii is known to have a complex life cycle and infect almost all kinds of warm-blooded animals around the world. The brain of the host could be persistently infected by cerebral cysts, and a variety of psychiatric disorders such as schizophrenia and suicide have been reported to be related with latent toxoplasmosis. The infected animals showed fear reduction and a tendency to be preyed upon. However, the mechanism of this “parasites manipulation” effects have not been elucidated. Here, we reviewed the recent infection prevalence of toxoplasmosis and the evidence of mental and behavioral disorders induced by T. gondii and discussed the related physiological basis including dopamine dysregulation and gamma-aminobutyric acid (GABA) pathway and the controversial opinion of the necessity for cerebral cysts existence. Based on the recent advances, we speculated that the neuroendocrine programs and neurotransmitter imbalance may play a key role in this process. Simultaneously, studies in the evaluation of the expression pattern of related genes, long noncoding RNAs (lncRNAs), and mRNAs of the host provides a new point for understanding the mechanism of neurotransmitter dysfunction induced by parasite manipulation. Therefore, we summarized the animal models, T. gondii strains, and behavioral tests used in the related epigenetic studies and the responsible epigenetic processes; pinpointed opportunities and challenges in future research including the causality evidence of human psychiatric disorders, the statistical analysis for rodent-infected host to be more vulnerable preyed upon; and identified responsible genes and drug targets through epigenetics.
“Omics” Technologies - What Have They Told Us About Uropathogenic Escherichia coli Fitness and Virulence During Urinary Tract Infection?
Authors: Torres-Puig Sergi , García Vanesa , Stærk Kristian , Andersen Thomas E. , Møller-Jensen Jakob , Olsen John E. , Herrero-Fresno Ana
Published: February 2022

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infection (UTI), a widespread infectious disease of great impact on human health. This is further emphasized by the rapidly increase in antimicrobial resistance in UPEC, which compromises UTI treatment. UPEC biology is highly complex since uropathogens must adopt extracellular and intracellular lifestyles and adapt to different niches in the host. In this context, the implementation of forefront ‘omics’ technologies has provided substantial insight into the understanding of UPEC pathogenesis, which has opened the doors for new therapeutics and prophylactics discovery programs. Thus, ‘omics’ technologies applied to studies of UPEC during UTI, or in models of UTI, have revealed extensive lists of factors that are important for the ability of UPEC to cause disease. The multitude of large ‘omics’ datasets that have been generated calls for scrutinized analysis of specific factors that may be of interest for further development of novel treatment strategies. In this review, we describe main UPEC determinants involved in UTI as estimated by ‘omics’ studies, and we compare prediction of factors across the different ‘omics’ technologies, with a focus on those that have been confirmed to be relevant under UTI-related conditions. We also discuss current challenges and future perspectives regarding analysis of data to provide an overview and better understanding of UPEC mechanisms involved in pathogenesis which should assist in the selection of target sites for future prophylaxis and treatment.
The Intriguing Role of TLR Accessory Molecules in Cardiovascular Health and Disease
Authors: Bezhaeva Taisiya , Karper Jacco , Quax Paul H. A. , de Vries Margreet R.
Published: February 2022

Activation of Toll like receptors (TLR) plays an important role in cardiovascular disease development, progression and outcomes. Complex TLR mediated signaling affects vascular and cardiac function including tissue remodeling and repair. Being central components of both innate and adaptive arms of the immune system, TLRs interact as pattern recognition receptors with a series of exogenous ligands and endogenous molecules or so-called danger associated molecular patterns (DAMPs) that are released upon tissue injury and cellular stress. Besides immune cells, a number of structural cells within the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts and cardiac myocytes express TLRs and are able to release or sense DAMPs. Local activation of TLR-mediated signaling cascade induces cardiovascular tissue repair but in a presence of constant stimuli can overshoot and cause chronic inflammation and tissue damage. TLR accessory molecules are essential in guiding and dampening these responses toward an adequate reaction. Furthermore, accessory molecules assure specific and exclusive TLR-mediated signal transduction for distinct cells and pathways involved in the pathogenesis of cardiovascular diseases. Although much has been learned about TLRs activation in cardiovascular remodeling, the exact role of TLR accessory molecules is not entirely understood. Deeper understanding of the role of TLR accessory molecules in cardiovascular system may open therapeutic avenues aiming at manipulation of inflammatory response in cardiovascular disease. The present review outlines accessory molecules for membrane TLRs that are involved in cardiovascular disease progression. We first summarize the up-to-date knowledge on TLR signaling focusing on membrane TLRs and their ligands that play a key role in cardiovascular system. We then survey the current evidence of the contribution of TLRs accessory molecules in vascular and cardiac remodeling including myocardial infarction, heart failure, stroke, atherosclerosis, vein graft disease and arterio-venous fistula failure.
Characterization of the Full-Sized Pore Structure and Controlling Factors of the Coal-Bearing Shale in the Wuxiang Block, South-Central Qinshui Basin, China
Authors: Zhang Xueqing , Li Xianqing , Yang Jingwei , Zhang Boxiang , Sun Jian , Yu Zhenfeng
Published: February 2022

The characterization of the full-sized pore structure is important for the evaluation and prediction of the reservoir of shale gas with strong heterogeneity. It is of great scientific significance to explore the pore structure characteristics of overmature coal-bearing shale. Core descriptions, X-ray diffraction (XRD), vitrinite reflectance (Ro), field emission scanning electron microscopy (FE-SEM), high-pressure mercury intrusion porosimetry (MIP), and low-pressure N2/CO2 gas adsorption (N2-/CO2-GA) experiments were performed on overmature coal-bearing shale samples from the Wuxiang block, south-central Qinshui Basin, China. The results show that the total organic carbon (TOC) ranged from 0.29 to 8.36%, with an average of 3.84%, and the organic matter (OM) is dominated by type III kerogen. The minerals in the shale primarily consist of clay (43–85.5%, averaging 52.1%) and quartz (12.6–61.2%, averaging 43.5%). The major clay minerals are illite-smectite (I/S) and illite, ranging from 22.5 to 55.6% (mean 41.4%) and 8.7–52.7% (mean 32%), respectively. FE-SEM images reveal that intraparticle pores (IntraP pores) and interparticle pores (InterP pores) are widely developed in clay minerals, and organic pores are occasionally present. Mesopores make the greatest contribution to the total pore volume (PV), and micropores are the major contributors to the specific surface area (SSA). Clays are the main controllers of micropore development. Mesopores developed in the clay mineral layers are promoted by I/S but inhibited by illite. Macropores and microfractures are mainly developed in clays and quartz and do not correlate significantly with the TOC, or mineral composition, due to the influence of compaction and cementation. The TOC and minerals affect pore structure characteristics mainly by influencing micropores.