Major Players Research Articles

UPR-Activated IRE1 Signaling Pathway Promotes Malignant Growth of Breast Cancer

Initially, it was believed that the unfolded protein response (UPR) was a network signal that synchronized apoptotic and adaptive responses to the buildup of unfolded proteins in the endoplasmic reticulum (ER). The endoplasmic reticulum stress sensor IRE1 is a major player in the UPR, and overactivation of IRE1 can promote a variety of pathological phenomena, such as diabetes, neurodegenerative diseases, and cancer. Under endoplasmic reticulum stress, IRE1 is activated through autophosphorylation and oligomerization, leading to conformational changes in the RNase domain, thereby promoting two signaling pathways: 1) unconventional splicing of XBP1 and 2) regulated IRE1 dependence Decay (RIDD). Research has revealed that aggressive B-type breast cancer cells typically have an overexpressed and amplified IRE1 gene. Through the RIDD mechanism, IRE1 processes and regulates the breakdown of a fraction of tumor-suppressing micro-RNA, which in breast cancer cells results in the Ras oncogene GTPase. RAB3B is elevated. This article reveals the mechanism of action of the IRE1 signaling pathway and the RIE1-RIDD-miRNA pathway in promoting the malignant development of luminal breast cancer.

MicroRNA-124-3p Modulates Alpha-Synuclein Expression Levels in a Paraquat-Induced in vivo Model for Parkinson's Disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. Although PD etiology is not fully understood, alpha (α)-synuclein is a key protein involved in PD pathology. MicroRNAs (miRNA), small gene regulatory RNAs that control gene expression, have been identified as biomarkers and potential therapeutic targets for brain diseases, including PD. In particular, miR-124 is downregulated in the plasma and brain samples of PD patients. Recently we showed that the brain delivery of miR-124 counteracts 6-hydroxydopamine-induced motor deficits. However, its role in α-synuclein pathology has never been addressed. Here we used paraquat (PQ)-induced rat PD model to evaluate the role of miR-124-3p in α-synuclein accumulation and dopaminergic neuroprotection. Our results showed that an intranigral administration of miR-124-3p reduced the expression and aggregation of α-synuclein in the substantia nigra (SN) of rats exposed to PQ. NADPH oxidases (NOX), responsible for reactive oxygen species generation, have been considered major players in the development of α-synuclein pathology. Accordingly, miR-124-3p decreased protein expression levels of NOX1 and its activator, small GTPase Rac1, in the SN of PQ-lesioned rats. Moreover, miR-124-3p was able to counteract the reduced levels of pituitary homeobox 3 (PITX3), a protein required for the dopaminergic phenotype, induced by PQ in the SN. This is the first study showing that miR-124-3p decreases PQ-induced α-synuclein levels and the associated NOX1/Rac1 signaling pathway, and impacts PITX3 protein levels, supporting the potential of miR-124-3p as a disease-modifying agent for PD and related α-synucleinopathies.

Competitive Strategies and Performance of Kenya Airways Limited in Nairobi County, Kenya

Kenya Airways has experienced significant financial losses over a prolonged period, which has led to the requirement of a government bailout and the adoption of a restructuring initiative. Kenya Airways is a major player in the Kenyan aviation sector but has struggled to stay profitable compared to Ethiopian Airlines. Ethiopian Airlines has reported consistent profits for several years, in contrast. Kenya Airways is adopting competitive tactics to improve its performance, but there is a dearth of empirical research on the subject. The objective of this study was to analyse the impact of competitive strategies on the performance of Kenya Airways. The purpose of the study was to examine the impact of differentiation, cost leadership, focus, and innovation on the performance of Kenya Airways Limited. This study was anchored on the following theories: porter’s generic strategies model, dynamic capabilities, resource-based view, strategy-structure-performance, and balanced score card. This study employed a descriptive inquiry approach. The focus group for the study was comprised of a total of 180 staff members of Kenya Airways Limited. The sample size consisted of 124 employees, who were selected using a basic random sampling technique. A semi-structured questionnaire was used to collect primary data. This research assessed the accuracy of the research tool by utilizing the viewpoints of experts through a content validity method. Cronbach's alpha co-efficient was utilized to evaluate the dependability of the research instrument, and a minimum threshold of 0.7 was established. Data was analysed using descriptive statistics using means and standard deviations and inferential statistics. The study made use of correlation analysis and multiple regression analysis to deduce connections among different variables. Differentiation strategy had a positive and significant effect on performance of Kenya Airways of (β= 0.513, p < 0.05). Cost leadership strategy had a positive and significant effect on performance of Kenya Airways of (β=0.458, p < 0.05). Focus strategy had a positive and significant effect on performance of Kenya Airways of (β= 0.540, p < 0.05). Innovation strategy had a positive and significant effect on performance of Kenya Airways of (β=0.651, p < 0.05). The study concluded that differentiation strategy improves the performance of Kenya Airways. Cost leadership strategy helps to improve the performance of Kenya Airways Limited. Focus strategy enhances performance of Kenya Airways Limited and innovation strategy helps to improve performance of Kenya Airways Limited. The study recommended that the company should continue to offer unique features that sets it apart from other airlines. The company should operate efficiently in order to keep costs low.

Organic farming promotes the abundance of fungi keystone taxa in bacteria-fungi interkingdom networks.

Soil bacteria-fungi interactions are essential in the biogeochemical cycles of several nutrients, making these microbes major players in agroecosystems. While the impact of the farming system on microbial community composition has been extensively reported in the literature, whether sustainable farming approaches can promote associations between bacteria and fungi is still unclear. To study this, we employed 16S, ITS, and 18S DNA sequencing to uncover how microbial interactions were affected by conventional and organic farming systems on maize crops. The Bray-Curtis index revealed that bacterial, fungal, and arbuscular mycorrhizal fungi communities were significantly different between the two farming systems. Several taxa known to thrive in healthy soils, such as Nitrosophaerales, Orbiliales, and Glomus were more abundant in the organic farming system. Constrained ordination revealed that the organic farming system microbial community was significantly correlated with the β-glucosidase activity, whereas the conventional farming system microbial community significantly correlated with soil pH. Both conventional and organic co-occurrence interkingdom networks exhibited a parallel node count, however, the former had a higher number of edges, thus being denser than the latter. Despite the similar amount of fungal nodes in the co-occurrence networks, the organic farming system co-occurrence network exhibited more than 3-fold the proportion of fungal taxa as keystone nodes than the conventional co-occurrence network. The genera Bionectria, Cercophora, Geastrum, Penicillium, Preussia, Metarhizium, Myceliophthora, and Rhizophlyctis were among the fungal keystone nodes of the organic farming system network. Altogether, our results uncover that beyond differences in microbial community composition between the two farming systems, fungal keystone nodes are far more relevant in the organic farming system, thus suggesting that bacteria-fungi interactions are more frequent in organic farming systems, promoting a more functional microbial community.

Exploring the entrepreneurial landscape of university-industry collaboration on public university spin-off creation: A systematic literature review

Research into the factors influencing university-industry collaboration on public university spin-offs creation has focused on management, entrepreneurship, technology and innovation. This research began with a careful systematic literature review of 4427 scientific papers published in the last ten years (2014–2023) and accessible in the prestigious Web of Science core collection. A quantitative methodology was used, complemented by the use of the visual analysis tool Posit PBC™, formerly known as R Cloud Studio. This comprehensive approach facilitated the seamless ingestion of raw data into Biblioshyni, which is a web-based platform specialised in bibliometric analysis. This review has revealed compelling trends, particularly in terms of increasing diversity, the emergence of United Kingdom as a major player, and the central role of university-industry collaboration. Our systematic review identified influential authors in the field, including the prolific contributions of scholars such as D. Radicid, S. Ropers, Y. Li and R. Owen. We also identified important research institutions, such as Utrecht University in Netherlands, Lund University in Sweden and The University of Manchester in the UK. In addition, we have shown that countries such as the United Kingdom, China and USA have made a significant contribution to the volume of publications. The results highlighted a marked increase in the phenomenon of univeristy spin-offs over the past decade, as evidenced by the exponential growth in both publication output and citation rates. This empirical revelation was underpinned by a rigorous exploration of the Web of Science database, using a carefully crafted set of keywords. Thirty-seven pivotal studies were selected for in-depth review through a sophisticated selection process that adhered to the rigorous standards of the PRISMA methodology. The aim of this review is to improve understanding and encourage deeper exploration of spin-off-based public universities through collaboration between academia and industry.

How to ensure the recovery of family businesses in a crisis situation? Case of the Moroccan family business Maghreb Steel

Learning outcomes After completion of the case study, students will be able to examine the financial implications of Maghreb Steel’s substantial investment in the Blad Assolb complex in 2007 within the restructuring plan; explore how this decision influenced the company’s financial health and strategic position in the steel market, within the context of the restructuring plan; assess the impact of the 2008 economic crisis within the restructuring plan; analyze how the crisis affected the company’s pricing strategies, profitability and overall business strategy; investigate the financial and strategic consequences of the hot rolling activity initiated as a result of the Blad Assolb project within the company’s restructuring plan; and critique how this venture impacted the company’s operations, cost structure and competitiveness in the steel industry, aligned with the restructuring plan. Case overview/synopsis This case study deals with the only flat steel producer in Morocco: Maghreb Steel, the Moroccan family-owned company created in 1975 by the Sekkat family. It was a leading steel company. At the beginning, the company was specialized in the field of steel tubes, but thanks to its growth ambitions, the Sekkat family had made Maghreb Steel a major player in the Moroccan steel sector. In the same logic of development, the top management of Maghreb Steel launched in 2007 in the adventure to create the first production complex of cold rolling in Morocco – an investment that pushed Maghreb Steel to resort to a debt of more than 6bn dirhams (DH) with a consortium of six banks and would have allowed the company a huge leap in growth, except that the decision-makers of the group Sekkat could not see coming the economic crisis of 2008 causing the fall of steel prices by 62% compared to 2007. Thus, from its effective launch in 2010, the activity of hot rolling would become, for the company, a regrettable orientation. Moreover, the national market could not absorb all the production of the complex that the company called Blad Assolb. In response to this difficult situation, Maghreb Steel decided to store its goods to avoid selling at a loss. Faced with this situation of sectoral crisis and deterioration of its activity, Maghreb Steel lost its ability to honor its financial commitments with the banking consortium. From then on, the company became a case of failure, and the recovery measures had not ceased to be duplicated by the various stakeholders: State, Sekkat family, creditors and management of the company, having only one objective in mind: Save Maghreb Steel! This said, the present case study is dedicated to the financial and strategic analysis of the current situation and the evolution of the company throughout the crisis period to finally propose a suitable recovery plan to save Maghreb Steel. Complexity academic level The case study can be taught to students of master’s degrees in financial management as a synthesis of finance courses. It can also be used to train executives and managers working in family businesses as part of professional certification training. Supplementary materials Teaching notes are available for educators only. Subject code CSS 1: Accounting and finance.

Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis

ABSTRACT This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.

Nanoparticles synthesis in microwave plasmas: peculiarities and comprehensive insight

Low-pressure plasma processes are routinely used to grow, functionalize or etch materials, and thanks to some of its unique attributes, plasma has become a major player for some applications such as microelectronics. Plasma processes are however still at a research level when it comes to the synthesis and functionalization of nanoparticles. Yet plasma processes can offer a particularly suitable solution to produce nanoparticles having very peculiar features since they enable to: (i) reach particle with a variety of chemical compositions, (ii) tune the size and density of the particle cloud by acting on the transport dynamics of neutral or charged particles through a convenient setting of the thermal gradients or the electric field topology in the reactor chamber and (iii) manipulate nanoparticles and deposit them directly onto a substrate, or codeposit them along with a continuous film to produce nanocomposites or (iv) use them as a template to produce 1D materials. In this article, we present an experimental investigation of nanoparticles synthesis and dynamics in low-pressure microwave plasmas by combining time-resolved and in-situ laser extinction and scattering diagnostics, QCL absorption spectroscopy, mass spectrometry, optical emission spectroscopy and SEM along with a particle transport model. We showed for the first time the thermophoresis-driven dynamic of particle cloud in electrodless microwave plasmas. We showed that this effect is linked to particular fluctuations in the plasma composition and results in the formation of a void region in the bulk of the plasma surrounded by a particle cloud in the peripherical post-discharge. We also reveals and analyze the kinetics of precursor dissociation and molecular growth that result in the observed nanoparticle nucleation.

The Role of Non-State Actors in Establishing the Halal Ecosystem in Indonesia

Amidst the global growth of the Muslim population, the need for products or services that comply with sharia law has become unavoidable. As the country with the largest Muslim population in the world, Indonesia has declared itself to become a major player in the global halal industry. This can be seen from the changes made by Indonesia in the last decade, both in policy and governance aspects to form an effective halal sector ecosystem as planned in the Indonesia Islamic Economic Masterplan 2019-2024. However, amid several policies implemented by the government, the role of non-state actors, including but not limited to large industries, business groups and MSMEs, community organizations or NGOs, and product influencers, increases and mainstreaming the halal industry in Indonesia cannot be ruled out. Based on a study of several literature related to the halal industry in Indonesia, researchers see that most of the research on the halal industry in Indonesia focuses on discussing strategy and the government as well as opportunities and challenges for Indonesia in developing the halal industry. Therefore, the study aims to discuss the role of non-state actors in forming the halal industrial ecosystem in Indonesia.

Salinity as a key factor affecting viral activity and life strategies in alpine lakes

AbstractViruses are major players in the biosphere, yet little is known about their dynamics and life strategies in alpine lakes, particularly those on the Tibetan Plateau. We investigated microbial abundance, viral dynamics, and viral life strategies in 10 high‐altitude Tibetan lakes and found that they harbor high levels of active viruses. Salinity was identified as a crucial factor influencing viral abundance, dynamics, as well as viral life strategies. Lytic and lysogenic viral productions in moderate‐ and high‐salinity lakes were significantly higher than those in freshwater lakes. A trade‐off between viral life strategies resulted in a switch from lysis to lysogeny in high‐salinity lakes. Virus‐mediated cell lysis and virus decay in sampled Tibetan lakes could release about 162.72 and 2.84 μg C L−1 d−1, respectively. These findings revealed the crucial role of viruses in the carbon cycle of Tibetan lakes, and a switch in viral life strategies may impact their contribution to the carbon cycle. The potential impact of salinity changes triggered by climate change on the carbon cycle in alpine lakes worldwide is highlighted.

Shifting Sands: US Gulf Policy Recalibrates As China's Regional Ambitions Grow

AbstractSince Iraq's invasion of Kuwait in the 1990s, the United States has played the role of security guarantor in the Gulf, and despite prevailing concerns of American retrenchment, it retains a strong military footprint across the region. But China's emergence as a major player in the Gulf—with its geopolitical ambitions, thirst for foreign oil, and attractive offer of business and investment with a “look the other way” policy on human rights—has stoked fears about the eclipse of American power. While the Gulf remains of strategic importance to the US global strategy, Washington's readjustment of its regional goals suggests that it is recalibrating. Drawing on the literature of foreign policy change, this analysis uses three case studies to examine Washington's recalibration toward the Gulf under the Biden presidency: US engagement with the Iran nuclear deal, US defense agreements with the Gulf Cooperation Council (GCC), and US‐GCC tech relations, specifically tensions with China over the use of Huawei technology. This article is part of a special issue on the responses of Gulf countries to rising Sino‐American competition, edited by Andrea Ghiselli, Anoushiravan Ehteshami, and Enrico Fardella.

IL-6 levels dominate the serum cytokine signature of severe epidermolysis bullosa: A prospective cohort study.

Systemic inflammation is considered a major player in the pathogenesis of epidermolysis bullosa (EB), but its pattern has only been described in small heterogeneous cohorts. There is controversy if and how systemic inflammation should be therapeutically targeted. We examined serum proinflammatory, anti-inflammatory, and itch related cytokines in a paediatric cohort of 29 patients with junctional and dystrophic EB. The cytokine that emerged as the most relevant was measured in a validation cohort of 42 patients during follow-up visits over 2 years. IL-6 showed the most consistent and highest aberration dominating systemic inflammation. IL-6 correlated with wound body surface area (BSA) in both, finding and validation cohorts. Patients with less than 3% wound BSA had normal IL-6, while IL-6 levels significantly increased at more than 5% and 10% of wound BSA. TGF-β was only marginally elevated in patients with severe recessive dystrophic EB, while TNF-α, IFN-γ and IL-1β varied inconsistently. Patients reporting itch showed elevations in type 2 immunity (IgE, TSLP, IL4 and/or IL-31, respectively). Our data suggest a dominant skin barrier and wound healing inflammatory pattern in junctional and dystrophic EB that depends on the wound area and not on the EB type. In EB, itch mediators may be similar to other pruritic disorders.

Factors Affecting Utilization of Information and Communication Technology (ICT) in Agricultural Sector: A Case Study in Upper Brahmaputra Valley Zone of Assam, India

In a country like India agriculture is the major economic players in economic aspects, which is the great source of revenue is more than 50% of the population of India. The country’s economic sector is based on the agricultural activities that play a significant role in the national development. Of late, ICT plays a significant role in the development of agriculture. It is widely acknowledged that improved information flow benefits both individual businesses and the agriculture industry. Nonetheless, gathering and sharing information is frequently expensive and challenging. By using information technology (IT), it is possible to lower the cost of information dissemination while simultaneously providing more information to all stakeholders involved in the agriculture industry. But the part of agriculture to the economy as well as the economic condition of the farmers is not what they should have been in this era of technology in a state like Assam. The aim of this study is to find the utilization in agricultural sector in the upper Brahmaputra valley Zone of Assam. This paper tries to discuss the factors affecting utilization of ICT tools in agriculture by using Binary Logistics Regression Model. Apart from higher level of education (.252) and size of land holding (.003), other factors like age (-.076), extension contact (-.282) and participation in media (-3.554) are found to be negatively influenced in the knowledge of ICT in agriculture among the farmers in the study area. Organzing awareness and training programme may help the farmers to utilize ICT in agricultural sector.

Sensing and regulation of C and N metabolism - novel features and mechanisms of the TOR and SnRK1 signaling pathways.

Carbon (C) and nitrogen (N) metabolisms are tightly integrated to allow proper plant growth and development. Photosynthesis is dependent on N invested in chlorophylls, enzymes, and structural components of the photosynthetic machinery, while N uptake and assimilation rely on ATP, reducing equivalents, and C-skeletons provided by photosynthesis. The direct connection between N availability and photosynthetic efficiency allows the synthesis of precursors for all metabolites and building blocks in plants. Thus, the capacity to sense and respond to sudden changes in C and N availability is crucial for plant survival and is mediated by complex yet efficient signaling pathways such as TARGET OF RAPAMYCIN (TOR) and SUCROSE-NON-FERMENTING-1-RELATED PROTEIN KINASE 1 (SnRK1). In this review, we present recent advances in mechanisms involved in sensing C and N status as well as identifying current gaps in our understanding. We finally attempt to provide new perspectives and hypotheses on the interconnection of diverse signaling pathways that will allow us to understand the integration and orchestration of the major players governing the regulation of the CN balance.

Citizens’ participation in local energy communities: the role of technology as a stimulus

ABSTRACT Because of their focus on the acquisition of new technologies, local energy communities are increasingly being recognised as major players in the current energy transition and revealing the valuable role of technological solutions in sustainable development. Nevertheless, the success of these communities is not limited to the acquisition of technologies. Instead, it is strongly dependent on citizen participation. Prior literature has focused much more on the institutional and policy factors than on the roles of citizens and their participation in such communities, and indirectly on sustainability. To address the lack, this study aims to explain the determinants of citizen participation in local energy communities by developing a research model grounded on the stimulus-organism-response (S-O-R) framework, and then through a mixed-methods design, study the impact of technological factors as a stimulus on more social outcomes, namely the organism and response behaviours. Our results highlight the strong impact of sustainable technologies and gamification in citizens’ attitudes. Moreover, the research model reveals a strong influence of empowerment and pro-environmental behaviour in the citizen intention to participate in local energy communities.

The role of Rab27 in tick extracellular vesicle biogenesis and pathogen infection

BackgroundThe blacklegged tick, Ixodes scapularis, transmits most vector-borne diseases in the US. It vectors seven pathogens of public health relevance, including the emerging human pathogen Anaplasma phagocytophilum. Nevertheless, it remains critically understudied compared to other arthropod vectors. Ixodes scapularis releases a variety of molecules that assist in the modulation of host responses. Recently, it was found that extracellular vesicles (EVs) carry several of these molecules and may impact microbial transmission to the mammalian host. EV biogenesis has been studied in mammalian systems and is relatively well understood, but the molecular players important for the formation and secretion of EVs in arthropods of public health relevance remain elusive. RabGTPases are among the major molecular players in mammalian EV biogenesis. They influence membrane identity and vesicle budding, uncoating, and motility.MethodsUsing BLAST, an in silico pathway for EV biogenesis in ticks was re-constructed. We identified Rab27 for further study. EVs were collected from ISE6 tick cells after knocking down rab27 to examine its role in tick EV biogenesis. Ixodes scapularis nymphs were injected with small interfering RNAs to knock down rab27 and then fed on naïve and A. phagocytophilum-infected mice to explore the importance of rab27 in tick feeding and bacterial acquisition.ResultsOur BLAST analysis identified several of the proteins involved in EV biogenesis in ticks, including Rab27. We show that silencing rab27 in I. scapularis impacts tick fitness. Additionally, ticks acquire less A. phagocytophilum after rab27 silencing. Experiments in the tick ISE6 cell line show that silencing of rab27 causes a distinct range profile of tick EVs, indicating that Rab27 is needed to regulate EV biogenesis.ConclusionsRab27 is needed for successful tick feeding and may be important for acquiring A. phagocytophilum during a blood meal. Additionally, silencing rab27 in tick cells results in a shift of extracellular vesicle size. Overall, we have observed that Rab27 plays a key role in tick EV biogenesis and the tripartite interactions among the vector, the mammalian host, and a microbe it encounters.Graphical

Location versus ID: what matters to lung-resident memory T cells?

Tissue-resident memory T cells (TRM cells) are vital for the promotion of barrier immunity. The lung, a tissue constantly exposed to foreign pathogenic or non-pathogenic antigens, is not devoid of these cells. Lung TRM cells have been considered major players in either the protection against respiratory viral infections or the pathogenesis of lung allergies. Establishment of lung TRM cells rely on intrinsic and extrinsic factors. Among the extrinsic regulators of lung TRM cells, the magnitude of the impact of factors such as the route of antigen entry or the antigen natural tropism for the lung is not entirely clear. In this perspective, we provide a summary of the literature covering this subject and present some preliminary results on this potential dichotomy between antigen location versus antigen type. Finally, we propose a hypothesis to synthesize the potential contributions of these two variables for lung TRM cell development.

Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages.

Macrophages are the major players and orchestrators of inflammatory response. Expressed proteins and secreted cytokines have been well studied for two polar macrophage phenotypes-pro-inflammatory M1 and anti-inflammatory regenerative M2, but little is known about how the polarization modulates macrophage functions. In this study, we used biochemical and biophysical methods to compare the functional activity and mechanical properties of activated human macrophages differentiated from monocyte with GM-CSF (M0_GM) and M-CSF (M0_M) and polarized into M1 and M2 phenotypes, respectively. Unlike GM-CSF, which generates dormant cells with low activity, M-CSF confers functional activity on macrophages. M0_M and M2 macrophages had very similar functional characteristics-high reactive oxygen species (ROS) production level, and higher phagocytosis and survival compared to M1, while M1 macrophages showed the highest radical-generating activity but the lowest phagocytosis and survival among all phenotypes. All phenotypes decreased their height upon activation, but only M1 and M2 cells increased in stiffness, which can indicate a decrease in the migration ability of these cells and changes in their interactions with other cells. Our results demonstrated that while mechanical properties differ between M0 and polarized cells, all four phenotypes of monocyte-derived macrophages differ in their functional activities, namely in cytokine secretion, ROS production, and phagocytosis. Within the broad continuum of human macrophages obtained in experimental models and existing in vivo, there is a diversity of phenotypes with varying combinations of both markers and functional activities.

Fungal Microbiome of Alive and Dead Korean Fir in its Native Habitats

A rapid decline of Abies koreana has been reported in most of the natural alpine habitats in Korea. It is generally accepted that this phenomenon is due to climate change even though no clear conclusions have been drawn. Most research has focused on abiotic environmental factors, but studies on the relationships between A. koreana and soil fungal microbiomes are scarce. In this study, the rhizoplane and rhizosphere fungal communities in the alive and dead Korean fir trees from its three major natural habitats including Mt. Deogyu, Mt. Halla, and Mt. Jiri in Korea were investigated to identify specific soil fungal groups closely associated with A. koreana. Soil fungal diversity in each study site was significantly different from another based on the beta diversity calculations. Heat tree analysis at the genus level showed that Clavulina, Beauveria, and Tomentella were most abundant in the healthy trees probably by forming ectomycorrhizae with Korean fir growth and controlling pests and diseases. However, Calocera, Dacrymyces, Gyoerffyella, Hydnotrya, Microdochium, Hyaloscypha, Mycosymbioces, and Podospora were abundant in the dead trees. Our findings suggested that Clavulina, Beauveria, and Tomentella are the major players that could be considered in future reforestation programs to establish ectomycorrhizal networks and promote growth. These genera may have played a significant role in the survival and growth of A. koreana in its natural habitats. In particular, the genus Gyoerffyella may account for the death of the seedlings. Our work presented exploratory research on the specific fungal taxa associated with the status of A. koreana.

Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2 microglial cells and responses to neuropathic pain

Microglial are major players in neuroinflammation that have recently emerged as potential therapeutic targets for neuropathic pain. Glucose metabolic programming has been linked to differential activation state and function in microglia. Tumor necrosis factor α-induced protein 8-like-2 (TNFAIP8L2) is an important component in regulating the anti-inflammatory response. However, the role of TNFAIP8L2 in microglia differential state during neuropathic pain and its interplay with glucose metabolic reprogramming in microglia has not yet been determined. Thus, we aimed to investigate the role of TNFAIP8L2 in the status of microglia in vitro and in vivo. BV2 microglial cells were treated with lipopolysaccharides plus interferon-gamma (LPS/IFNγ) or interleukin-4 (IL-4) to induce the two different phenotypes of microglia in vitro. In vivo experiments were conducted by chronic constriction injury of the sciatic nerve (CCI). We investigated whether TNFAIP8L2 regulates glucose metabolic programming in BV2 microglial cells. The data in vitro showed that TNFAIP8L2 lowers glycolysis and increases mitochondrial oxidative phosphorylation (OXPHOS) in inflammatory microglia. Blockade of glycolytic pathway abolished TNFAIP8L2-mediated differential activation of microglia. TNFAIP8L2 suppresses inflammatory microglial activation and promotes restorative microglial activation in BV2 microglial cells and in spinal cord microglia after neuropathic pain. Furthermore, TNFAIP8L2 controls differential activation of microglia and glucose metabolic reprogramming through the MAPK/mTOR/HIF-1α signaling axis. This study reveals that TNFAIP8L2 plays a critical role in neuropathic pain, providing important insights into glucose metabolic reprogramming and microglial phenotypic transition, which indicates that TNFAIP8L2 may be used as a potential drug target for the prevention of neuropathic pain.