Complex Role Research Articles

The Expression and Functionality of CB1R-NMDAR Complexes Are Decreased in A Parkinson's Disease Model.

One of the hallmarks of Parkinson's disease (PD) is the alteration in the expression and function of NMDA receptor (NMDAR) and cannabinoid receptor 1 (CB1R). The presence of CB1R-NMDAR complexes has been described in neuronal primary cultures. The activation of CB1R in CB1R-NMDAR complexes was suggested to counteract the detrimental NMDAR overactivation in an AD mice model. Thus, we aimed to explore the role of this receptor complex in PD. By using Bioluminescence Resonance Energy Transfer (BRET) assay, it was demonstrated that α-synuclein induces a reorganization of the CB1R-NMDAR complex in transfected HEK-293T cells. Moreover, α-synuclein treatment induced a decrease in the cAMP and MAP kinase (MAPK) signaling of both CB1R and NMDAR not only in transfected cells but also in neuronal primary cultures. Finally, the interaction between CB1R and NMDAR was studied by Proximity Ligation Assay (PLA) in neuronal primary cultures, where it was observed that the expression of CB1R-NMDAR complexes was decreased upon α-synuclein treatment. These results point to a role of CB1R-NMDAR complexes as a new therapeutic target in Parkinson's disease.

Dealing with fibromyalgia in the family context: a qualitative description study

Headings purpose: Fibromyalgia (FM) is a chronic, nondegenerative disease with important limitations in patients. Its average global prevalence is 1.78%, and women are more affected than men (3:1). Due to the lack of objective diagnostic tools, it is a complex medical condition that is frequently unseen by patients’ relatives and doctors, which might nonetheless have a noticeable impact on the patient’s entourage. Material and Methods: This qualitative descriptive study aimed to elicit family members’ views on how FM affects their lives. It was conducted in two community health centers (one rural and one urban) from the Sagunto Health Department (Valencia Community, Spain). We included seven focus groups with 41 family members. We analyzed the data gathered with an inductive thematic semantic analysis approach using NVivo 12 software. Results: We identified four major themes: (1) fibromyalgia as a nosological entity or an invention that is always burdensome; (2) children and spouses as caregivers (or not); (3) adverse effects of fibromyalgia on the couple’s sexual life; and (4) harmful consequences of FM on the family economy. The findings showed a negative impact of the disease within the family context. Family members face complex and changing roles and difficulties when living with women with fibromyalgia. Conclusions: Relatives’ better understanding of the disease, greater acceptance of new family roles, and improvement of patients’ work conditions are all interventions that may help reduce the negative impact of FM in the family context.

Acute MK-801 increases measures of both sign-tracking and goal-tracking in male Sprague-Dawley rats

Sign-tracking is a Pavlovian conditioned approach behavior thought to be important in understanding cue-driven relapse to drug use, and strategies for reducing sign-tracking may have some benefit in preventing relapse. A previous study successfully employed the NMDA receptor antagonist MK-801 in preventing the development of sign-tracking (but not goal-tracking) in a conditioned approach task. In this study, we focused on whether MK-801 would have similar effects on previously established sign-tracking behavior. MK-801 was administered after training in a standard sign−/goal-tracking task using a retractable lever as a conditioned stimulus and a sucrose pellet as unconditioned stimulus. It was found that MK-801 increased measures of both sign- and goal-tracking in subjects who had previously learned the task. The NMDA receptor appears to play a complex role in governing behavior related to sign-tracking.

Species-specific duplicated FMRFaR-like gene A62 regulates spontaneous locomotion in Apolygus lucorum.

Apolygus lucorum, a major cotton pest, has undergone a significant expansion of the FMRFaR gene within the GPCR superfamily, resulting in two classes of GPCR, namely FMRFaR (A54-55) and newly duplicated FMRFaR-like (A56-62). Notably, FMRFaR-like genes, particularly A62, show enhanced expression in the legs and wings of adults, indicating their potential role in locomotion. Employing A62 as a representative of FMRFaR-like, our study investigates the influence of FMRFa, FMRFaR, and FMRFaR-like on locomotion and development of A. lucorum. FMRFaR and FMRFa exhibit comparable temporal and tissue expression patterns, whereas the FMRFaR-like genes within A. lucorum exhibit completely distinct evolutionary and expression patterns compared to classical FMRFaR. RNA interference (RNAi) experiments revealed that suppressing FMRFa expression results in complete lethality in A. lucorum, but neither FMRFaR nor A62 exhibit the same effect after RNAi. Suppressing the expression of FMRFa only decreases the expression of the A54 gene simultaneously, suggesting that A54 may function as a classical FMRFaR activated by FMRFa. RNAi of A62 leads to wing malformation and a significant reduction in spontaneous movement behavior in A. lucorum. Further transcriptomic analysis revealed that A62 affects the A. lucorum's movement behavior through energy metabolism pathways and motor protein pathways. Our study unveils the unique and complex roles of FMRFa and its receptor in A. lucorum. These findings provide valuable insights into potential targets for pest control strategies aimed at managing A. lucorum populations in cotton fields. © 2024 Society of Chemical Industry.

Demethylzeylasteral protects against renal interstitial fibrosis by attenuating mitochondrial complex I-mediated oxidative stress

Ethnopharmacological relevanceRenal interstitial fibrosis (RIF) is a main pathological process in chronic kidney disease (CKD). Demethylzeylasteral (DML), a major component of Tripterygium wilfordii Hook. f., has anti-renal fibrosis effects. However, its mechanism of action remains incompletely understood. Aim of the studyThe present study was designed to comprehensively examine the effects of DML on RIF and the underlying mechanisms. Materials and methodsPathological experiments were performed to determine the therapeutic effect of DML on a mouse model of UUO-induced RIF. To determine the novel mechanisms underlying the therapeutic effects of DML against RIF, a comprehensive transcriptomics analysis was performed on renal tissues, which was further verified by a series of experiments. ResultsPathological and immunohistochemical staining showed that DML inhibited UUO-induced renal damage and reduced the expression of fibrosis-related proteins in mice. Transcriptomic analysis revealed that the partial subunits of mitochondrial complex (MC) I and II may be targets by which DML protects against RIF. Furthermore, DML treatment reduced mitochondrial reactive oxygen species (ROS) levels, consequently promoting ATP production and mitigating oxidative stress-induced injury in mice and cells. Notably, this protective effect was attributed to the inhibition of MC I activity, suggesting a crucial role for this specific complex in mediating the therapeutic effects of DML against RIF. ConclusionsThis study provides compelling evidence that DML may be used to treat RIF by effectively suppressing mitochondrial oxidative stress injury mediated by MC I. These findings offer valuable insights into the pharmacological mechanisms of DML and its potential clinical application for patients with CKD.

Inside Cover Picture

Plenty of advanced methods have been developed for tracing RNA, including directly chemical RNA labeling, metabolic RNA labeling, proximity‐dependent RNA labeling, etc. These RNA labeling strategies have greatly enhanced our learning about complex roles and functions of RNA. For the deeper insight of RNA biology, there is still a constant need to develop newer RNA labeling methods. More details are discussed in the article by Weng et al. on page 790—801.image

Understanding the role of Leisure Involvement and Choice Complexity on Choice overload in booking of leisure activities online among Young Consumers

People are faced with an oversupply of almost ever type of good. Due to the large number of options, it has become very important for service providers to understand, how customers act when they book leisure activities online. As far as the researcher knows, no one has looked into how having too many options affects people's decisions when they book leisure activities online before. This study looks at the difference between leisure activities done at home and while on holiday, taking into account the issue of choice overload when booking leisure activities online. There is a plan to use an integrated research approach that utilizes cognitive dissonance as well as spillover theories to testhypotheses. This study employed Gen Y (17-37 years) who have visited Goa in the last six months. The study's conclusions have consequences for both tourism-related businesses and consumers, guiding how they act, their emotions, judgments, and behaviors toward evaluating the alternatives.

The role of economic complexity in shaping the energy-growth nexus: Evidence from cross-country panel data

The study investigated the interplay between energy consumption (EN), economic growth (EG), and economic complexity across 59 countries from 2000 to 2018. Employing panel data methods, the research examined various models to estimate long-term effects while addressing unobserved heterogeneity and potential biases. Results indicate significant relationships between EG, EN, and economic complexity. Notably, the economic complexity index (ECI) displayed a positive effect on economic development, while trade openness and foreign direct investment showed varying impacts. The study identified a positive association between EG and EN, suggesting that increased energy consumption accompanies economic growth. However, a higher capital-to-labor ratio was associated with lower EN, indicating a substitution effect. Of particular note is the significant positive impact of the interaction between ECI and EN on GDP across various models. In the Country Fixed Effects Model, a one-unit increase in the interaction correlated with a 0.026 unit increase in GDP (p < 0.001). Similarly, significant positive relationships were observed in the Panel EGLS and FMOLS models, with coefficients of 0.055 and 0.031, respectively (p < 0.001 and p = 0.011). Conversely, all models consistently demonstrated a negative relationship between economic complexity and GDP, with coefficients ranging from -0.062 to -0.089 (p < 0.001). These findings underscore the importance of considering economic complexity and energy consumption in policy interventions aimed at promoting sustainable economic growth. Policymakers are encouraged to adopt comprehensive approaches that account for the complex interplay of various factors influencing economic development and energy consumption to formulate effective strategies.

Anger and Political Conflict Dynamics

Emotions shape strategic conflict dynamics. However, the precise way in which strategic and emotional concerns interact to affect international cooperation and contention are not well understood. We propose a model of intergroup conflict under incomplete information in which agents are sensitive to psychological motivations in the form of anger. Agents become angry in response to worse-than-expected outcomes due to actions of other players. Aggression may be motivated by anger or by beliefs about preferences of members of the other group. Increasing one group’s sensitivity to anger makes that group more aggressive but reduces learning about preferences, which makes the other group less aggressive in response to bad outcomes. Thus, anger has competing effects on the likelihood of conflict. The results have important implications for understanding the complex role of anger in international relations and, more generally, the interplay between psychological and material aims in both fomenting and ameliorating conflict.

Insights into the role of β-MnO2 and oxalic acid complex expediting ozonation: Structural properties and mechanism

The complexation between metal oxides and organic acid plays an important role in the water treatment. However, the mechanism of complex in catalytic ozonation process (HCO) has not been studied yet. In this study, a β-MnO2-oxalic acid (β-MnO2-OA) complex was constructed and used in HCO for pCBA degradation (β-MnO2/OA/O3). The addition of OA enhanced not only k value of β-MnO2/OA/O3 process by 4 times that of ozonation alone, but also had advantageous effects on co-degradation of contaminant and OA. The 90.4 % of pCBA and 65.2 % of OA degradation were achieved at pH 4.0 within 10 mins by the incorporation of OA (10 mg/L) and β-MnO2 (50 mg/L). Systematic characterization techniques (XPS, H2-TPR, and etc.) confirmed the enhanced electron transfer ability and redox property of β-MnO2-OA complex. More oxygen vacancies and reactive oxygen species (ROS) were generated through facilitating oxygen species migration. Besides, sodium pyrophosphate tests demonstrated that Mn3+ was mainly responsible for the formation of β-MnO2-OA complex. Scavenger experiments identified surface-•OH and liquid-•OH as major reactive radicals for pCBA degradation, while other ROS were the radicals involved in OA removal. Finally, a feasible mechanism involving solid–liquid interface reaction was elaborated, which presented a potential strategy improving catalytic ozonation performance.

Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1.

The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an essential enzyme of the base excision repair pathway of non-distorting DNA lesions. In response to genotoxic treatments, APE1 is highly secreted (sAPE1) in association with small-extracellular vesicles (EVs). Interestingly, its presence in the serum of patients with hepatocellular or non-small-cell-lung cancers may represent a prognostic biomarker. The mechanism driving APE1 to associate with EVs is unknown, but is of paramount importance in better understanding the biological roles of sAPE1. Because APE1 lacks an endoplasmic reticulum-targeting signal peptide, it can be secreted through an unconventional protein secretion endoplasmic reticulum-Golgi-independent pathway, which includes an endosome-based secretion of intraluminal vesicles, mediated by multivesicular bodies (MVBs). Using HeLa and A549 cell lines, we investigated the role of endosomal sorting complex required for transport protein pathways (either-dependent or -independent) in the constitutive or trichostatin A-induced secretion of sAPE1, by means of manumycin A and GW4869 treatments. Through an in-depth biochemical analysis of late-endosomes (LEs) and early-endosomes (EEs), we observed that the distribution of APE1 on density gradient corresponded to that of LE-CD63, LE-Rab7, EE-EEA1 and EE-Rab 5. Interestingly, the secretion of sAPE1, induced by cisplatin genotoxic stress, involved an autophagy-based unconventional secretion requiring MVBs. The present study enlightens the central role played by MVBs in the secretion of sAPE1 under various stimuli, and offers new perspectives in understanding the biological relevance of sAPE1 in cancer cells.

Focusing on the role of protein kinase mTOR in endometrial physiology and pathology: insights for therapeutic interventions.

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase crucial for cellular differentiation, proliferation, and autophagy. It shows a complex role in the endometrium, influencing both normal and pathogenic conditions. mTOR promotes the growth and maturation of endometrial cells, enhancing endometrial receptivity and decidualization. However, it also contributes to the development of endometriosis (EMs) and endometrial cancer (EC), thus emerging as a therapeutic target for these conditions. In this review, we summarize recent research progress on the mTOR signalling pathway in the endometrium. This provides insights into female endometrial structure and function and guides the prevention and treatment of related diseases.

Neuromodulator hydrogen sulfide attenuates sickness behavior induced by lipopolysaccharide

Sickness behavior reflects a state of altered physiology and central nervous system function that occurs during systemic infection or inflammation, serving as an adaptive response to illness. This study aims to elucidate the role of hydrogen sulfide (H2S) in regulating sickness behavior and neuroinflammatory responses in a rat model of systemic inflammation. Adult male Wistar rats were treated with lipopolysaccharide (LPS) to induce sickness behavior. Intracerebroventricular (i.c.v.) pretreatments included aminooxyacetic acid (AOAA), an inhibitor of H2S synthesis, and sodium sulfide (NaHS), an H2S donor. Behavioral assays were conducted, along with the assessment of astrocyte activation, as indicated by GFAP expression in the hypothalamus. Pretreatment with NaHS mitigated LPS-induced behavioral changes, including hypophagia, social and exploratory deficits, without affecting peripheral cytokine levels, indicating a central modulatory effect. AOAA, conversely, accentuated certain behavioral responses, suggesting a complex role of endogenous H2S in sickness behavior. These findings were reinforced by a lack of effect on plasma interleukin levels but significant reduction in GFAP expression. Our findings support the central role of H2S in modulating neuroinflammation and sickness behavior, highlighting the therapeutic potential of targeting H2S signaling in neuroinflammatory conditions.

Empirical analysis of the economic complexity boost on the impact of energy transition on economic growth: A panel data study of 124 countries

This study investigates the moderating role of economic complexity in the relationship between energy transition and economic growth, utilizing panel data from 124 countries spanning 2000–2020 and employing the robust weighted least squares (RWLS) estimation method. Our findings indicate an overall negative impact of energy transition on economic growth. Notably, economic complexity emerges as a positive moderator, alleviating the adverse effects of energy transition. This novel insight challenges existing literature, contributing to a more comprehensive understanding of the interplay between renewable energy adoption, economic growth, and economic complexity. Policymakers should acknowledge the intricate dynamics involved in transitioning to renewable energy sources and consider the role of economic complexity in shaping outcomes.

Gathering a bountiful harvest: the impacts of cultural ecosystem service experiences on management practices and agrobiodiversity in urban community gardens

ABSTRACT In addition to their food security and ecological benefits, urban community gardens support human well-being in numerous non-material ways. In this paper, we investigate whether experience of these cultural ecosystem services (CES) shapes how gardeners choose to manage the garden ecosystem, which may influence the ability of these multifunctional green spaces to provide other local ecosystem services (ES). Using questionnaires, in-depth interviews, and plant community analysis, we assess the relationship between perception of CES by community gardeners, the management practices they utilize, and the agroecological characteristics of their garden plots, such as presence and prevalence of species that provide regulating and supporting ES. We find that while almost all survey participants report sociocultural benefits of gardening, experience of these CES varies significantly between gardeners, with garden structure influencing which group of benefits is most perceived. Experience of some CES was also correlated with local ecological knowledge and use of certain sustainable garden management practices, such as utilizing integrated pest management strategies and planting a wide variety of species, but not with observed non-provisioning plant agrobiodiversity. These results provide important insights into the complex role that CES play in encouraging environmental stewardship and shaping ecological outcomes in collectively managed urban green spaces.

Investigation of cuproptosis regulator-mediated modification patterns and SLC30A7 function in GBM.

Copper-dependent controlled cell death (cuproptosis) is a novel cell death modality that is distinct from known cell death mechanisms. Nonetheless, the potential role of the cuproptosis regulator in tumour microenvironment (TME) of GBM remains unknown. Based on 13 widely recognised cuproptosis regulators, the cuproptosis regulation patterns and the biological characteristics of each pattern were comprehensively assessed in GBMs. Machine learning strategies were used to construct a CupScore to quantify the cuproptosis regulation patterns of individual tumours. A PPI network was constructed to predict core-associated genes of cuproptosis regulators. The function of the novel cuproptosis regulators SLC30A7 was examined by in vitro and in vivo experiment. We identified three distinct cuproptosis regulation patterns, including immune activation, metabolic activation, and immunometabolic double deletion patterns. The CupScore was shown to predict the abundance of tumour inflammation, molecular subtype, stromal activity, gene variation, signalling pathways, and patient prognosis. The low CupScore subtype was characterised by immune activation, isocitrate dehydrogenase mutations, sensitivity to chemotherapy, and clinical benefits. The high CupScore subtype was characterised by activation of the stroma and metabolism and poor survival. Novel cuproptosis regulator SLC30A7 knockdown inhibited the cuproptosi via JAK2/STAT3/ATP7A pathway in GBM. Cuproptosis regulators have been shown to play a vital role in TME complexity. Constructing CupScores were trained to evaluate the regulation patterns of cuproptosis in individual tumours. The novel cuproptosis-related genes SLC30A7 was involved in regulation the tumorigenicity of GBM cell via JAK2/STAT3/ATP7A pathway in vitro and in vivo.

Mapping cooperation: insights into Colombia's humanitarian response to migration from Venezuela

IntroductionSince 2015, Colombia has faced a significant humanitarian challenge, receiving 2.9 million displaced Venezuelans. This study examines organizational cooperation in the humanitarian response to this migration crisis, aiming to understand the coordination dynamics among key organizations and actors.MethodsOur research combined interviews and web scraping to gather data on key actors and their relationships in the humanitarian response. We employed Social Network Analysis (SNA) to examine these relationships and the collaborative strategies among entities, focusing on how they address the migration challenges.ResultsThe results indicate that cooperation occurred through mediated channels, where established NGOs collaborated via coordination mechanisms established by international non-governmental organizations (INGOs), often involving diaspora volunteer-based organizations and through ad-hoc coordination. We also identified that organizations specializing in specific activities often exhibited limited coordination with others operating in the same sector. Lastly, the results suggest that coordination mechanisms played a crucial role in driving activities and facilitating the diversification of responses, partly through allocating financial resources.DiscussionThis study contributes to the humanitarian aid and migration literature, focusing on Colombia's migration response. It employs a mixed-methods approach, including Social Network Analysis (SNA), to explore the dynamics within humanitarian networks. It highlights the role of the Venezuelan diaspora NGOs, challenging the conventional view of migrants solely as aid recipients. The research uncovers the complex roles of intermediaries and coordination mechanisms, offering new insights into constructing effective humanitarian network structures. It advocates for a collaborative and inclusive approach to managing migration situations.

Super SDKs: Tracking personal data and platform monopolies in the mobile

In this article we address the question ‘what is tracking in the mobile ecosystem’ through a comprehensive overview of the Software Development Kit (SDK). Our research reveals a complex infrastructural role for these technical objects connecting end-user data with app developers, third parties and dominant advertising platforms like Google and Facebook. We present an innovative theoretical framework which we call a data monadology to foreground this interrelationship, predicated on an economic model that exchanges personal data for the infrastructural services used to build applications. Our main contribution is an SDK taxonomy, which renders them more transparent and observable. We categorise SDK services into three main categories: (i) Programmatic AdTech for monetisation; (ii) App Development, for building, maintaining and offering additional artificial intelligence features and (iii) App Extensions which more visibly embed third parties into apps like maps, wallets or other payment services. A major finding of our analysis is the special category of the Super SDK, reserved for platforms like Google and Facebook. Not only do they offer a vast array of services across all three categories, making them indispensable to developers, they are super conduits for personal data and the primary technical means for the expansion of platform monopolisation across the mobile ecosystem.

Molecular insight into the binding properties of marine algogenic dissolved organic matter for polybrominated diphenyl ethers and their combined effect on marine zooplankton

Polybrominated diphenyl ethers (PBDEs) are widespread in marine ecosystems, despite the limits placed on several congeners, and pose a threat to marine organisms. Many coexisting factors, especially dissolved organic matter (DOM), affect the environmental behavior and ecological risk of PBDEs. Since blooms frequently occur in coastal waters, we used algogenic DOM (A-DOM) from the diatom Skeletonem costatum and examined the interaction of A-DOM with 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47). Moreover, their combined effect on the rotifer Brachionus plicatilis was analyzed. During the stationary period, A-DOM had more proteins than polysaccharides, and 7 extracellular proteins were identified. A-DOM fluorescence was statically quenched by BDE-47, and amide, carbonyl, and hydroxyl groups in A-DOM were involved. Molecular docking analysis showed that all 5 selected proteins of A-DOM could spontaneously bind with BDE-47 and that hydrophobic interactions, van der Waals forces and pi-bond interactions existed. The reproductive damage, oxidative stress and inhibition of mitochondrial activity induced by BDE-47 in rotifers were relieved by A-DOM addition. Transcriptomic analysis further showed that A-DOM could activate energy metabolic pathways in rotifers and upregulate genes encoding metabolic detoxification proteins and DNA repair. Moreover, A-DOM alleviated the interference effect of BDE-47 on lysosomes, the extracellular matrix pathway and the calcium signaling system. Alcian blue staining and scanning electron microscopy showed that A-DOM aggregates were mainly stuck to the corona and cuticular surface of the rotifers; this mechanism, rather than a real increase in uptake, was the reason for enhanced bioconcentration. This study reveals the complex role of marine A-DOM in PBDEs bioavailability and enhances the knowledge related to risk assessments of PBDE-like contaminants in marine environments.

Ostwald Ripening of Ag2Te Precipitates in Thermoelectric PbTe: Effects of Crystallography, Dislocations, and Interatomic Bonding

AbstractNanostructuring is important for designing thermoelectrics. Yet, nanoprecipitates are thermodynamically unstable and coarsen through Ostwald ripening. Here, the Ostwald ripening of Ag2Te in PbTe and its resulting impact on thermoelectric performance is investigated. Numerous Guinier‐Preston zones and platelet Ag2Te precipitates in the sample quenched from a single‐phase region is observed. Upon annealing, these platelet precipitates grow into big lath‐shaped second phases by consuming small Ag‐rich clusters. The crystallographic orientation relationships between Ag2Te and PbTe are unraveled by scanning transmission electron microscopy and modeled by first‐principles calculations. The interfaces with low lattice mismatch determine the morphology of Ag2Te in PbTe. Atom probe tomography reveals different chemical bonding mechanisms for PbTe and Ag2Te, which are metavalent and iono‐covalent, respectively. This leads to an acoustic phonon mismatch at the precipitate‐matrix interface. Yet, the electrons are also scattered by these interfaces, resulting in poor electrical properties in the as‐quenched sample. In contrast, the annealed sample contains abundant Ag‐decorated dislocations by activating the Bardeen‐Herring source. These dislocations strongly scatter phonons while maintaining a good electron transmission, contributing to a higher thermoelectric performance. This work demonstrates the complex role of microstructure morphologies, compositions, and bonding mechanisms in thermoelectric response, providing insights into structural design for thermoelectrics.