Abstract: The urban-rural conflicts in the city of Santo Tomás have contributed to the disorderly growth of the population, due in part to the deficiencies of urban planning and especially due to the territorial conflict. The study has focused on the urban-rural relationship (district and provincial capital versus peasant community) that is framed in a scenario of rapid growth of the city towards the territory of the peasant community. The objective of this study was to identify deficiencies in territorial and urban management, as well as their relationship with regulatory mechanisms related to urban development. The work methodology consisted of the analysis of the legal instruments for urban management and territorial management by the peasant community; For this, interviews were carried out with key social actors. The results indicate a gap in these aspects in Peruvian legislation, as well as a complex network of interests that does not contribute to the resolution of urban management problems.

Resumen: Los conflictos urbano-rurales en la ciudad de Santo Tomás han contribuido al desordenado crecimiento de la población, debido en parte a las deficiencias de la planificación urbana y sobre todo por el conflicto territorial. El estudio se ha enfocado en la relación urbano-rural (capital distrital y provincial versus comunidad campesina) que se enmarca en un escenario de rápido crecimiento de la ciudad hacia el territorio de la comunidad campesina. El objetivo de este estudio fue identificar las deficiencias en la gestión territorial y urbana, como su relación con los mecanismos normativos conexos con el desarrollo urbano. La metodología de trabajo consistió en el análisis de los instrumentos legales para la gestión urbana como de la gestión territorial por la comunidad campesina; para ello se realizó entrevistas a los actores sociales claves. Los resultados indican un vacío en estos aspectos en la legislación peruana, así como un complejo entramado de intereses que no contribuye a la resolución de los problemas de la gestión urbana.

RESUMEN El propósito de la investigación es examinar los sistemas de planificación y sus mecanismos regulatorios para entender cómo se organizan y regulan, ya sea parcial o completamente, dependiendo de la organización para lograr la consecución de objetivos. Las aportaciones teóricas de la investigación se centran en la conceptualización de la teoría de sistemas. El aporte metodológico se basa en el desarrollo de un esquema secuencial y lógico con la aplicación de un dendrograma de variables, que permite eliminar superposiciones entre el conjunto de conceptos analizados. Las conclusiones de la investigación permiten comprobar que las organizaciones son entidades dinámicas y cambiantes que se ven inevitablemente impactadas por el entorno en el que operan; además las instituciones funcionan sinérgicamente desde puntos de vista interrelacionados e interdependientes.

ABSTRACT The purpose of the research is to examine planning systems and their regulatory mechanisms to understand how they are organized and regulated, either partially or completely, depending on the organization to achieve the attainment of objectives. The theoretical contributions of the research are centered on the conceptualization of systems theory. The methodological contribution is based on the development of a sequential and logical scheme with the application of a dendrogram of variables, which allows eliminating overlaps between the set of concepts analyzed. The conclusions of the research show that organizations are dynamic and changing entities that are inevitably impacted by the environment in which they operate; in addition, institutions function synergistically from interrelated and interdependent points of view.

This article delves into the multifaceted mechanisms driving evolution, exploring the foundational principles of natural selection alongside advanced theories of cybernetics, symbiogenesis, and autopoiesis. Charles Darwin's concept of natural selection highlights the gradual adaptation of organisms, favoring traits that enhance survival and reproduction. This principle is further examined through the lens of sexual selection, which focuses on traits that increase reproductive success. Cybernetic theories, particularly those proposed by Stafford Beer, introduce regulatory functions and homeostatic balances that underscore the dynamic relationship between organisms and their environments. The role of symbiosis, as articulated in symbiogenesis, reveals how interspecies cooperation leads to significant evolutionary changes, such as the development of essential cellular organelles. The concept of autopoiesis and natural drift offers a paradigm where evolutionary change is a continuous adaptive process, maintaining structural and functional integrity within living systems. This perspective is expanded through the theory of system differentiation, which emphasizes the role of sexual reproduction and genetic recombination in driving species diversification and ecosystem complexity. Integrating these diverse frameworks, the article presents a comprehensive view of evolutionary processes, from the inheritance of acquired characteristics to the generation of new genetic variations through symbiosis and horizontal gene transfer. By synthesizing these insights, the article underscores the interconnectedness and resilience of living systems, offering profound implications for understanding biodiversity and the adaptive capabilities of life on Earth.

Este artículo profundiza en los mecanismos multifacéticos que impulsan la evolución, explorando los principios fundamentales de la selección natural junto con las teorías avanzadas de la cibernética, la simbiogénesis y la autopoiesis. El concepto de selección natural de Charles Darwin destaca la adaptación gradual de los organismos, favoreciendo los rasgos que mejoran la supervivencia y la reproducción. Este principio se examina más a fondo a través de la lente de la selección sexual, que se centra en los rasgos que aumentan el éxito reproductivo. Las teorías cibernéticas, en particular las propuestas por Stafford Beer, introducen funciones reguladoras y equilibrios homeostáticos que subrayan la relación dinámica entre los organismos y sus entornos. El papel de la simbiosis, tal como se articula en la simbiogénesis, revela cómo la cooperación entre especies conduce a cambios evolutivos significativos, como el desarrollo de orgánulos celulares esenciales. El concepto de autopoiesis y deriva natural ofrece un paradigma en el que el cambio evolutivo es un proceso adaptativo continuo, que mantiene la integridad estructural y funcional dentro de los sistemas vivos. Esta perspectiva se amplía a través de la teoría de la diferenciación de sistemas, que enfatiza el papel de la reproducción sexual y la recombinación genética en el impulso de la diversificación de especies y la complejidad de los ecosistemas. Integrando estos diversos marcos, el artículo presenta una visión integral de los procesos evolutivos, desde la herencia de características adquiridas hasta la generación de nuevas variaciones genéticas a través de la simbiosis y la transferencia horizontal de genes. Al sintetizar estas ideas, el artículo subraya la interconexión y la resiliencia de los sistemas vivos, ofreciendo profundas implicaciones para la comprensión de la biodiversidad y las capacidades de adaptación de la vida en la Tierra.

ABSTRACT The objective of this research aims to accomplish a critical evaluation of the normative frameworks and public policies established for the right to adequate food in Latin America. As a result of the assessment, it is observed that in the countries analyzed, the development of legal and policy frameworks is still required, which must be strengthened and detailed following the most up-to-date international standards, to guarantee the right to adequate food for all people. Without robust legal frameworks, strong institutional capacities, and sufficient transversal mechanisms for the attention to food as a full right, the design and implementation of public policies will not be appropriate and comprehensive and will not have the desired impacts. Deficiencies in the structural supports for regulations and policies generate unequal impacts among the countries of the region that highlight the vulnerability of Latin America.

RESUMEN El objetivo de la investigación fue realizar una evaluación crítica de los marcos normativos y las políticas públicas establecidas para el derecho a la alimentación adecuada en América Latina. Como resultado de la valoración se observa que en los países analizados todavía se requiere del desarrollo de marcos legales y de políticas que es necesario afianzar y detallar de acuerdo con los estándares internacionales más actualizados, con objeto de garantizar el derecho a la alimentación adecuada para todas las personas. Sin marcos legales robustos, capacidades institucionales fuertes y mecanismos transversales suficientes para la atención de la alimentación como derecho pleno, el diseño y la implementación de políticas públicas no serán apropiados e integrales y no tendrán los impactos deseados. Las deficiencias en los sustentos estructurales para la normativa y las políticas generan impactos desiguales entre los países de la región que resaltan la vulnerabilidad de América Latina.

Abstract This study investigates day-of-the-week effects in the digital market, with a focus on Bitcoin and Ethereum, spanning from July 1st, 2020, to December 31st, 2023, in the post-COVID-19 period. Employing parametric and non-parametric tests alongside the GARCH (1,1) model, market dynamics was analized. The findings indicate the presence of a day-of-the-week effect in Ethereum, characterized by notable return variations across different days, while Bitcoin exhibits no discernible calendar anomalies, suggesting enhanced market efficiency. Ethereum’s susceptibility to these effects underscores ongoing market complexities. Disparities in calendar anomalies stem from evolving market dynamics, methodological differences, and the speculative nature of cryptocurrency trading. Furthermore, the decentralized and global market complicates the accurate identification of market-wide effects. This study provides experimental findings on day-of-the-week effects in the digital market, facilitating investors in refining trading strategies and risk management. Further research is warranted to explore underlying mechanisms and monitor regulatory and technological developments for investor insights.

Resumen Este estudio investiga los efectos del día de la semana en el mercado digital, con un enfoque en bitcoin y ethereum, abarcando desde el 1º de julio de 2020 hasta el 31 de diciembre de 2023, en el período posterior al COVID-19. Empleando pruebas paramétricas y no paramétricas junto con el modelo GARCH (1,1), se analizó la dinámica del mercado. Los hallazgos indican un efecto significativo del día de la semana en ethereum, caracterizado por notables variaciones de rendimiento entre diferentes días, mientras que bitcoin no muestra anomalías de calendario discernibles, lo que sugiere una mayor eficiencia del mercado. La susceptibilidad de ethereum a estos efectos subraya las complejidades actuales del mercado. Las disparidades en las anomalías del calendario surgen de la evolución de la dinámica del mercado, las diferencias metodológicas y la naturaleza especulativa del comercio de criptomonedas. Además, el mercado descentralizado y global complica la identificación precisa de los efectos en todo el mercado. Este estudio proporciona evidencia empírica sobre los efectos del día de la semana en el mercado de criptomonedas, lo que facilita a los inversionistas refinar las estrategias comerciales y la gestión de riesgos. Se justifica realizar más investigaciones para explorar los mecanismos subyacentes y monitorear los desarrollos regulatorios y tecnológicos para obtener información de los inversionistas.

Digital information and data are crucial drivers of progress in various industries, including mining, where data-driven decision making optimizes resource extraction, enhances safety, and ensures sustainability. The adoption of digital technologies like artificial intelligence (AI) and the Internet of Things has amplified the importance of digital information. However, the integrity and security of this information are paramount, leading to the exploration of blockchain technology as a potential solution for secure digital value exchange in mining. This research examines blockchain's capabilities, drawing insights from its applications in sectors like banking, government, healthcare, and entertainment, and evaluates their relevance to mining's core value chain processes. The study identifies blockchain's distributed ledger technology, cryptographic security, and decentralization as unique advantages that can revolutionize mining by enhancing transaction speed, reducing costs, and improving supply chain transparency and compliance with sustainability standards. Blockchain's transparent and auditable records can enhance business transparency, fostering trust among stakeholders, including investors and regulatory bodies. The technology's consensus mechanisms and smart contracts further promote trust in collaborative ventures. This research provides a foundational understanding for decision-makers in the mining industry to evaluate blockchain's feasibility and potential return on investment, guiding strategic planning and resource allocation for blockchain applications. By leveraging blockchain, mining companies can optimize operations, improve sustainability practices, and establish a robust foundation for future growth, positioning blockchain as a transformative technology in the sector.

Abstract Between 37 and 63% of the logged timber in Peru has an illegal origin. This study aims to describe this supply chain in Ucayali region. The main contribution is the elaboration (and diagramming) of a sequence of processes, activities, and tasks (supported by the collection of management documents, field interviews and observation, based on the crime-script methodology), and the identification of mechanisms of evasion of environmental, tax and labour controls which explain the illegal origin. The severe gap between the supply chain and the regulatory structure developed by the State shows formal instruments supported by declarative mechanisms that lead to proposing the idea of a State that performs control, carrying out a formal theatricalization of surveillance, while assuming the existence of a widespread illegal logic.

Resumo Entre 37 e 63% da madeira extraída no Peru tem origem ilegal. Este estudo tem como objetivo descrever essa cadeia de suprimentos na região Ucayali. A principal contribuição é a elaboração (e diagramação) de uma sequência de processos, atividades e tarefas (apoiada na coleta de documentos de gestão, entrevistas de campo e observação, com base na metodologia crime-script), e a identificação de mecanismos de evasão de crimes. controles ambientais, fiscais e trabalhistas que explicam a origem ilegal. A grave lacuna entre a cadeia de abastecimento e a estrutura regulatória desenvolvida pelo Estado evidencia instrumentos formais apoiados em mecanismos declarativos que levam a propor a ideia de um Estado que exerce o controle, realizando um processo de teatralização formal da vigilância, ao mesmo tempo que assume a existência duma estendida lógica ilegal.

Resumen Entre 37 y 68% de la madera peruana tendría origen ilegal. El objetivo de este estudio es describir esta cadena de suministro en la región de Ucayali. El principal aporte es la elaboración y diagramación de una secuencia de eslabones, actividades y tareas (sostenida en la recolección de documentos de gestión, entrevistas en terreno y observación, basada en la metodología de los crime-scripts), mediante la cual se identifican mecanismos de evasión de los controles ambientales, tributarios y laborales, que explicarían el origen ilegal. Se identifica una severa brecha entre la cadena de suministro y la estructura normativa desarrollada por el Estado, lo que muestra instrumentos formales sostenidos en mecanismos declarativos que conducen a plantear la idea de un Estado que “performa” el control, realizando una teatralización formal de la vigilancia, mientras asume la existencia de una lógica ilegal extendida.

ABSTRACT Excess body weight has become a global epidemic and a significant risk factor for developing chronic diseases, which are the leading causes of worldwide morbidities. Adipose tissue (AT), primarily composed of adipocytes, stores substantial amounts of energy and plays a crucial role in maintaining whole-body glucose and lipid metabolism. This helps prevent excessive body fat accumulation and lipotoxicity in peripheral tissues. In addition, AT contains endothelial cells and a substantial population of immune cells (constituting 60-70% of non-adipocyte cells), including macrophages, T and B lymphocytes, and natural killer cells. These resident immune cells engage in crosstalk with adipocytes, contributing to the maintenance of metabolic and immune homeostasis in AT. An exacerbated inflammatory response or inadequate immune resolution can lead to chronic systemic low-grade inflammation, triggering the development of metabolic alterations and the onset of chronic diseases. This review aims to elucidate the regulatory mechanisms through which immune cells influence AT function and energy homeostasis. We also focus on the interactions and functional dynamics of immune cell populations, highlighting their role in maintaining the delicate balance between metabolic health and obesity-related inflammation. Finally, understanding immunometabolism is crucial for unraveling the pathogenesis of metabolic diseases and developing targeted immunotherapeutic strategies. These strategies may offer innovative avenues in the rapidly evolving field of immunometabolism. (Rev Invest Clin. 2024;76(2):65-79)

Abstract Purpose: The objective of this paper is to investigate the direction of the causal relationship between dividend policy (DP) and earnings management (EM). Design/methodology/approach: This research utilizes the panel data analysis to investigate the causal relationship between EM and DP. It provides empirical insights based on a sample of 280 French nonfinancial companies listed on the CAC All-Tradable index during the period of 2008-2015. The study initiates with a Granger causality examination on the unbalanced panel data and employs a dynamic panel approach with the generalized method of moments (GMM). It further estimates the empirical models simultaneously using the three-stage least squares (3SLS) method and the iterative triple least squares (iterative 3SLS) method. Findings: The estimation of our various empirical models confirms the presence of a bidirectional causal relationship between DP and EM. Practical implications: Our study highlights the prevalence of EM in the French context, particularly within DP. It underscores the need for regulatory bodies, the Ministry of Finance, external auditors and stock exchange organizers to prioritize governance mechanisms for improving the quality of financial information disclosed by companies. Originality/value: This research is, to the best of our knowledge, the first is to extensively investigate the reciprocal causal relationship between DP and EM in France. Previous studies have not placed a significant emphasis on exploring this bidirectional link between these two variables.

Abstract The clinical manifestations of cutaneous leishmaniasis (CL) depend not only on the infecting species involved, but also on the immune response of the individual. Although not yet well understood in humans, parasite survival and persistence are related to the cytokine profile and T cell proliferation, with the Th1 profile being related to cure, and the Th2 profile to disease progression. Considering the need for studies focused on the species with the highest circulation in the state of Amazonas, this study aimed to analyze the immunoregulation stimulated by soluble antigens (SLAs) of Leishmania (L.) amazonensis and Leishmania (V.) guyanensis in human lymphocytes in vitro, in order to understand the immune response of patients with CL. Lymphoproliferation was evaluated against stimuli of SLAs from L. amazonensis (100 µg/mL), SLAs from L. guyanensis (100 µg/mL) and phytohemagglutinin (10 µg/mL) using a BrdU Cell Proliferation ELISA kit after 72 h of incubation. Quantification of the cytokines IL-1b, IL-6, IL-8, IL-10, IL-12 and TNF was performed using the BD™ cytometric bead array human Th1/Th2/Th17 cytokine kit. Our results demonstrated that soluble antigens from L. amazonensis and L. guyanensis stimulated the lymphoproliferation of PBMCs from patients primo-infected with CL. Among the cytokines dosed, the highest concentrations were of IL-6 and IL-8, thus demonstrating that the soluble antigens evaluated are capable of inducing regulatory mechanisms. CL (CL involved individual humans proliferation Th cure progression Amazonas (SLAs L (L. V. V (V. vitro 100 µg/mL, µgmL µg/mL , µg mL 10 (1 7 incubation IL1b, IL1b ILb IL 1b, 1b b IL-1b IL6, IL6 6, 6 IL8, IL8 8, 8 IL-8 IL10, IL10 10, IL-10 IL12 12 IL-1 BD Th1Th2Th17 ThThTh Th17 Th1/Th2/Th1 primoinfected primo infected dosed IL- mechanisms (L (V 1 ( IL1 Th1Th2Th1 Th1/Th2/Th Th1Th2Th

Resumo As manifestações clínicas da leishmaniose cutânea (LC) dependem não apenas da espécie infectante envolvida, mas também da resposta imune do indivíduo. Apesar de ainda não bem esclarecido em humanos, a sobrevivência e persistência do parasito estão relacionados ao perfil de citocinas e proliferação de células T, relacionando-se a cura ao perfil Th1, e a progressão da doença ao perfil Th2. Considerando a necessidade de estudos voltados para as espécies de maior circulação no estado do Amazonas, este trabalho teve como objetivo analisar a imunorregulação estimulada por antígenos solúveis (SLAs) de Leishmania (L.) amazonensis e Leishmania (V.) guyanensis em linfócitos humanos in vitro, afim de compreender a resposta imune de pacientes com LC. A linfoproliferação foi avaliada frente a estímulos de SLAs de L. amazonensis (100 μg/mL), SLAs de L. guyanensis (100 μg/mL) e Phytohemagglutinin (10 μg/mL) utilizando BrdU Cell Proliferation ELISA Kit após 72h de incubação. A quantificação das citocinas IL-1b, IL-6, IL-8, IL-10, IL-12 e TNF foi realizada por BD™ Cytometric Bead Array (CBA) Human Th1/Th2/Th17 Cytokine Kit. Nossos resultados demonstraram que os antígenos solúveis de L. amazonensis e L. guyanensis estimularam a linfoproliferação de PBMCs de pacientes primoinfectados com LC. Entre as citocinas dosadas, as de maiores concentrações foram de IL-6 e IL-8, demonstrando que os antígenos solúveis avaliados são capazes de induzir mecanismos regulatórios. LC (LC envolvida indivíduo T relacionandose relacionando se Th1 Th Th2 Amazonas (SLAs L (L. V. V (V. vitro 100 μg/mL, μgmL μg/mL , μg mL 10 (1 h incubação IL1b, IL1b ILb IL 1b, 1b b IL-1b IL6, IL6 6, 6 IL8, IL8 8, 8 IL-8 IL10, IL10 10, IL-10 IL12 12 IL-1 BD CBA (CBA Th1Th2Th17 ThThTh Th17 Th1/Th2/Th1 dosadas IL- regulatórios (L (V 1 ( IL1 Th1Th2Th1 Th1/Th2/Th Th1Th2Th

Abstract Steroids and gonadotrophins are essential for the regulation of late stages of preantral development and antral follicular development. Although the luteinizing hormone receptor (LHCGR) has been detected in the preantral follicles of rats, rabbits, and pigs, its expression, in bovine fetal ovary, has not been demonstrated. Based on this, we aimed to investigate the expression of the LHCGR and LHCGR mRNA binding protein (LRBP), as well as, to quantify bta-miR-222 (a regulatory microRNA of the LHCGR gene) during the development of bovine fetal ovary. In summary, LHCGR expression was observed in the preantral follicle in bovine fetal ovary, from oogonias to primordial, primary and secondary stages, and the mRNA abundance was lower on day 150 than day 60. However, the mRNA abundance of LRBP followed the opposite pattern. Similar to LRBP, the abundance of bta-miR-222 was higher on day 150 than day 60 or 90 of gestation. The LHCGR protein was detected in oogonia, primordial, primary, and secondary follicles. Moreover, both oocytes and granulosa cells showed positive immunostaining for LHCGR. In conclusion, we suggest the involvement of LHCGR/LRBP/bta-mir222 with mechanisms related to the development of preantral follicles in cattle. (LHCGR rats rabbits pigs ovary demonstrated this , (LRBP) btamiR222 btamiR bta miR 222 bta-miR-22 a gene summary primordial 15 However pattern 6 9 gestation oogonia Moreover conclusion LHCGR/LRBP/btamir222 LHCGRLRBPbtamir222 LHCGRLRBPbtamir LHCGR/LRBP/bta mir222 mir LHCGR/LRBP/bta-mir22 cattle (LRBP btamiR22 22 bta-miR-2 1 btamir222 btamir LHCGR/LRBP/btamir22 LHCGRLRBPbtamir22 LHCGRLRBPbta mir22 LHCGR/LRBP/bta-mir2 btamiR2 2 bta-miR- btamir22 LHCGR/LRBP/btamir2 LHCGRLRBPbtamir2 mir2 LHCGR/LRBP/bta-mir bta-miR btamir2 LHCGR/LRBP/btamir

BACKGROUND The availability of genes and protein sequences for parasites has provided valuable information for drug target identification and vaccine development. One such parasite is Bartonella quintana, a Gram-negative, intracellular pathogen that causes bartonellosis in mammalian hosts. OBJECTIVE Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to B. quintana. METHODS AND FINDINGS To explore these aspects, we have adopted a subtractive proteomics approach to analyse the proteome of B. quintana. By subtractive proteins between the host and parasite proteome, a set of proteins that are likely unique to the parasite but absent in the host were identified. This analysis revealed that out of the 1197 protein sequences of the parasite, 660 proteins are non-homologous to the human host. Further analysis using the Database of Essential Genes predicted 159 essential proteins, with 28 of these being unique to the pathogen and predicted as potential putative targets. Subcellular localisation of the predicted targets revealed 13 cytoplasmic, eight membranes, one periplasmic, and multiple location proteins. The three-dimensional structure and B cell epitopes of the six membrane antigenic protein were predicted. Four B cell epitopes in KdtA and mraY proteins, three in lpxB and BQ09550, whereas the ftsl and yidC proteins were located with eleven and six B cell epitopes, respectively. MAINS CONCLUSIONS This insight prioritises such proteins as novel putative targets for further investigations on their potential as drug and vaccine candidates. development quintana Gramnegative, Gramnegative Gram negative, negative Gram-negative hosts pathogenesis aspects identified 119 66 nonhomologous non homologous 15 2 1 cytoplasmic membranes periplasmic threedimensional dimensional BQ09550 BQ respectively candidates 11 6 BQ0955 BQ095 BQ09 BQ0

Abstract Objectives Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. Methods Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. Results MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p< 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1β and Nuclear Transcription Factor-κB (NF-κB) (p< 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p< 0.05). Conclusion NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis. (NPC practice present unsatisfactory miRNAs (miRNAs cancer Therefore mechanisms subjects EpsteinBarr Epstein Barr EBV (EBV n group separately Highthroughput High throughput dualluciferase dual luciferase RealTime Real Time RTqPCR RT qPCR (RT-qPCR miR99a5p miRap miR 99a 5p p BAZ2A. BAZA . BAZ (BAZ2A) Kit8 Kit 8 Kit- cytometry viability ability blot MiR99a5p MiRap MiR p< (p 0.05. 005 0.05 0 05 0.05) Protein1 Protein 1 Protein- MCP1, MCP1 MCP , (MCP1) VEGFA, VEGFA (VEGFA) IL1β ILβ IL 1β β FactorκB κB NFκB NF (NF-κB miR99a5p. 5p. Furthermore miR99a5p/BAZ2A miR99a5pBAZ2A miRapBAZA 5p/BAZ2A axis (BAZ2A 00 0.0 (MCP1 (VEGFA pBAZ 5pBAZ2A pBAZA 0. (MCP

Abstract Genomic effect variants associated with survival and protection against complex diseases vary between populations due to microevolutionary processes. The aim of this study was to analyse diversity and distribution of effect variants in a context of potential positive selection. In total, 475 individuals of Lithuanian origin were genotyped using high-throughput scanning and/or sequencing technologies. Allele frequency analysis for the pre-selected effect variants was performed using the catalogue of single nucleotide polymorphisms. Comparison of the pre-selected effect variants with variants in primate species was carried out to ascertain which allele was derived and potentially of protective nature. Recent positive selection analysis was performed to verify this protective effect. Four variants having significantly different frequencies compared to European populations were identified while two other variants reached borderline significance. Effect variant in SLC30A8 gene may potentially protect against type 2 diabetes. The existing paradox of high rates of type 2 diabetes in the Lithuanian population and the relatively high frequencies of potentially protective genome variants against it indicate a lack of knowledge about the interactions between environmental factors, regulatory regions, and other genome variation. Identification of effect variants is a step towards better understanding of the microevolutionary processes, etiopathogenetic mechanisms, and personalised medicine. processes total 47 highthroughput throughput andor or technologies preselected pre selected polymorphisms nature significance SLCA SLC A SLC30A factors regions variation mechanisms medicine 4

Purpose This study aims to propose an innovative model that integrates variables and examines the influence of internet usage expertise, perceived risk and attitude toward information control on privacy concerns (PC) and, consequently, in consumers’ willingness to disclose personal information online. The authors also propose to test the mediation role of trust between PCs and willingness to disclose information. Trust is not a predictor of PC but a causal mechanism – considering that the focus is to understand consumers’ attitudes and behavior regarding the virtual environment (not context-specific) (Martin, 2018). Design/methodology/approach The authors developed a survey questionnaire based on the constructs that compose the proposed model to collect data from 864 respondents. The survey questionnaire included the following scales: internet usage expertise from Ohanian (1990); perceived risk, attitude toward information control, trust and willingness to disclose personal information online from Malhotra et al. (2004); and PC from Castañeda and Montoro (2007). All items were measured on a Likert seven-point scale (1 = totally disagree; 7 = totally agree). To obtain Westin’s attitudinal categories toward privacy, respondents answered Westin’s three-item privacy index. For data analysis, the authors applied covariance-based structural equation modeling. Findings First, the proposed model explains the drivers of consumers’ disposition to provide personal information at a level that surpasses specific contexts (Martin, 2018), bringing the analysis to consumers’ level and considering their general perceptions toward data privacy. Second, the findings provide inputs to propose a better definition of Westin’s attitudinal categories toward privacy, which used to be defined only by individuals’ information privacy perception. Consumers’ perceptions about their abilities in using the internet, the risks, their beliefs toward information control and trust also help to delimitate and distinguish the fundamentalists, the pragmatics and the unconcerned. Research limitations/implications Some limitations weigh the theoretical and practical implications of this study. The sample size of pragmatic and unconcerned respondents was substantially smaller than that of fundamentalists. It might be explained by applying Westin’s self-report index to classify the groups according to their score regarding PCs. Most individuals affirm having a great concern for their data privacy but still provide online information for the benefit of personalization – known as the privacy paradox (Zeng et al., 2021). It leads to another limitation of this research, given the lack of measures that classify respondents by considering their actual behavior toward privacy. Practical implications PC emerges as an important predictor of consumer trust and willingness to disclose their data online, and trust also influences this disposition. Managers need to implement actions that effectively reduce consumers’ concerns about privacy and increase their trust in the company – e.g. adopting a clear and transparent policy on how the data collected is stored, treated, protected and used to benefit the consumer. Regarding the perception of risk, if managers convince consumers that the data collected on the internet is protected, they tend to be less concerned about privacy. Social implications The results suggest different aspects influencing the willingness to disclose personal information online, including different responses considering consumers’ PCs. Through their policies and legislation, the authors understand that governments must be attentive to this aspect, establishing regulations that protect consumers’ data in the virtual environment. In addition to regulatory policies, education campaigns can be carried out for both consumers and managers to raise the discussion about privacy and the availability of information in the online environment, demonstrating the importance of protecting personal data to benefit the government, consumers and organizations. Originality/value Although there is increasing research on consumers’ privacy, studies have not considered their attitudinal classifications – high, moderate and low concern – as moderators of willingness to disclose information online. Researchers have also increased attention to the antecedents of PCs and disclosure of information but overlooked possible mechanisms that explain the relationship between them. (PC consequently contextspecific context context-specific Martin, Martin (Martin 2018. 2018 . 2018) Designmethodologyapproach Design methodology approach 86 scales 1990 (1990) al 2004 (2004) 2007. 2007 (2007) sevenpoint seven point 1 ( disagree agree. agree agree) Westins Westin s threeitem three item covariancebased covariance modeling First 2018, , Second Consumers risks fundamentalists limitationsimplications selfreport self report Zeng 2021. 2021 2021) eg e g e.g stored treated legislation aspect government organizations Originalityvalue Originality value high them 201 8 199 (1990 200 (2004 (2007 202 20 19 (199 (200 2 (19 (20 (2