Active Role Research Articles

A therapeutic leap: how myosin inhibitors moved from cardiac interventions to skeletal muscle myopathy solutions.

The myosin inhibitor mavacamten has transformed the management of obstructive hypertrophic cardiomyopathy (HCM) by targeting myosin ATPase activity to mitigate cardiac hypercontractility. This therapeutic mechanism has proven effective for patients with HCM independent of having a primary gene mutation in myosin. In this issue of the JCI, Buvoli et al. report that muscle hypercontractility is a mechanism of pathogenesis underlying muscle dysfunction in Laing distal myopathy, a disorder characterized by mutations altering the rod domain of β myosin heavy chain. The authors performed detailed physiological, molecular, and biomechanical analyses and demonstrated that myosin ATPase inhibition can correct a large extent of muscle abnormalities. The findings offer a therapeutic avenue for Laing distal myopathy and potentially other myopathies. This Commentary underscores the importance of reevaluating myosin activity's role across myopathies in general for the potential development of targeted myosin inhibitors to treat skeletal muscle disorders.

Denosumab Induces Neoplastic Stromal Cell Apoptosis via p62 Downregulation Dependent on Autophagy Pathway in Giant Cell Tumour of Bone.

As the only humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL) for giant cell tumour of bone (GCTB) therapy, denosumab has limited antitumour effect on neoplastic stromal cells. Nevertheless, its mechanism of action has not yet been clarified. A previous study has revealed that p62 may play an important role in the antitumour activity of denosumab. The study aimed to investigate if the mechanism by which denosumab inhibits GCTB neoplastic stromal cells growth is via p62 modulation and other related mechanisms. p62 expression before and after denosumab therapy was analysed by RT‒qPCR, western blot, ELISA, and immunohistochemical assays. Two primary neoplastic stromal cells were isolated from fresh GCTB tumour tissue (L cell) and metastatic tissue (M cell). Cell proliferation, migration, apoptosis, and autophagy were investigated in p62 knockdown neoplastic stromal cells transfected by short hairpin RNA lentivirus in vitro. Tumor growth was evaluated in the chick chorioallantoic membrane model in vivo. p62 expression was found to be downregulated following denosumab therapy. The patients with a decrease in p62 expression had lower recurrence-free survival rates. The proliferation of M cells was not inhibited by denosumab therapy, but it was restored by p62 knockdown. Moreover, p62 knockdown inhibited tumour growth in vivo. Denosumab induced M cell apoptosis and arrested the cell cycle at the G1/G0 transition and these effects were also enhanced by p62 knockdown. Autophagic flux assays revealed p62 modulation to be dependent on autophagy following denosumab incubation. Denosumab induced neoplastic stromal cells apoptosis via p62 downregulation dependent on autophagy pathway. The combination of p62 and RANKL knockdown might be a better strategy than RANKL knockdown alone for GCTB targeted therapy.

Screen time, sleep, brain structural neurobiology, and sequential associations with child and adolescent psychopathology: Insights from the ABCD study.

The precise roles of screen media activity (SMA) and sleep problems in relation to child/adolescent psychopathology remain ambiguous. We investigated temporal relationships among sleep problems, SMA, and psychopathology and potential involvement of thalamus-prefrontal-cortex (PFC)-brainstem structural covariation. This study utilized data from the Adolescent Brain Cognitive Development study (n = 4,641 ages 9-12) at baseline, Year1, and Year2 follow-up. Cross-Lagged Panel Models (CLPMs) investigated reciprocal predictive relationships between sleep duration/problems, SMA, and psychopathology symptoms. A potential mediating role of baseline Thalamus-PFC-brainstem covariation on SMA-externalizing relationships was examined. Participants were divided into discovery (n = 2,359, 1,054 girls) and replication (n = 2,282, 997 girls) sets. CLPMs showed 1) bidirectional associations between sleep duration and SMA in late childhood, with higher frequency SMA predicting shorter sleep duration (β = -0.10 [95%CI: -0.16, -0.03], p = 0.004) and vice versa (β= -0.11 [95%CI: -0.18, -0.05], p < 0.001); 2) externalizing symptoms at age 10-11 predicting sleep problems (β = 0.11 [95%CI: 0.04, 0.19], p = 0.002), SMA (β = 0.07 [95%CI: 0.01, 0.13], p = 0.014), and internalizing symptoms (β = 0.09 [95%CI: 0.05, 0.13], p < 0.001) at age 11-12; and 3) externalizing behavior at age 10-11 partially mediating the relationship between baseline thalamus-PFC-brainstem covariation and SMA at age 11-12 (indirect effect = 0.032 [95%CI: 0.003, 0.067], p-value = 0.030). Findings were replicable. We found bi-directional SMA-sleep-duration associations in late childhood. Externalizing symptoms preceded future SMA and sleep disturbances and partially mediated relationships between structural brain covariation and SMA. The findings emphasize the need for understanding individual differences and developing and implementing integrated strategies addressing both sleep concerns and screen time to mitigate potential impacts on psychopathology.

Mulberry branch fiber improved lipid metabolism and egg yolk fatty acid composition of laying hens via the enterohepatic axis

BackgroundThe utilization of mulberry branch fiber (MF), the largest by-product of the sericulture industry, is an important issue. Supplementation with MF as a dietary fiber for poultry may serve as a useful application. However, little is known about the effects of MF on liver lipid metabolism and egg yolk fatty acid composition of laying hens and their underlying mechanisms. In this study, we performed a multi-omics investigation to explore the variations in liver lipid metabolism, egg yolk fatty acid composition, gut microbiota, and the associations among them induced by dietary MF in laying hens.ResultsDietary MF had no harmful effects on the laying performance or egg quality in laying hens. The enzyme activities associated with lipid metabolism in the liver were altered by the addition of 5% MF, resulting in reduced liver fat accumulation. Furthermore, dietary 5% MF induced the variation in the fatty acid profiles of egg yolk, and increased the polyunsaturated fatty acid (PUFA) content. We observed a significant reduction in the diversity of both gut bacteria and changes in their compositions after the addition of MF. Dietary MF significantly increased the abundance of genes involved in fatty acid biodegradation, and short-chain fatty acids biosynthesis in the gut microbiota of laying hens. The significant correlations were observed between the liver lipid metabolism enzyme activities of hepatic lipase, lipoprotein lipase, and total esterase with gut microbiota, including negative correlations with gut microbiota diversity, and multiple correlations with gut bacteria and viruses. Moreover, various correlations between the contents of PUFAs and monounsaturated fatty acids in egg yolk with the gut microbiota were obtained. Based on partial-least-squares path modeling integrated with the multi-omics datasets, we deduced the direct effects of liver enzyme activities and gut bacterial compositions on liver fat content and the roles of liver enzyme activities and gut bacterial diversity on egg yolk fatty acid composition.ConclusionsThe results indicate that dietary MF is beneficial to laying hens as it reduces the liver fat and improves egg yolk fatty acid composition through the enterohepatic axis.CByDGCz_6LcoMs-GQqtpHGVideo Graphical

Finite-Time Output-Feedback Formation Control for High-Order Nonlinear Multiagent Systems With Obstacle Avoidance

This paper investigates the finite-time formation control problem for high-order nonlinear multiagent systems (MASs) with the consideration of obstacle avoidance, unmeasurable states and dead-zone input. A neural networks k-filter observer is designed to estimate the unmeasurable states and cope with the problem of dead-zone input. Also, by using an integral-multiplicative tangent Lyapunov-barrier function (LBF), the obstacle avoidance mission can be completed for MASs without dynamic mismatching. Then, combining the finite-time method and the backstepping theory, an output-feedback finite-time controller is designed for high-order nonlinear MASs. Theoretical analysis indicates that the control algorithm can not only make agents accomplish the formation obstacle avoidance task but also guarantee the boundedness of signals in the system. A simulation demonstrates the effectiveness of the proposed control algorithm. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —This article studies the formation obstacle avoidance problem for MASs which plays an important role in transportation, exploration and rescue activities. Unmeasurable states and dead-zone input, which often occur in practice, are also considered and handled by a neural networks k-filter observer. An integral-multiplicative tangent LBF is utilized to complete the obstacle avoid task which is necessary for actual systems. Moreover, to be more feasible in industrial applications, the finite-time control strategy is used in the controller design.

Study of Structural Elucidation, Degradation Kinetics and Antimicrobial Analysis of Copper (II) Sesame-Soap Complexes with Urea and Thiourea Ligand in Non-aqueous Solvents

Abstract: Surfactants have great importance in biological and drug industries and the complexes of metallic soaps with various ligands are used in approximately every region of national economy. Therefore, our keen interest to study of degradation kinetics and biological importance of Cu (II) surfactants in non-aqueous and non-polar solvent benzene. Present research work has been initiated with synthesis, systematic study of structural elucidation, thermal degradation, kinetics and biocidal activities of copper (II) sesame-soap complexes with macrocyclic nitrogen and sulphur containing donar ligands like urea and thiourea. The thermal degradation of copper (II) sesame-soap complexes were carried out for analysis of degradation kinetics and estimation of kinetic and thermodynamic parameters using different methods at heating rate 10oC min-1. Copper (II) sesame-soap complexes of such ligands have also been analysed against Staphylococus aureus. This research work consolidates the synthesis of copper (II) sesame soap-urea and thiourea complexes by conventional methods and the structure of these complexes were assigned according to elemental analysis and molecular weight determinations. IR, NMR and ESR spectral studies have also been done to understand structural aspects. The anti-microbial activities of copper (II) sesame-soap urea and thiourea complexes have been evaluated by testing against Staphylococus aureus. The present research work includes information of thermal analysis using TGA technique to find out their kinetic and thermodynamic parameters by using diverse equations such as Coats-Redfern equation, Horowitz-Metzger equation, Broido equation, Piloyan–Novikova equation. Moreover, the results obtained from anti-microbial screening have been used to analyze the anti-microbial activities of copper (II) sesame-soap urea and thiourea complexes against gram-positive bacteria Staphylococus aureus. These results show that complexes of copper ion co-ordinated with different nitrogen, oxygen and sulphur containing ligands, are very important in the field of pharmaceutical chemistry due to its significant role in the inhibition activity. The study of these complexes concludes that the synthesized complexes were found to possess appreciable bactericidal properties at different concentrations because chelation increases the anti-microbial potency.

Social participation of rheumatoid arthritis patients: Does illness perception play a role?

Social participation is an important aspect associated with health-related outcomes in chronic diseases. However, little is known about the factors that may affect participation in patients with rheumatoid arthritis (RA). We aimed to examine whether pain, fatigue, anxiety, depression, and illness perception are associated with social participation in patients with RA when controlled for clinical and sociodemographic variables. We also analysed the mediating role of illness perception in the association between physical and psychological variables on social participation. We included 157 RA patients (84.7% females; mean age 56.4 ± 13.9 years) who completed the Participation Scale, Brief Illness Perception Questionaire, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, 36-item Short Form Health Survey, and the Visual Analogue Scale. Multiple linear regressions and mediation analyses were used to analyze the data. In the final regression models, illness perception (β = .42; p ≤ .001) and functional disability (β = .21; p ≤ .05) were associated with social participation. Income (β = -.18; p ≤ .05) lost its significance when physical variables were added to the model, and pain (β = .24; p ≤ .05) and fatigue (β = -.24; p ≤ .05) when psychological distress was added. No significant role of anxiety, depression, disease activity, or age was identified using regression analyses. Illness perception mediated the association of pain, fatigue, anxiety, and depression with social participation, and the indirect effect varied from 65% to 98%. Illness perceptions may significantly diminish the impacts of pain, fatigue, anxiety, and depression on social participation in individual RA patients. Therefore, RA patients could benefit from psychological interventions aimed at tackling negative illness perceptions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Individual Alpha Frequency Contributes to the Precision of Human Visual Processing.

Brain oscillatory activity within the alpha band has been associated with a wide range of processes encompassing perception, memory, decision-making, and overall cognitive functioning. Individual alpha frequency (IAF) is a specific parameter accounting for the mean velocity of the alpha cycling activity, conventionally ranging between ∼7 and ∼13 Hz. One influential hypothesis has proposed a fundamental role of this cycling activity in the segmentation of sensory input and in the regulation of the speed of sensory processing, with faster alpha oscillations resulting in greater temporal resolution and more refined perceptual experience. However, although several recent theoretical and empirical studies would support this account, contradictory evidence suggests caution and more systematic approaches in the assessment and interpretation of this hypothesis. For example, it remains to be explored to what degree IAF shapes perceptual outcomes. In the present study, we investigated whether inter-individual differences in bias-free visual contrast detection threshold in a large sample of individuals in the general population (n = 122) could be explained by inter-individual differences in alpha pace. Our results show that the contrast needed to correctly identify target stimuli (individual perceptual threshold) is associated with alpha peak frequency (not amplitude). Specifically, individuals who require reduced contrast show higher IAF than individuals requiring higher contrasts. This suggests that inter-individual differences in alpha frequency contribute to performance variability in low-level perceptual tasks, supporting the hypothesis that IAF underlies a fundamental temporal sampling mechanism that shapes visual objective performance, with higher frequencies promoting enhanced sensory evidence per time unit.

Non-majored English Students’ Learning Autonomy through Extensive Listening at a Public University

Enhancing English language proficiency, especially in listening skills, is crucial for students completing General English Courses at universities in Vietnam these days. Unfortunately, non-majored English students are often overlooked in assessments of this vital skill in their final exams, resulting in a lack of autonomy in their language learning, particularly in listening. This research explored students' perspectives on fostering autonomy through extensive listening activities, conducting a qualitative case study with 10 non-majored English students. Interviews revealed that extensive listening motivated students’ learning and improved their listening skills. However, despite these benefits, the findings highlighted a need for educators to play a more active role in designing and delivering comprehensive guidance in extensive listening strategies. This study contributed valuable insights to the ongoing discourse on optimizing learning autonomy in English language education.&#x0D;  

Communication Management Mafindo Samarinda as An Anti-Hoax Facilitator

In the digital information age, the spread of misinformation or hoaxes is a serious challenge for society. The Anti-Defamation, Hoax, and Intolerance Community Organization (Mafindo) in Samarinda has become a facilitator in efforts to prevent and overcome the spread of hoaxes. This study aims to analyze communication management applied by Mafindo Samarinda as an anti-hoax facilitator. The research method used is a case study with a qualitative approach. Data was obtained through interviews with Mafindo Samarinda members, observations of activities carried out, and analysis of documents related to anti-hoax campaigns that have been run by this organization. The results showed that Mafindo Samarinda implemented a well-planned communication management strategy. They use various communication channels, such as social media, seminars, and workshops, to disseminate correct information and educate the public on how to identify hoaxes. In addition, Mafindo Samarinda also collaborates with various parties, including the government and educational institutions, in a joint effort to fight the spread of hoaxes. Nevertheless, the challenges faced by Mafindo Samarinda are not small. An active role from all levels of society is needed to ensure the success of this anti-hoax program. Therefore, effective communication management needs to be continuously developed and adapted to technological developments and community dynamics.

Prendersi Cura: Taking care of nature in Perugia, Italy

Cities need more green spaces to adapt to climate change and facilitate community resilience. However, successfully managing green spaces is challenging. City governments consistently employ top-down management practices that limit the benefits, usage, and perception of such spaces as Nature. Further, current management practices overlook socio-cultural factors important to residents. Using the existing categories of urban green spaces (UGS) and informal green spaces (IGS), this article situates the cultural practice prendersi cura as a way to conceptualize successful, bottom-up green space management. The term prendersi cura, meaning “to take care of” in Italian, emerged through interviews in Perugia, Italy, and reflects the socio-ecological value of IGS and the disconnect between residents and city-managed UGS. This study employed mixed methods, combining 10 weeks of participant observation, 13 interviews, and GIS analysis to understand the relationship between Perugians and their green spaces. Results indicate that interviewees did not describe city-supported UGS (i.e. top-down green spaces like parks or historic gardens) as Nature, even if they were areas of dense vegetation and recognized by the City of Perugia in GIS analyses. In contrast, interviewees described IGS (i.e. community gardens, vacant lots, or potted plants) that were unrecognized in city GIS visualizations as Nature, indicating a stronger attachment to green spaces when interviewees had active roles in their management or witnessed community-based management practices. This paper demonstrates the importance of managing green spaces through a socio-ecological framework that considers user perceptions and cultural values. To allow greening initiatives to reach their full potential, it is critical to embrace local values and participation in management practices.

The Role of the Matahari Women's Group in Forest Area Management through the Village Forest Scheme in the Social Forestry Program in Sekabuk Village, Sadaniang District, Mempawah Regency.

This study aims to determine the role of Sekabuk Village women's involvement in managing forest areas through the Social Forestry Program (PS). The method used in this study is a qualitative research method with a descriptive approach. The data source in the study was obtained through semi-structural, in-depth interviews with 7 key informants, which were determined through purposive sampling techniques. The writing of this thesis aims to provide an understanding of the implementation of social forestry programs involving the role of women in Sekabuk Village. The problem of the lack of involvement of women in resource management around the area that occurs in Sekabuk Village is quite interesting to study, considering that most of the Sekabuk Village area is a forest area. Based on the research conducted, the participation of women in Sekabuk Village was obtained through granting forest management rights by issuing group decrees, increasing women's capacity by providing training, developing forest-based economic businesses for women's groups, providing women's empowerment in forest area management, and conducting supervision and evaluation. So, the role of Sekabuk Village women in playing an active role in forest area management was revealed.

Handwoven interior accessories from palm leaves as sustainable elements

PurposeThis paper argues that cultures with the same climate have similar handicrafts as they have similar cultivation and identical raw materials. This study focuses on how mountainous, coastal and hot regions partaking in similar crafts and cultural heritage use palm leaves and analyses the resulting handicrafts' similarities.Design/methodology/approachA review of mapping these samples establishes this similarity in the traditional industries of some civilizations' cultural heritage from countries sharing similar climates.FindingsThe handwoven crafts using palm leaves were significant patrimonial artifacts in different societies' and communities' cultural heritage. Our studies revealed that climate plays an active role in influencing all aspects of humanity’s life. It affects the construction methods and style, agriculture and lifestyles.Research limitations/implicationsTraditional handwoven palm leaf product models, especially plates and baskets, are studied from South America, Africa, Gulf Countries and Asia.Practical implicationsAdditionally, this paper focuses on preserving these treasures as an essential part of interior elements as accessories for most inhabitants of these areas.Social implicationsCultural heritage also embraces intangible aspects such as skills passed down through generations within a particular society. The tangible and intangible elements complement each other and contribute to an overall legacy.Originality/valueCultural heritage reflects a society’s way of life carried down through the years across lands, items, customs and aesthetic concepts. People are the gatekeepers of society, as they preserve their way of life for future generations to emulate. Tangible artistic and cultural heritage comprises artifacts. It comprises all human evidence and expressions, such as traditional handicrafts, pictures, documents, books and manuscripts.

Qualitative and Quantitative Analytical Techniques of Nucleic Acid Modification Based on Mass Spectrometry for Biomarker Discovery.

Nucleic acid modifications play important roles in biological activities and disease occurrences, and have been considered as cancer biomarkers. Due to the relatively low amount of nucleic acid modifications in biological samples, it is necessary to develop sensitive and reliable qualitative and quantitative methods to reveal the content of any modifications. In this review, the key processes affecting the qualitative and quantitative analyses are discussed, such as sample digestion, nucleoside extraction, chemical labeling, chromatographic separation, mass spectrometry detection, and data processing. The improvement of the detection sensitivity and specificity of analytical methods based on mass spectrometry makes it possible to study low-abundance modifications and their biological functions. Some typical nucleic acid modifications and their potential as biomarkers are displayed, and efforts to improve diagnostic accuracy are discussed. Future perspectives are raised for this research field.

Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments.

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in PFC activity during early life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the PFC of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the PFC during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the PFC we performed single-nucleus RNA-sequencing. Maternal separation led to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life PFC inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of PFC activity during early life in behavioral expression in adulthood.

Whole Transcriptome Sequencing of Peripheral Blood Identifies the Alzheimer's Disease-Related circRNA-miRNA-lncRNA Pathway.

Previous studies on transcriptional profiles suggested dysregulation of multiple RNA species in Alzheimer's disease. However, despite recent investigations revealing various aspects of circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks in Alzheimer's Disease (AD) pathogenesis, few genome-wide studies have explored circRNA-associated profiles in AD patients exhibiting varying degrees of cognitive loss. To investigate the potential pathogenesis-related molecular biological changes in the various stages of AD progression. Whole transcriptome sequencing was performed on the peripheral blood of 7 normal cognition (NC) subjects, 8 patients with mild cognitive impairment, 8 AD patients with mild dementia (miD), and 7 AD patients with moderate dementia (moD). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to predict the potential functions of the maternal genes of microRNAs (miRNAs), circRNAs and long non-coding RNAs (lncRNAs). The construction of ceRNA network was performed between the NC group and each diseased group based on the differently expressed RNAs. In total, 3568 mRNAs, 142 miRNAs, 990 lncRNAs, and 183 circRNAs were identified as significantly differentially expressed across the four groups. GO and KEGG enrichment analysis revealed the significant roles of GTPase activity and the MAPK signaling pathway in AD pathogenesis. A circRNA-miRNA-lncRNA ceRNA pathway, characterized by the downregulated hsa-miR-7-5p and upregulated hsa_circ_0001170, was identified based on the differentially expressed RNAs between the NC group and the moD group. The study suggests that circRNAs may be independent of messenger RNAs (mRNAs) in AD pathogenesis and holds promise as potential biomarkers for AD clinical manifestations and pathological changes.

Preparing Tomorrow’s Leaders: The Role of Co-Curricular Activities in Shaping Business and Accountancy Students at Pilgrim Christian College, Cagayan de Oro City, Philippines

Co-curricular activities are fundamental in nurturing the hidden abilities of students. They play a significant role in education by fostering personal growth and fostering a sense of unity among students. The study evaluated the role of co-curricular activities in the development of Business and Accountancy students at Pilgrim Christian College conducted by co-curricular organizations. The study used a descriptive method of research and used surveys to gather the primary data. Findings of gender data revealed that more of the members of co-curricular organizations who participated in the co-curricular activities were females, only a few were males and the majority of the members of JPIA and BSS student organizations were at age greater than 19 years old but lesser than 21 years old. More of the members of the co-curricular organizations had their perceptions that co-curricular activities were valuable to their development. The majority of the SBA students favoured that co-curricular activities headed and sponsored by JPIA and BSS were beneficial to their development both in the physical and intellectual aspects. On the other hand, more of the members and officers of the co-curricular organizations who were involved in the co-curricular activities had a conflict of schedule on their duties as working students and their class schedules as regular students. The study concluded that the majority of the members of the co-curricular organizations who participated in the co-curricular activities learned and practiced teamwork, confidence, motivation, and leadership, and more of the SBA students who joined the co-curricular activities practiced all of the PCC values such as Faith, Integrity, Responsibility, Excellence, and Service (FIRES).

Peculiarities of aristocratic education at the beginning of the 19th century

AbstractThis paper examines the education of the Hungarian aristocracy in the period from 1790 to 1848. Since the progressive-minded members of this social class, which was highly qualified by European standards, played a significant role in promoting culture and education, especially since the Reform Era, I wanted to find out what educational characteristics underpinned their education. I explored the question of what trends prevailed in the different directions of home education and how the political, social and intellectual challenges and changes in the first half of the 19th century affected private education. In the course of the research, I applied the traditional method of educational history, source and document analysis and the analytical (deductive) research strategy. After studying the Hungarian, German and English literature on the subject, I examined and evaluated the primary sources available in Hungary - diaries, memoirs, journal articles, autobiographical writings, records of foreign travellers, archival and manuscript sources. In addition to asserting their primary power interests and their role as patrons, a small but crucial group of aristocrats took an active role in raising the level of national culture and education. They championed the cause of education, founded educational institutions and thus became mediators of culture for other strata of society. Their education, enlightened thinking and European erudition undoubtedly contributed to their recognition of this role and task and their commitment to it.

Implementation of Project Based Learning Method in Developing Cognitive Abilities of Children Aged 5-6 Years Through Loose Parts Media

This study aims to explore the implementation of Project Based learning (PBL) method in developing cognitive abilities of children aged 5-6 years through loose parts media. The research used a descriptive qualitative approach with a focus on observing the implementation of learning activities at 'Aisyiyah Bustanul Athfal 3 Kindergarten, Southeast Pontianak. Data were obtained through observation, interviews, and document analysis. The results showed that the PBL method applied through loose parts media was effective in developing cognitive abilities of children aged 5-6 years. Careful planning, the active role of teachers in supporting activities, and the use of interesting media are important factors in the successful implementation of this method. In addition, the results also showed that children showed progress in problem solving, logical thinking and symbolic thinking through active participation in learning activities. The findings make an important contribution to the understanding of the use of the PBL method and loose parts media in the context of early childhood education and provide practical guidance for educators to improve the quality of learning in early childhood education institutions.

Paxillin phase separation promotes focal adhesion assembly and integrin signaling.

Focal adhesions (FAs) are transmembrane protein assemblies mediating cell-matrix connection. Although protein liquid-liquid phase separation (LLPS) has been tied to the organization and dynamics of FAs, the underlying mechanisms remain unclear. Here, we experimentally tune the LLPS of PXN/Paxillin, an essential scaffold protein of FAs, by utilizing a light-inducible Cry2 system in different cell types. In addition to nucleating FA components, light-triggered PXN LLPS potently activates integrin signaling and subsequently accelerates cell spreading. In contrast to the homotypic interaction-driven LLPS of PXN in vitro, PXN condensates in cells are associated with the plasma membrane and modulated by actomyosin contraction and client proteins of FAs. Interestingly, non-specific weak intermolecular interactions synergize with specific molecular interactions to mediate the multicomponent condensation of PXN and are efficient in promoting FA assembly and integrin signaling. Thus, our data establish an active role of the PXN phase transition into a condensed membrane-associated compartment in promoting the assembly/maturation of FAs.