Search Results (330)

Oligodendroglial cells are the myelinating glial cells of the central nervous system (CNS), and their morphological differentiation is a prerequisite for efficient myelin formation, which is essential for proper neuronal function. While oligodendroglial morphological changes normally proceed through tightly regulated developmental transitions, disruption of the underlying molecular mechanisms can lead to aberrant cellular phenotypes characterized by either premature, insufficient, or excessive differentiation. Although the phosphatidylinositol 3-kinase (PI3K) and its downstream Akt kinase signaling are well established as major drivers of oligodendrocyte morphological differentiation, myelination, and CNS white matter formation, how its negative regulator, phosphatase and tensin homolog (PTEN), is involved in the regulation of oligodendroglial morphogenesis remains incompletely understood. Recent genetic studies have highlighted a spectrum of disorders caused by PTEN dysfunction, conceptually established but currently evolving as PTENopathy, which has been partially associated with white matter abnormalities. Here, we report that, in an experimental model using the FBD-102b cell line, a well-established model of oligodendroglial cell differentiation, chemical inhibition of PTEN enhances pronounced morphological changes characterized by widespread membranes, accompanied by increased expression of differentiation and/or myelin marker proteins. We then focused on Rho family small GTPases, central regulators of cell morphogenesis, and examined their potential involvement downstream of this signaling. Expression of the RhoG-binding domain (RBD) of engulfment and cell motility 1 (ELMO1) attenuated the increased morphological changes. Similarly, inhibition of downstream Akt signaling also reversed these changes. Taken together, these results provide insight into how balanced regulation between PTEN and downstream signaling molecules governs oligodendroglial cell differentiation and suggest that dysregulation of this signaling equilibrium may contribute to cellular phenotypes relevant to disease-associated cellular alterations. Full article

Gaucher disease (GD) is characterized by the accumulation of glucosylceramide within lysosomes due to mutations in the GBA1 gene, which encodes the enzyme glucocerebrosidase. Current treatments are ineffective for patients suffering from severe neuronopathic forms of the disease. In this context, new therapeutic approaches for neuronopathic GD forms are needed. Lysosomal and mitochondrial dysfunction associated with increased oxidative stress and disturbances in the autophagic process have been described in GD. Here, we address c-Abl-RIPK3 signaling and its contribution to the accumulation of dysfunctional mitochondria in GD. Fibroblasts from patients with GBA1 mutations and neurons treated with the glucocerebrosidase inhibitor CBE exhibited alterations in the ΔΨm and mitochondrial morphology, as well as reduced capacity to form autophagosomes. Pharmacological inhibition of c-Abl or RIPK3 restored mitochondrial function and promoted autophagosome formation, along with an increase in autophagic engulfment of mitochondria in both GD models. In conclusion, the c-Abl-RIPK3 signaling pathway contributes to mitochondrial dysfunction and blockade of autophagy components in the mitochondria, both of which are altered in the neuronopathic forms of GD. Full article

Phagocytosis and migration in macrophages share key regulators, including Rho family GTPases; however, whether phagocytic membrane extension generates a transient, whole-cell polarity that coordinates migration and spatial prioritization of engulfment remains unclear. Here, we investigated the spatiotemporal coupling between membrane extension and cell migration using opsonized microneedles, which enable controlled stimulation together with long-range membrane extension and backtracking dynamics. During single-needle stimulation, membrane extension was tightly coupled to directional migration, whereas membrane retraction showed weaker coupling. In sequential stimulation with two microneedles, ongoing phagocytosis suppressed competing membrane extension at spatially opposite locations, and a reversal in migration direction was accompanied by initiation of membrane extension toward the second needle. Third-needle experiments further revealed a polarized spatial distribution of phagocytic responsiveness across the cell surface. Consistently, uniform stimulation with multiple opsonized microbeads demonstrated sequential, one-at-a-time engulfment even under near-simultaneous target attachment. These results support a model in which phagocytic membrane extension establishes transient, whole-cell polarity that spatially gates engulfment and coordinates whole-cell migration. The microneedle manipulation platform provides a powerful approach for dissecting the spatiotemporal regulation of phagocytosis and for understanding macrophages as adaptive living micromachines integrating mechanical inputs, transient polarity formation, and sequential target processing. Full article

Trogocytosis is the process of engulfment of a portion of a cell’s membrane by another cell. This process is characterized by the transfer of membrane fragments and proteins between adjacent cells without their complete fusion or phagocytosis, which distinguishes it from classical cellular uptake pathways. In the immune system, the initiating signal for trogocytosis is antigen presentation or the interaction of the Fc receptor with an antibody bound to the cell. During trogocytosis, T cells transfer not only the MHC molecule with the antigenic peptide, but also the costimulatory molecules CD80, CD86, OX-40 and others. As a result of trogocytosis, cells can transfer various surface molecules, acquire new immunological properties, and modulate each other’s activity. This review examines the basic mechanisms of trogocytosis, the involvement of T2-mediated immunity components in trogocytosis, and its possible role in allergies. Full article

Accumulation of misfolded proteins is implicated in neurodegenerative diseases. One of these is Huntington’s disease, which is caused by an expansion of trinucleotide (CAG) repeats in exon 1 of huntingtin gene (HTT). This expansion results in the production of mutant huntingtin exon1 protein (mHttEx1) containing polyglutamine tracks that is prone to cytotoxic aggregation. These mHttEx1 aggregates range from small soluble aggregates to large insoluble inclusion bodies. The mechanisms to clear mHttEx1 aggregates include ubiquitin-dependent proteasomal degradation and autophagy. For the proteasomal degradation of mHttEx1, ubiquitinated protein is first recognized by the Cdc48 complex for extraction and unfolding. For autophagy, mHttEx1 inclusion bodies are engulfed by an autophagosome, which fuses with the vacuole/lysosome and delivers cargo for vacuolar degradation. We name this autophagy IBophagy. In this study, we further show that the ubiquitination of mHttEx1 by the E3 ligase San1, its extraction and unfolding by the Cdc48 complex, and subsequent proteasomal degradation are all essential steps for mHttEx1 IBophagy in budding yeast, revealing a new layer of autophagy regulation and mHttEx1 cytotoxicity. Full article

Background/Objectives: Adults with congenital heart disease (ACHD) are at increased risk for mental health problems, particularly depression and anxiety. Emerging evidence suggests that psychological rather than purely medical factors may play a decisive role in explaining individual differences in emotional adjustment. However, comprehensive models integrating multiple cognitive and emotional domains remain scarce. This study aimed to identify the psychological variables most strongly associated with depressive and anxiety symptoms in ACHD when considered simultaneously to inform priorities for psychosocial interventions. Methods: A total of 1136 ACHD (aged 18–85 years; 59.7% female) from the National Register for Congenital Heart Defects, Berlin, completed an online survey assessing depression, anxiety, emotion regulation, illness perceptions, and illness identity. Correlational and multiple regression analyses were conducted, controlling for sociodemographic characteristics, CHD severity, and secondary diseases. Significance level for regression models was set at p < 0.025 due to Bonferroni correction. Results: Rumination showed the strongest positive correlations with both depression and anxiety, whereas acceptance was most negatively correlated. In multiple regression analyses, rumination (highest unique variance explanation with semi-partial R² = 0.068 resp. 0.072) and illness engulfment emerged as the most strongly associated predictors of depressive and anxiety symptoms. Illness-related concerns were not significant predictors. Conclusions: The findings highlight the key role of repetitive negative thinking and an engulfed illness identity in the development of emotional distress among ACHD. Psychotherapeutic interventions targeting rumination, fostering psychological distance from illness identity, and promoting a multifaceted self-concept may be particularly beneficial in this population. Full article

Long-term exposure of plastics to the environment causes them to disintegrate, resulting in the formation of micro/nanoplastics as well as the release of additives and chemicals into the soil. The micro/nanoplastics are able to readily migrate into the soil, destabilize the soil microbiota, and finally enter crop plants. Endocytosis, apoplastic transport, root adsorption, transpiration pull, stomatal entry, and crack-entry mode are well-known pathways by which microplastics enter into plants. Roots of vegetable crops were able to transfer 0.2 µm–1.0 µm of microplastics through root adsorption and by transpiration pull to the xylem and then further transported them to the plant tissues through apoplastic pathways. Beads of 1000 nm size were also engulfed by BY-2 protoplast cells through endocytosis. Micro and nanoplastics that enter crops affected the physiological and biochemical activities of the plants. Aquaporins were needed to aid the symplastic pathway which made the symplastic pathway difficult for MPs/NPs transport. Microplastics block seed capsules and roots of seedlings, thereby negatively affecting the uptake and efficient use of nutrients supplied. Photosynthesis of plants was affected due to the reduction in chlorophyll contents. Exposing soils to MPs/NPs drastically affected the pH, EC, and bulk density of the soil. This review focused on bridging the knowledge gap with understanding how microplastics prevent nutrient uptake and nutrient use efficiency in plants. This understanding is essential for assessing the broader ecological impacts of plastic contamination and for developing effective mitigation strategies. Further research is needed on microorganisms capable of degrading plastics, as well as on developing analytical methods for detecting plastics in soil and plant tissues. Also, further research on how to replace plastic mulching and still provide the same benefits as plastic mulch is needed. Full article

Vitamin B12 (B12) is a strong antioxidant and a cofactor for methionine synthase supporting DNA/RNA/protein methylation. We previously demonstrated that oral high-dose B12 supplement mitigates diabetic cardiomyopathy in Akita diabetic mice expressing twice the normal levels of Elmo1 (Engulfment and cell motility 1). To assess how B12 prevents early kidney damage, we treated Elmo1^HH mice and diabetic Elmo1^HH Ins2^Akita/+ mice with or without B12 in drinking water starting at 8 weeks of age. At 16 weeks, markedly reduced mesangial expansion was detected in the B12-treated diabetic kidneys (22% of glomeruli affected vs. 70% in the untreated diabetic kidneys). RNAseq analysis of the kidneys revealed that B12 suppressed expression of genes for adaptive immune response, while it upregulated those for solute carrier transporters and antioxidant genes. Strikingly, B12 treatment suppressed activators of circadian rhythm, Clock and Bmal1, and upregulated repressors like Cry1/2, Per1-3 and Dbp, suggesting a shift in their rhythmicity. B12 also upregulated linker histone H1 variants, and enhanced chromatin stability and cell cycle regulation. In BU.MPT proximal tubular cells in culture, B12 shifted forward the circadian expression phase of Bmal1 and Per1. Taken together, B12 supplement effectively mitigates early development of diabetic nephropathy in diabetic mice, potentially involving regulation of circadian rhythm. Full article

Sea urchin eggs are surrounded by a network of extracellular matrix, consisting of the jelly coat (JC) and vitelline layer (VL). While the voluminous JC evokes acrosomal reaction in the approaching sperm, the tight VL ensheathing the plasma membrane of the subjacent microvilli is known to be the subcellular site where ‘sperm receptors’ reside. In this study, we have examined the roles of JC and VL at fertilization in a combinatorial approach utilizing two different pretreatments of the eggs: (i) incubation with dithiothreitol (DTT) in alkaline seawater to remove JC and VL, (ii) masking the egg extracellular matrix with a carbohydrate-binding protein concanavalin A (Con A). Surprisingly, the results showed that the DTT-denuded eggs still engulfed sperm at fertilization, even more effectively than intact eggs, as multiple sperm entered. On the other hand, Con A appeared to interfere with sperm entry in a dose-dependent manner and to delay the onset of the Ca²⁺ wave in intact eggs after the cortical Ca²⁺ release, representing sperm–egg fusion. This prolonged time lag in triggering the Ca²⁺ wave at fertilization was associated with compromised dynamics of the subplasmalemmal actin filaments in Con A-pretreated eggs. By using Alexa Fluor 633 Con A and BPA-C8-Cy3, respectively, we also report unprecedented fluorescent labeling of the egg JC and the spontaneous ‘acrosomal protrusion’ on the head of Paracentrotus lividus sperm diluted in natural seawater. Combined with electron microscopy observations of intact and denuded eggs, our results suggest that the glycoconjugate on the egg surface contributes to the fertilization signal transduction, affecting the Ca²⁺ wave via actin cytoskeletal changes and sperm entry. Full article

Brain damage caused by hypoxia-ischemia is a serious complication for a newborn with possible life-long sequelae. To develop targeted neuroprotective strategies, it is essential to understand the mechanisms of injury, particularly the role of microglial phagocytosis, which may contribute to neuronal loss after hypoxia-ischemia. The aim was to evaluate neuronal cell death by phagocytosis in neonatal hypoxia-ischemia by investigating key signaling molecules and the effect of gene deletion of the phagocytic receptor Myeloid-epithelial-reproductive tyrosine kinase (MerTK) in a neonatal mouse model. MerTK, growth arrest–specific 6, and genes related to phagoptosis were regulated in the brain 6–72 h after hypoxic ischemia. Brain injury was reduced in MerTK knock-out vs. wild-type mice by 48% in gray matter (p = 0.002) and by 32% in white matter (p = 0.04). There was a near 40% reduction in NeuN immunoreactivity in microglia in MerTK knock-out mice vs. wild-type (p = 0.03) indicating attenuation of neuronal phagocytosis by microglia. In summary, the reduction in microglial neuronal engulfment and brain injury in MerTK-deficient mice strongly indicates that phagoptosis contributes to neuronal loss after neonatal hypoxia-ischemia. This insight suggests that targeting MerTK-mediated phagocytosis may represent a potential therapeutic approach in neonatal hypoxia-ischemic brain injury. Full article

Dysbiosis of the gut microbiota and dysregulated immune responses are key pathological features in both the onset and progression of Crohn’s disease. We propose a phagocyte–bacteria diffusion model with a time delay to explore their dynamic interactions and impact on the progression of Crohn’s disease. We first supplement the proof of the positivity, boundedness, existence, uniqueness, and global stability of the solutions for the ordinary differential system without time delay. Then we examine the stability of the positive equilibrium point and the occurrence of a Hopf bifurcation. By applying normal form and center manifold theory, we determine the direction of the bifurcation and the stability of the bifurcating periodic solution. Numerical simulations are used to verify the theoretical results. We find that the time delay significantly slows the system’s approach to a steady state. With a fixed delay, increased intestinal permeability prolongs the stabilization time. Conversely, with fixed intestinal permeability, a larger delay renders the system more prone to oscillations. Furthermore, a higher maximum engulfment rate by phagocytes reduces bacterial biomass but prolongs stabilization, whereas an increased phagocyte death rate shortens it. Additionally, an elevated bacterial growth rate increases both the bacterial biomass and the stabilization time. These results enhance our understanding of the dynamic equilibrium in immune systems. Full article

Background/Objectives: This study aimed to describe how adolescents with attention-deficit/hyperactivity disorder (ADHD) perceive their diagnosis identity and examine its correlation with executive functions (EFs), self-management abilities, and quality of life (QoL). Methods: A total of 66 adolescents with ADHD, aged 12 to 18 years (M = 15.21, SD = 1.84), completed self-report questionnaires, including the Illness Identity Questionnaire, Behavior Rating Inventory of Executive Function, Self-Control and Self-Management Scale, and Pediatric QoL Inventory. We used ANOVA with Bonferroni post hoc tests to assess differences in diagnosis identity domains and Pearson correlations to examine correlations between diagnosis identity, EFs, self-management, and QoL. Results: Adolescents reported significantly higher ADHD Acceptance feelings compared to Rejection, Engulfment, and Enrichment, F (2.38, 149.89) = 32.41, p < 0.001. Total diagnosis identity score was strongly associated with self-management (r = 0.61, p < 0.001). While no significant correlations were found with overall EF or QoL, significant associations did emerge with their sub-scores. Regression analyses indicated that self-monitoring, social QoL, and self-evaluation together explained 45% of the variance in diagnosis identity. The Engulfment dimension of identity was a significant negative predictor of executive functioning (R² = 0.15), self-management (R² = 0.35), and QoL (R² = 0.17). Conclusions: Promoting a positive diagnosis identity may improve functional and emotional outcomes in adolescents with ADHD. In turn, better functional and emotional outcomes may help them embrace a diagnosis identity that is more positive. Full article

The present article focuses on the assessment of the potential advantages and disadvantages of the utilisation of modern building inventory technologies in crisis situations, using a case study of Ukraine, currently engulfed in armed conflict. The following methods are described in detail: laser scanning, 360-degree camera images, and photo series. The authors conducted an in-depth SWOT/TOWS analysis, adapted to the specifics of the post-conflict environment, with a view to the future reconstruction of damaged buildings. The originality of the study lies in the use of a modified, quantitative version of the conventional SWOT analysis, supplemented with a weighting and rating system, which allowed for a more accurate assessment of the effectiveness of various technologies, including laser scanning. While the study focuses on the Ukrainian context, the authors emphasise that the developed methodology is universal and can be successfully applied to other critical areas, such as regions affected by earthquakes, floods, fires, or technological disasters. A modified SWOT/TOWS analysis can serve as a valuable tool in crisis management and infrastructure reconstruction during emergencies, providing the data necessary for making rational and effective decisions regarding the use of modern technologies in construction. The analysis revealed that, of the analysed inventory strategies, only laser scanning technology fits the so-called “maxi-maxi” strategy, a scenario in which both internal resources and external capabilities are maximised. The remaining two strategies were designated as “maxi-mini,” signifying that their implementation is associated with elevated levels of risk despite their inherent advantages. It is imperative to acknowledge the existence of substantial external threats that persist. Nevertheless, this does not constitute a complete rejection of the concept. This study examines armed conflict as a research context for a selection of buildings in Ukraine. The analysis was constrained to the three most prevalent methods: The use of TLS, SfM, and 360-degree cameras is also a key component of the methodology. Full article

Deep-sea mussels of the genus Bathymodiolus exhibit adaptability to nutrient-poor deep-sea environments by establishing nutritional intracellular symbiosis with chemosynthetic bacteria harbored within the gill epithelial cells. However, this poses a conflict for the innate immune system of the host, which must balance the tolerance of beneficial symbiotic bacteria with the need to eliminate exogenous microbes. This review synthesizes existing knowledge and recent findings on Bathymodiolus japonicus to outline the cellular and molecular mechanisms governing this symbiotic relationship. In the host immune system, hemocytes are responsible for systemic defense, whereas gill cells are involved in local symbiotic acceptance. Central to the establishment of symbiosis is the host’s phagocytic system, which non-selectively engulfs bacteria but selectively retains symbionts. We highlight a series of cellular events in gill cells involving the engulfment, selection, retention and/or digestion of symbionts, and the regulatory mechanism of phagocytosis through mechanistic target of rapamycin complex 1, which connects bacterial nutrient supply with host immune and metabolic responses. This integrated model of symbiosis regulation, which links immunity, metabolism, and symbiosis, provides a fundamental framework for understanding how hosts establish and maintain a stable coexistence with microbes, offering a new perspective on symbiotic strategies in diverse organisms. Full article

Ischemia–reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) and a major driver of progression to chronic kidney disease (CKD). Oxidative stress is recognized as a central mediator of this transition. Engulfment and Cell Motility 1 (ELMO1) regulates cytoskeletal remodeling and reactive oxygen species generation through Rac1 activation, but its contribution to CKD progression remains poorly defined. To investigate this, we established a unilateral renal IRI model in wild-type (WT) and Elmo1-overexpressing (Elmo1^H/H) mice and evaluated kidney function one and four months post-IRI. Compared with WT, Elmo1^H/H mice developed more severe kidney dysfunction, including an elevated plasma cystatin C and urinary albumin-to-creatinine ratio, reduced estimated glomerular filtration rate (eGFR), and pronounced fibrosis and glomerular injury observed by light and electron microscopy. Molecular analysis confirmed the dysregulation of redox-related pathways by RT-qPCR, with RNA sequencing showing enrichment of oxidative stress signatures. A subset of mice received chronic vitamin B12 (B12) supplementation following IRI to evaluate its therapeutic potential. Vitamin B12 supplementation improved kidney function, reduced fibrosis, preserved glomerular structure, and normalized the expression of antioxidant genes in both groups. These findings identify Elmo1 as a driver of redox-mediated kidney injury and support vitamin B12 as a promising antioxidant therapy for AKI-to-CKD progression. Full article