Search Results (65)

Odontogenesis, the development of teeth, is a complex, multistage process that unfolds from early embryogenesis through tooth eruption and maturation. It serves as a classical model of organogenesis due to the intricate reciprocal interactions between cranial neural crest-derived mesenchyme and oral epithelium. This narrative review synthesizes current scientific knowledge on human tooth development, tracing the journey from the embryological origins in the first branchial arch to the formation of a fully functional tooth and its supporting structures. Key morphogenetic stages—bud, cap, bell, apposition, and root formation—are described in detail, highlighting the cellular events and histological features characterizing each stage. We discuss the molecular and cellular regulatory networks that orchestrate odontogenesis, including the conserved signaling pathways (Wnt, BMP, FGF, SHH, EDA) and transcription factors (e.g., PAX9, MSX1/2, PITX2) that drive tissue patterning and cell differentiation. The coordinated development of supporting periodontal tissues (cementum, periodontal ligament, alveolar bone, gingiva) is also examined as an integral part of tooth organogenesis. Finally, developmental anomalies (such as variations in tooth number, size, and form) and the fate of residual embryonic epithelial cells are reviewed to underscore the clinical significance of developmental processes. Understanding the normal course of odontogenesis provides crucial insight into congenital dental disorders and lays a foundation for advances in regenerative dental medicine. Full article

Tooth agenesis is among the most prevalent congenital anomalies affecting human dentition, characterized by the developmental absence of one or more teeth. This condition may be present in either syndromic or non-syndromic forms, with significant implications for oral function, aesthetics, and craniofacial development. This narrative review aims to provide a comprehensive overview of tooth agenesis, defining its classification, genetic underpinnings, epidemiological aspects, phenotypic features, and therapeutic approaches. Recent advances in genetic research have identified numerous causative genes, notably EDA, MSX1, WNT10A, and PAX9, each associated with specific patterns of missing teeth and involved in isolated and/or syndromic forms. Additionally, genes such as TSPEAR, LRP6, PITX2, and GREM2 contribute to varying degrees of severity and tooth distribution, often blurring the lines between syndromic and isolated cases. The genotype-phenotype correlations underscore the complexity of the underlying molecular pathways involved in odontogenesis. From a therapeutic perspective, the management of tooth agenesis requires a multidisciplinary approach, often involving orthodontic, prosthetic, and surgical interventions tailored to the severity of tooth loss and patient age. Early diagnosis represents a crucial role in treatment planning, facilitating timely intervention during growth and enhancing long-term outcomes. In conclusion, tooth agenesis remains a complex clinical condition with a strong genetic basis. A patient-centered and interdisciplinary strategy is essential to address both functional and psychosocial needs. Full article

Acrylamide is a class 2A carcinogen with neurotoxicity and genotoxicity. In addition to industrial production, it is ubiquitous in high-temperature heated high-carbohydrate foods. Numerous studies have confirmed the toxicity of ACR on reproduction. Implantation and decidualization are crucial processes during the establishment of pregnancy in rodents and humans. However, its effect on uterine implantation and decidualization remains poorly understood. The objective of this study is to elucidate the mechanism by which ACR affects implantation and decidualization in mice. ACR is exposed in the daily drinking water of female mice, and the dose is calculated according to the body weight of the mice. After 3 months of administration at concentrations of 0, 20, and 30 mg ACR/kg/d, female mice are mated with male mice to induce pregnancy. Compared to the control group, ACR treatment significantly reduces the number of embryo implantations and litter size. ACR treatment leads to abnormal expression of endometrial receptivity-related molecules in the luminal epithelium on day 4 of pregnancy, including a decrease in p-STAT3 level and an increase in MUC1 and MSX1 levels. The level of decidualization-related molecules is obviously downregulated by ACR. Furthermore, ACR treatment results in abnormality of oxidative stress- and ferroptosis-related protein levels at the implantation site on day 5. In conclusion, acrylamide can impair mouse implantation and decidualization by disrupting oxidative stress and ferroptosis. Full article

Type VII osteogenesis imperfecta (OI), caused by recessive CRTAP mutations, is predominantly lethal in the first year of life. Due to its early lethality, little is known about bone dysplasia mechanism. RNA-seq analysis of differentiated osteoblasts of siblings with a non-lethal homozygous CRTAP-null variant showed an enrichment of gene ontology terms involved in DNA replication and cell cycle compared to control. BrdU incorporation confirmed a ≈2-fold increase in proliferation in non-lethal proband osteoblasts in comparison to control cells. In addition, the expression of cyclin dependent kinase inhibitor 2A (CDKN2A), encoding a protein involved in cell cycle inhibition, was significantly reduced (>50%) in CRTAP-null osteoblasts, while cyclin B1 (CCNB1), encoding a promoter of the cell cycle, was enhanced. Ossification and bone and cartilage development gene ontology pathways were enriched among upregulated genes throughout osteoblast differentiation, as was protein secretion. Ingenuity pathway analysis indicated an upregulation of BMP2 signaling, supported by increase in both BMP2 and MSX2, an early BMP2-responsive gene, by qPCR. Throughout differentiation, CRTAP-null osteoblasts showed a decrease in transcripts related to cell adhesion and extracellular matrix organization pathways. We propose that increased proliferation and osteogenesis of type VII OI osteoblasts may be stimulated through upregulation of BMP2 signaling, altering bone homeostasis, and leading to weaker bones. Full article

Background: Tooth agenesis is the most frequently occurring genetic developmental anomaly in clinical dentistry. The MSX1 gene, essential for tooth development, has been associated with non-syndromic tooth agenesis. This study aims to identify novel MSX1 variants associated with this condition and to understand their impact on tooth development. Methods: This study involved the genetic analysis of two children presenting with non-syndromic tooth agenesis. Conservation analysis and 3D structural modeling were conducted to assess the pathogenicity of these variants. Additionally, a review of 108 patients with known MSX1 variants was performed to identify patterns of tooth agenesis. Results: We discovered two novel MSX1 variants, c.823 T>G and c.890 A>G, located in the second exon of the MSX1 gene. The identified MSX1 variants, c.823 T>G and c.890 A>G, were predicted to be pathogenic. Conservation analysis showed that the impacted amino acids are highly conserved across species, and 3D structural analysis indicated potential disruptions to protein function. Among the 108 patients reviewed, a consistent pattern of tooth agenesis was observed, with the most frequently missing teeth being the maxillary second premolars, the mandibular second premolars, and the maxillary first premolars. Conclusions: This research broadens the known range of MSX1 gene variants and deepens our comprehension of the genetic foundations of non-syndromic tooth agenesis. The findings provide valuable insights for genetic counseling and future research into tooth development, emphasizing the importance of MSX1 in dental anomalies. Full article

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks’ gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it. Full article

Deciduous tooth agenesis is a severe craniofacial developmental defect because it affects masticatory function from infancy and may result in delayed growth and development. Here, we aimed to identify the crucial pathogenic genes and clinical features of patients with deciduous tooth agenesis. We recruited 84 patients with severe deciduous tooth agenesis. Whole-exome and Sanger sequencing were used to identify the causative variants. Phenotype–genotype correlation analysis was conducted. We identified 54 different variants in 8 genes in 84 patients, including EDA (73, 86.9%), PAX9 (2, 2.4%), LRP6 (2, 2.4%), MSX1 (2, 2.4%), BMP4 (1, 1.2%), WNT10A (1, 1.2%), PITX2 (1, 1.2%), and EDARADD (1, 1.2%). Variants in ectodysplasin A (EDA) accounted for 86.9% of patients with deciduous tooth agenesis. Patients with the EDA variants had an average of 15.4 missing deciduous teeth. Mandibular deciduous central incisors had the highest missing rate (100%), followed by maxillary deciduous lateral incisors (98.8%) and mandibular deciduous lateral incisors (97.7%). Our results indicated that EDA gene variants are major pathogenic factors for deciduous tooth agenesis, and EDA is specifically required for deciduous tooth development. The results provide guidance for clinical diagnosis and genetic counseling of deciduous tooth agenesis. Full article

The analysis of the spatial distribution of drinking water temperature (DWT) in the drinking water distribution system (DWDS) can allow for the detection of hotspots and the identification of suitable mitigation interventions to enhance the climate resilience. For this purpose, a water temperature model is implemented in EPANET-MSX and coupled with the hydraulic model of the DWDS in the town of Almere (the Netherlands). This model is then used to assess the effectiveness of a range of interventions against the unwanted water warming under a climate scenario of an extreme air temperature increase in a Dutch summer. Finally, a solution scenario is suggested to comply with the Dutch legislative limit of 25 °C on DWT at the tap. Full article

Temperature is a crucial factor that can influence chemical and microbiological activities within building water systems. Due to factors like widespread water conservation programs or shutdowns resulting from events like the COVID-19 pandemic, water stagnation in these systems can escalate, impacting water temperature. By integrating EPANET-MSX with field data, this study seeks to simulate and analyze spatial and temporal fluctuations in water temperature and microbial growth resulting from temperature variations. The simulated temperature data and Legionella concentrations at three points are compared with field data during a period of three weeks. Overall, the modeled showerhead temperatures show good alignment with the monitored data, although underestimations occur in specific locations and time periods. The comparison between actual Legionella measurements and simulated concentrations, considering only temperature effects, demonstrates better alignment with field data for daily flushing showers. However, as stagnation increases, discrepancies between the modeled data and actual measurements suggest that other factors, such as available nutrients, may limit growth. Full article

Predicting Legionella concentrations reaching users through building water systems requires a comprehensive water quality modeling approach. We integrate various frameworks and data to test the effect of nutrient availability, temperature, chlorine, and biofilm interactions in modeling Legionella. We show that neglecting biofilm detachment underestimates concentrations up to 5.5 logs, while including it increases estimates by 4.2 logs. This study identifies critical factors and uncertainty sources for characterizing the Legionella fate and transport phenomena within buildings. Full article

Drinking water disinfection by water utilities aims to ensure the safety and high quality of the provided water; however, it can pose a threat to human health due to the formation of disinfection byproducts (DBPs). The prediction and modeling of DBPs are challenging tasks due to the complex reactions within water distribution networks (WDN). To address this challenge, we introduce a virtual testbed based on a realistic WDN in Cyprus that utilizes the EPANET and EPANET-MSX engines to model multi-species reactions for the execution of simulation experiments under various conditions regarding the formation and fate of two families of DBPs within WDNs. Full article

Pro-B- and pre-B-cells are consecutive entities in early B-cell development, representing cells of origin for B-cell precursor acute lymphoid leukemia (BCP-ALL). Normal B-cell differentiation is critically regulated by specific transcription factors (TFs). Accordingly, TF-encoding genes are frequently deregulated or mutated in BCP-ALL. Recently, we described TF-codes which delineate physiological activities of selected groups of TF-encoding genes in hematopoiesis including B-cell development. Here, we exploited these codes to uncover regulatory connections between particular TFs in pro-B- and pre-B-cells via an analysis of developmental TFs encoded by NKL and TALE homeobox genes and by ETS and T-box genes. Comprehensive expression analyses in BCP-ALL cell lines helped identify validated models to study their mutual regulation in vitro. Knockdown and overexpression experiments and subsequent RNA quantification of TF-encoding genes in selected model cell lines revealed activating, inhibitory or absent connections between nine TFs operating in early B-cell development, including HLX, MSX1, IRX1, MEIS1, ETS2, ERG, SPIB, EOMES, and TBX21. In addition, genomic profiling revealed BCP-ALL subtype-specific copy number alterations of ERG at 21q22, while a deletion of the TGFbeta-receptor gene TGFBR2 at 3p24 resulted in an upregulation of EOMES. Finally, we combined the data to uncover gene regulatory networks which control normal differentiation of early B-cells, collectively endorsing more detailed evaluation of BCP-ALL subtypes. Full article

As on-orbit space cameras evolve toward larger apertures, wider fields of view, and deeper cryogenic environments, achieving absolute radiometric calibration using an all-optical path blackbody reference source in orbit becomes increasingly challenging. Consequently, stars have emerged as a novel in-orbit standard source. However, due to differences in camera bands, directly obtaining the stellar radiance flux corresponding to specific camera bands is not feasible. In order to address this challenge, we propose a method for estimating radiance flux based on the MSX star catalog, which integrates a dual-band thermometry method with an improved grey wolf optimization (I-GWO) algorithm. In an experiment, we analyzed 351 stars with temperatures ranging from 4000 to 7000 K. The results indicate that our method achieved a temperature estimation accuracy of less than 10% for 83.5% of the stars, with an average estimation error of 5.82%. Compared with previous methods based on star catalogs, our approach significantly enhanced the estimation accuracy by 75.4%, improved algorithm stability by 91.3%, and reduced the computation time to only 3% of that required by other methods. Moreover, the on-orbit star calibration error using our stellar radiance flux estimation method remained within 5%. This study effectively leveraged the extensive data available in star catalogs, providing substantial support for the development of an infrared star calibration network, which holds significant value for the in-orbit calibration of large-aperture cameras. Future research will explore the potential applicability of this method across different spectral bands. Full article

In this study, Fe₃O₄/Ag magnetite-silver (MSx) nanocomposites were investigated as catalysts for advanced oxidation processes by coupling the plasmonic effect of silver nanoparticles and the ferromagnetism of iron oxide species. A surfactant-free co-precipitation synthesis method yielded pure Fe₃O₄ magnetite and four types of MSx nanocomposites. Their characterisation included structural, compositional, morphological and optical analyses, revealing Fe₃O₄ magnetite and Ag silver phases with particle sizes ranging from 15 to 40 nm, increasing with the silver content. The heterostructures with silver reduced magnetite particle aggregation, as confirmed by dynamic light scattering. The UV–Vis spectra showed that the Fe:Ag ratio strongly influenced the absorbance, with a strong absorption band around 400 nm due to the silver phase. The oxidation kinetics of organic pollutants, monitored by in situ luminescence measurements using rhodamine B as a model system, demonstrated the higher performance of the developed catalysts with increasing Ag content. The specific surface area measurements highlighted the importance of active sites in the synergistic catalytic activity of Fe₃O₄/Ag nanocomposites in the photo-Fenton reaction. Finally, the straightforward fabrication of diverse Fe₃O₄/Ag heterostructures combining magnetism and plasmonic effects opens up promising possibilities for heterogeneous catalysis and environmental remediation. Full article

Cherubism is nowadays classified as an autoimmune disease and was first described in 1933. Although suspected at that time to be the result of defective tooth development, it was primarily classified as a bone disease caused by a mutation in the SH3BP2 gene. Despite a knock-in mouse model, phenotypic signs in the jaw area were not reproducible in this model. The features of classical cherubism can be attributed to a disturbed formation of the dental placode of the second molar. Since 2019, it has become clear that inhibition of the WNT pathway leads to the accumulation of SH3BP2 via tankyrase inhibition. As the dental placode is triggered via WNT (in epithelia) and MSX1 (in mesenchyme), aplasia of the second and third molars occurs due to a block in the WNT pathway. The mesenchymal part, which occurs prior to the body plan regulation of the WNT/MSX1 pathway, remains unaffected and provides the substrate for the giant cell granuloma. Considering macrophage polarization and the role of the extracellular matrix in general, cherubism is situated in the field of tension between autoimmune diseases and cancer. In this sense, we see the cause of cherubism in a WNT-related dysregulation, which can be proven postnatally in the neural crest-related tooth development of the replacement tooth ridge, both genotypically and phenotypically. Full article