Search Results (4,144)

Background: The PITX1 gene encodes a transcription factor that plays a crucial role in the development of the lower limbs, pelvis, and structures derived from the first branchial arch. Pathogenic variants in PITX1 are associated with a limited spectrum of rare disorders, including congenital talipes equinovarus with or without long bone anomalies and/or mirror-image polydactyly, and Liebenberg syndrome. In 2020, a novel clinical phenotype, Mandibular–Pelvic–Patellar (MPP) syndrome, resulting PITX1 missense variants, was proposed. Case presentation: We report the fourth documented case of MPP syndrome worldwide, identified in a 17-year-old female patient presenting with congenital lower limb deformities, patellar aplasia, and micrognathia. Whole-genome sequencing revealed a heterozygous PITX1 missense variant NM_002653.5: c.412A>C, p.(Lys138Gln). The clinical phenotype included knee flexion contractures and severe equinovarus and planovalgus foot deformities requiring multiple staged reconstructive surgical procedures. Conclusions: This case supports recognition of MPP syndrome as a clinically and genetically distinct PITX1-related disorder. Our findings expand the phenotypic spectrum of MPP syndrome and suggest that severe congenital foot deformities represent a consistent and clinically relevant feature of this condition. Full article

Metallic seismic dampers are an effective tool for reducing structural damage during seismic events. While previous reviews have often focused on cataloging device types, this review presents a deep analysis of the underlying science governing their performance. Particular emphasis is placed on advanced computational methods, such as non-linear kinematic hardening (e.g., Chaboche) and micromechanical damage models (e.g., GTN), which are essential for accurately predicting low-cycle fatigue and fracture. Furthermore, advances in materials science are analyzed, ranging from low-yield-strength (LYS) steels to self-centering shape memory alloys (SMAs). Finally, the influence of manufacturing processes (including additive manufacturing) is explored, and critical future challenges in design, modeling, and long-term durability are identified. This analysis provides a foundational resource for researchers seeking to advance beyond simple phenomenological design toward physics-based prediction of damper performance. Full article

This study describes the clinical and genetic features of Meesmann epithelial corneal dystrophy (MECD) in two unrelated families and reports new genotype–phenotype associations. Ten patients from a Lebanese family (n = 4) (Family 1) and a Spanish family (n = 6) (Family 2) underwent ophthalmologic evaluation, in vivo confocal microscopy (IVCM), anterior segment optical coherence tomography (AS-OCT) with epithelial thickness mapping (ET-map), and targeted next-generation sequencing (NGS) using a custom-designed 133-gene panel associated with anterior segment dystrophies. In Family 1, a novel homozygous KRT12 c.1181T>C (p.Leu394Pro) variant was identified in the symptomatic proband and his clinically asymptomatic brother, while both parents, who were first cousins, were heterozygous for this nucleotide variant. The proband also carried the heterozygous KRT3 c.250C>T (p.Arg84Trp) variant, which has been previously reported but, to our knowledge, has not been described in co-occurrence until now. In addition, the proband showed a complex phenotype with signs of MECD and epithelial basal membrane alterations consistent with epithelial basement membrane dystrophy (EBMD). In Family 2, four affected members carried the KRT3 c.1492G>A (p.Glu498Lys) variant in heterozygosity, which has been previously described. The elderly members affected showed typical signs of MECD and EBMD. To our knowledge, these concomitant alterations have not been previously described with genetical confirmation. In conclusion, this study provides the first evidence that the co-occurrence of variants in two Meesmann corneal dystrophy-associated genes (KRT3 and KRT12) can jointly account for the disease phenotype. We also highlight the association of MECD with EBMD in both families. Characterization using IVCM and AS-OCT ET-Map provides a deeper understanding of the morphological changes and phenotypic variability in MECD, confirming the utility of this multimodal imaging approach for diagnosis and management. Full article

The pygmy hippopotamus (Choeropsis liberiensis, Morton, 1849) is classified as Endangered by the International Union for the Conservation of Nature (IUCN). Compared to other large, threatened mammals, this species remains relatively understudied and new findings indicate potential welfare concerns, emphasizing the need for further research on the species welfare in zoological institutions. One approach to improving welfare in captivity is through environmental enrichment. This study investigated the effects of olfactory enrichment on three individual pygmy hippopotamuses through behavioral analysis and heat-map visualization. Using continuous focal sampling, several behaviors were influenced by the stimuli, with results showing a general decrease in inactivity and an increase in environmental engagement and interaction, particularly through scenting behavior. To further enhance behavioral quantification, machine learning techniques were applied to video data, comparing manual and automated behavior classification using the pose estimation program SLEAP. Four behaviors Standing, Locomotion, Feeding/Foraging, and Lying Down were compared. A confusion matrix, time budgets, and Kendall’s Coefficient of Concordance (W) were used to assess agreement between methods. The results showed a strong and moderate agreement between manual and automated annotations, for the female and calf, respectively. This demonstrates the potential of automation to complement behavioral observations in future welfare monitoring. Full article

Current research on glial cells has primarily focused on central nervous system glial cells (CNS glia), with relatively fewer studies on EGCs. Given the critical role of EGCs in maintaining intestinal homeostasis and neural function, this study aimed to investigate their immunomodulatory effects under inflammatory conditions. Primary EGCs were isolated and an inflammatory model was established by treatment with lipopolysaccharide (LPS). Following LPS induction, cellular samples were collected for transcriptomic analysis to identify differentially expressed genes. The analysis revealed that 88 genes were significantly altered, with 60 upregulated and 28 downregulated. Through Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping, and protein–protein interaction (PPI) network analysis, several key regulatory genes were identified: chemokine-related genes (IL8L2, IL8L1, CCL4, CCL5, and CX3CL1); negative feedback regulation-related genes (TNFAIP3 and ZC3H12A); homeostasis-maintaining genes (C1QB and LY86); and arachidonic acid metabolism-related genes (PTGS2 and GGT2). Under LPS stimulation without impairing EGC viability, EGCs may recruit immune cells by regulating the aforementioned genes. Additionally, arachidonic acid and its metabolites likely play important regulatory roles in EGC-mediated immunomodulation. These findings provide new theoretical insights and potential targets for further elucidating the pathogenesis of intestinal inflammation and developing targeted therapies. Full article

The gravitational wave event GW190521 seems to be the only BH merger event possibly correlated with an electromagnetic counterpart, which appeared about 34 days after the GW event. This work aims to confirm that the electromagnetic bump towards the Active Galactic Nucleus (AGN) J1249+3449 can be explained within the framework of the gravitational microlensing phenomenon. In particular, considering the data of the Zwicky Transient Facility (ZTF), what emerges from a detailed analysis of the observed light curve using three fitting models (Point Source Point Lens, Finite Source Point Lens, Uniform Source Binary Lens) is that the optical bump can be explained as a microlensing event caused by a lens with mass $\sim$0.1 $M_{\odot }$, lying in the host galaxy of the AGN in question. Full article

Technological advancements have significantly improved cattle farming, particularly in sensor-based activity monitoring for health management, estrus detection, and overall herd supervision. However, such a sensor-based monitoring framework often illustrates several issues, such as high cost, animal discomfort, and susceptibility to false measurement. This study introduces a vision-based cattle activity monitoring approach deployed in a commercial Nestlé dairy farm, specifically one that is estrus-focused, where overhead cameras capture unconstrained herd behavior under variable lighting, occlusions, and crowding. A custom dataset of 2956 Images are collected and then annotated into four fine-grained behaviors—standing, lying, grazing, and estrus—enabling detailed analysis beyond coarse activity categories commonly used in prior livestock monitoring studies. Furthermore, computer vision-based deep learning algorithms are deployed on this dataset to classify the aforementioned classes. A comparative analysis of YOLOv8 and YOLOv9 is provided, which clearly illustrates that YOLOv8-L achieved a mAP of 91.11%, whereas YOLOv9-E achieved a mAP of 90.23%. Full article

This work investigates the differences between the monthly and 13-month smoothed sunspot numbers since 1749, using data from sunspot number (version 2). The distribution of the differences is centered near zero, with 74% of all values lying between −20 and +20, and only 1% exceeding ±70. Positive and negative differences are nearly balanced in total number, although the distribution of the monthly differences is moderately asymmetric (skewness = −0.55) and high kurtosis (>3), confirming leptokurtic behavior with sharper peak around zero and heavier tails than a Gaussian distribution. Spikes, defined in each tail using the 95th and 5th percentile, occurred in nearly all solar cycles studied, predominantly around solar cycle maxima and in cycles with higher solar activity. Moreover, the five most extreme cases with a difference of more than 100 occur in five solar cycles, ranging from below to above average. Additionally, we analyze the recent behavior of Solar Cycle 25. The significant increase in the monthly sunspot number in August 2024 (it reached 216, the highest since 2001) raised questions about the potential future intensity of Solar Cycle 25. As the sunspot number series evolved, this difference between the maximum monthly and 13-month smoothed series decreased to 55.1 (with data through October 2025), placing Solar Cycle 25 within the historical relationship between maximum monthly and 13-month smoothed sunspot number, and the largest monthly deviations. Our results show that spikes are a recurrent feature of solar activity and can provide useful diagnostics for shorter-term solar cycle variability. Full article

Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility is limited by poor kinase selectivity caused by high sequence conservation within Src-family ATP-binding sites. Here, we combine surface plasmon resonance (SPR) and X-ray crystallography to define saracatinib recognition by the Fyn kinase domain (KD). SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar affinity and markedly slower dissociation. We determined the crystal structure of the Fyn KD-saracatinib complex at 2.22 Å resolution. The kinase adopts an active-like conformation with the DFG motif and αC-helix in the ‘in’ state and a conserved β3 αC Lys-Glu salt bridge. Saracatinib occupies the adenine and ribose pockets, and engages the hinge through direct and water-mediated hydrogen bonding while complementing a hydrophobic back pocket by van der Waals contacts. Comparison with reported saracatinib-bound structures of other kinases suggests that the active-state geometry observed for Fyn creates a pocket not observed in inactive-like complexes, providing a structural handle for designing Fyn-selective inhibitors. Comparison with all saracatinib-bound kinase co-structures currently available in the PDB (ALK2 and PKMYT1) indicates a conserved monodentate hinge binding mode but kinase-dependent αC-helix conformations, providing a structural rationale for designing Fyn-selective analogues. Full article

This study presents a comprehensive geospatial framework for assessing coastal vulnerability and ecosystem service distribution along the Greek coastline, one of the longest and most diverse in Europe. The framework integrates two complementary components: a Coastal Erosion Vulnerability Index applied to all identified beach units, and Coastal Flood Risk Indexes focused on low-lying and urbanized coastal segments. Both indices draw on harmonized, open-access European datasets to represent environmental, geomorphological, and socio-economic dimensions of risk. The Coastal Erosion Vulnerability Index is developed through a multi-criteria approach that combines indicators of physical erodibility, such as historical shoreline retreat, projected erosion under climate change, offshore wave power, and the cover of seagrass meadows, with socio-economic exposure metrics, including land use composition, population density, and beach-based recreational values. Inclusive accessibility for wheelchair users is also integrated to highlight equity-relevant aspects of coastal services. The Coastal Flood Risk Indexes identify flood-prone areas by simulating inundation through a novel point-based, computationally efficient geospatial method, which propagates water inland from coastal entry points using Extreme Sea Level (ESL) projections for future scenarios, overcoming the limitations of static ‘bathtub’ approaches. Together, the indices offer a spatially explicit, scalable framework to inform coastal zone management, climate adaptation planning, and the prioritization of nature-based solutions. By integrating vulnerability mapping with ecosystem service valuation, the framework supports evidence-based decision-making while aligning with key European policy goals for resilience and sustainable coastal development. Full article

To improve the gel quality of low-salt shrimp surimi gel (SSG) from Pacific white shrimp (Litopenaeus vannamei), L-arginine (L-Arg), L-lysine (L-Lys), and L-proline (L-Pro) were used as partial substitutes for NaCl. The effect of the three amino acids on gel properties, protein conformation, microstructure, and in vitro digestion of low-salt SSG were systematically analyzed. Macro-/microstructural analyses revealed that L-Arg, L-Lys, and L-Pro promoted denser three-dimensional networks in low-salt SSG with smaller pore sizes. Compared with the low-salt control (LC) group, the addition of L-Arg, L-Lys, and L-Pro significantly increased the gel strength of low-salt SSG. Cooking loss was significantly decreased from 10.80% (LC group) to 1.89–4.31%. Protein solubility and turbidity results demonstrated that all amino acids markedly enhanced protein solubilization and inhibited protein aggregation. L-Arg and L-Lys mainly promoted hydrogen and disulfide bonds, but reduced hydrophobic interactions and ionic bonds. L-Arg impaired digestibility only in the gastric phase, whereas L-Lys suppressed digestibility across both gastric and intestinal phases. Through molecular docking technology, ASN-238 and LYS-187 of myosin (the dominant gel-forming protein) are the key shared binding residues with three amino acids. These findings suggest that amino acids provide a feasible approach to specifically modulate the gel characteristics of low-salt surimi products. Full article

Background/Objectives: The aim of our study was to evaluate the transverse stiffness of selected soft tissues in the knee joint region on the previously injured and uninjured sides of female handball players and non-athlete women, in the lying and standing positions, and to investigate the relationship between stiffness, age, sporting practice, and clinical assessments of the knees. Methods: A total of 25 young female handball players (the SPORT group) and 27 healthy non-athletic individuals (the CONTROL group) were examined. The MyotonPRO device was used to measure the stiffness of the patellar tendon (PT), rectus femoris (RF), and biceps femoris (BF) muscles on both sides and in both positions. The function of the knee joints was clinically assessed using the Knee Outcome Survey—Sports Activities Scale and the Lysholm Knee Scoring Scale. Results: ANOVA indicated a significant effect of group (p < 0.003) on the PT’s stiffness, and a significant effect of position (p < 0.0001) on the PT, RF, and BF muscle stiffness. The SPORT group demonstrated significantly higher PT transverse stiffness when lying down (p < 0.01), but not when sitting up (p > 0.05), compared to the CONTROL group. Significant negative correlations were found between PT stiffness and both clinical scales in the SPORT group (rho from −0.39 to −0.71, p < 0.05). Conclusions: In female handball players, only the patellar tendon transverse stiffness was higher than in the control group. While this higher stiffness could indicate an adaptive rebuilding process, it was negatively correlated with the clinical assessment of joint function, meaning poorer knee joint function. Full article

The first measurements of the magnetic dipole hyperfine structure constants A in singly ionized thulium revealed substantial discrepancies with the corresponding theoretical calculations. Subsequent measurements expanded the very limited available dataset and demonstrated that two of the previously reported experimental A values were incorrect, thereby motivating new theoretical calculations. In this work, we employ the configuration interaction method to calculate the A constants for several low-lying levels in Tm ii, with the random-phase-approximation corrections also taken into account. Our results show good agreement with the new experimental data and provide reliable predictions for additional states where measurements are not yet available. Full article

The metal-binding periplasmic protein CusF has been proposed as a bifunctional tag that enhances the solubility of recombinant proteins and enables purification using Cu affinity chromatography. However, evidence for its performance remains limited to a few model proteins. Here, we evaluated CusF as a solubility tag for two heterologous proteins: a putative poly(A)-polymerase from Enterococcus faecalis (Efa PAP) and the red fluorescent protein mCherry. The proteins were fused to CusF, expressed in E. coli BL21 (DE3) pLysS and Rosetta 2 (DE3) strains, and assessed for solubility and IMAC binding. Native Efa PAP was completely insoluble under all tested conditions, and fusion to CusF did not improve its solubility. Similarly, CusF–mCherry accumulated predominantly in the insoluble fraction, with only trace amounts detectable in soluble lysates. Soluble CusF–mCherry did not bind Cu²⁺-charged IMAC resin, while moderate binding to Ni²⁺-charged resin was attributable to the vector-encoded His tag rather than CusF. These results indicate that CusF does not universally enhance protein solubility and may not consistently bind Cu-based IMAC resin. Our findings expand empirical knowledge of solubility tag performance and emphasize the necessity of testing multiple tags to identify optimal strategies for recombinant protein production. Full article

Coastal settlements worldwide face increasing threats from erosion, and the Monrovia coastline in Liberia is no exception. This study investigates shoreline dynamics along a 20.5 km stretch of Monrovia’s coast, which is characterized by low-lying elevations, gentle slopes, and sandy beaches. Using Landsat satellite imagery (1986–2025), supported by Sentinel-2 MSI and qualitative validation drone data, we analyzed historical shoreline change with remote sensing and GIS techniques. Shorelines were extracted using a band-ratio thresholding method and quantified with the Digital Shoreline Analysis System (DSAS 5.0), applying end-point rate (EPR), linear regression rate (LRR), and net shoreline movement (NSM). Exploratory projections for 2036 and 2046 were generated using a Kalman Filter model integrated into DSAS. Results show maximum historical erosion rates of up to 3.8 m/yr and accretion rates of up to 5.9 m/yr, with shoreline retreat reaching 150 m and advance up to 194 m. Erosion hotspots are projected for Hotel Africa, Westpoint, New Kru Town, and the JFK–ELWA corridor, while areas near the St. Paul and Mesurado estuaries are expected to accrete. These findings confirm historical trends and suggest that Monrovia will continue to face significant shoreline change, with implications for natural habitats, infrastructure, land loss, and population displacement. Full article