Search Results (2,341)

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

The barbel chub (Squaliobarbus curriculus) exhibits remarkable resistance to grass carp reovirus (GCRV), a devastating pathogen in aquaculture. To reveal the molecular basis of this resistance, we investigated complement factor D (DF)—a rate-limiting serine protease governing alternative complement pathway activation. Molecular cloning revealed that the barbel chub DF (ScDF) gene encodes a 1251-bp cDNA sequence translating into a 250-amino acid protein. Crucially, bioinformatic characterization identified a unique N-glycosylation site at Asn¹³⁹ in ScDF, representing a structural divergence absent in grass carp (Ctenopharyngodon idella) DF (CiDF). While retaining a conserved Tryp_SPc domain harboring the catalytic triad (His⁶¹, Asp¹⁰⁹, and Ser²⁰⁴) and substrate-binding residues (Asp¹⁹⁸, Ser²¹⁹, and Gly²²¹), sequence and phylogenetic analyses confirmed ScDF’s evolutionary conservation, displaying 94.4% amino acid identity with CiDF and clustering within the Cyprinidae. Expression profiling revealed constitutive ScDF dominance in the liver, and secondary prominence was observed in the heart. Upon GCRV challenge in S. curriculus kidney (SCK) cells, ScDF transcription surged to a 438-fold increase versus uninfected controls at 6 h post-infection (hpi; p < 0.001)—significantly preceding the 168-hpi response peak documented for CiDF in grass carp. Functional validation showed that ScDF overexpression suppressed key viral capsid genes (VP2, VP5, and VP7) and upregulated the interferon regulator IRF9. Moreover, recombinant ScDF protein incubation induced interferon pathway genes and complement C3 expression. Collectively, ScDF’s rapid early induction (peaking at 6 hpi) and multi-pathway coordination may contribute to barbel chub’s GCRV resistance. These findings may provide molecular insights into the barbel chub’s high GCRV resistance compared to grass carp and novel perspectives for anti-GCRV breeding strategies in fish. Full article

Social media platforms like Instagram significantly shape destination images and influence tourist behavior. Understanding how different cities are represented and perceived on these platforms is crucial for effective tourism marketing. This study provides a comparative analysis of Instagram content and engagement patterns in Seoul and Tokyo, two major Asian metropolises, to derive actionable marketing insights. We collected and analyzed 59,944 public Instagram posts geotagged or location-tagged within Seoul (n = 29,985) and Tokyo (n = 29,959). We employed a mixed-methods approach involving content categorization using a fine-tuned convolutional neural network (CNN) model, engagement metric analysis (likes, comments), Valence Aware Dictionary and sEntiment Reasoner (VADER) sentiment analysis and thematic classification of comments, geospatial analysis (Kernel Density Estimation [KDE], Moran’s I), and predictive modeling (Gradient Boosting with SHapley Additive exPlanations [SHAP] value analysis). A validation analysis using balanced samples (n = 2000 each) was conducted to address Tokyo’s lower geotagged data proportion. While both cities showed ‘Person’ as the dominant content category, notable differences emerged. Tokyo exhibited higher like-based engagement across categories, particularly for ‘Animal’ and ‘Food’ content, while Seoul generated slightly more comments, often expressing stronger sentiment. Qualitative comment analysis revealed Seoul comments focused more on emotional reactions, whereas Tokyo comments were often shorter, appreciative remarks. Geospatial analysis identified distinct hotspots. The validation analysis confirmed these spatial patterns despite Tokyo’s data limitations. Predictive modeling highlighted hashtag counts as the key engagement driver in Seoul and the presence of people in Tokyo. Seoul and Tokyo project distinct visual narratives and elicit different engagement patterns on Instagram. These findings offer practical implications for destination marketers, suggesting tailored content strategies and location-based campaigns targeting identified hotspots and specific content themes. This study underscores the value of integrating quantitative and qualitative analyses of social media data for nuanced destination marketing insights. Full article

Leather biodegradation is a complex microbial process with increasing relevance for sustainable waste management. In this study, we investigated bacterial communities responsible for the degradation of leather treated with different tanning agents (chrome, Zeolite, Biole^®) using high-throughput 16S rRNA gene sequencing and metatranscriptomic analysis. Proteobacteria, Bacteroidetes, and Patescibacteria emerged as the dominant phyla, while genera such as Acinetobacter, Pseudomonas, and Sphingopyxis were identified as key contributors to enzymatic activity and potential metal resistance. A total of 1302 enzymes were expressed across all the conditions, including 46 proteases, with endopeptidase La, endopeptidase Clp, and methionyl aminopeptidase being the most abundant. Collagen samples exhibited the highest functional diversity and total enzyme expression, whereas chrome-treated samples showed elevated protease activity, indicating selective pressure from heavy metals. Differential enzyme expression patterns were linked to both the microbial identity and tanning chemistry, revealing genus- and treatment-specific enzymatic signatures. These findings deepen our understanding of how tanning agents modulate the microbial structure and function and identify proteases with potential applications in the bioremediation and eco-innovation of leather waste processing. Full article

Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of COVID-19, it is not known whether these drugs directly affect SMCs. Accordingly, the present study investigated the ability of three approved COVID-19 antiviral drugs to influence SMC function. Treatment of SMCs with remdesivir (RDV), but not molnupiravir or nirmatrelvir, inhibited cell proliferation, DNA synthesis, and migration without affecting cell viability. RDV also stimulated an increase in heme oxygenase-1 (HO-1) expression that was not observed with molnupiravir or nirmatrelvir. The induction of HO-1 by RDV was abolished by mutating the antioxidant responsive element of the promoter, overexpressing dominant-negative NF-E2-related factor-2 (Nrf2), or treating cells with an antioxidant. Finally, silencing HO-1 partly rescued the proliferative and migratory response of RDV-treated SMCs, and this was reversed by carbon monoxide and bilirubin. In conclusion, the induction of HO-1 via the oxidant-sensitive Nrf2 signaling pathway contributes to the antiproliferative and antimigratory actions of RDV by generating carbon monoxide and bilirubin. These pleiotropic actions of RDV may prevent occlusive vascular disease in COVID-19. Full article

Rootstocks are widely used in viticulture as an agronomic measure to cope with biotic and abiotic stresses. In winegrapes, the aroma is one of the major factors defining the quality of grape berries and wines. In the present work, the grape aroma and wine aroma of Cabernet Sauvignon (CS) grafted on three rootstocks were investigated to inform the selection of rootstocks to utilize. 1103P, 5A, and SO₄ altered the composition of aromatic volatiles in CS grapes and wines. Among them, 5A and SO₄ had less effect on green leaf volatiles in the berries and wines, while 1103P increased green leaf volatile concentrations, up-regulating VvADH2 expression in both vintages. VvLOXA, VvLOXC, VvHPL1, VvADH1, VvADH2, and VvAAT were co-regulated by vintage and rootstock. Orthogonal partial least squares regression analysis (OPLS-DA) showed that the differential compounds in CS/1103P and CS berries were dominated by green leaf volatiles. Furthermore, the concentrations of 1-hexanol in the CS/1103P wines were significantly higher than in the other treatments in the two vintages. 1103P altered the expression of genes in the LOX-HPL pathway and increased the concentration of grape green leaf volatiles such as 1-hexanol and 1-hexanal, while vine vigor also affected green leaf volatile concentrations, the combination of which altered the aromatic composition of the wine and gave it more green flavors. Full article

The life-cycle carbon emissions (LCCE) assessment of dairy barns is crucial for identifying low-carbon transition pathways and promoting the sustainable development of the dairy industry. We applied a life cycle assessment approach integrated with building information modeling and EnergyPlus to establish a full life cycle inventory of the material quantities and energy consumption for dairy barns. The LCCE was quantified from the production to end-of-life stages using the carbon equivalent of dairy barns (CEDB) as the functional unit, expressed in kg CO₂e head⁻¹ year⁻¹. A carbon emission assessment model was developed based on the “building–process–energy” framework. The LCCE of the open barn and the lower profile cross-ventilated (LPCV) barn were 152 kg CO₂e head⁻¹ year⁻¹ and 229 kg CO₂e head⁻¹ year⁻¹, respectively. Operational carbon emissions (OCE) accounted for the largest share of LCCE, contributing 57% and 74%, respectively. For embodied carbon emissions (ECE), the production of building materials dominated, representing 91% and 87% of the ECE, respectively. Regarding carbon mitigation strategies, the use of extruded polystyrene boards reduced carbon emissions by 45.67% compared with stone wool boards and by 36% compared with polyurethane boards. Employing a manure pit emptying system reduced carbon emissions by 76% and 74% compared to manure scraping systems. Additionally, the adoption of clean electricity resulted in a 33% reduction in OCE, leading to an overall LCCE reduction of 22% for the open barn and 26% for the LPCV barn. This study introduces the CEDB to evaluate low-carbon design strategies for dairy barns, integrating building layout, ventilation systems, and energy sources in a unified assessment approach, providing valuable insights for the low-carbon transition of agricultural buildings. Full article

Tree diseases affecting Camellia japonica have emerged as a significant threat to the health and longevity of this ornamental tree, particularly in countries where this tree species is widely distributed and cultivated. Among these, Pestalotiopsis spp. have been frequently reported and are considered one of the most impactful fungal pathogens, causing leaf blight or leaf spot, in multiple countries. Understanding the etiology and distribution of these diseases is essential for effective management and conservation of C. japonica populations. The traditional methods based on pathogen isolation and pure culture cultivation for diagnosis of tree diseases are labor intensive and time-consuming. In addition, the frequent coexistence of the major pathogens with other endophytes within a single C. japonica tree, coupled with inconsistent symptom expression and the occurrence of pathogens in asymptomatic hosts, further complicates disease diagnosis. These challenges highlight the urgent need to develop more rapid, accurate, and efficient diagnostic or monitoring tools to improve disease monitoring and management on trees, including C. japonica. To address these challenges, we applied a metagenomic approach to screen fungal communities within C. japonica trees. This method enabled comprehensive detection and characterization of fungal taxa present in symptomatic and asymptomatic tissues. By analyzing the correlation between fungal dominance and symptom expression, we identified key pathogenic taxa associated with disease manifestation. To validate the metagenomic approach, we employed a combined strategy integrating metagenomic screening and traditional fungal isolation to monitor foliar diseases in C. japonica. The correlation between dominant taxa and symptom expression was confirmed. Simultaneously, traditional isolation enabled the identification of a novel species, Pestalotiopsis, as the causal agent of leaf spot disease on C. japonica. In addition to confirming previously known pathogens, our study led to the discovery and preliminary characterization of a novel fungal taxon with pathogenic potential. Our findings provide critical insights into the fungal community of C. japonica and lay the groundwork for developing improved, rapid diagnostic tools for effective disease monitoring and management of tree diseases. Full article

Background: Mycosis fungoides (MF), the most prevalent cutaneous T cell lymphoma, features clonal CD4⁺ T cell proliferation within a Th2-dominant microenvironment. Interleukin-4 (IL-4) promotes disease progression while Brentuximab Vedotin (BV), an anti-CD30 antibody–drug conjugate, shows efficacy but faces resistance challenges. Methods: We conducted a narrative literature review (2010–2024) synthesizing evidence on IL-4 signaling and BV’s efficacy in MF to develop a theoretical framework for combination therapy. Results: IL-4 may modulate CD30 expression and compromise BV’s effectiveness through immunosuppressive microenvironment remodeling. Theoretical mechanisms suggest that IL-4 pathway inhibition could reprogram the microenvironment toward Th1 dominance and restore BV sensitivity. However, no direct experimental evidence validates this combination, and safety concerns including potential disease acceleration require careful evaluation. Conclusions: The proposed IL-4/BV combination represents a biologically compelling but unproven hypothesis requiring systematic preclinical validation and biomarker-driven clinical trials. This framework could guide future research toward transforming treatment approaches for CD30-positive MF by targeting both malignant cells and their immunologically permissive microenvironment. Full article

Background/Objectives: Truncating mutations in PALB2, a critical component of the BRCA1-PALB2-BRCA2 homologous recombination repair complex, are associated with increased risk and aggressiveness of breast cancer. The consequences of PALB2 truncation on the expression, localization, and functional dynamics of the scaffold protein IQGAP1 were investigated in this study based on two cases of truncated PALB2 human breast invasive ductal carcinoma (IDC), specifically, c.1240C>T (p.Arg414*) and c.2257C>T (p.Arg753*). Methods: Using confocal microscopy, we examined co-expression patterns of IQGAP1 with PALB2, PCNA, CK7, and β-tubulin in tumor tissues from both control cancer and PALB2-mutated cases. Results: In PALB2-truncated tumors, IQGAP1 exhibited enhanced peripheral and plasma membrane localization with elevated co-localization levels compared to controls, suggesting altered cytoskeletal organization. PALB2 truncation increased nuclear and cytoplasmic N-terminal PALB2 immunoreactivity, indicating the presence of truncated isoforms disrupting the homologous recombination repair system. Co-expression analyses with PCNA revealed an inverse expression pattern between IQGAP1 and proliferation markers, suggesting S-phase cell cycle-dependent heterogeneity. Furthermore, the loss of IQGAP1 dominance over CK7 and β-tubulin in mutant tumors, along with persistent intercellular spacing, implied a loss of cell–cell cohesion and the acquisition of invasive traits. Conclusions: These data support a model where PALB2 truncation triggers a reorganization of IQGAP1 that disrupts its canonical structural functions and facilitates tumor progression via enhanced motility and impaired cell–cell interaction. IQGAP1 thus serves as both a functional effector and potential biomarker in PALB2-mutated IDC, opening novel paths for diagnosis and targeted therapeutic intervention. Full article

The germin-like protein (GLP) family plays vital roles for plant growth, stress adaptation, and defense; however, its evolutionary dynamics and functional diversity in halophytes remain poorly characterized. Here, we present the genome-wide analysis of the GLP family in the halophytic forage alkaligrass (Puccinellia tenuiflora), which identified 54 PutGLPs with a significant expansion compared to other plant species. Phylogenetic analysis revealed monocot-specific clustering, with 41.5% of PutGLPs densely localized to chromosome 7, suggesting tandem duplication as a key driver of family expansion. Collinearity analysis confirmed evolutionary conservation with monocot GLPs. Integrated gene structure and motif analysis revealed conserved cupin domains (BoxB and BoxC). Promoter cis-acting elements analysis revealed stress-responsive architectures dominated by ABRE, STRE, and G-box motifs. Tissue-/organ-specific expression profiling identified root- and flower-enriched PutGLPs, implying specialized roles in stress adaptation. Dynamic expression patterns under salt-dominated stresses revealed distinct regulatory pathways governing ionic and alkaline stress responses. Functional characterization of PutGLP37 demonstrated its cell wall localization, dual superoxide dismutase (SOD) and oxalate oxidase (OXO) enzymatic activities, and salt stress tolerance in Escherichia coli, yeast (Saccharomyces cerevisiae INVSc1), and transgenic Arabidopsis. This study provides critical insights into the evolutionary innovation and stress adaptive roles of GLPs in halophytes. Full article

In 2021, the National Centre for Religious Studies in New Zealand published the new religious education curriculum for Catholic schools in Aotearoa New Zealand. While in many ways, very like other religious education curricula, from its naming in Māori before English, Tō Tātou Whakapono Our Faith shines a light on the role of culture and language in the transmission and expression of faith. This paper is written in two parts. Part 1 of this paper provides an examination of the key curriculum documents and website to find that Tō Tātou Whakapono Our Faith is unique in three ways. First, it enjoys a level of security in the dominant presence of Catholics in the Catholic school, guaranteed by the Integration Act of 1975. Second, it offers flexibility in approach, necessary for a curriculum with national status, and finally, it demonstrates an extraordinary commitment to the inclusion of Māori culture and language. Part 2 of this paper takes up the inclusion of Māori culture and language to offer a response to the call that Māori need to be allowed to develop a theology from within their own culture and language. It proposes that the introduction of a new hermeneutical lens in the study of scripture, one that would replicate the practice of the Bible authors who drew freely on their own experience and language to speak of God, could provide a simple but effective way of developing such a theology. It is in Part 2 that the significance of the subtitle of this paper will become apparent. Full article

The framing of water infrastructure in the news influences how the public perceives future infrastructure development and associated social-environmental risks. This study examines English-language newspaper coverage of the Ken-Betwa river link, the first component of India’s National River Linking Program (INRLP) to receive approval. Data for this analysis comprised 316 newspaper articles, collected via a keyword search in LexisNexis API, from seven Indian English-language newspapers (Free Press Journal (India), Hindustan Times, Indian Express, The Economic Times, The Hindu, The Times of India (TOI), and Times of India (Electronic Edition)) published between 2004 and 2022. By applying LDA topic modeling, a type of generative probabilistic model, to this dataset, this study examines how evolving media narratives frame water infrastructure in India. Our results identify 23 distinct topics and three dominant frames: (1) a government policy frame, (2) INRLP comparative frame, and (3) environmental conservation frame. We find that these frames evolve, with early coverage emphasizing feasibility and government-led negotiations, and later articles highlighting environmental risks. Our analysis shows how media discourse reflects institutional logic and infrastructure milestones. This study demonstrates the value of computational methods for longitudinal media analysis, has the potential to reveal shifts in public discourse, and highlights power dynamics in environmental reporting. Full article

To elucidate the interactions among fatty acid metabolism, immune status, and gut microbiota, both cultured and wild Coilia nasus from the Yangtze River were examined in China. The results demonstrated that wild C. nasus exhibited markedly higher lipid and docosahexaenoic acid (DHA) contents, a greater ratio of total ω-3 PUFAs to total ω-6 PUFAs, and more active antioxidant enzymes compared to cultured C. nasus. However, the shear force, water-holding capacity, and total n-6 PUFA content were lower in wild C. nasus. Transcriptome analysis revealed distinct gene expression patterns: wild C. nasus upregulated immune-related genes, while cultured C. nasus downregulated genes related to fatty acid metabolism. Significant differences were observed in alpha and beta diversity between cultured and wild groups. LEfSe analysis identified Clostridium_T, Escherichia, and Glutamicibacter as biomarkers for cultured C. nasus, while eight genera, including Pseudomonas_E and Sphingomonas_L, were predominant in wild C. nasus. Modular analysis identified five modules linked to immune functions and fatty acid metabolism. Clostridium_T, Sphingomonas_L, and Pseudomonas_E were dominant in the first two modules, with Pseudomonas_E and Clostridium_T as key regulators of fatty acid metabolism and immune processes. These differences, likely due to gut microbiota variations, provide insights for C. nasus nutritional studies. Full article

The multi-domain muscle protein titin provides elasticity and mechanosensing functions to the sarcomere. Titin’s PEVK domain is intrinsically disordered due to the presence of a large number of prolines and highly charged residues. Although PEVK does not have canonical actin-binding motifs, it has been shown to bind F-actin. Here, we explored whether the PEVK domain may also affect actin assembly. We cloned the middle, 733-residue-long segment (called PEVKII) of the full-length PEVK domain, expressed in E. coli and purified by using His- and Avi-tags engineered to the N- and C-termini, respectively. Actin assembly was monitored by the pyrene assay in the presence of varying PEVKII concentrations. The structural features of PEVKII-associated F-actin were studied with atomic force microscopy. The added PEVKII enhanced the initial and log-phase rates of actin assembly and the peak F-actin quantity in a concentration-dependent way. However, the critical concentration of actin polymerization was unaltered. Thus, PEVK accelerates actin polymerization by facilitating its nucleation. This effect was highlighted in the AFM images of F-actin–PEVKII adsorbed to the supported lipid bilayer. The sample was dominated by radially symmetric complexes of short actin filaments. PEVK’s actin polymerization-modulating effect may, in principle, have a function in regulating sarcomeric actin length and turnover. Altogether, titin’s PEVK domain is not only a non-canonical actin-binding protein that regulates sarcomeric shortening, but one that may modulate actin polymerization as well. Full article