Search Results (10,951)

Anderson–Fabry disease is a hereditary, progressive, multisystemic lysosomal storage disorder caused by a functional deficiency of the enzyme α-galactosidase A (α-GalA). This defect is due to mutations in the GLA gene, located in the long arm of the X chromosome (Xq21-22). Functional deficiency of the α-GalA enzyme leads to reduced degradation and accumulation of its substrates, predominantly globotriaosylceramide (Gb3), which accumulate in the lysosomes of numerous cell types, giving rise to the symptomatology. Clinical diagnosis can still be difficult today due to the peculiarities of the disease, which presents with clinical manifestations that overlap with those of other pathologies and a wide possibility of differential diagnoses, which lead to missed diagnoses, misdiagnosis, or a diagnostic delay. Patients with clinical suspicion of Fabry disease undergo a diagnostic workup that includes an evaluation of α-GALA enzyme activity, genetic analysis of the GLA gene, and the measurement of blood Lyso-Gb3, a soluble derivative of Gb3. In this paper, we describe four novel mutations identified in the GLA gene which are associated with absent or reduced α-GalA activity, pathological accumulation of the specific substrate, and characteristic clinical manifestations of Fabry disease. We identified two mutations (c.583insGAATA and p.Y207X) that result in the formation of a premature translation stop codon, resulting in a truncated protein and thus a completely non-functional enzyme. The other two identified gene alterations (p.G261C and c.786G>T, which determine p.W262C) are missense mutations that cause reduced α-GALA activity, the accumulation of blood Lyso-Gb3, and symptoms consistent with Fabry disease, and therefore may be associated with this disorder. The identification of these new mutations in patients with symptoms attributable to Fabry disease increases the molecular knowledge of the GLA gene and provides important support to the clinician, for a more accurate and timely diagnosis of the pathology. Full article

This research develops and applies a tool that allows the breakdown of time objectives to the same level of detail traditionally applied to cost, while also providing a favorable production scheme to ensure the project quality. This tool introduces an innovative approach to planning and execution monitoring through cascading dashboards, representing production packages and activities across designated project zones. This approach reinterprets the Last Planner System for jobs on-site in conjunction with the Location-Based Management System. The primary dashboard facilitates the management of complex work structures—typically involving hundreds of rows in Gantt chart representations or numerous lines in Line of Balance diagrams—while enabling the easy identification of activity cycles and gaps between activities in each zone. The tool offers a four-dimensional planning visualization—what, where, when, and who—enhancing the understanding of activity sequences and workflows across project zones, while also contributing to product quality improvement. Furthermore, it has been demonstrated through its application that the tool provides reliable, real-time information that supports decision-making, optimizes resource allocation, and improves overall project competitiveness. Full article

Anthropogenic activity leads to changes in sediment dynamics, creating imbalances in sediment distributions across the landscape. These imbalances can be variable within a littoral system, with adjacent areas experiencing sediment starvation and excess sediment. Historically, sediments were viewed as an inconvenient biproduct destined for disposal; however, beneficial use of dredge material (BUDM) is a practice that has grown as a preferred methodology for utilizing sediment as a resource to help alleviate the sediment imbalances within a system. BUDM enables organizations to adopt a more innovative and sustainable sediment management approach that also provides ecological, economic, and social co-benefits. Although location data are available on BUDM sites, especially in the US, there is limited understanding on how these sites evolve within the larger landscape, which is necessary for quantifying the co-benefits. To move towards BUDM more broadly, new tools need to be developed to allow researchers and managers to understand the effects and benefits of this practice. The National Exposed Sediment Search and Inventory (NESSI) was built to show the capability of using machine learning techniques to identify dredged sediments. A combination of satellite imagery data obtained and processed using Google Earth Engine and machine learning algorithms were applied at known dredged material placement sites to develop a time series of dredged material placement events and subsequent site recovery. These disturbance-to-recovery time series are then used in a landscape analysis application to better understand site evolution within the context of the surrounding areas. Full article

Background: Falls are a frequent and serious problem for older adults, especially for those living with Parkinson’s. The relationship between falls and physical activity is complex, and people often restrict activity following a fall. Exercise is an important aspect of reducing further risk of a fall and a key component of the management of Parkinson’s. The aim of this study was to understand the types of activity they are engaged in, the environments in which they take place, and the experience of people with and without Parkinson’s who have fallen. Method: Seventeen people with Parkinson’s and thirteen older adults who had experienced at least one fall in the previous year were recruited to this mixed methods study. Activity levels were captured over one week using accelerometers and body-worn cameras, allowing the type and location of activity to be recorded and analysed. This information informed an interview. Results: Findings showed that although both groups often achieved up to 10,000 steps per day, this was in very short bouts of activity. Sedentary activity, such as watching television, dominated the findings. Participants were aware of the benefits of being active but described many barriers to achieving the level of activity they would like to. Full article

This paper introduces key ideas and issues in the changing debates on heritage practices and sustainability. It draws attention to the capacities of heritage to activate and unfold new meanings and increase the resilience of territories and landscapes—namely depopulated ones—through slow curating processes. We will argue that slow curating processes cultivate ‘slower’ ways of knowing, act as seedbeds of emergence and as catalysts to transformation that recuperate the pieces of a fragmented territory while also helping to re-locate its existence—its past, its present and its future—in balance with and within a constellation of living networks. Through heritage criticality, we will investigate territory interpretation and intervention examples that adopt disruptive, cross-, inter-, and trans-disciplinary approaches, including artistic, architectural, urban, performative, and curatorial practice, as effects and methods of slow curating taken as a public activity. We will pay special attention to its production contexts (reasons, subjects…), to what and how resonance dispositions and axes are produced within these non-linear public acts, and how the co-presence of past and the future is extended so heritage public acts may engender new forms—of knowledge, being…—and become a resource for current times. Full article

The Andean paramos are unique and biodiverse environments. Located between the upper limit of forest and perpetual snow, they provide ecosystem services, especially freshwater supply; however, anthropogenic activities and climate change have altered their distribution and composition. This paper analyses the influence of altitude and climatic factors on the floristic composition of the páramos. A quasi-experimental study was used in three altitudinal gradients, collecting geolocalised data on species and bioclimatic variables. Principal component analysis, using the HJ-Biplot visualisation technique and k-means clustering algorithms, was applied to explore the relationships between factors. It was determined that the lower zone is nuanced by the presence of Solanaceae, which are important for human food. In the middle zone, there is a high diversity, with the Ericaceae and Caprifoliaceae families standing out, while in the upper zone, the Ericaceae and Gentianaceae families are accentuated. The PCA reveals that strata 2 and 3 share family taxa, while stratum 1 shows differences. Altitude and precipitation directly influence the distribution of species in each stratum; the Asteraceae family is dominant in the canton for its contribution to the principal components. Full article

Chemical pollution in freshwater ecosystems poses a significant environmental threat, often hindering access to safe drinking water for human populations. The Olifants River Basin in South Africa is particularly vulnerable due to escalating mining and agricultural activities, and domestic waste discharged into the rivers. In this study, the risk posed to humans by exposure to potentially toxic elements (PTEs) in water from two rivers, the Blyde and Steelpoort, was assessed. Water samples were collected from upstream, midstream, and downstream locations of these rivers, and the concentrations of eight PTEs (Arsenic, Cadmium, Chromium, Iron, Manganese, Nickel, Lead, and Zinc) were determined using inductively coupled plasma-optical emission spectrophotometry. Furthermore, two pathways of exposure, direct ingestion and dermal absorption, were used to evaluate their potential impacts on human health. The findings indicate that direct ingestion poses a greater risk to human health compared to dermal absorption. While PTEs may pose little non-carcinogenic risk for adults, higher risk was observed in children. This is an indication that children are at higher risk using water from the rivers, sometimes without any form of treatment. When carcinogenic risks (CRs) were computed for both adults and children for As, Cr, Ni, and Pb levels, the CR values were above the threshold limit, except for Pb, indicating a potential carcinogenic risk. This study underscores the need for regular monitoring of chemical pollution, and the implementation of effective mitigation strategies to safeguard both river ecosystems and human health, including proper treatment of water for domestic and agricultural purposes. Full article

It is well known that carbonyl compounds play an important role in air pollution and the formation of secondary pollutants, such as peroxyacetyl nitrates (PAN). Additionally, airborne carbonyls have been described as cytotoxic, mutagenic and carcinogenic. In this research, several carbonyl compounds, including aldehydes and ketones, as well as ozone, were monitored during a campaign conducted in July and September-October 2023 at Golf Ciudad Real, a golf course located in a non-industrial area of a south-central province in Spain. Extraction and analysis were carried out following procedures outlined by Radiello^®. Analyses were performed using HPLC-DAD and UV-Visible spectrophotometry. Ozone shows seasonal variation (temperature-dependent) concentrations displaying lower values in September/October. Among all the identified carbonyls, butanal was the most abundant, accounting for 40% of the total concentration. The C₁/C₂ and C₂/C₃ ratios were also calculated to provide information about the main emissions sources of the analyzed carbonyl compounds, indicating that mainly anthropogenic sources contribute to air quality in the area. The data were further supported by Quantitative Structure-Activity Relationship (QSAR) models using the ProtoPRED online server, which employs in silico methods based on European Chemicals Agency (ECHA) regulations to assess the (eco)toxicity of the measured carbonyl compounds. Full article

Background/Objectives: The highly polymorphic Major Histocompatibility Complex (MHC) genomic region, located on the short arm of chromosome 6, is implicated genetically in Parkinson’s disease (PD), a progressive neurodegenerative disorder with motor and non-motor symptoms. Previously, we reported significant associations between SINE-VNTR-Alu (SVA) expression quantitative trait loci (eQTLs) and Human Leucocyte Antigen (HLA) class I genotypes in PD. In this study, we aimed to evaluate SVA associations and their regulatory effects on transposable element (TE) transcription in the MHC class I region. Methods: Transcriptome data from the peripheral blood cells of 1530 individuals in the Parkinson’s Progression Markers Initiative (PPMI) cohort were reanalyzed for TE and gene expression using publicly available bioinformatics tools, including Salmon and Matrix-eQTL. Results: Four structurally polymorphic SVAs regulated the transcription of 18 distinct clusters of 235 TE loci, comprising LINEs (33%), SINEs (19%), LTRs (35%), and ancient transposon DNA elements (12%) located near HLA genes. The transcribed TEs were predominantly short, with an average length of 445 nucleotides. The regulatory effects of these SVAs varied significantly in terms of TE types, numbers, and transcriptional activation or repression. The SVA-regulated TE RNAs in blood cells appear to function as enhancer-like elements, differentially influencing the expression of HLA class I genes, non-HLA genes, and noncoding RNAs. Conclusions: These findings highlight the roles of SVAs and their associated TEs in the complex regulatory networks governing coding and noncoding gene expression in the MHC class I region, with potential implications for immune function and disease susceptibility. Full article

In this paper, a new anti-scour device combined with a perforated baffle and ring-wing plate is proposed to enhance the traditional method for better protection of bridge piers from local scour. Based on computational fluid dynamics (CFD), the orthogonal experiments investigated the general laws of the influence of the main factors, such as the ratio of baffle perforated, the position of baffle, and the height of ring-wing plate on the anti-scour effect. Under the protection of the combined device, the maximum scour depth reduction rate in front of the pier is between 65.18% and 81.01%, while that at the side of the pier is between 52.63% and 68.42%. Especially when the perforated ratio is 20%, the baffle is 2d (d is diameter of the pier) away from the pier, and the ring-wing plate is located at 1/3 of water depth, the anti-scour effect is the best. Also, the flow field around the pier under the protection of the combined device is further investigated. The results show that the structure blocks the down-flow actively and diverts and dissipates the flow energy to decrease flow below the critical velocity of sediment. Thus, the device combined with perforated baffle and ring-wing plate has a prominent anti-scour effect and provides a basis for further studies and engineering application. Full article

WiFi-based human sensing has emerged as a transformative technology for advancing sustainable living environments and promoting well-being by enabling non-intrusive and device-free monitoring of human behaviors. This offers significant potential in applications such as smart homes and sustainable urban spaces and healthcare systems that enhance well-being and patient monitoring. However, current research predominantly addresses single-user scenarios, limiting its applicability in multi-user environments. In this work, we introduce “MultiSenseX”, a cutting-edge system leveraging a multi-label, multi-view Transformer-based architecture to achieve simultaneous localization and activity recognition in multi-occupant settings. By employing advanced preprocessing techniques and utilizing the Transformer’s self-attention mechanism, MultiSenseX effectively learns complex patterns of human activity and location from Channel State Information (CSI) data. This approach transcends traditional sequential methods, enabling accurate and real-time analysis in dynamic, multi-user contexts. Our empirical evaluation demonstrates MultiSenseX’s superior performance in both localization and activity recognition tasks, achieving remarkable accuracy and scalability. By enhancing multi-user sensing technologies, MultiSenseX supports the development of intelligent, efficient, and sustainable communities, contributing to SDG 11 (Sustainable Cities and Communities) and SDG 3 (Good Health and Well-being) through safer, smarter, and more inclusive urban living solutions. Full article

The objective of this study was to determine how application of dolomitic limestone and stocking methods (continuous stocking or deferred stocking) affect the soil compaction, sheep grazing location, height, and nutritional value of pastures when the pasture growth rate is at its maximum. A 4 ha field at Mitra farm—University of Évora—was divided into four plots: P1 and P2—without application of dolomitic limestone, continuous stocking (CS), and deferred stocking (DS), respectively—and P3 and P4—with application of dolomitic limestone, DS (2.3 AUE), and CS (1 AUE), respectively. In DS, animals were placed and removed from the plots depending on the height of the pasture (entry ≥ 10 cm; removal ≤ 5 cm). Throughout the pasture’s vegetative cycle, several measurements of pasture height and cut were carried out. From the beginning of March to the beginning of June, animal behavior was observed (animals’ activity grazing and location) by trained observers through binoculars on six dates. The results show the following: (i) the application of dolomitic limestone combined with CS provided higher values of pasture height; (ii) there were no significant differences in pasture quality between treatments; (iii) DS led to 50% more sheep grazing days that CS; (iv) there were no significant differences in soil compaction between CS and DS; and (v) the stocking methods and the application of dolomitic limestone did not seem to change the grazing pattern between treatments. This study constitutes a basis to support more informed decisions by agricultural managers and may also contribute to maintaining balance in the Montado ecosystem, as well as increasing the efficiency of livestock production systems based on rainfed pastures. Full article

Autoimmune diseases are complex conditions characterized by immune-mediated tissue damage and chronic inflammation. Protease-activated receptor 2 (Par2) has been implicated in these diseases, exhibiting dual roles that complicate its therapeutic potential. This review examines the perplexing functions of Par2, which promotes inflammation through immune cell activation while facilitating tissue healing in damaged organs. By analyzing findings across diverse autoimmune conditions, including rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease, we highlight how the context and location of Par2 activation determine its effects. Recent studies from our laboratory have resolved some of these contradictions by distinguishing Par2’s immune-mediated inflammatory roles from its tissue-reparative functions. These insights pave the way for context-specific therapeutic strategies, such as selective Par2 modulators, that can mitigate inflammation while enhancing tissue repair. However, achieving such precision in modulation remains a significant challenge, necessitating further research into Par2’s signaling pathways. This review underscores Par2’s complexity and its transformative potential in autoimmune disease management, offering a nuanced perspective on its duality and therapeutic implications. Full article

The human body contains ~10¹⁴ cells—each of which is separated by a lipid bilayer, along with its organeller. Unsaturated fatty acids are located on the external layer and, as a result, are particularly exposed to harmful factors, including xenobiotics and ionising radiation. During this activity, lipid peroxidation products are generated, e.g., 4-hydroxy-2-nonenal (HNA), 4-oxo-2(E)-nonenal (ONE), and malondialdehyde (MDA). The mentioned aldehydes can react with cytosolic 2′-deoxynucleosides via Michael addition. In this paper, the following adducts have been taken into theoretical consideration: ε-dCyt, H-ε-dAde, ε-dCyt, H-ε-dAde, H-ε-dGua, R/S-OH-PdGua, N2,3-ε-dGua, M1-dGua, N1-ε-dGua, and HNE-dGua. The presence of the above molecules can alter a cell’s antioxidant pool. With this in mind, the adiabatic ionisation potential (AIP) and vertical ionisation potential (VIP), as well as the spin and charge distributions, are discussed. For this purpose, DFT studies were performed at the M06-2x/6-31++G** level of theory in the aqueous phase (both non-equilibrated (NE) and equilibrated (EQ) solvent–solute interaction modes), together with a Hirshfeld charge and spin distribution analysis. The obtained results indicate that the AIPs of all the investigated molecules fell within a range of 5.72 and 5.98 eV, which is consistent with the reference value of 7,8-dihydro-8-oxo-2′-deoxyguanosine (^OXOdGua), 5.78 eV. N2,3-ε-dGua and M1-dGua were the only exceptions, whose VIP and AIP were noted as higher. The electronic properties analysis of 2′-deoxynucleoside adducts with lipid peroxidation products reveals their potential influence on the cells’ antioxidant pool, whereby they can affect the communication process between proteins, lipids, and nucleotides. Full article

Central Asia, located at the heart of Eurasia, is renowned for its varied climate and vertical vegetative distribution, which support diverse biomes and position it as a global biodiversity hotspot. Despite this ecological richness, Central Asia’s fungal diversity, particularly wood-inhabiting macrofungi, remains largely unexplored. This study investigates the diversity, ecological roles, and potential distribution of poroid Hymenochaetoid fungi in the region. By conducting field surveys, collecting basidiomes, and reviewing the literature and herbarium records from five Central Asian countries, we compiled a comprehensive checklist of these fungi. In total, 43 Hymenochaetoid species belonging to 18 genera were identified, with Inonotus, Phellinus, and Phylloporia being the most species-rich. Notably, Inonotus hispidus and Phellinus igniarius were found to be the most widespread species. These macrofungi play essential ecological roles as saprotrophs and pathogens of various identified host plant families, aiding in lignin degradation and exhibiting diverse enzymatic activities. For the first time, we modelled the potential distribution patterns of Hymenochaetoid fungi in Central Asia, revealing that their distribution is strongly influenced by host plant availability and temperature-related factors. The three most critical variables were host plant density, annual temperature range (Bio7), and mean temperature of the warmest quarter (Bio10). The distribution of suitable habitats is uneven, with highly suitable areas (4.52%) concentrated in the mountainous border regions between Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan. These results underscore the significance of specific environmental conditions for the growth and survival of Hymenochaetoid fungi in this region. Our findings highlight the urgent need for continued mycological and host plant research and expanded conservation initiatives to document and preserve macrofungal and botanical biodiversity in this under-explored area. In light of climate change, the collected mycological and botanical data provide a valuable reference for promoting forest health management globally. Full article