Search Results (73)

Background: Mucopolysaccharidosis type IIIC (MPS IIIC) is a rare lysosomal storage disorder caused by pathogenic variants in the HGSNAT gene. Data from large patient cohorts remain scarce, particularly in Latin America. Methods: We retrospectively analyzed clinical, biochemical, and genetic data from patients diagnosed with MPS IIIC through the MPS Brazil Network. Diagnosis was based on reduced activity of acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), elevated urinary glycosaminoglycans (uGAGs), and/or molecular genetics tests. Results: A total of 101 patients were confirmed with MPS IIIC, representing one of the largest cohorts worldwide. Females accounted for 60% of cases. The mean age at symptom onset was 5.4 ± 3.9 years, while the mean age at diagnosis was 11.7 ± 6.9 years, reflecting a 6-year diagnostic delay. Most patients initially presented with developmental delay (82%) and facial dysmorphism (80%), whereas behavioral manifestations were less frequently identified (25%), suggesting a milder phenotype than previously reported. Genetic information was available for 28% of patients, showing recurrent alleles (c.372-2A>G, c.252dupT) and several novel mutations, which expand the mutational spectrum of the disease. Genotype–phenotype similarities with Portuguese, Italian, and Chinese cases suggest shared ancestry contributions. Regional differences included earlier diagnoses in the North of Brazil and high consanguinity rates in the Northeast region. Conclusions: This study describes the largest Brazilian cohort of MPS IIIC, documenting novel variants and regional heterogeneity. Findings highlight diagnostic delays, ancestry influences, and the urgent need for disease-modifying therapies. Full article

Domoic acid (DA), produced by Pseudo-nitzschia diatoms, is the one of the major toxin threats from harmful algal blooms (HABs) on the west coast of the United States. DA events vary in magnitude, timing, and duration, and elucidating drivers for individual events is a persistent challenge. Monterey Bay experiences near-annual DA events and hosts long-term HAB monitoring at the Santa Cruz Municipal Wharf (SCW). Here we characterize two toxin events, occurring in May 2023 and March 2024. The events were similar in magnitude and duration, but an exploration of physical, biological, and chemical dynamics revealed distinct environmental drivers. These differences resulted in a significant deviation in cellular DA (cDA) within the same species of Pseudo-nitzschia. In addition, opportunistic solid-phase adsorption toxin tracking (SPATT) was used for environmental metabolomics. The novel application of SPATT revealed 159 metabolites that were strongly correlated with DA in both events and produced a spectral match to a new marine natural product using Global Natural Products Social Molecular Networking (GNPS). This work takes a multivariable approach to understanding toxin drivers and lends proof of concept for the integration of environmental metabolomics in HAB monitoring. Full article

Background/Objectives: Sanfilippo Syndrome type B or Mucopolysaccharidosis type IIIB (MPS IIIB, OMIM 252920) is a lysosomal storage disease caused by deficiency of alpha-N-acetylglucosaminidase (NAGLU, E.C. 3.2.1.50) due to pathogenic variants in the NAGLU gene (17q21.2). The disease is characterized by progressive neurological manifestations, marked by cognitive decline, with relatively mild somatic involvement. We aim to present relevant information on a cluster of MPS IIIB identified in Ecuador, particularly regarding their clinical, biochemical, genetic, demographic, and ancestry characteristics. Methods: We present a characterization of a clinical, biochemical, genetic and demographic cluster of MPS IIIB patients in Ecuador, located in four main regions: Manabí, Guayas, Los Ríos, and Santo Domingo de los Tsáchilas. The patients included were diagnosed due to increased levels of urinary glycosaminoglycans (uGAG), plus deficient activity of NAGLU, and/or identification of biallelic pathogenic mutations in the NAGLU gene. Patients’ charts were reviewed for biochemical findings, medical history, clinical manifestations and assessments. Results: We present the results of clinical, biochemical, genetic and demographic characterization of a cluster in Ecuador with 24 patients identified with Sanfilippo syndrome type IIIB, resulting in an estimated incidence of 1.5/100,000. The mean age at diagnosis was 8.8 years, with symptom onset at 4.5 years on average. All patients exhibited elevated levels of uGAG and undetectable NAGLU activity, and all of them presented the c.1487T>C (p.Leu496Pro) variant in the NAGLU gene in homozygosis, indicating a possible founder effect, with the exception of one heterozygous one (p.Leu496Pro/p.Arg482Gln). A positive correlation between age of diagnosis and the concentration of one isoform of heparan sulfate (HS-OS) was found (p < 0.05). Clinical findings included neuropsychomotor developmental delay (75%), neurological regression (65%), hepatomegaly (55%), growth deficiency (50%), coarse facies (45%) and hernia (40%). Male patients presented earlier onset of symptoms. Maternal ancestry was successfully determined for 21 of the 24 patients. The majority were of Native American ancestry (71.4%), followed by European (19%), African (4.8%), and Asian (4.8%) lineages. Haplogroup A was the most prevalent (42.9%), followed by haplogroups D (19%), C, U, and H (each 9.5%), and R and L2 (each 4.8%). Conclusions: Ancestry can indicate a possible mechanism to explain the heterogeneous symptomatic presentation. These findings highlight the need for further research on genetic and environmental influences on disease severity in this population. Full article

Petroglyph motifs from 23 sites and 37 panels in northern Georgia and western North Carolina foothills and mountains are analyzed within their archaeological, ethnographic, and landscape contexts. The Track Rock Tradition comprises 10 chronologically sequenced marking categories: (1) Cupules/Meanders/Open Circles; (2) Soapstone Extraction cars; (3) Vulva Shapes; (4) Figures; (5) Feet/Hands/Tracks; (6) Nested Circles; (7) Cross-in-Circles; (8) Spirals; (9) Straight Lines; and (10) Thin Incised Lines. Dating spans approximately 3800 years. Early cupules and meanders predate 3000 years ago, truncated by Late Archaic soapstone extraction. Woodland period (3000–1050 years ago) motifs include vulva shapes, figures, feet, tracks, and hands. Early Mississippian concentric circles date to 1050–600 years ago, while Middle Mississippian cross-in-circles span 600–350 years ago. Late Mississippian spirals (350–200 years ago) and post-contact metal tool incisions represent the most recent phases. The Track Rock Tradition differs from western Trapp and eastern Hagood Mill traditions. Given the spatial overlap with Iroquoian-speaking Cherokee territory, motifs are interpreted through Cherokee beliefs, supplemented by related Muskogean Creek ethnography. In Cherokee cosmology, the matrilocal Thunderers hierarchy includes the Female Sun/Male Moon, Selu (Corn Mother)/Kanati (Lucky Hunter), Medicine Woman/Judaculla (Master of Game), and Little People families. Ritual practitioners served as intermediaries between physical and spirit realms through purification, fasting, body scratching, and rock pecking. Meanders represent trails, rivers, and lightning. Cupules and lines emphasize the turtle appearance of certain rocks. Vulva shapes relate to fertility, while tracks connect to life-giving abilities. Concentric circles denote townhouses; cross-in-circles and spirals represent central fires. The tradition shows continuity in core beliefs despite shifting emphases from hunting (Woodland) to corn cultivation (Mississippian), with petroglyphs serving as necessary waypoints for spiritual supplicants. Full article

The response time of Artificial Neural Network (ANN) inference is critical in embedded systems processing sensor data close to the source. This is particularly important in applications such as predictive maintenance, which rely on timely state change predictions. This study enables estimation of model response times based on the underlying platform, highlighting the importance of benchmarking generic ANN applications on edge devices. We analyze the impact of network parameters, activation functions, and single- versus multi-threading on response times. Additionally, potential hardware-related influences, such as clock rate variances, are discussed. The results underline the complexity of task partitioning and scheduling strategies, stressing the need for precise parameter coordination to optimise performance across platforms. This study shows that cutting-edge frameworks do not necessarily perform the required operations automatically for all configurations, which may negatively impact performance. This paper further investigates the influence of network structure on model calibration, quantified using the Expected Calibration Error (ECE), and the limits of potential optimisation opportunities. It also examines the effects of model conversion to Tensorflow Lite (TFLite), highlighting the necessity of considering both performance and calibration when deploying models on embedded systems. Full article

Electrospinning with sequential layer deposition has been reported for various applications such as tissue scaffolds, shape memory materials, and separations. However, the effect of layering on the mechanical properties is not fully understood. In this work, layered structures of thermoplastic polyurethane (TPU) and nylon were selected as a model system to investigate the effect of sequential layer deposition on mechanical properties. Evidence of the layered structure was indicated by scanning electron microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR) experiments. Layering TPU with nylon resulted in a 60-fold increase in the Young’s modulus. The Young’s modulus of the layered structure was reasonably predicted by the Voigt rule of mixtures. Furthermore, the Young’s modulus changes without any statistically significant change in elongation at break compared to a single layer of nylon. Thus, the elongation at break was dictated by the stiffer material, despite being present at a lower volume fraction. Overall, electrospinning with sequential layer deposition electrospinning is an effective approach for tuning the mechanical properties and surface chemistry of electrospun materials independently, which may be of interest for applications in tissue engineering and separations. Full article

Viticulture is facing challenges, like the impact of climate change and various pests and pathogens. Alongside powdery and downy mildew, black rot is one of the most prevalent fungal diseases in European wine-growing regions. The focus of grapevine breeding research has so far been mainly on resistance to mildew diseases, and marker-assisted selection (MAS) in breeding material is possible for the most important resistance loci. However, only a few loci have been described for black rot resistance and these cannot yet be used for MAS. Thus, the characterization of genetic resistance to black rot and the establishment of closely linked genetic markers is important for the breeding of cultivars with multifungal resistances. In this study, an improved SSR marker-based genetic map of the biparental mapping population V3125 (‘Schiava Grossa’ x ‘Riesling’) x ‘Börner‘ (Vitis riparia x Vitis cinerea) was used to perform QTL analysis for black rot resistance. A total of 195 F1 individuals were analyzed at 347 SSR marker positions distributed on all 19 chromosomes. QTL analysis detected two QTLs conferring resistance to black rot on linkage groups 14 (Rgb1) and 16 (Rgb2). Our results revealed for the first time that Rgb1 and Rgb2 are derived from the wild species V. riparia. The presence of both loci in F1 individuals showed a clear additive effect for black rot resistance, supporting the breeding strategy of pyramiding two or more resistance factors to achieve a stronger overall resistance. Full article

Staphylococcus aureus is a leading cause of severe infections in humans and animals, and the emergence of multidrug-resistant strains highlights the need to develop effective vaccines to prevent such diseases. Epitope-based vaccines use short antigen-derived peptides corresponding to immune epitopes, which are administered to trigger protective humoral and cellular immune responses. In this study, in silico MHC affinity measurement methods were used to predict possible binding regions, and five 20-mer synthetic TRAP peptides (TRAPP) were synthesized. Epitope-based vaccines, named PT and PTR, incorporating the identified CD4⁺ T and B cell epitopes, were constructed. Peptides TRAP_20–39 and TRAP_94–113 elicited significant peptide-stimulated T-cell proliferation responses in vivo. Additionally, high levels of IFN-γ and IL-17A, along with moderate levels of IL-4, were detected in ex vivo stimulated CD4⁺ T cells isolated from rTRAP- and TRAPP-immunized mice, suggesting that these peptides are classified as Th1 and Th17 epitopes. Immunization with PT or PTR induces robust humoral and cellular immune responses. Moreover, the epitope-based vaccine, PT, exhibited a stronger protective immune response than the intact TRAP in a murine systemic S. aureus infection model. Based on the results presented herein, an epitope-based vaccine is a promising and potentially more effective candidate. Full article

Hydrogen is expected to play an important role in decarbonizing different heavy industries and the transportation sector. Water electrolysis is, therefore, one of the most rapidly spreading energy technologies, with PEM electrolyzers taking a continuously increasing share in the technology mix. Most often, the aim is to form green hydrogen, utilizing electricity exclusively of renewable origin. The intermittency of such sources, however, poses several technological challenges and financial questions. Focusing on PEM electrolyzers, we discuss the effect of pressure, temperature, and reaction rate changes, induced by the intermittent operation, and general thoughts regarding system component erosion caused by the regular start–stop cycles are also considered. As a case study, we present a high-level techno-economic analysis of data from a pilot 1 MW PEM electrolysis system, coupled to a 20 MW PV farm, deployed in Hungary. We underscore the importance of the often overlooked local regulations and financial incentives, which strongly influence the most beneficial operation scenario. Full article

Understanding the behavior of carbon dioxide (CO₂) under varying thermodynamic conditions is essential for optimizing processes such as Carbon Capture and Storage (CCS) and supercritical fluid extraction. This study employs molecular dynamics (MD) simulations with the EPM2 and TraPPE-small force fields to examine CO₂ phase behavior, structural characteristics, and transport properties across a temperature range of 228–500 K and pressures from 1 to 150 atm. Our findings indicate a good agreement between simulated and experimental liquid–vapor coexistence curves, validating the capability of both force fields to model CO₂ accurately in a wide range of thermodynamical conditions. Radial distribution functions (RDFs) reveal distinct interaction patterns in liquid and supercritical phases, while mean squared displacement (MSD) analyses show diffusivity increasing from $5.2\times {10}^{-9}$ m²/s at 300 K to $1.8\times {10}^{-8}$ m²/s at 500 K. Additionally, response functions such as the heat capacity effectively capture phase transitions. These findings provide quantitative insights into CO₂ phase behavior and transport properties, enhancing the predictive reliability of simulations for CCS and related industrial technologies. This work bridges gaps in the CO₂ modeling literature and highlights the potential of MD simulations in advancing sustainable applications. Full article

Nitrogen (N) derived from the decomposition of litter from cover crops can contribute to the mineral nutrition of citrus trees. This study aimed to assess the prior contribution of N derived from the decomposition of forage radish (Raphanus sativus) and black oats (Avena strigosa) to Satsuma mandarin tree N demand. Forage radish and black oats were grown and enriched with ¹⁵N stable isotope. Two studies were conducted on (1) non-bearing, potted satsuma mandarin seedlings for 120 days in the greenhouse (Experiment 1) and (2) bearing field-growing Satsuma mandarin trees for 270 days (Experiment 2). Tree growth and total N and ¹⁵N concentrations were determined in annual and perennial organs of citrus and soil. The highest value of N derived from the decomposition of cover crop root residues was observed in the leaves and roots of non-bearing trees, while the highest amount of N derived from shoot residue decomposition was observed in the leaves of bearing trees. The results showed little contribution of the decomposition of residues of forage radish and black oats on the total N budget of annual and perennial organs of both bearing and non-bearing Satsuma mandarin trees, probably because the climatic conditions promoted a fast N mineralization and possible losses through volatilization and leaching. Full article

The TRAPP (TRAnsport Protein Particle) protein complex is a multi-subunit complex involved in vesicular transport between intracellular compartments. The TRAPP complex plays an important role in endoplasmic reticulum-to-Golgi and Golgi-to-plasma membrane transport, as well as autophagy. TRAPP complexes comprise a core complex, TRAPPI, and the association of peripheral protein subunits to make two complexes, known as TRAPPII and TRAPPIII, which act as Guanine Nucleotide Exchange Factors (GEFs) of Rab11 and Rab1, respectively. Rab1 and Rab11 are GTPases that mediate cargo selection, packaging, and delivery during pre- and post-Golgi transport in the secretory pathway. Rab1 is also required for the first step of macroautophagy, a cellular recycling pathway. Pathogenic variants in genes encoding protein subunits of the TRAPP complex are associated with a range of rare but severe neurological, skeletal, and muscular disorders, collectively called TRAPPopathies. Disease-causing variants have been identified in multiple subunits of the TRAPP complex; however, little is known about the underlying disease mechanisms. In this review, we will provide an overview of the current knowledge surrounding disease-associated variants of the TRAPP complex subunits, propose new insights into the underlying disease pathology, and suggest future research directions into the underlying disease mechanisms. Full article

Arabidopsis LIM proteins are named after the initials of three proteins Lin-11, Isl-1, and MEC-3, which belong to a class of transcription factors that play an important role in the developmental regulation of eukaryotes and are also involved in a variety of life processes, including gene transcription, the construction of the cytoskeleton, signal transduction, and metabolic regulation. Plant LIM proteins have been shown to regulate actin bundling in different cells, but their role in immunity remains elusive. Mitogen-activated protein kinases (MAPKs) are a family of conserved serine/threonine protein kinases that link upstream receptors to their downstream targets. Pathogens produce pathogen-associated molecular patterns (PAMPs) that trigger the activation of MAPK cascades in plants. Recently, we conducted a large-scale phosphoproteomic analysis of PAMP-induced Arabidopsis plants to identify putative MAPK targets. One of the identified phospho-proteins was WLIM2A, an Arabidopsis LIM protein. In this study, we investigated the role of WLIM2A in plant immunity. We employed a reverse-genetics approach and generated wlim2a knockout lines using CRISPR-Cas9 technology. We also generated complementation and phosphosite-mutated WLIM2A expression lines in the wlim2a background. The wlim2a lines were compromised in their response to Pseudomonas syringae Pst DC3000 but showed enhanced resistance to the necrotrophic fungus Botrytis cinereae. Transcriptome analyses of wlim2a mutants revealed the deregulation of immune hormone biosynthesis and signaling of salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) pathways. The wlim2a mutants also exhibited altered stomatal phenotypes. Analysis of plants expressing WLIM2A variants of the phospho-dead or phospho-mimicking MAPK phosphorylation site showed opposing stomatal behavior and resistance phenotypes in response to Pst DC3000 infection, proving that phosphorylation of WLIM2A plays a crucial role in plant immunity. Overall, these data demonstrate that phosphorylation of WLIM2A by MAPKs regulates Arabidopsis responses to plant pathogens. Full article

In viticulture, pathogens like the oomycete Plasmopara viticola, the causal agent of downy mildew, can cause severe yield loss and require extensive application of plant protection chemicals. Breeders are generating pathogen-resistant varieties exploiting American and Asian wild Vitis germplasm as sources of resistance. Several loci mediating resistance to P. viticola have been identified in the past but may be overcome by specifically adapted strains of the pathogen. Aiming to find and characterize novel loci, a cross population with Vitis amurensis ancestry was investigated searching for resistance-correlated quantitative trait loci (QTL). As a prerequisite, a genetic map was generated by analyzing the 244 F₁ individuals derived from a cross of the downy mildew susceptible Vitis vinifera cultivar ‘Tigvoasa’ and the resistant V. amurensis pBC1 breeding line We 90-06-12. This genetic map is based on the information from 627 molecular markers including 56 simple sequence repeats and 571 rhAmpSeq markers. A phenotypic characterization of the progeny showed a clear segregation of the resistance traits in the F₁ population after an experimental inoculation of leaf discs with downy mildew. Combining genetic and phenotypic data, an analysis for QTL revealed a major locus on linkage Group 9 that correlates strongly with the resistance to downy mildew. The locus was mapped to a region of about 80 kb on the PN40024 (12x.V2) grapevine reference genome. This genomic region co-localizes with the formerly identified locus Rpv10 from the grapevine cultivar ‘Solaris’. As we found different allele sizes of the locus-linked SSR markers than those characterizing the known Rpv10 locus and differences in the sequence of a candidate gene, it was regarded as a haplotype variant and named Rpv10.2. Full article

The use of renewable fuels in place of fossil fuels in internal combustion engines is regarded as a viable method for achieving zero-impact-emission powertrains. However, to achieve the best performance with these fuels, these engines require further optimization, which is achieved through new combustion strategies and the use of advanced ignition systems such as prechambers. Since simulations greatly accelerate this development, accurate simulation models are needed to accurately predict the combustion phenomenon, which requires a deep understanding of the ignition phenomenon as it significantly affects combustion. This work presents a comprehensive experimental methodology to study sparks under engine conditions, providing quantitative data to improve and validate ignition simulation models. The goal was to determine the volume generated by sparks under engine conditions that can initiate combustion and use this information to improve simulation results to match the experimental results. The visible sparks were observed with high-speed cameras to understand their time-resolved evolution and interaction with the flow. The heat transfer from the plasma was also visualized using a modified Background-Oriented Schlieren technique. The information gained from the experimental observations was used to improve an ignition simulation model. Since the velocity of the plasma was found to be slower than the surrounding flow, a user-defined parameter was included to calibrate the velocity of the simulated plasma particles. This parameter was calibrated to match the simulated spark length to the experimental spark length. In addition, since the previous simulation model did not take the heat transfer from the plasma into account, the simulated plasma particles were coupled to have heat transfer to the surroundings. Based on a comparison of the simulation results with the experimental results, the improved approach was found to provide a better physical representation of the spark ignition phenomenon. Full article