Search Results (44)

Copper and nickel ions play pivotal, albeit distinct, roles as essential trace elements in living systems, and primarily serve as co-factors for a range of enzymes. However, as with all trace metal ions, excessive concentrations can exert adverse toxicological properties. Interestingly, the incorporation of these in cell culture media can establish novel chemical interactions, with their speciation status markedly influencing characteristics, including cell maturation, and cellular uptake mechanisms. Thus, the primary objective of this study was to investigate and determine the speciation status (i.e., complexation) of nickel(II) and copper(II) ions by biomolecules present in RPMI 1640 mammalian cell culture medium using virtually non-invasive high-resolution proton NMR analysis, an investigation of much relevance to now routine studies of their toxicological actions towards cultured cells. Samples of the above aqueous culture medium were ¹H NMR-titrated with increasing added concentrations of 71–670 µmol/L Ni(II)(aq.), and 0.71–6.7, 7.1–67 and 71–670 µmol/L Cu(II)(aq.), in duplicate or triplicate. ¹H NMR spectra were acquired on a JEOL ECZ-600 spectrometer at 298 K. Results demonstrated that addition of increasing concentrations of Ni(II) and Cu(II) ions to the culture medium led to the selective broadening of a series of biomolecule resonances, results demonstrating their complexation by these agents. The most important complexants for Ni(II) were histidine > glutamine > acetate ≈ methionine ≈ lysine ≈ threonine ≈ branched-chain amino acids (BCAAs) > asparagine ≈ aspartate > tyrosine ≈ tryptophan, whereas for Cu(II) they were found to be histidine > glutamine > phenylalanine ≈ tyrosine ≈ nearly all remaining aliphatic metabolites (particularly the wealth of amino acids detectable) > 4-hydroxyphenylacetate (trace culture medium contaminant), in these orders. However, Cu(II) had the ability to influence the linewidths of these signals at much lower added levels (≤7 µmol/L) than that of Ni(II), the broadening effects of the latter occurring at concentrations which were approximately 10-fold greater. Virtually all of these added metal ion-induced resonance modifications were, as expected, reversible on addition of equivalent or excess levels of the chelator EDTA. From this study, changes in the co-ordination sphere of metal ions in physiological environments can give rise to marked modifications in their physicochemical properties (e.g., redox potentials, electronic charges, the potential catalytic generation of reactive oxygen species (ROS), and cell membrane passages). Moreover, given that the above metabolites may also function as potent hydroxyl radical (^●OH) scavengers, these findings suggest that generation of this aggressively reactive oxidant directly from Cu(II) and Ni(II) ions in physiologically-relevant complexes may be scavenged in a ‘site-dependent’ manner. This study is of further relevance to trace metal ion research in general since it enhances our understanding of the nature of their interactions with culture medium biomolecules, and therefore provides valuable information regarding their overall chemical and biological activities, and toxicities. Full article

The concept of using ‘acid-adapted’ challenge cultures in the microbial validation of food processes that incorporate an acidic treatment is that they would be more resistant to acid and require a robust process to obtain targeted log reductions. The recent confirmation that acid-adapted Salmonella challenge cultures for droëwors and biltong processes are more sensitive to those processes than non-adapted cultures changes that preference for the use of non-adapted cultures for validation studies with these specific processes. However, it is difficult to achieve > 5-log reductions with non-adapted cultures, one of two USDA-FSIS parameters available for validation of processes that are not aligned with traditional process conditions for dried beef products in the USA (i.e., beef jerky). A natural multipurpose (flavor, antimicrobial) commercial product, described as a refined liquid smoke flavorant, provided >7-log reductions with droëwors when challenged with non-adapted cultures of Salmonella (5-serovar mixture), Shiga toxigenic Escherichia coli (STEC, four-strain mixture), and Listeria monocytogenes (four-strain mixture) as well as a >7-log reduction with biltong processing (vs Salmonella). Comparisons between standard droëwors and biltong processes (all <5-log reductions) using non-adapted challenge cultures vs. the same formulation plus 0.75% pyrolyzed liquid smoke extracts (Flavoset) showed greater and significant (p < 0.05) reductions in duplicate trials with triplicate samples at each sampling point in each trial (total n = 6) when analyzed by repeated measures analysis of variance (RM-ANOVA). Although sold as a flavorant, this study examines the antimicrobial properties of Flavoset 5400L to improve the safety of droëwors and biltong by achieving a >5-log reduction with non-adapted pathogenic challenge cultures. Validation processes for droëwors and biltong established with these parameters should result in greater safety of marinaded, non-thermally processed meats from traditional foodborne pathogens commonly associated with meats or meat processing environments. Full article

Caleosins (CLOs) or peroxygenases (PXGs), a class of structural proteins of lipid droplets (LDs), comprise a small family of multifunctional proteins widely involved in oil accumulation, organ development, and stress responses. Despite the proposal of two clades termed H and L in Arabidopsis thaliana, their evolution in the order Brassicales has not been well established. In this study, the first genome-wide analysis of the caleosin family was conducted in papaya (Carica papaya), a Caricaceae plant without any recent whole-genome duplication (WGD). A high number of five members representing both H and L clades were identified from the papaya genome. Further identification and comparison of 68 caleosin genes from 14 representative plant species revealed seven orthogroups, i.e., H1–4 and L1–3, where H1 and L1 have already appeared in the basal angiosperm Amborella trichopoda, supporting their early divergence before angiosperm radiation. Five CpCLO genes belong to H1 (1) and L1 (4), and extensive expansion of the L1 group was shown to be contributed to by species-specific tandem and transposed duplications, which may contribute to environmental adaptation. Orthologous and syntenic analyses uncovered that lineage-specific expansion of the caleosin family in Brassicales relative to A. trichopoda was largely contributed to by tandem duplication and recent WGDs, as well as the ancient γ whole-genome triplication (WGT) shared by all core eudicots. Independent gain or loss of certain introns and apparent expression divergence of caleosin genes were also observed. Tissue-specific expression analysis showed that CpCLO2 and −5 are constitutively expressed, whereas others appear to be tissue-specific, implying function divergence. Interestingly, the H-forms CpCLO1 and RcCLO1 were shown to exhibit similar expression profiles to most oleosin genes that are preferentially expressed oil-rich tissues such as seeds/endosperms, shoots, and calluses, implying their putative involvement in oil accumulation, as observed in Arabidopsis. The results obtained from this study provide a global view of CpCLO genes and insights into lineage-specific family evolution in Brassicales, which facilitates further functional studies in papaya and other non-model species. Full article

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition often associated with genetic syndromes. Structural variants on the long arm of chromosome 15 (15q) are recurrently implicated in syndromic ASD, yet their phenotypic spectrum remains insufficiently characterized in diverse populations. We retrospectively analyzed clinical and molecular data from three patients with ASD treated at a Brazilian public reference center who also presented neurological and systemic comorbidities. Genetic investigations included G-banded karyotyping, chromosomal microarray analysis (CMA), methylation assays, and multiplex ligation-dependent probe amplification (MLPA) when indicated. Variants were classified according to ACMG guidelines and correlated with individual phenotypes. Case 1 showed an 8.4 Mb triplication at 15q11.2–q13.1 encompassing SNRPN, UBE3A, and GABRB3, which are associated with epilepsy, delayed neuropsychomotor development, and dysmorphic traits. Case 2 presented a 418 kb duplication at 15q13.3 involving CHRNA7 and OTUD7A, a variant of uncertain significance correlated with intellectual disability, speech apraxia, and self-injurious behavior. Case 3 demonstrated extensive loss of heterozygosity at 15q11.2–q13.1 and 15q21.3–q26.2, which is compatible with maternal uniparental disomy and Prader–Willi syndrome, manifesting hypotonia, seizures, and global delay. These findings underscore the potential involvement of the 15q region in syndromic ASD and related neurological comorbidities, highlighting the diverse pathogenic mechanisms and the importance of comprehensive genomic profiling for diagnosis, counseling, and individualized care. Full article

KNOX genes play crucial roles in cell-fate determination and body plan specification during early embryogenesis. However, the specific gene structure and functional differentiation of KNOXs in Brassica napus is still unclear. We investigated KNOX genes in Brassica rapa (B. rapa), Brassica oleracea (B. oleracea), and Brassica napus (B. napus), which are polyploidy models with genome triplication after Arabidopsis-Brassiceae divergence. In total, 15, 14, and 32 KNOX genes were identified in B. rapa, B. oleracea, and B. napus, respectively. Phylogenetic analysis classified BnKNOXs (B. napus) into three classes with conserved domain organization. Synteny analysis indicated that BnKNOXs family expansion during allopolyploidization was mainly due to whole-gene and segmental duplications. Cis-element, gene structure, and expression pattern analyses showed high conservation within the same group. RNA-seq and qRT-PCR results divided BnKNOXs into three classes with distinct expression patterns: Class I exhibited moderate and specific expression in buds and inflorescence tips; Class III showed specific low expression in seeds and stamens; while the second class showed expression in most tissues. Sub-cellular localization results showed that the three candidate genes from the three classes exhibited distinct subcellular localizations, with BnSTM-C and BnKNAT3a-A predominantly in the nucleus and BnKNATM1-A in the cytoplasm indicating different expression patterns. Collectively, these findings provide a foundation for further functional studies of BnKNOX genes in B. napus. Full article

Childhood obesity and overweight are linked to subclinical inflammatory conditions. The present manuscript aimed to undertake a scoping review exploring the relationship between childhood obesity and salivary biomarkers to answer the following question: “Are salivary biomarkers trustful factors/indicators for childhood obesity?” The main search terms used were: “obesity and salivary biomarkers and children” (Pubmed, Scielo, Scopus, Embase databases: 1999–2025). Assessed articles were carefully classified according to a predetermined criterion (Newcastle–Ottawa Scale), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were considered. Papers involving children >13 years, duplicates/triplicates, literature reviews, and non-related to the question addressed were excluded. More than 30 salivary biomarkers were assessed in the thirteen studies appraised. Three studies were rated as having a high level of evidence, two as moderate, and eight as having a low level. Fourteen biomarkers were found to be significantly increased in childhood obesity/overweight (p < 0.05): leptin, insulin, α-amylase, tumor necrosis factor α, interleukin 6, vascular endothelial growth factor-A, C-reactive protein, monocyte chemotactic protein-1, resistin, phosphate, nitric oxide, interleukin 1β, uric acid and fetuin-A; and three were found to be significantly decreased (p < 0.05): adiponectin, secretory immunoglobulin A, and interleukin-12p70. In conclusion, the present review supported the idea that saliva might be a promising diagnostic tool in early life and that it is a significant source of obesity biomarkers in children. Full article

The objective of the present work was to investigate a possible processing route for a currently discarded material, niobium mineral tailings containing rare earth elements, from the largest niobium producer worldwide (CBMM), for use as a raw material for valuable products such as ferroniobium and rare earth concentrate. A study was conducted on the kinetics of the carbothermic reduction from hematite to magnetite (magnetizing roasting). Thermogravimetric tests performed in duplicate or triplicate were conducted at three different temperatures (700 °C, 800 °C and 900 °C) for 1 h with two times the stoichiometric quantity of the reductant (charcoal). Scanning electron microscopy (SEM) and X-ray diffraction (XRD) showed small amounts of magnetite in the samples reduced at 700 °C and 800 °C. At 900 °C, in accordance with the XRD analysis (Rietveld), almost all hematite was reduced to magnetite. The kinetic model that showed the best fitting was the Ginstling–Brounshtein model. The apparent activation energy was evaluated to be 206 kJ/mol, which is similar to the values reported in the literature for the activation energy of the Boudouard reaction. Full article

This study characterizes the evolution of the tumor necrosis factor superfamily (TNFSF) across vertebrate lineages, both cyclostomes and gnathostomes, by combining sequence similarity and synteny data for the genes from 23 model species. The available evidence supports a simple model in which most of the diversity found in living species can be attributed to the expansion of four genes found in an ancestor of all vertebrates before the first of the genome duplications that occurred in the vertebrate lineages. It is inferred that the ancestor of all cyclostomes possessed only six TNFSF genes. A cyclostome-specific genome triplication had little effect on the total number of these genes. The ancestor of all gnathostomes, due to the effect of a second genome duplication plus additional single-gene duplications, already had 21 TNFSF genes. In several gnathostome lineages, particularly in some tetrapods, the TNF superfamily has significantly contracted due to numerous gene losses. This evolutionary model provides a framework for exploring functional data, showing that the descendants of different ancestral genes have acquired distinct roles, most prominently in the innate and adaptive immune systems, which led to a species-specific refinement of which TNFSF genes were conserved or lost. Several data hitherto difficult to interpret (the interactions of very different TNFSF ligands with the same receptors; the ability of the same ligands to bind alternative receptors, with or without death domains; and the cooperation of different ligands in specific functions) can be explained as consequences of the evolutionary history of the TNF superfamily. Full article

The Solanaceae family occupies a significant position, and the study of resistance genes within this family is extremely valuable. Therefore, our goal is to examine disease resistance genes based on the high-quality representative genomes of Solanaceae crops, and to develop corresponding Simple Sequence Repeat (SSR) molecular markers. Among nine representative Solanaceae species, we identified 819 NBS-LRR genes, which were further divided into 583 CC-NBS-LRR (CNL), 54 RPW8-NBS-LRR (RNL), and 182 TIR-NBS-LRR (TNL) genes. Whole genome duplication (WGD) has played a very important role in the expansion of NBS-LRR genes in Solanaceae crops. Gene structure analysis showed the striking similarity in the conserved motifs of NBS-LRR genes, which suggests a common ancestral origin, followed by evolutionary differentiation and amplification. Gene clustering and events like rearrangement within the NBS-LRR family contribute to their scattered chromosomal distribution. Our findings reveal that the majority of NBS-LRR family genes across all examined species predominantly localize to chromosomal termini. The analysis indicates the significant impact of the most recent whole genome triplication (WGT) on the NBS-LRR family genes. Moreover, we constructed Protein–Protein Interaction (PPI) networks for all 819 NBS-LRR genes, identifying 3820 potential PPI pairs. Notably, 97 genes displayed clear interactive relationships, highlighting their potential role in disease resistance processes. A total of 22,226 SSRs were detected from all genes of nine Solanaceae species. Among these SSRs, we screened 43 NBS-LRR-associated SSRs. Our study lays the foundation for further exploration into SSR development and genetic mapping related to disease resistance in Solanaceae species. Full article

FCS-like zinc finger (FLZ) proteins are plant-specific regulatory proteins, which contain a highly conserved FLZ domain, and they play critical roles in plant growth and stress responses. Although the FLZ family has been systematically characterized in certain plants, it remains underexplored in Brassica species, which are vital sources of vegetables, edible oils, and condiments for human consumption and are highly sensitive to various abiotic stresses. Following the whole-genome triplication events (WGT) in Brassica, elucidating how the FLZ genes have expanded, differentiated, and responded to abiotic stresses is valuable for uncovering the genetic basis and functionality of these genes. In this study, we identified a total of 113 FLZ genes from three diploid Brassica species and classified them into four groups on the basis of their amino acid sequences. Additionally, we identified 109 collinear gene pairs across these Brassica species, which are dispersed among different chromosomes, suggesting that whole-genome duplication (WGD) has significantly contributed to the expansion of the FLZ family. Subcellular localization revealed that six representative BolFLZ proteins are located in the nucleus and cytoplasm. Yeast two-hybrid assays revealed that 13 selected BolFLZs interact with BolSnRK1α1 and BolSnRK1α2, confirming the conservation of the SnRK1α-FLZ module in Brassica species. Expression profile analysis revealed differential expression patterns of BolFLZ across various tissues. Notably, the expression levels of seven BolFLZ genes out of the fifteen genes analyzed changed significantly following treatment with various abiotic stressors, indicating that the BolFLZ genes play distinct physiological roles and respond uniquely to abiotic stresses in Brassica species. Together, our results provide a comprehensive overview of the FLZ gene family in Brassica species and insights into their potential applications for enhancing stress tolerance and growth in Chinese kale. Full article

Background/Objectives: Developmental and epileptic encephalopathy 9 (DEE9) (MIM #300088) affects heterozygous females and males with somatic pathogenic variants, while male carriers with hemizygous PCDH19 pathogenic variants are clinically unaffected. There are hundreds of pathogenic single nucleotide variants in the PCDH19 gene reported in the literature, which lead to the loss of function of the PCDH19 protein. To date, no phenotypes associated with overexpression or copy number gains have been described in this gene. Methods and results: We present a female patient with a de novo triplication in the Xq21.3–q22.1 chromosomal region, which includes the PCDH19 gene, which implies an unbalanced dose gain. This patient displayed a phenotype of epileptic encephalopathy compatible with DEE9. By comparison, another male patient with a similar duplication showed mild developmental delay and autism but never developed epilepsy. Conclusions: Here, we propose the dose gain of PCDH19 as a new pathogenic mechanism that results in a phenotype similar to that found in patients with loss-of-function variants in PCDH19, when present in a heterozygous state. Full article

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease worldwide; therefore, since its initial description, significant progress has been made, yet a mystery remains regarding its pathogenesis and elusive root cause. The widespread distribution of pathological α-synuclein (αSyn) aggregates throughout the body raises inquiries regarding the etiology, which has prompted several hypotheses, with the most prominent one being αSyn-associated proteinopathy. The identification of αSyn protein within Lewy bodies, coupled with genetic evidence linking αSyn locus duplication, triplication, as well as point mutations to familial Parkinson’s disease, has underscored the significance of αSyn in initiating and propagating Lewy body pathology throughout the brain. In monogenic and sporadic PD, the presence of early inflammation and synaptic dysfunction leads to αSyn aggregation and neuronal death through mitochondrial, lysosomal, and endosomal functional impairment. However, much remains to be understood about αSyn pathogenesis, which is heavily grounded in biomarkers and treatment strategies. In this review, we provide emerging new evidence on the current knowledge about αSyn’s pathophysiological impact on PD, and its presumable role as a specific disease biomarker or main target of disease-modifying therapies, highlighting that this understanding today offers the best potential of disease-modifying therapy in the near future. Full article

Food contact surfaces can harbor and transmit pathogens leading to outbreaks. Decontamination strategies that are user- and environmentally-friendly without toxic by-product formation are needed. Novel UV-C light-emitting diode (LED) technologies are being explored to deliver the required dose to inactivate viruses in food-processing environments. The objective of this study was to compare the effects of 279 nm UV-C LED to 254 nm UV-C against hepatitis A virus (HAV) and feline calicivirus (FCV, a cultivable human norovirus surrogate) on stainless-steel, ceramic, and glass surfaces. Viruses were surface spread on sterile stainless-steel or ceramic coupons (100 μL on 2 × 2 cm²), or glass discs (50 μL on 1 × 1 cm²), air-dried, and UV-C-treated for up to 3.75 min (surface dose = 0–49.2 mJ/cm² for HAV and 0–24.6 mJ/cm² for FCV). Each triplicate treatment was assayed in duplicate, and data were statistically analyzed. The D₁₀-values for HAV treated with UV-C at 254 nm on stainless-steel, ceramic, and glass were 9.48 ± 0.34, 14.53 ± 2.52, and 6.91 ± 1.93 mJ/cm², while with UV-C LED at 279 nm were 19.53 ± 2.45, 26.05 ± 0.60, and 8.77 ± 2.08 mJ/cm², respectively. The D₁₀-values for FCV treated with UV-C at 254 nm on stainless-steel, ceramic, and glass were 3.65 ± 0.06, 6.25 ± 1.90, and 4.69 ± 0.03 mJ/cm², while with UV-C LED at 279 nm were 7.097 ± 2.11, 8.31 ± 2.12, and 7.88 ± 0.86 mJ/cm², respectively. Higher 279 nm UV-C doses were needed to inactivate HAV and FCV compared to 254 nm UV-C on the tested surfaces. Novel UV-C LED systems using appropriate doses show promise to inactivate foodborne viruses on food contact surfaces. Full article

The cerebellum, a major feature of the hindbrain, lies posterior to the pons and medulla and inferior to the posterior part of the cerebrum. It lies beneath the tentorium cerebelli in the posterior cranial fossa and consists of two lateral hemispheres connected by the vermis. The cerebellum is primarily supplied by three arteries originating from the vertebrobasilar system: the superior cerebellar artery (SCA), the anterior inferior cerebellar artery (AICA), and the posterior inferior cerebellar artery (PICA). However, variations of the cerebellar arteries may occur, such as duplication of the SCA, SCA creating a common trunk with the posterior cerebral artery, triplication of the AICA, and agenesis of PICA, amongst others. Knowledge of the arterial anatomy of the cerebellum is crucial, as inadequate blood supply to this region can result in diminished motor functioning, significantly impacting the quality of life for patients. The present study demonstrated the importance of adequate anatomical knowledge of the arteries supplying the cerebellum. The PubMed and Embase databases were searched to gather articles on the anatomical characteristics and variations of the arterial supply of the cerebellum. It is the most comprehensive and up-to-date review available in the literature. The possible variations of these vessels may be clinically silent or present with clinical symptoms such as neurovascular compression syndromes of the cranial nerves and aneurysms. With a comprehensive understanding of the cerebellar arterial system, physicians can enhance their diagnostic and treatment capabilities, ultimately leading to more effective management of cerebellar vascular-related issues and other neurological deficits. Full article

Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM’s concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the SON gene due to a balanced reciprocal translocation; (2) disruption of the NBEA gene due to an inverted insertion; (3) disruption of the TSC2 gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions. Full article