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The Journal of Biological Chemistry Jun 2024Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np),...
Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np), a type-1 transmembrane glycoprotein, display deafness, multiple cognitive deficiencies, and reduced expression of plasma membrane calcium (Ca) ATPases (PMCAs) in cochlear hair cells and brain neurons. In this study, we transferred the deafness causing missense mutations pitch (C315S) and audio-1 (I122N) into human Np (hNp) constructs and investigated their effects at the molecular and cellular level. Computational molecular dynamics show that loss of the disulfide bridge in hNp causes structural destabilization of immunoglobulin-like domain (Ig) III and that the novel asparagine in hNp results in steric constraints and an additional N-glycosylation site in IgII. Additional N-glycosylation of hNp was confirmed by PNGaseF treatment. In comparison to hNp, transfection of hNp and hNp into HEK293T cells resulted in normal mRNA levels but reduced the Np protein levels and their cell surface expression due to proteasomal/lysosomal degradation. Furthermore, hNp and hNp failed to promote exogenous PMCA levels in HEK293T cells. In hippocampal neurons, expression of additional hNp or hNp was less efficient than hNp to elevate endogenous PMCA levels and to accelerate the restoration of basal Ca levels after electrically-evoked Ca transients. We propose that mutations leading to pathological Np variants, as exemplified here by the deafness causing Np mutants, can affect Np-dependent Ca regulatory mechanisms and may potentially cause intellectual and cognitive deficits in humans.
PubMed: 38879011
DOI: 10.1016/j.jbc.2024.107474 -
Heliyon Jun 2024Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a...
Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a crispy texture. Frying potato slices initiates the Maillard reaction, resulting in chemical changes that enhance taste, color, and texture, but also undesired acrylamides, which are suspected carcinogens. The application of pulsed electric field (PEF) technology is commonly used in French fry processing operations to prolong cutting blade sharpness and reduce waste, energy consumption, and water usage. Despite these attributes, PEF systems have not yet gained widespread adoption by potato chip producers. In the current study, Lamoka potatoes were PEF-treated prior to continuous frying into potato chips. The effect of specific energy at 0.75 kJ/kg (Low-PEF) and 1.5 kJ/kg (High-PEF) and electric field strength of 1 kV/cm, frequency of 24 kV, and pulse width of 6 μs versus untreated (control) samples was studied, then batches of 250 g of slices were fried at 170 °C or 185 °C for two frying times to obtain potato chips with acrylamide levels below the California Proposition 65 limit (275 ng/g). The Lamoka potato chip product quality metrics that were assessed include moisture, fat, reducing sugars, asparagine, acrylamide, chip color, and texture. PEF treatment of Lamoka potatoes resulted in chips fried in 10 % less time, lower oil content by 8 %, and a decrease of reducing sugars by 19.2 %, asparagine by 42.0 %, and acrylamide by 28.9 %. The PEF fried chips were lighter in color but maintained textural attributes compared to continuous frying cooking. The process of frying potato slices at 170 °C for 150 s with High-PEF yielded potato chips with acrylamide content below the California Proposition 65 limit; which speaks to the health implications for consumers and the quality and safety of these chips.
PubMed: 38873662
DOI: 10.1016/j.heliyon.2024.e31790 -
Amino Acids Jun 2024Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often...
Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (n = 7) and perinatal (n = 5) causes. Plasma D-asparagine and the D/L-serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma D-asparagine and the D/L-serine ratio, but dexamethasone treatment did not. Thus, plasma D-asparagine and the D/L-serine ratio can be useful markers for renal function in children.
Topics: Child; Animals; Humans; Asparagine; Renal Insufficiency, Chronic; Child, Preschool; Serine; Mice; Male; Female; Adolescent; Biomarkers; Prospective Studies; Dexamethasone; Stereoisomerism; Creatinine; Kidney
PubMed: 38844708
DOI: 10.1007/s00726-024-03400-x -
Frontiers in Psychiatry 2024Understanding the mechanisms underlying maternal postpartum depression (PPD) and its effects on offspring development is crucial. However, research on the association...
INTRODUCTION
Understanding the mechanisms underlying maternal postpartum depression (PPD) and its effects on offspring development is crucial. However, research on the association between maternal PPD, gut microbiota, and offspring neurodevelopment remains limited. This study aimed to examine the association of maternal PPD symptoms with early gut microbiome, gut metabolome, and neurodevelopment in infants at 6 months.
METHODS
Maternal PPD symptoms were assessed using the Edinburgh Postpartum Depression Scale (EPDS) at 42 days postpartum. Infants stool samples collected at 42 days after birth were analyzed using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) detection. Infant neurodevelopment was measured at 6 months using the Ages and Stages Questionnaire, Third Edition (ASQ-3). Correlations between gut microbiota, metabolites and neurodevelopment were identified through co-occurrence network analysis. Finally, mediation analyses were conducted to determine potential causal pathways.
RESULTS
A total of 101 mother-infant dyads were included in the final analysis. Infants born to mothers with PPD symptoms at 42 days postpartum had lower neurodevelopmental scores at 6 months. These infants also had increased alpha diversity of gut microbiota and were abundant in and , while depleted abundance of , , and Furthermore, alterations were observed in metabolite levels linked to the Alanine, aspartate, and glutamate metabolic pathway, primarily characterized by decreases in N-Acetyl-L-aspartic acid, L-Aspartic acid, and L-Asparagine. Co-occurrence network and mediation analyses revealed that N-Acetyl-L-aspartic acid and L-Aspartic acid levels mediated the relationship between maternal PPD symptoms and the development of infant problem-solving skills.
CONCLUSIONS
Maternal PPD symptoms are associated with alterations in the gut microbiota and neurodevelopment in infants. This study provides new insights into potential early intervention for infants whose mother experienced PPD. Further research is warranted to elucidate the biological mechanisms underlying these associations.
PubMed: 38835546
DOI: 10.3389/fpsyt.2024.1385229 -
Scientific Reports Jun 2024Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer's disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory...
Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer's disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory responses of primary neurons to potentially circulating, blood-brain barrier (BBB) permeable metabolites associated with AD, T2D, or both. We identified nine metabolites associated with protective or detrimental properties of AD and T2D in literature (lauric acid, asparagine, fructose, arachidonic acid, aminoadipic acid, sorbitol, retinol, tryptophan, niacinamide) and stimulated primary mouse neuron cultures with each metabolite before quantifying cytokine secretion via Luminex. We employed unsupervised clustering, inferential statistics, and partial least squares discriminant analysis to identify relationships between cytokine concentration and disease-associations of metabolites. We identified MCP-1, a cytokine associated with monocyte recruitment, as differentially abundant between neurons stimulated by metabolites associated with protective and detrimental properties of AD and T2D. We also identified IL-9, a cytokine that promotes mast cell growth, to be differentially associated with T2D. Indeed, cytokines, such as MCP-1 and IL-9, released from neurons in response to BBB-permeable metabolites associated with T2D may contribute to AD development by downstream effects of neuroinflammation.
Topics: Alzheimer Disease; Animals; Diabetes Mellitus, Type 2; Mice; Neurons; Chemokine CCL2; Interleukin-9; Blood-Brain Barrier; Cells, Cultured
PubMed: 38830911
DOI: 10.1038/s41598-024-62155-3 -
Scientific Reports Jun 2024In this study, changes in bioactive compound contents and the in vitro biological activity of mixed grains, including oats, sorghum, finger millet, adzuki bean, and... (Comparative Study)
Comparative Study
In this study, changes in bioactive compound contents and the in vitro biological activity of mixed grains, including oats, sorghum, finger millet, adzuki bean, and proso millet, with eight different blending ratios were investigated. The total phenolic compounds and flavonoid contents ranged from 14.43-16.53 mg gallic acid equivalent/g extract and 1.22-5.37 mg catechin equivalent/g extract, respectively, depending on the blending ratio. The DI-8 blend (30% oats, 30% sorghum, 15% finger millet, 15% adzuki bean, and 10% proso millet) exhibited relatively higher antioxidant and anti-diabetic effects than other blending samples. The levels of twelve amino acids and eight organic acids in the grain mixes were measured. Among the twenty metabolites, malonic acid, asparagine, oxalic acid, tartaric acid, and proline were identified as key metabolites across the blending samples. Moreover, the levels of lactic acid, oxalic acid, and malonic acid, which are positively correlated with α-glucosidase inhibition activity, were considerably higher in the DI-blending samples. The results of this study suggest that the DI-8 blend could be used as a functional ingredient as it has several bioactive compounds and biological activities, including anti-diabetic activity.
Topics: Antioxidants; Edible Grain; Hypoglycemic Agents; Flavonoids; Phenols; Plant Extracts; Glycoside Hydrolase Inhibitors; Amino Acids
PubMed: 38825591
DOI: 10.1038/s41598-024-63660-1 -
ACS Omega May 2024Spidroin, with robust mechanical performance and good biocompatibility, could fulfill broad applications in material science and biomedical fields. Development of...
Spidroin, with robust mechanical performance and good biocompatibility, could fulfill broad applications in material science and biomedical fields. Development of miniature spidroin has made abundant fiber production economically feasible, but the mechanical properties of artificial silk still fall short of natural silk. The mechanism behind mechanical properties of spidroin usually focuses on β-microcrystalline regions; the effect of amorphous regions was barely studied. In this study, residue tyrosines (Y) were designed to replace asparagine (N)/glutamic acid (Q) in the characteristic motifs (GGX)n in amorphous regions for performance enhancement of spidroin; the mutants presented lower free energy and significantly exhibited stronger van der Waals and electrostatic interactions, which might result from π-π stacking interactions between the phenyl rings in the side chain of tyrosine. Additionally, the soluble expressions of wild-type spidroin and mutant spidroin were achieved when heterologously expressed in , with yields of 560 mg/L (2REP), 590 mg/L (2REPM), 240 mg/L (4REP), and 280 mg/L (4REPM). Significantly, secondary structure analysis confirmed that the mutant spidroin more avidly forms more β-sheets than the wild-type spidroin, and aggregation morphology suggested that mutant spidroin displayed better self-assembly capacity and was easier to form artificial spider silk fibers; in particular, self-assembled 4REPM nanofibrils had an average modulus of 11.2 ± 0.35 GPa, about 2 times higher than self-assembled silk nanofibrils and almost the same as that of native spider dragline silk fibers (10-15 GPa). Thus, we first demonstrated a new influence mechanism of the amorphous region's characteristic motif on the self-assembly and material properties of spidroin. Our study provides a reference for the design of high-performance material proteins and their heterologous preparation.
PubMed: 38799334
DOI: 10.1021/acsomega.4c02477 -
Foods (Basel, Switzerland) May 2024Plant factories offer a promising solution to some of the challenges facing traditional agriculture, allowing for year-round rapid production of plant-derived foods....
Plant factories offer a promising solution to some of the challenges facing traditional agriculture, allowing for year-round rapid production of plant-derived foods. However, the effects of conditions in plant factories on metabolic nutrients remain to be explored. In this study, we used three rice accessions (KongYu131, HuangHuaZhan, and Kam Sweet Rice) as objectives, which were planted in a plant factory with strict photoperiods that are long-day (12 h light/12 h dark) or short-day (8 h light/16 h dark). A total of 438 metabolites were detected in the harvested rice grains. The difference in photoperiod leads to a different accumulation of metabolites in rice grains. Most metabolites accumulated significantly higher levels under the short-day condition than the long-day condition. Differentially accumulated metabolites were enriched in the amino acids and vitamin B6 pathway. Asparagine, pyridoxamine, and pyridoxine are key metabolites that accumulate at higher levels in rice grains harvested from the short-day photoperiod. This study reveals the photoperiod-dependent metabolomic differences in rice cultivated in plant factories, especially the metabolic profiling of taste- and nutrition-related compounds.
PubMed: 38790844
DOI: 10.3390/foods13101544 -
Tropical Medicine and Infectious Disease May 2024Alveolar echinococcosis (AE) stands as a perilous zoonotic affliction caused by the larvae of . There is an imperative need to explore novel therapeutic agents or lead...
Alveolar echinococcosis (AE) stands as a perilous zoonotic affliction caused by the larvae of . There is an imperative need to explore novel therapeutic agents or lead compounds for the treatment of AE. Asparagusic acid, characterized by its low toxicity and possessing antimicrobial, antioxidant, and anti-parasitic attributes, emerges as a promising candidate. The aim of this study was to investigate the in vivo and in vitro efficacy of asparagusic acid against . Morphological observations, scanning electron microscopy, ROS assays, mitochondrial membrane potential assays, and Western blot were used to evaluate the in vitro effects of asparagusic acid on protoscoleces. The effects of asparagusic acid on vesicles were assessed via PGI release, γ-GGT release, and transmission electron microscopy observations. CellTiter-Glo assays, Caspase3 activity assays, flow cytometry, and Western blot were used for an evaluation of the effect of asparaginic acid on the proliferation and apoptosis of germinal cells. The in vivo efficacy of asparagusic acid was evaluated in a murine AE model. Asparagusic acid exhibited a pronounced killing effect on the protoscoleces post-treatment. Following an intervention with asparagusic acid, there was an increase in ROS levels and a decline in mitochondrial membrane potential in the protoscolex. Moreover, asparagusic acid treatment resulted in the upregulation of PGI and γ-GGT release in metacestode vesicles, concomitant with the inhibition of germinal cell viability. Furthermore, asparagusic acid led to an enhanced relative expression of Caspase3 in the culture supernatant of both the protoscoleces and germinal cells, accompanied by an increase in the proportion of apoptotic germinal cells. Notably, asparagusic acid induced an augmentation in Bax and Caspase3 protein expression while reducing Bcl2 protein expression in both the protoscoleces and germinal cells. In vitro cytotoxicity assessments demonstrated the low toxicity of asparagusic acid towards normal human hepatocytes and HFF cells. Additionally, in vivo experiments revealed that asparagusic acid administration at doses of 10 mg/kg and 40 mg/kg significantly reduced metacestode wet weight. A histopathological analysis displayed the disruption of the germinal layer structure within lesions post-asparagusic acid treatment, alongside the preservation of laminated layer structures. Transmission electron microscopy further revealed mitochondrial swelling and heightened cell necrosis subsequent to the asparagusic acid treatment. Furthermore, asparagusic acid promoted Caspase3 and Bax protein expression while decreasing Bcl2 protein expression in perilesional tissues. Subsequently, it inhibited the expression of Ki67, MMP2, and MMP9 proteins in the perilesional tissues and curbed the activation of the PI3K/Akt signaling pathway within the lesion-host microenvironmental tissues. Asparagusic acid demonstrated a pronounced killing effect on , suggesting its potential as a promising therapeutic agent for the management of AE.
PubMed: 38787043
DOI: 10.3390/tropicalmed9050110 -
Environmental Microbiology Reports Jun 2024In coastal marine ecosystems, kelp forests serve as a vital habitat for numerous species and significantly influence local nutrient cycles. Bull kelp, or Nereocystis...
In coastal marine ecosystems, kelp forests serve as a vital habitat for numerous species and significantly influence local nutrient cycles. Bull kelp, or Nereocystis luetkeana, is a foundational species in the iconic kelp forests of the northeast Pacific Ocean and harbours a complex microbial community with potential implications for kelp health. Here, we report the isolation and functional characterisation of 16 Nereocystis-associated bacterial species, comprising 13 Gammaproteobacteria, 2 Flavobacteriia and 1 Actinomycetia. Genome analyses of these isolates highlight metabolisms potentially beneficial to the host, such as B vitamin synthesis and nitrogen retention. Assays revealed that kelp-associated bacteria thrive on amino acids found in high concentrations in the ocean and in the kelp (glutamine and asparagine), generating ammonium that may facilitate host nitrogen acquisition. Multiple isolates have genes indicative of interactions with key elemental cycles in the ocean, including carbon, nitrogen and sulphur. We thus report a collection of kelp-associated microbial isolates that provide functional insight for the future study of kelp-microbe interactions.
Topics: Kelp; Ecosystem; Whole Genome Sequencing; Bacteria; Nitrogen; Genome, Bacterial; Pacific Ocean; Phylogeny; Gammaproteobacteria; Seawater; Carbon
PubMed: 38778582
DOI: 10.1111/1758-2229.13270