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Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic synapses in medial prefrontal cortic (mFPC) neurons. Ketamine induced profound changes in a number of molecular pathways in a mouse model for chronic stress. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling was decreased after chronic administration of corticosterone but increased following ketamine administration in most of the excitatory neurons. Similar decrease of PCP signaling in excitatory neurons was predicted in dorsolateral prefrontal cortical (dl-PFC) neurons of patients with major depressive disorder (MDD). We showed that the basolateral amygdala (BLA)-projecting infralimbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Conditionally knocking out Celsr2 and Celsr3 or Prickle2 in the BLA-projecting IL PFC neurons abolished ketamine-induced synapse restoration and behavioral remission. Therefore, PCP proteins in IL PFC-BLA neurons mediate synapse restoration induced by of low-dose ketamine.

Cranial irradiation used to control brain malignancies invariably leads to progressive and debilitating declines in cognition. Clinical efforts implementing hippocampal avoidance and NMDAR antagonism, have sought to minimize dose to radiosensitive neurogenic regions while normalizing excitatory/inhibitory (E/I) tone. Results of these trials have yielded only marginal benefits to cognition, prompting current studies to evaluate the potential of systemic extracellular vesicle (EV) therapy to restore neurocognitive functionality in the irradiated brain. Here we tested the hypothesis that EVs derived from inhibitory but not excitatory neuronal cultures would prove beneficial to cognition and associated pathology. Rats subjected to a clinically relevant, fractionated cranial irradiation paradigm were given multiple injections of either GABAergic- or glutamatergic-derived EV and subjected to behavioral testing. Rats treated with GABAergic but not glutamatergic EVs showed significant improvements on hippocampal- and cortical-dependent behavioral tasks. While each treatment enhanced levels of the neurotrophic factors BDNF and GDNF, only GABAergic EVs preserved granule cell neuron dendritic spine density. Additional studies conducted with GABAergic EVs, confirmed significant benefits on amygdala-dependent behavior and modest changes in synaptic plasticity as measured by long-term potentiation. These data point to a potentially more efficacious approach for resolving radiation-induced neurological deficits, possibly through a mechanism able to restore homeostatic E/I balance.

The ventral pallidum (VP) contains GABA and glutamate neurons projecting to ventral tegmental area (VTA) whose stimulation drives approach and avoidance, respectively. Yet little is known about the mechanisms by which VP cell types shape VTA activity and drive behavior. Here, we found that both VP GABA and glutamate neurons were activated during approach to reward or by delivery of an aversive stimulus. Stimulation of VP GABA neurons inhibited VTA GABA, but activated dopamine and glutamate neurons. Remarkably, stimulation-evoked activation was behavior-contingent such that VTA recruitment was inhibited when evoked by the subjects own action. Conversely, VP glutamate neurons activated VTA GABA, as well as dopamine and glutamate neurons, despite driving aversion. However, VP glutamate neurons evoked dopamine in aversion-associated ventromedial nucleus accumbens (NAc), but reduced dopamine release in reward-associated dorsomedial NAc. These findings show how heterogeneous VP projections to VTA can be engaged to shape approach and avoidance behaviors.

Astrocytes, the most abundant non-neuronal cell type in the mammalian brain, are crucial circuit components that respond to and modulate neuronal activity through calcium (Ca2+) signalling1-7. Astrocyte Ca2+ activity is highly heterogeneous and occurs across multiple spatiotemporal scales-from fast, subcellular activity3,4 to slow, synchronized activity across connected astrocyte networks8-10-to influence many processes5,7,11. However, the inputs that drive astrocyte network dynamics remain unclear. Here we used ex vivo and in vivo two-photon astrocyte imaging while mimicking neuronal neurotransmitter inputs at multiple spatiotemporal scales. We find that brief, subcellular inputs of GABA and glutamate lead to widespread, long-lasting astrocyte Ca2+ responses beyond an individual stimulated cell. Further, we find that a key subset of Ca2+ activity-propagative activity-differentiates astrocyte network responses to these two main neurotransmitters, and may influence responses to future inputs. Together, our results demonstrate that local, transient neurotransmitter inputs are encoded by broad cortical astrocyte networks over a minutes-long time course, contributing to accumulating evidence that substantial astrocyte-neuron communication occurs across slow, network-level spatiotemporal scales12-14. These findings will enable future studies to investigate the link between specific astrocyte Ca2+ activity and specific functional outputs, which could build a consistent framework for astrocytic modulation of neuronal activity.

Focal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint.

BackgroundThe neurobiology of treatment-resistant schizophrenia (TRS) is poorly understood, and meta-analytic consensus regarding magnetic resonance spectroscopic profiles of glutamate, choline-containing compounds, myo-inositol, and other metabolites in the condition is lacking.MethodsIn this meta-analysis, we examined published findings for N-acetylaspartate, choline-containing compounds (phosphocholine+glycerophosphocholine), myo-inositol, creatine+phosphocreatine, glutamate, and glutamate+glutamine in the anterior cingulate cortex and dorsal striatum in people with TRS versus non-TRS as well as TRS versus healthy control participants (HCs) and TRS versus ultra TRS (i.e., TRS with clozapine resistance). A MEDLINE search revealed 9 articles including 239 people with pooled TRS and ultra TRS, 59 with ultra TRS, 175 with non-TRS, and 153 (HCs) that met meta-analytic criteria.ResultsSignificant effects included higher anterior cingulate cortex phosphocholine+glycerophosphocholine and myo-inositol in the pooled TRS and ultra TRS group than in both the non-TRS group and HCs as well as higher dorsal striatal phosphocholine+glycerophosphocholine in ultra TRS versus HCs, but no differences in other regional metabolites.ConclusionsThe observed metabolite profile in TRS (higher phosphocholine+glycerophosphocholine and myo-inositol signal) is consistent with the hypothesis that TRS has a neuroinflammatory component, although this meta-analysis is not a critical test of that hypothesis. A similar profile is seen in healthy aging, which is known to involve increased neuroinflammation and glial activation. Because the overall number of datasets was low, however, results should be considered preliminary and highlight the need for additional studies of brain metabolites in TRS and their possible association with inflammatory processes.

Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron-astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.

In the present work, N-substituted glutamic acid, polyethylene and polypropylene glycols have been used to design biocompatible copolyesters via Steglich reactions. Due to the presence of alternating hydrophilic and hydrophobic blocks in their structures, these copolyesters are able to form self-stabilized nanoparticle dispersions in aqueous media. The lipophilic core of these nanoparticles can solubilize poorly water-soluble compounds and release them into a model of lipids in a human body. Moreover, the obtained copolyesters possess no cytotoxic effects over a wide concentration range. Thus, we conclude that obtained copolyesters show significant promise for further development as drug delivery systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • An injectable hydrogel to reduce the postoperative abdominal adhesion is designed. • A third-generation polyamide-amine dendrimer loads the Meloxicam for slow release. • The hydrogel has good in vitro and in vivo biosafety and biodegradability. • MX inhibits inflammatory responses and balances the fibrinolytic system. • The adhesion prevention is proved in a rat abdominal adhesion model. Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from ∼ 57.31 kPa to ∼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of ∼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management. [ABSTRACT FROM AUTHOR]

3‐methyl‐4‐(hetero)arylmethylidene isoxazole‐5(4H)‐one derivatives (4a‐r) derivatives (4a‐r) were synthesized by the multi‐component reactions. The multi‐component reactions (MCRs) of hydroxylamine hydrochloride, ethyl acetoacetate and aromatic/ heteroaromatic aldehyde catalyzed by novel Glutamic acid (Glu) as a biodegradable and eco‐friendly organocatalyst in ethanol on oil bath stirring at 60 °C. The final product homogeneity was examined by various spectroscopic techniques. In this work prepared compounds 4 q and 4 r are novel derivatives. The molecular dynamics of total energy and energy gap was calculated using DFT/B3LYP/6–31G (dp) method. The selected derivatives (4 l–r) screened against in vitro MCF‐7 breast cancer cell line by MTT assay, derivatives 4 l and 4 o displayed very good activity with IC50 of 6.57±2.31, and 21.93±1.34 as compared to doxorubicin of IC50 (3.69±0.17). Molecular docking studies were performed to evaluate interaction of PDB id: 1 M17 with led molecules of MCF‐7. Later, 1 M17 and 4 l underwent 200 ns molecular dynamics and simulation within physiological conditions, the outcomes showed that during the simulation, the ligand stayed in the same form. Further, the selected derivatives drug like computed using swissADME, and derivatives 4 l–r obeyed rule of Lipinski's. Furthermore, selected derivatives tested for electrochemical behavior using cyclic voltammetry, and compound 4 l and 4 q showed strong oxidation and reduction potential, thus these derivatives can present better antioxidant properties. [ABSTRACT FROM AUTHOR]

AbstractHb Youngstown [HBB:c.305A > C] is a rare unstable hemoglobin caused by the substitution of glutamic acid with alanine at codon 101 of the Beta globin chain. It causes hemolytic anemia in the heterozygous state. This is a case of a six-year-old Chinese-Javanese girl with heterozygous Hb Youngstown and clinical features of chronic hemolysis and iron overload. Hb Youngstown appears at the S window near to 4.6 minutes on high-performance liquid chromatography (HPLC) and can form a hybrid tetramer on alkaline gel electrophoresis seen as two distinct bands cathodal to A and close to F. For the first time, Hb Youngstown is captured with capillary electrophoresis (CE) and shown to be eluted at zone 8. Clinical presentation and Hb analysis results of this heterozygous Hb Youngstown overlap with heterozygous Hb Rush. They can only be differentiated at molecular level by Beta globin gene sequencing or intact mass spectrometry. [ABSTRACT FROM AUTHOR]

Ulva is an unutilized green seaweed that grows in the intertidal zone around the coast of Java Island, Indonesia. In this study, U. lactuca samples collected from three regions in south of Java Island (Cihara, Surade, and Tepus) were studied in terms of their chemical composition, physical properties and its bioactivity, to determine the best regions for establishing seaweed industries. The chemical characteristics differed significantly among different regions, where the seaweed from Tepus, Surade and Cihara had the highest content of protein (22.93%), carbohydrate (61.58%), and mineral (28.72%), respectively. The amino acids were dominated with L-aspartic acid and L-glutamic acid. All U. lactuca samples contained abundant pigments, such as chlorophylls and carotenoids, especially samples from Tepus. The highest content of crude ulvan was found in Surade seaweed (26.9%). Chemical and physical analyses showed the presence of S = O and C–O–S functional groups in ulvan, a sulfated polysaccharide unique to Ulva sp., with thermal degradation up to 220 °C. Crude ulvan from Surade and Tepus seaweed exhibited bioactivity to support proliferation of fibroblast cells at 100 and 1000 ppm, respectively. Based on the properties of U. lactuca, Tepus and Surade were identified as potential sites to establish aquaculture and/or processing industries. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Probiotics are increasingly used as starter cultures to produce fermented dairy products; however, few studies have investigated the role of probiotics in milk fermentation metabolism. The current study aimed to investigate whether adding Bifidobacterium animalis ssp. lactis Probio-M8 (Probio-M8) as a starter culture strain could improve milk fermentation by comparing the physicochemical characteristics and metabolomes of fermented milks produced by a commercial starter culture with and without Probio-M8. Our results showed that adding Probio-M8 shortened the milk fermentation time and improved the fermented milk texture and stability. Metabolomics analyses revealed that adding Probio-M8 affected mostly organic acid, AA, and fatty acid metabolism in milk fermentation. Targeted quantitative analyses revealed significant increases in various metabolites related to the sensory quality, nutritive value, and health benefits of the probiotic fermented milk, including 5 organic acids (acetic acid, lactic acid, citric acid, succinic acid, and tartaric acid), 5 EAA (valine, arginine, leucine, isoleucine, and lysine), glutamic acid, and 2 essential fatty acids (α-linolenic acid and docosahexaenoic acid). Thus, applying probiotics in milk fermentation is desirable. This study has generated useful information for developing novel functional dairy products. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Acute worsening of glycemic control in diabetic patients and new–onset type I diabetes were reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Latent autoimmune diabetes in adults (LADA) is defined as a slowly evolving immune–mediated diabetes. A few cases of LADA diagnosed after SARS-CoV-2 vaccination have been reported in the literature. This study aims to report LADA after mRNA-based SARS-CoV-2 vaccinations in subjects with a history of well-controlled type 2 diabetes. Methods: We report four cases with LADA diagnosed after mRNA-based SARS-CoV-2 vaccine, BNT162b2 (Pfizer-BioNTech). In the medical history, all subjects had well-controlled type 2 diabetes with oral anti-diabetic medication. One case had autoimmune thyroid disease. One subject was presented with diabetic ketoacidosis. Results: Glycemic control of the presented cases had deteriorated 6–10 weeks after BNT162b2 vaccination. All patients were male and had high levels of glutamic acid decarboxylase 65 antibody (GAD65ab). An intensive insulin regimen was initiated at the time of diagnosis. The need for insulin therapy in two patients disappeared during follow-up. Two subjects were managed with basal insulin and oral antidiabetics. GAD65ab disappeared just 1 year after the diagnosis of LADA in a subject. Conclusion: In case of impaired glycemic control after SARS-CoV-2 vaccination in a well-controlled diabetic patient, LADA should be considered. [ABSTRACT FROM AUTHOR]

BACKGROUND: The research about sustainable and alternative plant protein sources has accelerated with the increasing need for protein. Safflower meal has a potential to be used in protein production due to its high protein content. This research aimed to produce an alternative plant‐based protein powder using safflower meal. Both extraction and spray‐drying parameters of safflower protein powder production were optimized using response surface methodology to achieve maximum yield. Moreover, the physicochemical and functional properties of safflower protein were determined and compared with those of commercial protein powders (soy, sunflower, pea, fava bean, and rice). RESULTS: The optimum extraction conditions were found to be 33.06:1 mL−1 g solvent‐to‐meal ratio, pH 11.00, 23.34 °C extraction temperature, and 30.86 min extraction time, which were achieved with a protein yield response of 75.21%. The highest powder yield (51.28%) was recorded for drying conditions of inlet air temperature of 160.11 °C, aspiration rate of 54.17 m3 h−1, and feed flow rate of 16.01 mL min−1. According to the amino acid profile of safflower protein, the glutamic acid content (14 475 mg (100 g)−1) was highest, while the methionine content (96 mg (100 g)−1) was lowest. Moreover, safflower protein can be regarded as a high‐quality protein due to its high essential amino acid ratio (41.55%). The experiments showed that safflower protein had high solubility and good foam and emulsifying properties. CONCLUSION: Safflower protein could be a nutritional and functional protein source for the food industry. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter required for excitation/inhibition balance is synthesized by the glutamic acid decarboxylases (GADs) in GABAergic neurons. The levels and activity of GADs are strongly correlated with GABA and neural transmission. Dysregulation of GADs and GABA is associated with various neurological disorders. The study used psoralidin, found in the seeds of Psoralea corylifolia, to investigate its effect on GAD levels and regulatory mechanisms in primary cortical neurons. Psoralidin reduced GAD67 through transcriptional regulation. The reduction was not mediated by the N-methyl-D-aspartate receptor. Additionally, psoralidin attenuated the formation of inhibitory synapses in primary hippocampal neurons. [ABSTRACT FROM AUTHOR]

This study aimed to prepare and characterize Nile tilapia (Oreochromis niloticus) waste meal. The experimental design consisted of three treatments (carcass meal, mechanically separated meat meal - MSM, and head meal) and five replications of each treatment. Yield, microbiological quality, pH, water activity, proximate composition, energy value, mineral composition, fatty acid profile, amino acid composition, color, and particle size fractions and the geometric mean particle diameter (GMD) analyses were performed. Data were subjected to ANOVA, and means were compared by Tukey's test at P < 0.05. Carcass, mechanically separated meat, and head meals had a protein content of 56.45%, 78.60%, and 50.33%, respectively, a lipid content of 7.16%, 13.15%, and 4.58%, respectively, and an ash content of 32.61%, 4.26%, and 38.41%, respectively. The mean yield of fish waste meals was 13%. Oleic, palmitic, and linoleic acids were the major fatty acids in the three fish waste meals, and glutamic acid, leucine, lysine, and glycine were the major amino acids. Color analysis showed that lightness (L*) ranged from 55.32 to 77.19, redness (a*) from 4.44 to 4.88, and yellowness (b*) from 4.13 to 9.51. The GMD ranged from 0.37 to 0.99 mm. The results indicate that Nile tilapia waste meals have high nutritional value and adequate pH, water activity, and microbiological quality for use in human nutrition. [ABSTRACT FROM AUTHOR]

BACKGROUND: Energy‐saving and low‐carbon baking processes, as well as the need to determine the flavor‐forming mechanisms of baked dried tofu, are becoming increasingly necessary. The application of emerging catalytic infrared radiation (CIR) technology in baking of dried tofu is considered of high interest due to the low energy consumption and high baking efficiency compared to traditional baking methods. Hence, this study aimed to investigate the evolution of aroma compounds in baked dried tofu during the CIR baking process and reveal relevant relationships between physical qualities, potential flavor precursors and key volatile compounds. RESULTS: The results showed that the surface color of dried tofu gradually turned an appetizing golden yellow color during the rapid heating process, caused by the uniform infrared radiation from the radiant emitters. Meanwhile, the moisture of dried tofu experienced minimal reduction and the hardness of dried tofu gradually increased with the formation of crust on the surface. In addition, 49 volatile compounds were identified by headspace solid‐phase microextraction–gas chromatography–mass spectrometry and 13 substances – 1‐hexanol, 1‐octen‐3‐ol, 1‐pentanol, heptanal, nonanal, hexanal, (E,E)‐2,4‐decadienal, (E,Z)‐2,4‐decadienal, octanal, (E)‐2‐octenal, (E)‐2‐nonenal, 2‐heptanone and 2‐pentylfuran – were confirmed as key aroma compounds. Moreover, the amino acids aspartic acid, glutamic acid, isoleucine, lysine and arginine, and the fatty acids butyric, caprylic, capric, tridecanoic, stearic, oleic and linolenic were responsible for the unique flavor of CIR‐baked dried tofu. CONCLUSION: Consequently, the findings can provide a scientific basis for manufacturers to achieve precise quality control and large‐scale production of CIR‐baked dried tofu products. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence. Methods: Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed. Results: There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16). Conclusions: The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) has been employed to investigate brain metabolite concentrations in vivo, and they vary during neuronal activation, across brain activity states, or upon disease with neurological impact. Whether resting brain metabolites correlate with functioning in behavioral tasks remains to be demonstrated in any of the widely used rodent models. This study tested the hypothesis that, in the absence of neurological disease or injury, the performance in a hippocampal-dependent memory task is correlated with the hippocampal levels of metabolites that are mainly synthesized in neurons, namely N-acetylaspartate (NAA), glutamate and GABA. Experimentally naïve rats were tested for hippocampal-dependent spatial memory performance by measuring spontaneous alternation in the Y-maze, followed by anatomical magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in the hippocampus and cortex. Memory performance correlated with hippocampal concentrations of NAA (p = 0.024) and glutamate (p = 0.014) but not GABA. Concentrations of glutamate in the cortex also correlated with spatial memory (p = 0.035). In addition, memory performance was also correlated with the relative volume of the hippocampus (p = 0.041). Altogether, this exploratory study suggests that levels of the neuronal maker NAA and the main excitatory neurotransmitter glutamate are associated with physiological functional capacity. [ABSTRACT FROM AUTHOR]

Recently, increased attention has been paid to the raw materials of plants as a source of biologically active substances. Black rosehip (Rosa pimpinellifolia L.) fruits could be a good resource for potential functional components in the food, cosmetic and pharmaceutical industries. Also, drying can influence the composition of heat-sensitive phytochemicals. However, less attention is given to comparing black rosehip bioactive compounds particularly compositions of fatty acid, amino acids, and phenolic content in fresh and dried fruits. So in this study, the amino acid constituents (by amino acid analyzer), fatty acids (by GC–MS), mineral elements (by atomic absorption spectrometer), antioxidant (by DPPH) and phenolic compounds (by HPLC) present in fresh and dried fruits of black rosehip naturally grown in Iran were comprehensively investigated. The results showed that dried fruits had a lower level moisture by 51.55%, and a higher level of total phenolic compounds and total sugar by 786.20 mg GAE/100 g and 15.77 g/100 g, respectively. Chlorogenic acid and gallic acid were the major phenolic compounds (109.3 mg/g). Whilst, linoleic acid, oleic acid, and arachidic acid (85.34%) were the most dominant fatty acids. The most dominant amino acids were glutamic acid, phenylalanine, and arginine (29.41 g/100 g). Also, Fe and Mn as micro-elements were the most dominant elements. In general, the results illustrated the potentials and differences of black rosehip fruits grown in the Arasbaran region as promising resources for food sources, pharmaceutics, cosmetics, and breeding programs. Also, these findings confirm that black rosehip fruits contain significant amounts of secondary metabolites that may positively affect human health. [ABSTRACT FROM AUTHOR]

The formulation and delivery of macromolecules through the oral route pose considerable challenges due to factors such as large molecular weight, pH sensitivity, and limited formulation approaches. This challenge is compounded if the drug is poorly permeable, necessitating innovative drug delivery strategies. Vancomycin, a widely prescribed glycopeptide antibiotic, has an oral bioavailability of less than 10%, leading to predominantly intravenous administration and potential patient discomfort. This study explores the potential of the buccal route as a non-invasive, highly vascularised alternative route of administration, offering a rapid onset of action while bypassing the first-pass metabolism. In this study, vancomycin was coated with L-glutamic acid using an isothermal dry particle coater to modulate permeation through the buccal cell line, TR146. Results confirm significant impact of both amino acid concentration and dry particle coating on the rate and extent of drug permeability. With the introduction of L-glutamic acid and utilisation of the isothermal dry particle coater, vancomycin's permeation profile increased six-fold compared to the control due to the formation of drug ion-pair complex. Imaging studies showed the presence of layered micronized glutamic acid particles on the surface of dry coated vancomycin particles which confirms the role of dry coating and amino acid concentration in modulating drug permeation. Microbiology experiments in Staphylococcus aureus, minimum inhibitory concentration and biofilm disruption studies, provided confirmatory evidence of antimicrobial activity of dry coated glutamic acid-vancomycin ion pair particulate structure. This study demonstrates, for the first-time, buccal delivery of dry coated large molecule drug, vancomycin, through controlled deposition of amino acid using innovative particle coating strategy. [ABSTRACT FROM AUTHOR]

Glutamate is one of the most important excitatory neurotransmitters within the mammalian central nervous system. The role of glutamate in regulating neural network signaling transmission through both synaptic and extra‐synaptic paths highlights the importance of the real‐time and continuous monitoring of its concentration and dynamics in living organisms. Progresses in multidisciplinary research have promoted the development of electrochemical glutamate sensors through the co‐design of materials, interfaces, electronic devices, and integrated systems. This review summarizes recent works reporting various electrochemical sensor designs and their applicability as miniaturized neural probes to in vivo sensing within biological environments. We start with an overview of the role and physiological significance of glutamate, the metabolic routes, and its presence in various bodily fluids. Next, we discuss the design principles, commonly employed validation models/protocols, and successful demonstrations of multifunctional, compact, and bio‐integrated devices in animal models. The final section provides an outlook on the development of the next generation glutamate sensors for neuroscience and neuroengineering, with the aim of offering practical guidance for future research. [ABSTRACT FROM AUTHOR]

Fluorescence indicators capable of binding to human immunodeficiency virus-1 (HIV-1) trans-activation responsive (TAR) RNA are powerful tools for the exploratory studies of the identification of anti-HIV drug candidates. This work presents a new design strategy for fluorogenic indicators with a transactivator of transcription (Tat)-derived peptide based on the forced intercalation of thiazole orange (TO) dyes (FIT). The developed 9-mer FIT peptide (RKKRR-TO-RRR: named FiLuP) features the TO unit integrated onto a Dap (2,3-diaminopropionic acid) residue in the middle of the Tat peptide sequence; the Q (glutamic acid) residue in the Tat peptide (RKKRR-Q-RRR) is replaced with TO as if it were an amino acid surrogate. This facilitates a significant light-up response (450-fold at λem = 541 nm, Φfree = 0.0057, and Φbound = 0.61) upon binding to TAR RNA. The response of FiLuP is highly selective to TAR RNA over other non-cognate RNAs, and FiLuP maintains strong binding affinity (Kd = 1.0 ± 0.6 nM). Significantly, in contrast to previously developed Tat peptide-based FRET probes, FiLuP is able to discriminate between "competitive" and "noncompetitive" inhibitors when used in the fluorescence indicator displacement (FID) assay. The FID assay under stringent screening conditions is also possible, enabling super-strong competitive binders toward TAR RNA to be sieved out. [ABSTRACT FROM AUTHOR]

The current evaluation was conducted to investigate the chemical composition and functional properties of protein hydrolysates from different Satureja species. The major amino acids (mg/100 g protein) in the protein from different Satureja species were arginine (6.06–14.37), asparagine (1.39–17.06), glutamine (2.42–11.60), glutamic acid (6.34–9.32), beta‐aminoisobutyric acid (3.31–10.29), alanine (4.64–9.59), aspartic acid (5.73–9.54), proline (4.25–8.14), leucine (3.63–5.69), serine (2.64–4.83), lysine (1.89–4.56), glycine (0.96–5.27), valine (2.76–4.83), and phenylalanine (2.86–3.75). Protein hydrolysates from Satureja species exhibited comparable antioxidant activity (IC50 = 0.270–0.328 mg/mL), anti‐linoleic acid oxidation (IC50 = 0.231–0.301 mg/mL), anti‐lecithin oxidation (IC50 = 0.198–0.258 mg/mL), anti‐starch oxidation (IC50 = 0.201–0.277 mg/mL), anti‐amylase activity (IC50 = 0.314–0.337 mg/mL), and anti‐lipase activity (IC50 = 0.309–0.369 mg/mL). The physico‐chemical properties of gelatin dispersion were electrical conductivity (1197 microsiemens/cm), osmolarity (190 milliosmol/kg), surface tension (45 mN/m), particle size (179 nm), zeta potential (−48 mV), and viscosity (4.92 mPa.s). Techno‐functional characteristics of freeze‐dried gelatin particles were as follows: water content (7.68%), water solubility (84.57%), water swelling (151.33%), hygroscopicity (38.20%), hydrophobicity (6.50 μg/g), emulsification activity (68.54%), emulsification stability (57.86%), foam expansion activity (56.08%), foam stability (41.84%), oil‐holding capacity (1.96 g/g), and water‐holding capacity (4.45 g/g). Protein hydrolysate causes minor changes in the physico‐chemical and techno‐functional properties of gelatin. The current investigation introduces Satureja protein hydrolysate as a possible functional and techno‐functional ingredient for bioactive food products for treating diabetes and oxidative stress and as a natural preservative for the food industry. [ABSTRACT FROM AUTHOR]

Coral skeletal B/Ca (effectively B/CO 3 2–), in combination with boron isotopic composition (δ11B), has been used to reconstruct the dissolved inorganic carbon chemistry of coral calcification media and to explore the biomineralisation process and its response to ocean acidification. This approach assumes that B(OH) 4 −, the B species incorporated into aragonite, competes with dissolved inorganic carbon species for inclusion in the mineral lattice. In this study we precipitated aragonite from seawater in vitro under conditions that simulate the compositions of the calcification media used to build tropical coral skeletons. To deconvolve the effects of pH and [CO 3 2–] on boron incorporation we conducted multiple experiments at constant [CO 3 2–] but variable pH and at constant pH but variable [CO 3 2–], both in the absence and presence of common coral skeletal amino acids. Large changes in solution [CO 3 2–], from < 400 to >1000 µmol kg−1, or in precipitation rate, have no significant effect on aragonite B/Ca at pH total of 8.20 and 8.41. A significant inverse relationship is observed between solution [CO 3 2–] and aragonite B/Ca at pH total = 8.59. Aragonite B/Ca is positively correlated with seawater pH across precipitations conducted at multiple pH but this relationship is driven by the effect of pH on the abundance of B(OH) 4 – in seawater. Glutamic acid and glycine enhance the incorporation of B in aragonite but aspartic acid has no measurable effect. Normalising aragonite B/Ca to solution [B(OH) 4 –] creates K D B(OH)4− which do not vary significantly between pH treatments. This implies that B(OH) 4 – and CO 3 2– do not compete with each other for inclusion in the aragonite lattice at pH total 8.20 and 8.41. Only at high pH (8.59), when [B(OH) 4 –] is high, do we observe evidence to suggest that the 2 anions compete to be incorporated into the lattice. These high pH conditions represent the uppermost limits reliably measured in the calcification media of tropical corals cultured under present day conditions, suggesting that skeletal B/Ca may not reflect the calcification media dissolved inorganic carbon chemistry in all modern day corals. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy plays a crucial role in inhibiting viral replication and regulating the host’s immune response. The autophagy receptor SQSTM1/p62 (sequestosome 1) restricts viral replication by directing specific viral proteins to phagophores for degradation. In this study, we investigate the reciprocal relationship between Zika virus (ZIKV) and selective autophagy mediated by SQSTM1/p62. We show that NS2B3 protease encoded by ZIKV cleaves human SQSTM1/p62 at arginine 265 (R265). This cleavage also occurs with endogenous SQSTM1 in ZIKV-infected cells. Furthermore, overexpression of SQSTM1 inhibits ZIKV replication in A549 cells, while its absence increases viral titer. We have also shown that SQSTM1 impedes ZIKV replication by interacting with NS3 and NS5 and directing them to autophagic degradation, and that NS2B3-mediated cleavage could potentially alter this antiviral function of SQSTM1. Taken together, our study highlights the role of SQSTM1-mediated selective autophagy in the host’s antiviral defense against ZIKV and uncovers potential viral evasion strategies that exploit the host’s autophagic machinery to ensure successful infection.Abbreviation: Cas9: CRISPR-associated protein 9; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; DENV: dengue virus; GFP: green fluorescent protein; IFA: indirect immunofluorescence assay; KIR: KEAP1-interacting region; KO: knockout; LIR: MAP1LC3/LC3-interacting region; mAb: monoclonal antibody; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; pAb: polyclonal antibody; PB1: Phox/BEM1 domain; R265A, a SQSTM1 construct with the arginine (R) residue at position 265 replaced with glutamic acid (A); SQSTM1: sequestosome 1; SQSTM1-C, C-terminal fragment of SQSTM1; SQSTM1-N, N-terminal fragment of SQSTM1; SVV: Seneca Valley virus; TAX1BP1: Tax1 binding protein 1; TBD: TRAF6-binding domain; TCID50: 50% tissue culture infective dose; UBA: ubiquitin-associated domain; Ub: ubiquitin; WT: wild type; ZIKV: Zika virus; ZZ: ZZ-type zinc finger domain. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a critical condition with a wide range of triggers that cause heavy burden on public health. Despite its high incidence and mortality, the treatment of AKI still highly relies on hemodialysis, which is costly and usually accompanied by severe complications. Therefore, development of new therapeutic targets and methods for AKI is urgently needed. Herein, a ferroptosis‐targeting strategy for AKI treatment by rationally designed ferroptosis‐inhibitive polypeptide‐based polymersomes (polypeptosomes, FIPs) is proposed. Such FIPs are self‐assembled from poly(glutamic acid)‐block‐poly(methionine‐stat‐tyrosine) [PGA9‐b‐P(Met8‐stat‐PTyr13)]. The ferroptosis‐inhibition function of the FIPs arises from the rationally‐selected amino acid composition: P(Met‐stat‐Tyr) endows the FIPs with a high scavenging efficiency of over 90% toward different reactive oxygen species (ROS); while the glutamate and tyrosine residues, as well as the amide groups, can bind iron ions, thus blocking iron overload and lipid peroxide in cells. In vivo experiments confirm that the FIPs can effectively alleviate oxidative stress, inhibit ferroptosis, and restore kidney functions. Transcriptome sequencing further reveals the therapeutic mechanisms of FIPs. Overall, such polypeptosomes capable of blocking multiple pathways of ferroptosis open a new avenue for AKI treatment and provide fresh insights into the development of generalized therapies for inflammation. [ABSTRACT FROM AUTHOR]

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To explore the influence of raw materials from different cultivars on the quality of Sichuan dark tea, the raw materials of 4 tea cultivars were used in this study. The main chemicals and aroma components were analyzed by sensory evaluation, chemical analysis and gas chromato graphy-mass spectrometry (GC-MS) . The main components of Sichuan dark teas made from different tea cultivars were significantly different. The contents of water extract, tea polyphenols, catechins and caffeine of Sichuan dark teas from 'Zijuan' were the highest, which were 49.45%, 18.54%, 4.77%, and 4.21%, respectively, followed by Sichuan dark tea processed with 'Huangjinya' cultivar, all of them were significantly (P<0.05) higher than the Sichuan dark tea processed with 'Fuding Dabai' and 'Baiye 1'. The contents of L-asparagine, L-theanine, aspartic acid and glutamic acid were the highest of Sichuan dark teas from 'Huangjinya', which were 115.78, 279.86, 154.47, 70.76 mg/100 g, respectively, significantly (P<0.05) higher than Sichuan dark tea processed with other cultivars. Aroma analysis showed that main aroma components were alcohols, aldehydes, ketones, hydrocarbons and esters, accounting for more than 80% of the total aroma. The similarity rate of aroma between 'Fuding Dabai' and 'Baiye 1' was 0.98, and that of 'Huangjinya' and 'Zijuan' was 0.99. The Sichuan dark tea processed with the 'Baiye 1' had floral fragrance, and the Sichuan dark tea processed with the 'Zijuan' had ''stale flavor''. Sensory quality analysis showed that the comprehensive qualities of Sichuan dark teas from 'Fuding Dabai','Baiye 1' and 'Huangjinya' were the better, with a score of more than 82, while the Sichuan dark tea from 'Zijuan' had the lowest score. The Sichuan dark tea processed with 'Huangjinya' materials was rich in substances and had good comprehensive quality. The Sichuan dark tea processed with 'Baiye 1' material had floral fragrance, which could be used as a variety for processing advanced special Sichuan dark tea. The Sichuan dark tea processed with 'Zijuan' materials had high content of water extracts and tea polyphenols, with ''stale flavor''. It was suitable for blending and processing with other cultivars of low polyphenol content, and could be used as a blending variety for dark tea products with ''stale flavor''. [ABSTRACT FROM AUTHOR]

Upon degranulation, basophils and mast cells secrete an array of inflammatory mediators, including histamine, which leads to not only allergic inflammation but also other inflammatory diseases. We previously reported that an aqueous extract from enzyme-treated, dried sardine inhibits the degranulation of RBL-2H3 cells and attenuates the symptoms of Japanese cedar pollinosis in mice. This study evaluated an antiallergic effect of dipeptides containing acidic amino acid residue in an antigen-induced degranulation assay using RBL-2H3 cells. The result showed that acidic amino acid residue-containing dipeptides inhibit the degranulation of RBL-2H3 cells without cytotoxicity. Additionally, L-histidyl-L-glutamic acid (His-Glu), one of the acidic amino acid residue-containing dipeptides tested in this study, inhibited calcium ionophore-induced degranulation. We also found that His-Glu suppressed microtubule reorganization in RBL-2H3 cells after antigen stimulation. His-Glu slightly, but not significantly, suppressed the elevation of cytosolic calcium ion concentration leading to degranulation. Immunoblot analysis revealed that His-Glu significantly suppressed the phosphorylation of phosphoinositide 3-kinase and Akt, but not that of Syk or phospholipase Cγ. Overall results suggest that acidic amino acid residue-containing dipeptides can be used as food ingredients with an antiallergic effect. [ABSTRACT FROM AUTHOR]

Practical Application In this research, a novel kind of walnut (Juglans regia L.) peptides‐zinc (Zn‐WPs) chelate was obtained using the mass ratio of the walnut peptides (WPs) to ZnSO4.7H2O of 3.5:1 at pH 8.5 and 50°C for 84 min, with the chelation rate of 84.5%. In comparison to walnut peptides (WPs), the contents of aspartic acid and glutamic acid in Zn‐WPs chelate are approximately 27%, indicating that hydrophilic amino acids predominantly bind with walnut peptides. Following chelation with zinc ions, the ultraviolet‐visible (UV) characteristic absorption peak shifted from 213 nm to 210 nm, while the average particle size of the chelate increased to 8.0 ± 0.14 µm, presenting a loose spherical structure under scanning electron microscopy. These findings suggest the formation of new substances. Fourier‐transform infrared spectroscopy (FTIR) revealed carboxyl, amino, and peptide bonds as the chelation sites of WPs and zinc. The IC50 of walnut peptides‐zinc (Zn‐WPs) chelate is 2.91 mg/mL, indicative of a favorable DPPH radical scavenging rate. Furthermore, Zn‐WPs chelate microcapsules were produced via the spray drying method, achieving an encapsulation rate of 75.67 ± 0.83% under optimal conditions. These microcapsules demonstrate robust stability across diverse environmental conditions. This study underscores the potential of Zn‐WPs and its chelate microcapsules to enhance stability and bioactivity under varying circumstances.In this study, a new walnut peptide‐zinc (Zn‐WPs) chelate was prepared. The presence of zinc ions changes the structure and properties of walnut peptides and improves its stability. The production of Zn‐WPs chelate microcapsules enables Zn‐WPs to have strong in vitro stability under different pH and simulated gastrointestinal digestion conditions. These results provide novel insights for developing the walnut peptides as bioactive ingredients in functional foods. [ABSTRACT FROM AUTHOR]

Lacking strategies to simultaneously address the narrow interlayer spacing, irreversible phase transitions, dissolution and electrical transport issues of vanadium oxides is restricting their application in aqueous zinc‐ion batteries. Herein, to address these challenges concurrently, an organic‐inorganic hybrid cathode is explored, HNaV6O16·4H2O‐Glu (HNVO‐Glu), through a guest material‐mediated NVO synthesis strategy utilizing glutamic acid (Glu) to induce Na substituted by proton and enable crystal transformation of Na2V6O16·3H2O (NVO). Specially, Glu insertion kills three birds with one arrow: i) induces the formation of a structurally stable monoclinic HNaV6O16·4H2O phase by introducing H into the NVO framework, preventing structural phase change and collapse of NVO material; ii) acts as a pillar to expand the interlayer spacing, which improves the Zn2+ diffusion kinetics; moreover, the polar groups on the Glu surface weaken the electrostatic interaction between Zn2+ and the host materials, further enhancing the zinc‐ionic transport rate; iii) enhances the electrical conductivity of HNVO by converting the p‐type semiconductor into the n‐type semiconductor structure. Consequently, the HNVO‐Glu exhibits a high specific capacity (354.6 mAh g−1 at 1 A g−1), excellent Zn2+ diffusion capability (10−9 to 10−7 cm2 s−1) and outstanding cycling stability with a capacity retention of 87.2% after 12 000 cycles at 10 A g−1. [ABSTRACT FROM AUTHOR]

[Display omitted] • SB623 cells promote an increase of spike activity and number of network bursts. • SB623 cells in coculture with neurons are superior to astrocytes in promoting neuronal activity. • SB623 cells release higher levels of glutamate when compared to human astrocytes. • Tonic glutamate released by SB623 cells promotes an increase of neuronal activity. Mesenchymal stromal cells (MSCs) hold therapeutic potential for neurological disorders, but their impact on neuronal activity remains unclear. We investigated the effects of SB623 cells (Notch-1 intracellular domain-transfected MSCs) and parental MSCs on human induced pluripotent stem cell (iPSC)-derived neurons using multi-electrode arrays. SB623 cells significantly increased neuronal activity and oscillation in a dose-dependent manner, surpassing astrocytes in promoting network bursts. Strikingly, glutamatergic neurons showed a rapid increase in activity and bursts compared to GABAergic neurons, suggesting glutamate release from SB623 cells. We confirmed this by finding high glutamate levels in SB623 cell conditioned medium, which were reduced by glutaminase inhibition. Glutamate release was further implicated by the reduced excitability in co-cultures with astrocytes, known glutamate scavengers. Our findings reveal a novel mechanism for MSCs: promoting neuronal activity and network formation through tonic glutamate release, with potential implications for MSC-based therapies. [ABSTRACT FROM AUTHOR]

Chemically cross‐linked hydrogels are synthesized from a set of protected L‐lysine and L‐glutamic acid containing homo and copolypetides. Cross‐linking of the linear copolypeptides is achieved through the incorporation of L‐tryptophan and its reaction with hexamethylene bis(triazolinodione). Upon deprotection, hydrogels with oppositely charged polypeptides of different L‐lysine and L‐glutamic acid composition form pH‐dependent polyion complexes through electrostatic interaction. The obtained networks show distinct pH‐dependent differences in their water swelling and rheological properties. Hydrogels at pH 4 display higher strengths compared to pH 8 and their rheological properties scale with L‐lysine/L‐glutamic acid ratio. At pH 8 results suggests that ionic interactions and presumably secondary structure effects have a significant impact on the hydrogel properties. This is further evident from the influence of the copolypetide structures, random versus block copolypeptides, used in the cross‐linked hydrogel. None of the hydrogel shows any significant cytotoxicity against skin cell lines. [ABSTRACT FROM AUTHOR]

The issue of heavy metal pollution such as nickel poses a significant environmental concern, exerting detrimental effects on the growth and viability of plant life. Plants have various mechanisms to effectively manage heavy metal stress, including the ability to modify their amino acid type and content. This adaptive response allows plants to mitigate the detrimental effects caused by excessive heavy metal accumulation. The aim of this study was to investigate the effect of biofertilizers on nickel accumulation, nitrogen metabolism and amino acid profile of corn (Zea mays L.) cv. 'PL438' exposed to Ni stress. After disinfecting and soaking in water for 24 h, corn seeds were primed with bacterial biofertilizers (T2: NPK + FZ), fungal biofertilizers (T3: Arbuscular mycorrhizal fungi (AMF) + Trichoderma (T)), or a combination of them (T4: NPK + FZ + AMF + T) and were cultured by the hydroponic method in completely controlled conditions. Then, they were simultaneously exposed to nickel chloride at various rates (0, 75, or 150 µM) at the three-leaf stage. They were harvested two weeks later and were subjected to the measurement of Ni content, nitrate and nitrite content, nitrate reductase activity, and amino acid profile by high-performance liquid chromatography. The results showed that the application of Ni at higher rates increased Ni, nitrate, and nitrite contents and nitrate reductase activity. The study of Ni accumulation and TF revealed that Ni accumulated in the roots to a greater extent than in the shoots and TF was < 1 in all treatments. The shoot amino acid profile showed that the treatment of Ni+2 increased som amino acids such as aspartic acid, asparagine, serine, histidine, and glycine versus the control, whereas T4 Ni+2 increased aspartic acid, glutamic acid, threonine and arginine. The change in amino acids in Ni-treated plants may play a key role in their adaptation to Ni stress. The findings indicate that biofertilizers played a crucial role in mitigating the negative impacts of Ni on corn plants through alterations in amino acid composition and decreased absorption and translocation of Ni. [ABSTRACT FROM AUTHOR]

ASCT2 is an obligate exchanger of neutral amino acids, contributing to cellular amino acid homeostasis. ASCT2 belongs to the same family (SLC1) as Excitatory Amino Acid Transporters (EAATs) that concentrate glutamate in the cytosol. The mechanism that makes ASCT2 an exchanger rather than a concentrator remains enigmatic. Here, we employ cryo-electron microscopy and molecular dynamics simulations to elucidate the structural basis of the exchange mechanism of ASCT2. We establish that ASCT2 binds three Na+ ions per transported substrate and visits a state that likely acts as checkpoint in preventing Na+ ion leakage, both features shared with EAATs. However, in contrast to EAATs, ASCT2 retains one Na+ ion even under Na+-depleted conditions. We demonstrate that ASCT2 cannot undergo the structural transition in TM7 that is essential for the concentrative transport cycle of EAATs. This structural rigidity and the high-affinity Na+ binding site effectively confine ASCT2 to an exchange mode. ASCT2 is a Na+-dependent obligatory amino acid exchanger. Here, the authors untangle the structural basis of the exchange mechanism in ASCT2, revealing that structural rigidity and a high-affinity Na+ binding site effectively confine ASCT2 to an exchange mode. [ABSTRACT FROM AUTHOR]

Vinegar is commonly utilized in cooking and food preparation as a flavoring, preservative, and condiment. It can be made from various sources, including fruits, grains, and vegetables. This study produced vinegar from a wild edible mushroom, Russula delica Fr., using microwave-assisted enzymatic hydrolysis extraction. The nutritional composition, bioactivities, microbial quality, and volatile compounds were analyzed in the production process and final vinegar product. Sugar syrup as total soluble solids (TSS) and total phenolic content (TPC) were extracted from mushroom powder using commercial enzymes and yielded 5.60 ± 0.10°Brix and 7.01 ± 0.06 mg GAE/g substrate, respectively. The extracted syrup was rich in amino acids such as aspartic and glutamic acid, with glucose as the main type of sugar. Maximum alcohol content at 10.95 ± 0.21% (w/v) with 1.28 ± 0.23 mg GAE/mL TPC was obtained from Saccharomyces cerevisiae fermentation after 21 days, while highest acetic acid was obtained at 5.60 ± 0.42% w/v with 1.87 ± 0.14 mg GAE/mL of TPC content and 74.85 ± 1.24% of DPPH radical scavenging activity after surface fermentation using Acetobacter aceti TISTR 354. Thirteen volatile compounds, including acids, alcohols, and aldehydes, were found in the wild edible mushroom vinegar, contributing to the unique aroma of the product. This study presented the first report on the analysis of vinegar from a wild edible mushroom, R. delica Fr. which showed high nutritional value, antioxidant activity and volatile compounds, with the potential for future commercial production. [ABSTRACT FROM AUTHOR]

The present research examined the impact of L-glutamic acid (Glu) supplementation on the growth performance, muscle composition, gene expression correlated with muscle growth, and intestinal health of largemouth bass. There were 525 fish in total, which were distributed randomly into five groups. Each group had three replicates, and each replicate consisted of 35 fish. Groups with control and experimental diets were assigned glutamic acid amounts of 0.2%, 0.4%, 0.6%, and 0.8%. The findings demonstrated that glutamic acid supplementation enhanced growth performance, feed intake (FI), and condition factor (CF), with the best value being attained at 0.4% Glu. The mean muscle fiber area was increased and the muscle fiber density was decreased in the 0.6% Glu group. The levels of total amino acids and specific amino acids, such as glutamic acid, aspartic acid, leucine, valine, alanine, and glycine, were shown to be higher in the 0.6% Glu group. In the 0.6% Glu group, the mRNA expression levels of atrogin-1, murf-1, foxo3a, and 4e-bp1 were decreased compared to the control group. Conversely, the mRNA expression levels of myf5, myog, myod, s6k1, tor, akt, and pi3k were increased in the 0.6% Glu group compared to the control group. The 0.4% Glu group had higher intestinal amylase, lipase, and protease activities and greater villus height, villus width, and muscle thickness. In summary, Glu can support largemouth bass growth, muscular development, intestinal digestion, and absorption. [ABSTRACT FROM AUTHOR]

In order to explore the effects of glutamate on the growth performance, antioxidant capacity and protein metabolism of juvenile Chinese mitten crab, 0%, 1% and 2% glutamate were supplemented to low protein (30%) and normal protein (35%) diets, respectively. There were 5 parallel tanks in each treatment, and the feeding duration was 8 weeks. The results showed that dietary glutamate did not significantly affect the weight gain of Chinese mitten crab. Diets supplemented with 2% glutamate significantly decreased the crude protein of crabs. The T-AOC of crabs fed the 30% protein diets was significantly lower than crabs fed the 35% protein diets. At 30% protein level, the superoxide dismutase (SOD) activity significantly increased with the increase in glutamate content. Dietary glutamate significantly down-regulated the relative expressions of mTOR, PI3K, S6K1 and 4EBP at 35% protein level. In conclusion, dietary glutamate cannot significantly increase the growth of Chinese mitten crab, but it can improve the antioxidant capacity in Chinese mitten crab under low protein conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: We investigate how glutamate spillover affects information transfer by analyzing the mutual information between release and extrasynaptic locations. Through tetanic release simulations, we aim to quantify the efficiency of information transfer in the presence of excess glutamate. Our study seeks to offer insights into synaptic information processing and excitotoxicity. In our study, we simulate the release of glutamate, a neurotransmitter, from the presynaptic cell by modeling the diffusion of glutamate into both synaptic and extrasynaptic space around the synapse. We have also incorporated a new factor into our model: convection. This factor represents the process by which the body clears glutamate from the synapse. Due to this process, the physiological mechanisms that typically prevent glutamate from spreading beyond the synapse are altered. This results in a different distribution of glutamate concentrations, with higher levels outside the synapse than inside it. The variety of biological effects that occur in response to this extrasynaptic glutamate highlights the importance of preventing neurotransmitters from spreading beyond the synapse. We aim to explain the physical reasons behind these biological effects, which are observed as excitotoxicity. Our results show that preventing the spread of glutamate outside the synapse increases the amount of information exchanged within the synapse and its surroundings for frequencies of glutamate release up to 30–50 Hz, followed by a decrease. Additionally, we find that the rate at which glutamate is cleared from the synapse is effective at relatively low levels (≤0.5 nm/μs in our calculation grid) and remains constant at higher levels. [ABSTRACT FROM AUTHOR]

In this work, we present simulations of the optical rotation (OR) for five molecular crystals at density functional theory level with periodic boundary conditions (DFT‐PBC). Calculations are compared with experimental measurements and show semi‐quantitative agreement with experimental data for three of the crystals: tartatic acid, benzil, and pentaerythritol. For the other two crystals, aspartic acid and glutamic acid, the calculated data are in qualitative agreement with, but two orders of magnitude smaller than, the experimental data. We provide some arguments that support the theoretical predictions and suggest that the experiments should be revisited. We also find that the position of H centers provided in experimental X‐ray data is not sufficiently reliable for simulating OR, and better results are obtained when H atoms are allowed to relax while keeping heavier elements fixed at the experimental positions. Comparison with molecular cluster calculations with a better functional and a larger basis set indicate that the role of intermolecular interactions (reproduced with the PBC technique) is as or more important than the choice of model chemistry. Despite the current limitations in the level of theory that can be employed, these simulations provide a promising avenue to investigate the effect of intermolecular interactions on this sensitive electronic property of molecules and materials. [ABSTRACT FROM AUTHOR]

BACKGROUND: One of the greatest challenges in using Lactobacillus acidophilus as a probiotic is acid stress. The current research aimed to identify substances that help L. acidophilus resist acid stress; this was achieved through assessing its nutrient consumption patterns under various pH conditions. RESULTS: The consumption rates of alanine, uracil, adenine, guanine, niacin, and manganese were consistently higher than 60% for L. acidophilus LA‐5 cultured at pH 5.8, 4.9, and 4.4. The consumption rates of glutamic acid + glutamine and thiamine increased with decreasing pH and were higher than 60% at pH 4.9 and 4.4. The viable counts of L. acidophilus LA‐5 were significantly increased under the corresponding acidic stress conditions (pH 4.9 and 4.4) through the appropriate addition of either alanine (3.37 and 2.81 mmol L−1), glutamic acid + glutamine (4.77 mmol L−1), guanine (0.13 and 0.17 mmol L−1), niacin (0.02 mmol L−1), thiamine (0.009 mmol L−1), or manganese (0.73 and 0.64 mmol L−1) (P < 0.05). The viable counts of L. acidophilus LA‐5 cultured in a medium supplemented with combined nutritional factors was 1.02–1.03‐fold of the counts observed in control medium under all acid conditions (P < 0.05). CONCLUSION: Alanine, glutamic acid + glutamine, guanine, niacin, thiamine, and manganese can improve the growth of L. acidophilus LA‐5 in an acidic environment in the present study. The results will contribute to optimizing strategies to enhance the acid resistance of L. acidophilus and expand its application in the fermentation industry. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Extracellular proteases are a class of public good that support growth of Bacillus subtilis when nutrients are in a polymeric form. Bacillus subtilis biofilm matrix molecules are another class of public good that are needed for biofilm formation and are prone to exploitation. In this study, we investigated the role of extracellular proteases in B. subtilis biofilm formation and explored interactions between different public good producer strains across various conditions. We confirmed that extracellular proteases support biofilm formation even when glutamic acid provides a freely available nitrogen source. Removal of AprE from the NCIB 3610 secretome adversely affects colony biofilm architecture, while sole induction of WprA activity into an otherwise extracellular protease‐free strain is sufficient to promote wrinkle development within the colony biofilm. We found that changing the nutrient source used to support growth affected B. subtilis biofilm structure, hydrophobicity and architecture. We propose that the different phenotypes observed may be due to increased protease dependency for growth when a polymorphic protein presents the sole nitrogen source. We however cannot exclude that the phenotypic changes are due to alternative matrix molecules being made. Co‐culture of biofilm matrix and extracellular protease mutants can rescue biofilm structure, yet reliance on extracellular proteases for growth influences population coexistence dynamics. Our findings highlight the intricate interplay between these two classes of public goods, providing insights into microbial social dynamics during biofilm formation across different ecological niches. [ABSTRACT FROM AUTHOR]

Killer whales (Orcinus orca) occur seasonally in the eastern Canadian Arctic (ECA), where their range expansion associated with declining sea ice have raised questions about the impacts of increasing killer whale predation pressure on Arctic‐endemic prey.We assessed diet and distribution of ECA killer whales using bulk and compound‐specific stable isotope analysis (CSIA) of amino acids (AA) of 54 skin biopsies collected from 2009 to 2020 around Baffin Island, Canada.Bulk ECA killer whale skin δ15N and δ13C values did not overlap with potential Arctic prey after adjustment for trophic discrimination, and instead reflected foraging history in the North Atlantic prior to their arrival in the ECA. Adjusted killer whale stable isotope (SI) values primarily overlapped with several species of North Atlantic baleen whales or tuna. Amino acid (AA)‐specific δ15N values indicated the ECA killer whales fed primarily on marine mammals, having similar glutamic acid δ15N–phenylalanine δ15N (δ15NGlx‐Phe) and threonine δ15N (δ15NThr) as mammal‐eating killer whales from the eastern North Pacific (ENP) that served as a comparative framework. However, one ECA whale grouped with the fish‐eating ENP ecotype based δ15NThr.Distinctive essential AA δ13C of ECA killer whale groups, along with bulk SI similarity to killer whales from different regions of the North Atlantic, indicates different populations converge in Arctic waters from a broad source area. Generalist diet and long‐distance dispersal capacity favour range expansions, and integration of these insights will be critical for assessing ecological impacts of increasing killer whale predation pressure on Arctic‐endemic species. [ABSTRACT FROM AUTHOR]

1. An experiment was conducted to determine the effect of the source of fat (soybean oil or tallow) on the ileal endogenous amino acid (EAA) losses in broilers. 2. Three nitrogen (N)-free diets; a control diet with no added fat and test diets with 60 g/kg of either soybean oil or tallow were formulated. Titanium dioxide (5 g/kg) was added to all diets as an indigestible marker. Each diet was assigned to six replicate cages (eight birds per cage) from d 18 to 21 post-hatch. On d 21, the digesta were collected from the lower half of the ileum. 3. The endogenous losses of nitrogen and amino acids (AA) were lower (p = 0.08; p = 0.001) in broilers fed diets with soybean oil or tallow, respectively, compared to those fed the diet with no fat. Source of fat had no influence (p > 0.05) on EAA losses. 4. The most abundant AA in the ileal endogenous protein was glutamic acid, followed by aspartic acid, threonine, leucine, serine, valine and proline. In general, the concentrations of AA in the endogenous protein were lower (p < 0.05) with added fat. The exceptions were methionine, cysteine, proline and serine, which were unaffected. The effect of fat source on the AA contents of endogenous protein were inconsistent and differed depending on the AA. 5. The inclusion of fats decreased EAA losses which implied they have beneficial effects beyond direct energy contribution. It can be proposed that the reduction of EAA flow may be an additional mechanism contributing to the extra-caloric effect of dietary fats. [ABSTRACT FROM AUTHOR]

Alterations in the structure, function, and microcirculation of the thalamus, a key brain region involved in pain pathways, have previously been demonstrated in patients with painless and painful diabetic peripheral neuropathy (DPN). However, thalamic neurotransmitter levels including γ-aminobutyric acid (GABA) (inhibitory neurotransmitter) and glutamate (excitatory neurotransmitter) in different DPN phenotypes are not known. We performed a magnetic resonance spectroscopy study and quantified GABA and glutamate levels within the thalamus, in a carefully characterized cohort of participants with painless and painful DPN. Participants with DPN (painful and painless combined) had a significantly lower GABA:H2O ratio compared with those without DPN (healthy volunteers [HV] and participants with diabetes without DPN [no DPN]). Participants with painless DPN had the lowest GABA:H2O ratio, which reached significance compared with HV and no DPN, but not painful DPN. There was no difference in GABA:H2O in painful DPN compared with all other groups. A significant correlation with GABA:H2O and neuropathy severity was also seen. This study demonstrates that lower levels of thalamic GABA in participants with painless DPN may reflect neuroplasticity due to reduced afferent pain impulses, whereas partially preserved levels of GABA in painful DPN may indicate that central GABAergic pathways are involved in the mechanisms of neuropathic pain in diabetes. Article Highlights: The thalamus has been shown to play a key role in the cerebral mechanisms of diabetic peripheral neuropathy (DPN), but neurotransmitter levels have not been explored. We sought to determine the levels of excitatory (glutamate) and inhibitory (γ-aminobutyric acid [GABA]) neurotransmitter levels in the thalamus in participants with painful and painless DPN. Thalamic GABA levels were reduced in participants with painless DPN, with partially preserved levels seen in painful DPN. Alterations of thalamic GABAergic pathways could be involved in the central mechanisms of both painful and painless DPN. [ABSTRACT FROM AUTHOR]

In this work, a sustainable and efficient procedure for the synthesis of isoxazol-5(4H)-one and 1,2,4-triazoloquinazolinone derivatives via multi-component reactions using a natural deep eutectic solvent prepared from choline chloride and glutamic acid is described. The proposed methodology is capable of providing the requested products during acceptable reaction times in good to high yields under green conditions. The utilization of affordable, readily available, non-toxic, and bio-compatible reagents for the synthesis of the catalyst, a straightforward procedure for the preparation of the catalyst and products, simple work-up, and applicability in large-scale synthesis are the prominent features of this method. Also, the catalyst can be recovered easily and reused several times in the studied reactions. [ABSTRACT FROM AUTHOR]

Fish by-products can be converted into high-value-added products like fish protein hydrolysates (FPHs), which have high nutritional value and are rich in bioactive peptides with health benefits. This study aims to characterise FPHs derived from salmon heads (HPSs) and Cape hake trimmings (HPHs) using Alcalase for enzymatic hydrolysis and Subcritical Water Hydrolysis (SWH) as an alternative method. All hydrolysates demonstrated high protein content (70.4–88.7%), with the degree of hydrolysis (DH) ranging from 10.7 to 36.4%. The peptide profile of FPHs indicated the breakdown of proteins into small peptides. HPSs showed higher levels of glycine and proline, while HPHs had higher concentrations of glutamic acid, leucine, threonine, and phenylalanine. Similar elemental profiles were observed in both HPHs and HPSs, and the levels of Cd, Pb, and Hg were well below the legislated limits. Hydrolysates do not have a negative effect on cell metabolism and contribute to cell growth. HPSs and HPHs exhibited high 2,2′–azino-bis(3 ethylbenzthiazoline-6)-sulfonic acid (ABTS) radical scavenging activity, Cu2+ and Fe2+ chelating activities, and angiotensin-converting enzyme (ACE) inhibitory activity, with HPHs generally displaying higher activities. The α-amylase inhibition of both FPHs was relatively low. These results indicate that HPHs are a promising natural source of nutritional compounds and bioactive peptides, making them potential candidates for use as an ingredient in new food products or nutraceuticals. SWH at 250 °C is a viable alternative to enzymatic methods for producing FPHs from salmon heads with high antioxidant and chelating properties. [ABSTRACT FROM AUTHOR]

Calcium-binding peptides have gained significant attention due to their potential applications in various fields. In this study, we aimed to prepare, characterize, and evaluate the stability of calcium-binding peptides derived from chicken blood. Chicken hemoglobin peptides (CPs) were obtained by protease hydrolysis and were applied to prepare chicken hemoglobin peptide–calcium chelate (CP-Ca). The preparation conditions were optimized, and the characteristics and stability of CP-Ca were analyzed. The optimal chelating conditions were determined by single-factor and response surface tests, and the maximum calcium ion chelating rate was 77.54%. Amino acid analysis indicated that glutamic acid and aspartic acid motifs played an important role in the chelation of the calcium ions and CP. According to the characterization analysis, CP-Ca was a different substance compared with CP; calcium ions chelated CPs via the sites of carbonyl oxygen, carboxyl oxygen, and amino nitrogen groups; and after the chelation, the structure changed from a smooth homogeneous plate to compact granular. The stability analysis showed that CP-Ca was stable at different temperatures, pH, and gastrointestinal conditions. The study indicates that chicken blood is a promising source of peptide–calcium chelates, providing a theoretical basis for application in functional foods and improving the utilization value of chicken blood. [ABSTRACT FROM AUTHOR]