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Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neuromodulation in the retina is crucial for effective processing of retinal signal at different levels of illuminance. Intrinsically photosensitive retinal ganglion cells (ipRGCs), the neurons that drive nonimage-forming visual functions, express a variety of neuromodulatory receptors that tune intrinsic excitability as well as synaptic inputs. Past research has examined actions of neuromodulators on light responsiveness of ipRGCs, but less is known about how neuromodulation affects synaptic currents in ipRGCs. To better understand how neuromodulators affect synaptic processing in ipRGC, we examine actions of opioid and dopamine agonists have on inhibitory synaptic currents in ipRGCs. Although µ-opioid receptor (MOR) activation had no effect on γ-aminobutyric acid (GABA) currents, dopamine [via the D1-type dopamine receptor (D1R)]) amplified GABAergic currents in a subset of ipRGCs. Furthermore, this D1R-mediated facilitation of the GABA conductance in ipRGCs was mediated by a cAMP/PKA-dependent mechanism. Taken together, these findings reinforce the idea that dopamine's modulatory role in retinal adaptation affects both nonimage-forming and image-forming visual functions. NEW & NOTEWORTHY: Neuromodulators such as dopamine are important regulators of retinal function. Here, we demonstrate that dopamine increases inhibitory inputs to intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to its previously established effect on intrinsic light responsiveness. This indicates that dopamine, in addition to its ability to intrinsically modulate ipRGC activity, can also affect synaptic inputs to ipRGCs, thereby tuning retina circuits involved in nonimage-forming visual functions. [ABSTRACT FROM AUTHOR]

Tomatoes (Solanum lycopersicum L.) are nutrient-rich fruits with a high glutamic acid content, making them a suitable source for producing γ-aminobutyric acid (GABA) through the action of lactic acid bacteria (LAB). LAB plays a pivotal role in lactic fermentation, enhancing the taste and nutritional value of food products, often contributing to their health benefits. This study isolated GABA-producing LAB from tomatoes and assessed their potential for producing GABA-enriched fermented tomato juice. The results indicated the isolation of 15 LAB strains from the samples of five different tomatoes. All of these strains demonstrated the capability to produce GABA, with levels ranging from 1.732 to 3.113 mg/mL, as determined using thin-layer chromatography (TLC). Through sequencing, the promising strain TO42, identified as Weissella cibaria, was selected for tomato juice fermentation. Furthermore, GABA-enriched tomato juice was successfully fermented at 15 °Brix for 72 h, resulting in the highest recorded GABA and lactic acid content of 9.185 ± 0.398 mg/mL and 13.05 ± 1.56 g/L, respectively. [ABSTRACT FROM AUTHOR]

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions: Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

γ‐aminobutyric acid (GABA) has shown promise in enhancing crop tolerance to heavy metal stress. To improve the cadmium (Cd) phytoremediation capacity of hyperaccumulator Solanum nigrum var. humile, the effects of exogenous GABA on the growth and Cd accumulation of S. nigrum var. humile were studied. When exposed to Cd stress (0.1 mg/L) through irrigation, S. nigrum var. humile exhibited inhibited growth, characterized by decreased biomass and contents of photosynthetic pigments (chlorophyll a, chlorophyll b, total chlorophyll, and carotenoid). However, the application of exogenous GABA at 1 and 2 g/L increased various organs biomass and photosynthetic pigment content of S. nigrum var. humile to certain degree under Cd stress. Compared with the Cd treatment, the concentrations of 1 and 2 g/L GABA increased the shoot biomass by 8.24% and 16.62%, respectively. GABA also increased the Cd contents, bioconcentration factors, and Cd extractions in various organs of S. nigrum var. humile. Compared with the Cd treatment, the concentrations of 1 and 2 g/L GABA increased the shoot Cd extraction by 17.66% and 24.47%, respectively. Moreover, correlation and gray relational analyses showed that the shoot biomass, chlorophyll b content, and total chlorophyll content were the top three parameters closely related to shoot Cd extraction. These findings suggest that GABA can alleviate Cd‐induced stress in S. nigrum var. humile, thus enhancing its phytoremediation capacity for Cd‐contaminated soils. [ABSTRACT FROM AUTHOR]

Copyright of Taiwanese Journal of Agricultural Chemistry & Food Science is the property of Agricultural Chemical Society of Taiwan and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

White mold, caused by the necrotrophic fungus Sclerotinia sclerotiorum, is a challenging disease to common bean cultivation worldwide. In the current study, two non-proteinogenic amino acids (NPAAs), γ-aminobutyric acid (GABA) and ß-alanine, were suggested as innovative environmentally acceptable alternatives for more sustainable management of white mold disease. In vitro, GABA and ß-alanine individually demonstrated potent dose-dependent fungistatic activity and effectively impeded the radial growth and development of S. sclerotiorum mycelium. Moreover, the application of GABA or ß-alanine as a seed treatment followed by three root drench applications efficiently decreased the disease severity, stimulated plant growth, and boosted the content of photosynthetic pigments of treated S. sclerotiorum-infected plants. Furthermore, although higher levels of hydrogen peroxide (H2O2), superoxide anion (O2•-), and malondialdehyde (MDA) indicated that S. sclerotiorum infection had markedly triggered oxidative stress in infected bean plants, the exogenous application of both NPAAs significantly reduced the levels of the three studied oxidative stress indicators. Additionally, the application of GABA and ß-alanine increased the levels of both non-enzymatic (total soluble phenolics and flavonoids), as well as enzymatic (catalase [CAT], peroxidases [POX], and polyphenol oxidase [PPO]) antioxidants in the leaves of S. sclerotioruminfected plants and improved their scavenging activity and antioxidant efficiency. Applications of GABA and ß-alanine also raised the proline and total amino acid content of infected bean plants. Lastly, the application of both NPAAs upregulated the three antioxidant-related genes PvCAT1, PvCuZnSOD1, and PvGR. Collectively, the fungistatic activity of NPAAs, coupled with their ability to alleviate oxidative stress, enhance antioxidant defenses, and stimulate plant growth, establishes them as promising ecofriendly alternatives for white mold disease management for sustainable bean production. [ABSTRACT FROM AUTHOR]

• Conduction velocities of somatosensory pathway were experimentally determined in patients with succinic semialdehyde dehydrogenase deficiency (SSADHD), an inherited disorder of GABA metabolism. • Somatosensory latencies were delayed in SSADHD patients compared with healthy and disease controls. • The findings support the hypotheses that myelin sheath thickness is reduced in SSADHD. Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a genetic disorder resulting in abnormal regulation of γ-aminobutyric acid, lipid metabolism, and myelin biogenesis, leading to ataxia, seizures, and cognitive impairment. Since the myelin sheath is thinner in a murine model of SSADHD compared to a wild type, we hypothesized that this also holds for human brain. We tested whether the conduction velocity in the somatosensory pathway is accordingly delayed. Somatosensory evoked magnetic fields (SEF) produced by transcutaneous electrical stimulation of the median nerve were measured in 13 SSADHD patients, 11 healthy and 14 disease controls with focal epilepsy. The peak latencies of the initial four components (M1, M2, M3 and M4) were measured. The SEF waveforms and scalp topographies were comparable across the groups. The latencies were statistically significantly longer in the SSADHD group compared to the two controls. We found these latencies for the SSADHD, healthy and disease controls respectively to be: M1: (21.9 ± 0.8 ms [mean ± standard error of the mean], 20.4 ± 0.6 ms, and 21.0 ± 0.4 ms) (p < 0.05); M2: (36.1 ± 1.0 ms, 33.1 ± 0.6 ms, and 32.1 ± 1.1 ms) (p < 0.005); M3: (62.5 ± 2.4 ms, 54.7 ± 2.0 ms, and 49.9 ± 1.8 ms) (p < 0.005); M4: (86.2 ± 2.3 ms, 78.8 ± 2.8 ms, and 73.5 ± 2.9 ms) (p < 0.005). The SEF latencies are delayed in patients with SSADHD compared with healthy controls and disease controls. This is the first study that compares conduction velocities in the somatosensory pathway in SSADHD, an inherited disorder of GABA metabolism. The longer peak latency implying slower conduction velocity supports the hypothesis that myelin sheath thickness is decreased in SSADHD. [ABSTRACT FROM AUTHOR]

ABSTRACT: Tomatoes (Solanum lycopersicum L.) are nutrient-rich fruits with a high glutamic acid content, making them a suitable source for producing γ-aminobutyric acid (GABA) through the action of lactic acid bacteria (LAB). LAB plays a pivotal role in lactic fermentation, enhancing the taste and nutritional value of food products, often contributing to their health benefits. This study isolated GABA-producing LAB from tomatoes and assessed their potential for producing GABA-enriched fermented tomato juice. The results indicated the isolation of 15 LAB strains from the samples of five different tomatoes. All of these strains demonstrated the capability to produce GABA, with levels ranging from 1.732 to 3.113 mg/mL, as determined using thin-layer chromatography (TLC). Through sequencing, the promising strain TO42, identified as Weissella cibaria, was selected for tomato juice fermentation. Furthermore, GABA-enriched tomato juice was successfully fermented at 15 °Brix for 72 h, resulting in the highest recorded GABA and lactic acid content of 9.185 ± 0.398 mg/mL and 13.05 ± 1.56 g/L, respectively.

In this study, the fresh leaves of Yun kang 10 with one bud and two or three leaves in spring, summer and autumn were used as raw materials. After anaerobic treatment, white tea was processed by the same process. The quality differences of white tea made from raw materials in three seasons after anaerobic treatment were explored by sensory evaluation, physical and chemical composition determination and UHPLC-MS/MS high-throughput detection technology to detect the content of amino acid components. The results showed that there were significant differences in the quality of white tea in the three seasons. The dry tea of white tea in spring was bright green in color. The aroma was strong, lasting, high and intensive, and had a variety of aroma types such as flowery, honey, tip aroma, medicinal and the fragrance of unique process. The taste was strong, fresh, sweet and brisk. The color of tea soup was bright yellow. Infused leaf was soft and bright. The quality of sensory was the best. The contents of amino acids, soluble sugar, caffeine, water extract and flavonoids of white tea were the highest in spring, and the content of tea polyphenols white tea was the highest in summer. A total of twenty amino acids were detected, of which 18 amino acids were significantly different (P

Lactic acid bacteria (LAB) can produce γ-aminobutyric acid (GABA) with antioxidant properties and sedative effects when it binds to the GABA receptor in the human brain. LAB can also produce bacteriocin-like inhibitory substances (BLIS) with antimicrobial capabilities during carbohydrate fermentation. GABA and BLIS are natural compounds with potential health benefits and food preservation properties. Lactobacillus brevis C23 was co-cultured with three different LABs as inducers, which produced the highest GABA content and BLIS activity. They were cultured in various plant-based media to obtain an edible and better-tasting final product over commercially available media like MRS broth. A coconut-based medium with additives was optimized using response surface methodology (RSM) to increase GABA and BLIS production. The optimized medium for maximum GABA production (3.22 ± 0.01 mg/mL) and BLIS activity (84.40 ± 0.44%) was a 5.5% coconut medium containing 0.23% glucose, 1.44% Tween 20, 0.48% L-glutamic acid, and 0.02% pyridoxine. Due to the presence of GABA, the cell-free supernatant (CFS) as a postbiotic showed higher antioxidant activity than other food preservatives like nisin and potassium sorbate. Finally, microbiological tests on food samples showed that the postbiotic was more effective than other preservatives at combating the growth of LAB, molds and coliform bacteria, making it a possible food preservative. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the γ-aminobutyric acid (GABA) production ability of 20 Lactobacillus and 25 Bifidobacterium strains which were previously isolated in our laboratory. Effect of initial pH, incubation time, monosodium glutamate (MSG), and pyridoxal-5′-phosphate (PLP) concentration for highest GABA production by two potent bacterial strains, Levilactobacillus brevis LAB6 and Limosilactobacillus fermentum LAB19 were optimized in the MRS media. A threefold increase in GABA production at an initial pH 4.0, incubation time of 120 h in medium supplemented with 3% MSG and 400 μM of PLP for LAB6 and 300 μM for LAB19 lead to the production of 19.67 ± 0.28 and 20.77 ± 0.14 g/L of GABA, respectively. Coculturing both strains under optimized conditions led to a GABA yield of 20.02 ± 0.17 g/L. Owing to potent anti-inflammatory activity in-vitro, as reported previously, and highest GABA production ability of LAB6 (MTCC 25662), its whole-genome sequencing and bioinformatics analysis was carried out for mining genes related to GABA metabolism. LAB6 harbored a complete glutamate decarboxylase (GAD) gene system comprising gadA, gadB, and gadC as well as genes responsible for the beneficial probiotic traits, such as for acid and bile tolerance and host adhesion. Comparative genomic analysis of LAB6 with 28 completely sequenced Levilactobacillus brevis strains revealed the presence of 95 strain-specific genes-families that was significantly higher than most other L. brevis strains. [ABSTRACT FROM AUTHOR]

Objectiveγ-aminobutyric acid (GABA) is a neurotransmitter inhibitor that has beneficial effects on various health conditions such as hypertension, cognitive dysfunction, and anxiety. In this study, we investigated a novel yogurt naturally enriched with GABA using a Levilactobacillus brevis strain isolated in our laboratory; the specific optimum yogurt production conditions for this strain were determined.MethodsWe isolated an L. brevis strain and used it to produce yogurt naturally enriched with GABA. We explored the optimal conditions to enhance GABA yield, including fermentation temperature, inoculation amount, L-monosodium glutamate (L-MSG) concentration, fermentation time, and sucrose content. We also performed mixed fermentation with Streptococcus thermophilus and evaluated the quality of the yogurt.ResultsFollowing optimization (43°C, 8% inoculation amount, 1.5 g/L L-MSG, and 8% sucrose for 40 h of fermentation), the GABA yield of the yogurt increased by 2.2 times, reaching 75.3 mg/100 g. Mixed fermentation with S. thermophilus demonstrated favorable results, achieving a GABA yield akin to that found in some commercially available functional foods. Moreover, the viable microbe count in the GABA-enriched yogurt exceeded 1 × 108 cfu/mL, which is higher than that of commercial standards. The yogurt also exhibited a suitable water-holding capacity, viscosity, 3-week storage time, and favorable sensory test results.ConclusionThis study highlights the potential of naturally enriched GABA yogurt as a competitive commercial yogurt with beneficial health effects.

Seed priming is proved to be an efficient way to improve crop salt tolerance, which is a measure of pre-treating seed with various agents while obtaining enhancement to crop performance at growing stage. Gamma amino butyric acid (GABA) is a non-protein amino acid involved in various metabolic processes, and partially protects plants from environmental stress. Enhancing effects of GABA priming on germination characteristics and abiotic stress have been established in several crops. However, the effect and mechanism of GABA seed priming on salt tolerance of pepper (Capsicum annuum) are still unknown. In this study, a hybrid pepper variety of ‘Maoshu 360’ Chaotian pepper was used as material, the effects of seed priming with various concentrations of GABA (0, 1.0, 2.0, 4.0, 6.0, 8.0 μmol·L-1) on plant biomass, leaf osmotic regulating substance, leaf antioxidant capacity, leaf photosynthesis system, potassium and sodium ion uptake and distribution between leaves and shoots of pepper plants under 100 mmol·L-1 NaCl stress applied at 4-6 leaf stage were investigated. The results were as follows: (1) From the point of plant growth under salt stress, the best concentration of GABA for seed priming of pepper was 6.0 μmol·L-1, which greatly boosted the biomass of pepper plants under salt stress. (2) The mechanisms of GABA seed priming promoting salt tolerance of pepper were further analyzed. Seed priming increased the leaf contents of soluble sugar, soluble protein, chlorophyll and proline, decreased the leaf contents of O2- and malondialdehyde (MDA), enhanced the leaf activities of antioxidant enzymes, including super oxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX), and raised several chlorophyll fluorescence metrics, including Fv′/Fm′, qP_Lss, QY_Lss, NPQ_Lss and Rfd, reduced the K+ content and K+/Na+ ratio in roots and stems. (3) For a comprehensive understanding of the mechanisms of GABA seed priming promoting salt tolerance of pepper, grey correlation analysis was carried out. Based on results of grey correlation analysis, seed priming with GABA significantly alleviated salt stress to pepper plants by boosting the activities of the antioxidant enzymes POD and CAT as well as increasing the levels of osmotic regulators. In conclusion, seed priming with 6.0 μmol·L-1 GABA significantly increases salt tolerance of pepper seedlings, probably by improving antioxidant and osmotic regulating capacities of pepper plants.

Copyright of Harran Journal of Agricultural & Food Science is the property of Harran University, Faculty of Agriculture and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Approximately one-third of agricultural land worldwide is affected by salinity, which limits the productivity and sustainability of crop ecosystems. Plant-growth-promoting rhizobacteria (PGPR) are a potential solution to this problem, as PGPR increases crop yield through improving soil fertility and stress resistance. Previous studies have shown that Priestia megaterium ZS-3(ZS-3) can effectively help plants tolerate salinity stress. However, how ZS-3 regulates its metabolic adaptations in saline environments remains unclear. In this study, we monitored the metabolic rearrangement of compatibilisers in ZS-3 and combined the findings with genomic data to reveal how ZS-3 survives in stressful environments, induces plant growth, and tolerates stress. The results showed that ZS-3 tolerated salinity levels up to 9%. In addition, glutamate and trehalose help ZS-3 adapt to osmotic stress under low NaCl stress, whereas proline, K+, and extracellular polysaccharides regulate the osmotic responses of ZS-3 exposed to high salt stress. Potting experiments showed that applying the ZS-3 strain in saline and neutral soils could effectively increase the activities of soil acid phosphatase, urease, and invertase in both soils, thus improving soil fertility and promoting plant growth. In addition, strain ZS-3-GFP colonised the rhizosphere and leaves of Cinnamomum camphora well, as confirmed by confocal microscopy and resistance plate count analysis. Genomic studies and in vitro experiments have shown that ZS-3 exhibits a variety of beneficial traits, including plant-promoting, antagonistic, and other related traits (such as resistance to saline and heavy metal stress/tolerance, amino acid synthesis and transport, volatile compound synthesis, micronutrient utilisation, and phytohormone biosynthesis/regulatory potential). The results support that ZS-3 can induce plant tolerance to abiotic stresses. These data provide important clues to further reveal the interactions between plants and microbiomes, as well as the mechanisms by which micro-organisms control plant health. [ABSTRACT FROM AUTHOR]

The objectives of this study were to optimize the medium and culture conditions using a strong γ-aminobutyric acid (GABA) producer as a reference lactic acid bacterial strain, to screen and identify GABA-producing lactic acid bacterial isolates from kimchi, and to determine their extracellular GABA-producing abilities. Thin-layer chromatography was used to screen GABA-producing bacterial isolates and highperformance liquid chromatography was used to evaluate the bacterial GABA production abilities. Species-specific polymerase chain reaction analyses were used to identify GABA-producing bacterial isolates. The optimal medium and culture conditions were found to be the modified Man–Rogosa–Sharpe (MRS) broth (with an initial pH of 6.5) containing 4% sucrose, 5% glutamate, and 1% yeast extract at 37 °C for 5 days. After incubation under the optimized culture conditions, 217 kimchi bacterial isolates were screened to evaluate their respective GABA-producing abilities. Screening the 217 kimchi bacterial isolates identified 24 GABA-producing lactic acid bacterial isolates (11%): Lactobacillus plantarum (17), Lactobacillus brevis (six), and Leuconostoc mesenteroides (one), indicating that only a small proportion of the strains produce GABA in the culture broth. The extracellular GABA-producing abilities of the bacterial strains identified in this study varied even within the same species, ranging from 5.8 to 101.7 mM among the 17 GABA-producing L. plantarum isolates and from 8.5 to 88.6 mM among the six GABA-producing L. brevis isolates. In summary, three species of the 24 kimchi GABA-producing bacterial isolates were identified, including one rare species (L. mesenteroides) and the two most dominant species (L. brevis and L. plantarum). [ABSTRACT FROM AUTHOR]

White mold, caused by the necrotrophic fungus Sclerotinia sclerotiorum, is a challenging disease to common bean cultivation worldwide. In the current study, two non-proteinogenic amino acids (NPAAs), γ-aminobutyric acid (GABA) and ß-alanine, were suggested as innovative environmentally acceptable alternatives for more sustainable management of white mold disease. In vitro, GABA and ß-alanine individually demonstrated potent dose-dependent fungistatic activity and effectively impeded the radial growth and development of S. sclerotiorum mycelium. Moreover, the application of GABA or ß-alanine as a seed treatment followed by three root drench applications efficiently decreased the disease severity, stimulated plant growth, and boosted the content of photosynthetic pigments of treated S. sclerotiorum-infected plants. Furthermore, although higher levels of hydrogen peroxide (H2O2), superoxide anion (O2•−), and malondialdehyde (MDA) indicated that S. sclerotiorum infection had markedly triggered oxidative stress in infected bean plants, the exogenous application of both NPAAs significantly reduced the levels of the three studied oxidative stress indicators. Additionally, the application of GABA and ß-alanine increased the levels of both non-enzymatic (total soluble phenolics and flavonoids), as well as enzymatic (catalase [CAT], peroxidases [POX], and polyphenol oxidase [PPO]) antioxidants in the leaves of S. sclerotiorum-infected plants and improved their scavenging activity and antioxidant efficiency. Applications of GABA and ß-alanine also raised the proline and total amino acid content of infected bean plants. Lastly, the application of both NPAAs upregulated the three antioxidant-related genes PvCAT1, PvCuZnSOD1, and PvGR. Collectively, the fungistatic activity of NPAAs, coupled with their ability to alleviate oxidative stress, enhance antioxidant defenses, and stimulate plant growth, establishes them as promising eco-friendly alternatives for white mold disease management for sustainable bean production.

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and aims: As the immobility of inorganic phosphorus (P) in soil, the acquisition of P by sessile plants is limited. γ-Aminobutyric acid (GABA) as a signal molecule and a metabolite can regulate plants to cope with various stresses. However, whether GABA could contribute to the adaption to low P stress in apple plants remains unclear. Methods: This study combined different methods to detect the induction of auxin (IAA) synthesis by GABA to improve the tolerance of apple seedlings to low P stress (including growth and development analysis, reactive oxygen species (ROS) clearance effect, root structure analysis, multiple factorial analysis (MFA), gene expression analysis). Results: Exogenous GABA improved the growth of apple seedlings under low P conditions, reduced the ROS accumulation, and promoted the photosynthetic capacity. GABA contributed to the root system architecture and the development of mature area of root tips. In addition, the intervention of exogenous GABA interfered with the homeostasis of endogenous IAA and activated the expression of P starvation induction (PSI) gene, leading to the significantly increase of the P uptake in apple plants. Meanwhile, transgenic roots with overexpressing MdGAD1 enhanced the tolerance of apple seedlings to low P stress, improved the root development through regulating IAA signaling pathway, and significantly improved the P uptake of apple seedlings under low P conditions. Conclusion: All results suggested that GABA could contribute to the adaption of apple seedlings to low P conditions, by decreasing ROS accumulation, maintaining photosynthetic capacity, and increasing IAA level to improve the root development and the P absorption. [ABSTRACT FROM AUTHOR]

Mulberries, known for their high sugar content and rich bioactive compounds, have attracted attention for their potential health benefits. γ-Aminobutyric acid (GABA) is an amino acid with multiple physiological functions. To increase the GABA content and enhance the antioxidant capacity in fermented mulberry beverages, we screened a high-yielding strain, Lactobacillus brevis S3, known for its probiotic properties. L. brevis S3 demonstrated an excellent tolerance to simulated gastric acid, gastric juice, intestinal fluid, bile salts, osmotic pressure, and phenol, making it a safe and valuable probiotic candidate for mulberry fermentation. We attempted the addition of different nutritional components to enhance the GABA content in mulberry juice, including 1% yeast extract; 0.5% peptone; 0.01% metal ion complex (magnesium sulfate, manganese sulfate, and ferrous sulfate); combinations of yeast extract and peptone, and all three components. Mulberry juice supplemented with all three components reached a viable cell count of 1.2 × 1010 CFU/mL after 72 h. The antioxidant capacity and GABA titer were enhanced. The DPPH free radical scavenging capacity increased by 1.62 times, and the GABA content reached 7.48 g/L. By utilizing L. brevis S3 with excellent probiotic properties and supplementation with nutritional components, it is possible to produce low-sugar mulberry functional beverages with a high DPPH free radical scavenging capacity that are rich in GABA. [ABSTRACT FROM AUTHOR]

Objective This study investigated the effects of in ovo feeding of γ-aminobutyric acid (GABA) and embryonic thermal manipulation (ETM) on growth performance, organ indices, plasma biochemical parameters, hepatic antioxidant levels, and expression of lipid metabolism-related genes in broilers. Methods Two hundred and fifty eggs were assigned to one of four treatments: control eggs incubated under standard conditions (CON); eggs that received an in ovo injection of 10% GABA on day 17.5 of incubation (G10); thermally manipulated eggs between days 10 and 18 of incubation at 39.6°C for 6 h daily (TM); and eggs that received both treatments during incubation (G10+TM). After 28 days of rearing, five birds per treatment were selected for blood and organ sampling. Results No differences were found in hatchability or growth parameters among different treatment groups. Hepatic gene expression of catalase (CAT) and glutathione peroxidase 1 (GPx1) was upregulated (p = 0.046 and p = 0.006, respectively) in the G10+TM group, while that of nuclear factor erythroid 2–related factor 2 (NRF2) was upregulated (p = 0.039) in the G10 group. In addition, the relative gene expression of NADPH oxidase 1 (NOX1) was significantly lower (p = 0.007) in all treatment groups than that in the CON group. Hepatic fatty acid synthase (FAS) levels and average daily feed intake (ADFI) of last week showed a positive correlation (r = 0.50, p = 0.038). In contrast, the relative gene expression of the extracellular fatty acid-binding protein (EXFAB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were positively correlated (r = 0.48, p = 0.042 and r = 0.50, p = 0.031) with the overall ADFI of birds. Conclusion Taken together, the results of this study suggest that the combination of in ovo feeding of GABA and ETM can enhance hepatic antioxidant function in broilers.

γ-Aminobutyric acid (GABA) is a ubiquitous nonprotein amino acid that has multiple physiological functions and has received significant attention in the pharmaceutical and food industries. Although there are many GABA-producing bacteria, the high cost of strain cultivation limits its food additive and pharmaceutical raw material application. In our study, Lactobacillus hilgardii GZ2, a novel GABA-producing strain, was investigated. We attempted to replace nitrogen sources with silkworm pupae, the waste resource of the silk reeling industry, in GYP complex medium. The GABA titer reached 33.2 g/L by using 10 g/L silkworm pupae meal instead of tryptone. Meanwhile, the pH of fermentation was automatically controlled by adjusting the addition of glucose and monosodium glutamate. Finally, the highest GABA yield and productivity were 229.3 g/L and 3.2 g/L/h in L. hilgardii when silkworm pupae meal was replaced with tryptone combined with glucose and monosodium glutamate feeding. By utilizing the waste resource to reduce the cost of the nitrogen source and automatically controlling the pH in L. hilgardii, a hyper titer and productivity of GABA was generated for applications in the food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

GABA mediates inhibitory actions through various GABAA receptor subtypes, including 19 subunits in human GABAAR. Dysregulation of GABAergic neurotransmission is associated with several psychiatric disorders, including depression, anxiety, and schizophrenia. Selective targeting of α2/3 GABAARs can treat mood and anxiety, while α5 GABAA-Rs can treat anxiety, depression, and cognitive performance. GL-II-73 and MP-III-022, α5-positive allosteric modulators have shown promising results in animal models of chronic stress, aging, and cognitive disorders, including MDD, schizophrenia, autism, and Alzheimer's disease. Described in this article is how small changes in the structure of imidazodiazepine substituents can greatly impact the subtype selectivity of benzodiazepine GABAAR. To investigate alternate and potentially more effective therapeutic compounds, modifications were made to the structure of imidazodiazepine 1 to synthesize different amide analogs. The novel ligands were screened at the NIMH PDSP against a panel of 47 receptors, ion channels, including hERG, and transporters to identify on- and off-target interactions. Any ligands with significant inhibition in primary binding were subjected to secondary binding assays to determine their Ki values. The newly synthesized imidazodiazepines were found to have variable affinities for the benzodiazepine site and negligible or no binding to any off-target profile receptors that could cause other physiological problems. [ABSTRACT FROM AUTHOR]

γ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter implicated in neuropsychiatric disorders. The best method for quantifying GABA is proton magnetic resonance spectroscopy (1H MRS). Considering that accurate measurements of GABA are affected by slight methodological alterations, demonstrating GABA reproducibility in healthy volunteers is essential before implementing the changes in vivo. Thus, our study aimed to evaluate the back-to-back (B2B) and day-to-day (D2D) reproducibility of GABA+ macromolecules (GABA+) using a 3 Tesla MRI scanner, the new 32-channel head coil (CHC), and Mescher–Garwood Point Resolved Spectroscopy (MEGA-PRESS) technique with the scan time (approximately 10 min), adequate for psychiatric patients. The dorsomedial pre-frontal cortex/anterior cingulate cortex (dmPFC/ACC) was scanned in 29 and the dorsolateral pre-frontal cortex (dlPFC) in 28 healthy volunteers on two separate days. Gannet 3.1 was used to quantify GABA+. The reproducibility was evaluated by Pearson's r correlation, the interclass-correlation coefficient (ICC), and the coefficient of variation (CV%) (r/ICC/CV%). For Day 1, B2B reproducibility was 0.59/0.60/5.02% in the dmPFC/ACC and 0.74/0.73/5.15% for dlPFC. For Day 2, it was 0.60/0.59/6.26% for the dmPFC/ACC and 0.54/0.54/6.89 for dlPFC. D2D reproducibility of averaged GABA+ was 0.62/0.61/4.95% for the dmPFC/ACC and 0.58/0.58/5.85% for dlPFC. Our study found excellent GABA+ repeatability and reliability in the dmPFC/ACC and dlPFC. [ABSTRACT FROM AUTHOR]

Germinated soybean is rich in bioactive compounds such as γ-aminobutyric acid (GABA), polyphenols, and flavonoids. Thus, quantification of these components is critical for assessing nutritional value of soybean after germination and processing. In the current research, methods for determination of GABA, daidzein, genistein, and glycitein in germinated soybeans using high-performance liquid chromatography with ultraviolet-visible detector (HPLC-UV-VIS) were optimized. Then, soybean germination time was optimized in 'DT84' and 'DT51', two Vietnamese soybean cultivars. These cultivars were soaked for 1 h, 2 h, 3 h, 4 h, and 5 h with water-to-bean ratio of 1:5 at 26 - 28 °C to initiate germination. After being soaked, the seeds were germinated, dried, and ground into powder for quantification of GABA and isoflavone aglycones. The highest concentration of GABA, daidzein and genistein were reached after 1 h of bean soaking. Further, germinated 'DT51' had higher GABA and lower genistein and daidzein content than germinated 'DT84'. Previous studies had reported the extraction and quantification of GABA and isoflavone aglycones in various food matrices. However, in this study we performed optimization of these procedures in a soybean matrix and showed potential of germination as a low-cost processing to boost the nutritional quality of soybean. [ABSTRACT FROM AUTHOR]

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Objective: This study investigated the effects of in ovo feeding of γ-aminobutyric acid (GABA) and embryonic thermal manipulation (ETM) on growth performance, organ indices, plasma biochemical parameters, hepatic antioxidant levels, and expression of lipid metabolism-related genes in broilers. Methods: Two hundred and fifty eggs were assigned to one of four treatments: control eggs incubated under standard conditions (CON); eggs that received an in ovo injection of 10% GABA on day 17.5 of incubation (G10); thermally manipulated eggs between days 10 and 18 of incubation at 39.6°C for 6 h daily (TM); and eggs that received both treatments during incubation (G10+TM). After 28 days of rearing, five birds per treatment were selected for blood and organ sampling. Results: No differences were found in hatchability or growth parameters among different treatment groups. Hepatic gene expression of catalase (CAT) and glutathione peroxidase 1 (GPx1) was upregulated (p = 0.046 and p = 0.006, respectively) in the G10+TM group, while that of nuclear factor erythroid 2--related factor 2 (NRF2) was upregulated (p = 0.039) in the G10 group. In addition, the relative gene expression of NADPH oxidase 1 (NOX1) was significantly lower (p = 0.007) in all treatment groups than that in the CON group. Hepatic fatty acid synthase (FAS) levels and average daily feed intake (ADFI) of last week showed a positive correlation (r = 0.50, p = 0.038). In contrast, the relative gene expression of the extracellular fatty acid-binding protein (EXFAB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were positively correlated (r = 0.48, p = 0.042 and r = 0.50, p = 0.031) with the overall ADFI of birds. Conclusion: Taken together, the results of this study suggest that the combination of in ovo feeding of GABA and ETM can enhance hepatic antioxidant function in broilers. [ABSTRACT FROM AUTHOR]

The effect of fructose on γ-aminobutyric acid (GABA) content and its metabolic pathway in broccoli sprouts was investigated. The results demonstrated that the fructose treatment not only significantly increased the fresh weight, GABA, and glutamate contents in sprouts, but also promoted the activity of glutamic acid decarboxylase (GAD) and the expressions of BoGAD1 and BoGAD2. Meanwhile, fructose treatment inhibited the stem length of broccoli sprouts and enhanced the abscisic acid (ABA) production in comparison with the control. Ca2+, CaM contents, and BoCaM2 expression in broccoli sprouts were also stimulated after fructose treatment. Exogenous fructose increased inositol trisphosphate (IP3) content and activated the activity of phosphatidylinositol-specific phospholipase C (PI-PLC) and the expression of BoPLC2, contributing to Ca2+ influx into the cells. These results suggested that Ca2+ played an essential role in GABA enrichment under fructose treatment, which may be associated with GAD and PI-PLC. [ABSTRACT FROM AUTHOR]

Drought stress is an important factor limiting apple production. γ-Aminobutyric acid (GABA) exists widely in plants and participates in the response to abiotic stress as a metabolite or signaling molecule. The role of exogenous GABA in apple plants, response to long-term drought stress remains unclear. Our study confirmed that exogenous GABA affects the drought resistance of apple plants under long-term drought stress. We found that 1 mM exogenous GABA improved the resistance of apple seedlings to long-term drought stress. The plants showed better growth, less reactive oxygen radical accumulation, less damage to cell membranes and greater active photosynthetic capacity. Under long-term drought stress, exogenous GABA facilitated GABA shunt, resulting in more accumulation of organic acids, namely citric acid, succinic acid and malic acid, in roots and stems of apple seedlings. In addition, exogenous GABA upregulated the expression of cellulose-related genes and lignin-related genes, and activated secondary cell wall-related transcription factors to synthesize more cellulose and lignin. A multiple factorial analysis confirmed that the GABA shunt and the biosynthesis of cellulose and lignin substantially contributed to the growth of apple seedlings with the application of exogenous GABA under long-term drought stress. Our results suggested that exogenous GABA improved the resistance of apple seedlings to long-term drought stress by enhancing GABA shunt and secondary cell wall biosynthesis. [ABSTRACT FROM AUTHOR]

The negative control group (NC), and those STZ-induced hyperglycemic mice gavage supplemented with dH2O (STZ group), soybean residue (SR group), short time soybean residue fermentation (SSRF group) and longtime soybean residue fermentation (LSRF group). Surprisingly, inconsistent isoflavones content in soybean residues imply the efficacy in optimizing utilization of soy isoflavones in soy products demand more investigation. Keywords: soybean residue; Rhizopus oligosporus; Lactiplantibacillus plantarum; isoflavone; -aminobutyric acid (GABA); antioxidant; hyperglycemia; kidney; histopathology; diabetic mice; solid-state fermentation; blood glucose level monitoring; glucose tolerance test; kidney histopathological examination EN soybean residue Rhizopus oligosporus Lactiplantibacillus plantarum isoflavone -aminobutyric acid (GABA) antioxidant hyperglycemia kidney histopathology diabetic mice solid-state fermentation blood glucose level monitoring glucose tolerance test kidney histopathological examination 1716 15 11/17/22 20221101 NES 221101 1. Additionally, the STZ-induced hyperglycemic mice are gavage fed dH2O (STZ group), soybean residue (SR group), short time soybean residue fermentation (SSRF group) and longtime soybean residue fermentation (LSRF group). [Extracted from the article]

The beneficial effects of γ-aminobutyric acid (GABA) on oxidative damage and programmed cell death (PCD) in fresh-cut pumpkins were preliminarily demonstrated in our previous research. However, the mechanism by which GABA alleviates PCD in fresh-cut pumpkins remains unclear. In this study, we discovered that GABA treatment effectively reduced mitochondrial structural damage and membrane permeability while increasing the mitochondrial membrane potential (ΔΨm) in fresh-cut pumpkins compared to the control. Additionally, GABA-treated pumpkins exhibited higher adenosine triphosphate (ATP) content and energy charge, consistent with increased activity of H+-ATPase, succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and cytochrome c oxidase (COX). Conversely, the activity of alternative oxidase (AOX), Ca2+-ATPase, and K+-ATPase was reduced in GABA-treated pumpkins compared to the control. Moreover, key factors in apoptosis, such as the activity of six caspases and the gene expression of apoptosis-inducing factors (CmAIFs) and metacaspases (CmMCAs), were significantly decreased following GABA treatment. In conclusion, GABA effectively suppressed PCD in postharvest fresh-cut pumpkins by improving mitochondrial physiological properties and energy metabolism while inhibiting apoptosis-related factors. [Display omitted] ● GABA maintained normal ΔΨm, MPTP and ultrastructure of mitochondria. ● GABA increased energy charge by enhancing TCA cycle and electron transport chain. ● GABA decreased the activity and gene expression of apoptosis factors to inhibit PCD. [ABSTRACT FROM AUTHOR]

This study aimed to enrich corn and alfalfa silages with γ-aminobutyric acid (GABA) by utilizing high GABA-producing Lentilactobacillus buchneri. Eleven strains were screened and L. Buchneri YM9 was distinguished for its superiority in GABA production, and it was subsequently applied as an inoculant on whole-crop corn and alfalfa silage. The silage treatments were control (without inoculant), AH35 (non-GABA producing strain), YM9 (high-GABA producing strain), and 40788 (commercial GABA producing strain). The results revealed that in corn silage, pH significantly declined at the initial ensiling stage (3–7 days), with the control having the lowest pH after 90 days. The control also exhibited the highest lactic acid, while L. buchneri treatments had elevated acetic acid. Similar trends were observed in alfalfa silage, with 30 % dry matter (DM) showing lower pH and higher organic acids. YM9-inoculated corn silage had higher DM loss, reduced water-soluble carbohydrates (WSC), but increased crude protein (CP) content. YM9 and 40788 treatments in whole-crop corn silage had lower glutamate (Glu) content post-ensiling, signifying effective GABA production. YM9 treatment maintained stable and higher glutamate decarboxylase (GAD) activity, resulting in the highest GABA accumulation in corn silage (1.97 g/kg DM). Likewise, YM9 and 40788 demonstrated significantly higher GABA content in 30 % (7.6 and 6.51 g/kg DM) and 40 % (5.23 and 5.32 g/kg DM) DM alfalfa silage. Beyond enhancing fermentation and nutrient preservation, YM9 strain shows promise in enriching whole-crop corn and alfalfa with ample GABA concentration, potentially exerting anticipated biological functions when consumed by animals. • L. buchneri YM9 was selected for high GABA synthesis among the strains screened. • YM9 strain efficiently preserved the nutrients quality of corn and alfalfa silage. • The YM9 strain sufficiently enriched the silages with GABA during fermentation. [ABSTRACT FROM AUTHOR]

Approximately one-third of agricultural land worldwide is affected by salinity, which limits the productivity and sustainability of crop ecosystems. Plant-growth-promoting rhizobacteria (PGPR) are a potential solution to this problem, as PGPR increases crop yield through improving soil fertility and stress resistance. Previous studies have shown that Priestia megaterium ZS-3(ZS-3) can effectively help plants tolerate salinity stress. However, how ZS-3 regulates its metabolic adaptations in saline environments remains unclear. In this study, we monitored the metabolic rearrangement of compatibilisers in ZS-3 and combined the findings with genomic data to reveal how ZS-3 survives in stressful environments, induces plant growth, and tolerates stress. The results showed that ZS-3 tolerated salinity levels up to 9%. In addition, glutamate and trehalose help ZS-3 adapt to osmotic stress under low NaCl stress, whereas proline, K+, and extracellular polysaccharides regulate the osmotic responses of ZS-3 exposed to high salt stress. Potting experiments showed that applying the ZS-3 strain in saline and neutral soils could effectively increase the activities of soil acid phosphatase, urease, and invertase in both soils, thus improving soil fertility and promoting plant growth. In addition, strain ZS-3-GFP colonised the rhizosphere and leaves of Cinnamomum camphora well, as confirmed by confocal microscopy and resistance plate count analysis. Genomic studies and in vitro experiments have shown that ZS-3 exhibits a variety of beneficial traits, including plant-promoting, antagonistic, and other related traits (such as resistance to saline and heavy metal stress/tolerance, amino acid synthesis and transport, volatile compound synthesis, micronutrient utilisation, and phytohormone biosynthesis/regulatory potential). The results support that ZS-3 can induce plant tolerance to abiotic stresses. These data provide important clues to further reveal the interactions between plants and microbiomes, as well as the mechanisms by which micro-organisms control plant health.

Mulberries, known for their high sugar content and rich bioactive compounds, have attracted attention for their potential health benefits. γ-Aminobutyric acid (GABA) is an amino acid with multiple physiological functions. To increase the GABA content and enhance the antioxidant capacity in fermented mulberry beverages, we screened a high-yielding strain, Lactobacillus brevis S3, known for its probiotic properties. L. brevis S3 demonstrated an excellent tolerance to simulated gastric acid, gastric juice, intestinal fluid, bile salts, osmotic pressure, and phenol, making it a safe and valuable probiotic candidate for mulberry fermentation. We attempted the addition of different nutritional components to enhance the GABA content in mulberry juice, including 1% yeast extract; 0.5% peptone; 0.01% metal ion complex (magnesium sulfate, manganese sulfate, and ferrous sulfate); combinations of yeast extract and peptone, and all three components. Mulberry juice supplemented with all three components reached a viable cell count of 1.2 × 1010 CFU/mL after 72 h. The antioxidant capacity and GABA titer were enhanced. The DPPH free radical scavenging capacity increased by 1.62 times, and the GABA content reached 7.48 g/L. By utilizing L. brevis S3 with excellent probiotic properties and supplementation with nutritional components, it is possible to produce low-sugar mulberry functional beverages with a high DPPH free radical scavenging capacity that are rich in GABA.

Microglia have been suggested to be involved in the underlying mechanism of conditional fear memory formation by regulating inflammatory cytokines. However, the mechanism linking microglia and neuronal activity related to fear conditioning remains unclear. This study characterized the transcription profile of microglia in a fear memory conditional mouse model. Compared with those in control mice microglia, the most significantly induced genes were synapse-related, whereas immune-related genes were reduced due to fear memory consolidation. Whilst the increased expression of synapse-related genes was reversed after fear memory extinction, that of immunological genes was not, strongly suggesting a connection between microglia, neurons, and a dysregulated immune response following contextual fear conditioning. Furthermore, in the hippocampal microglia, we found that the expression of neurotransmitter release regulators, γ-aminobutyric acid (GABA) receptor GABRB3 and synapsin 1/2, increased under fear memory consolidation and restored (decreased) after extinction. In addition, compared with the transcription profile in peripheral monocytes, few overlapping genes were not enriched in biological processes. Taken together, the identified conditional fear stress-induced changes in mouse microglial transcription profiles suggest that microglia-neuron communication mediates contextual fear conditioning. • Synapse-related genes in microglia are changed by contextual fear conditioning. • Consolidation of fear memory induces immune dysfunction in microglia. • Microglial GABRB3 and Synapsin are changed during contextual fear conditioning. • Transcriptional profiles in microglia are different from the peripheral monocytes. [ABSTRACT FROM AUTHOR]

Gamma aminobutyric acid (GABA) is a non-proteinogenic amino acid and neurotransmitter that is produced in the islet at levels as high as in the brain. GABA is synthesized by the enzyme glutamic acid decarboxylase (GAD), of which the 65 kDa isoform (GAD65) is a major autoantigen in type 1 diabetes. Originally described to be released via synaptic-like microvesicles or from insulin secretory vesicles, beta cells are now understood to release substantial quantities of GABA directly from the cytosol via volume-regulated anion channels (VRAC). Once released, GABA influences the activity of multiple islet cell types through ionotropic GABAA receptors and metabotropic GABAB receptors. GABA also interfaces with cellular metabolism and ATP production via the GABA shunt pathway. Beta cells become depleted of GABA in type 1 diabetes (in remaining beta cells) and type 2 diabetes, suggesting that loss or reduction of islet GABA correlates with diabetes pathogenesis and may contribute to dysfunction of alpha, beta, and delta cells in diabetic individuals. While the function of GABA in the nervous system is wellunderstood, the description of the islet GABA system is clouded by differing reports describing multiple secretion pathways and effector functions. This review will discuss and attempt to unify the major experimental results from over 40 years of literature characterizing the role of GABA in the islet. [ABSTRACT FROM AUTHOR]

γ‐aminobutyric acid (GABA) is the major inhibitory neurotransmitter, and its levels in the synaptic space are controlled by the GABA transporter isoforms (GATs). GATs are structurally related to biogenic amine transporters but display interactions with distinct inhibitors used as anti‐epileptics. In this study, we engineer the binding pocket of Drosophila melanogaster dopamine transporter to resemble GAT1 and determine high‐resolution X‐ray structures of the modified transporter in the substrate‐free state and in complex with GAT1 inhibitors NO711 and SKF89976a that are analogs of tiagabine, a medication prescribed for the treatment of partial seizures. We observe that the primary binding site undergoes substantial shifts in subsite architecture in the modified transporter to accommodate the two GAT1 inhibitors. We also observe that SKF89976a additionally interacts at an allosteric site in the extracellular vestibule, yielding an occluded conformation. Interchanging SKF89976a interacting residue in the extracellular loop 4 between GAT1 and dDAT suggests a role for this motif in the selective control of neurotransmitter uptake. Our findings, therefore, provide vital insights into the organizational principles dictating GAT1 activity and inhibition. Synopsis: While γ‐aminobutyric acid (GABA) neurotransmitter release is vital to inhibitory synapse function and GABA transporters (GATs) are targeted by antiepileptic drugs, the mechanistic basis for their unique pharmacology remains elusive. Combining structural and biochemical analysis of engineered transporters, this study uncovers distinct features of the GAT binding pocket that dictate inhibitor interaction specificities. Substitution of 11 binding site residues results in a chimeric Drosophila melanogaster dopamine transporter with rat GAT1‐like inhibitor binding site (dDATGAT).Substrate‐free dDATGAT displays strongly altered binding site architecture with prominent subsites A and C′.GABA uptake inhibitors NO711 and SKF89976a bind dDATGAT within the primary binding site in the subsites A and C′.SKF89976a shows additional binding in the vestibule of dDAT displaying both competitive and noncompetitive inhibition.Modification of SKF89976a binding residues in the dDATGAT extracellular loop 4 affects neurotransmitter uptake activity. [ABSTRACT FROM AUTHOR]

Objectives: This study explores the connection between chronic stress and tinnitus, a phantom auditory perception, using an animal model., Methods: Rats were subjected to 2 h of daily restraint stress for 10 days. Tinnitus was assessed on the last day of stress exposure using the gap response of pre-pulse inhibition acoustic reflex, measured at 60 dB background sound level at 8, 16, and 20 kHz. Chronic stress-exposed rats were categorized into two groups: tinnitus (RTG) and non-tinnitus (RNTG). Various tests, including hearing assessments (distortion product otoacoustic emissions and auditory brainstem response), behavioral evaluations (elevated plus maze test and forced swimming test), and immunohistochemical studies in the auditory and limbic brain regions, were conducted to understand the relationship between chronic stress, tinnitus, and behavioral changes., Results: Following chronic restraint stress, 64.3% of the rats exhibited tinnitus with no audiometric changes. EPM and FST indicated an increase of anxiety- and depression-related behavior in RTG. Immunohistochemical analyses identified specific alterations in the expression of neurotransmitter receptors within brain regions implicated in tinnitus. Specifically, we observed a decrease in γ-aminobutyric acid A receptor α1 expression and an increase in glutamate receptor (N-methyl-D-aspartate receptor subunit 1 and receptor subunit 2B) expression in specific brain region. These changes suggest a reorganization of neural circuits associated with the tinnitus generation and behavioral changes of the rats after chronic stress exposure., Conclusion: Chronic stress alone can be a causal factor for the generation of tinnitus and behavioral changes through altered neural activities in tinnitus-related brain networks., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Long-distance signals play a vital role in plant stress response. γ-aminobutyric acid (GABA) has been proposed to be a signal and protects crops against diverse stresses. However, whether GABA acts as a long-distance signal to plant response to stresses remains unknown. Here, we found that the GABA content in cucurbita rootstocks, especially figleaf gourd, was significantly higher than that in cucumber. Figleaf gourd rootstock obviously enhanced cold tolerance and GABA accumulation in roots, xylem sap and leaves of grafting cucumber seedlings. Conversely, GABA synthesis inhibitor 3-mercaptopropionic acid (3-MPA) irrigation was more effective than its foliar application in inhibiting grafting-induced cold tolerance. Moreover, fluorescence microscopy confirmed that GABA can be transported from root to shoot through the xylem when the roots of grafted seedlings were fed with fluorescein isothiocyatate-labeled GABA under normal and cold stress conditions. Importantly, 3-MPA irrigation attenuated grafting-induced cold tolerance, as revealed by a decline in the GABA accumulation, the transcripts of ICE1, CBF1 and COR47, the activities of the antioxidant enzymes, and an increase in stomatal aperture. Collectively, our findings strongly support that GABA functions as a novel long-distance signal in figleaf gourd rootstock-induced cold tolerance of grafted cucumber seedlings by modulating CBF-signalling pathways, antioxidant system and stomatal aperture, providing new evidence for long-distance signaling-mediated cold response of plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Saline-alkali stress is a widely distributed abiotic stress that severely limits plant growth. γ-Aminobutyric acid (GABA) accumulates rapidly in plants under saline-alkali stress, but the underlying molecular mechanisms and associated regulatory networks remain unclear. Here, we report a MYB-like protein, I-box binding factor (SlMYBI), which positively regulates saline-alkali tolerance through induced GABA accumulation by directly modulating the glutamic acid decarboxylase (GAD) gene SlGAD1 in tomato (Solanum lycopersicum L.). Overexpression of SlGAD1 increased GABA levels and decreased reactive oxygen species (ROS) accumulation under saline-alkali stress, while silencing of SlGAD1 further suggested that SlGAD1 plays an active role in GABA synthesis and saline-alkali tolerance of tomato. In addition, we found that SlMYBI activates SlGAD1 transcription. Both overexpression of SlMYBI and editing of SlMYBI using CRISPR/Cas9 showed that SlMYBI regulates GABA synthesis by modulating SlGAD1 expression. Furthermore, the interaction of SlNF-YC1 with SlMYBI enhanced the transcriptional activity of SlMYBI on SlGAD1 to further improve saline-alkali tolerance in tomato. Interestingly, we found that ethylene signaling was involved in the GABA response to saline-alkali stress by RNA-seq analysis of SlGAD1-overexpressing lines. This study elucidates the involvement of SlMYBI in GABA synthesis regulation. Specifically, the SlMYBI-SlNF-YC1 module is involved in GABA accumulation in response to saline-alkali stress., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Neuromodulation in the retina is crucial for effective processing of retinal signal at different levels of illuminance. Intrinsically photosensitive retinal ganglion cells (ipRGCs), the neurons that drive nonimage-forming visual functions, express a variety of neuromodulatory receptors that tune intrinsic excitability as well as synaptic inputs. Past research has examined actions of neuromodulators on light responsiveness of ipRGCs, but less is known about how neuromodulation affects synaptic currents in ipRGCs. To better understand how neuromodulators affect synaptic processing in ipRGC, we examine actions of opioid and dopamine agonists have on inhibitory synaptic currents in ipRGCs. Although µ-opioid receptor (MOR) activation had no effect on γ-aminobutyric acid (GABA) currents, dopamine [via the D1-type dopamine receptor (D1R)]) amplified GABAergic currents in a subset of ipRGCs. Furthermore, this D1R-mediated facilitation of the GABA conductance in ipRGCs was mediated by a cAMP/PKA-dependent mechanism. Taken together, these findings reinforce the idea that dopamine's modulatory role in retinal adaptation affects both nonimage-forming and image-forming visual functions. NEW & NOTEWORTHY Neuromodulators such as dopamine are important regulators of retinal function. Here, we demonstrate that dopamine increases inhibitory inputs to intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to its previously established effect on intrinsic light responsiveness. This indicates that dopamine, in addition to its ability to intrinsically modulate ipRGC activity, can also affect synaptic inputs to ipRGCs, thereby tuning retina circuits involved in nonimage-forming visual functions.

Gamma aminobutyric acid (GABA) is a non-proteinogenic amino acid and neurotransmitter that is produced in the islet at levels as high as in the brain. GABA is synthesized by the enzyme glutamic acid decarboxylase (GAD), of which the 65 kDa isoform (GAD65) is a major autoantigen in type 1 diabetes. Originally described to be released via synaptic-like microvesicles or from insulin secretory vesicles, beta cells are now understood to release substantial quantities of GABA directly from the cytosol via volume-regulated anion channels (VRAC). Once released, GABA influences the activity of multiple islet cell types through ionotropic GABAA receptors and metabotropic GABAB receptors. GABA also interfaces with cellular metabolism and ATP production via the GABA shunt pathway. Beta cells become depleted of GABA in type 1 diabetes (in remaining beta cells) and type 2 diabetes, suggesting that loss or reduction of islet GABA correlates with diabetes pathogenesis and may contribute to dysfunction of alpha, beta, and delta cells in diabetic individuals. While the function of GABA in the nervous system is well-understood, the description of the islet GABA system is clouded by differing reports describing multiple secretion pathways and effector functions. This review will discuss and attempt to unify the major experimental results from over 40 years of literature characterizing the role of GABA in the islet.

γ-Aminobutyric acid (GABA) is a ubiquitous nonprotein amino acid that has multiple physiological functions and has received significant attention in the pharmaceutical and food industries. Although there are many GABA-producing bacteria, the high cost of strain cultivation limits its food additive and pharmaceutical raw material application. In our study, Lactobacillus hilgardii GZ2, a novel GABA-producing strain, was investigated. We attempted to replace nitrogen sources with silkworm pupae, the waste resource of the silk reeling industry, in GYP complex medium. The GABA titer reached 33.2 g/L by using 10 g/L silkworm pupae meal instead of tryptone. Meanwhile, the pH of fermentation was automatically controlled by adjusting the addition of glucose and monosodium glutamate. Finally, the highest GABA yield and productivity were 229.3 g/L and 3.2 g/L/h in L. hilgardii when silkworm pupae meal was replaced with tryptone combined with glucose and monosodium glutamate feeding. By utilizing the waste resource to reduce the cost of the nitrogen source and automatically controlling the pH in L. hilgardii, a hyper titer and productivity of GABA was generated for applications in the food and pharmaceutical industries.

GABA mediates inhibitory actions through various GABAA receptor subtypes, including 19 subunits in human GABAAR. Dysregulation of GABAergic neurotransmission is associated with several psychiatric disorders, including depression, anxiety, and schizophrenia. Selective targeting of α2/3 GABAARs can treat mood and anxiety, while α5 GABAA-Rs can treat anxiety, depression, and cognitive performance. GL-II-73 and MP-III-022, α5-positive allosteric modulators have shown promising results in animal models of chronic stress, aging, and cognitive disorders, including MDD, schizophrenia, autism, and Alzheimer’s disease. Described in this article is how small changes in the structure of imidazodiazepine substituents can greatly impact the subtype selectivity of benzodiazepine GABAAR. To investigate alternate and potentially more effective therapeutic compounds, modifications were made to the structure of imidazodiazepine 1 to synthesize different amide analogs. The novel ligands were screened at the NIMH PDSP against a panel of 47 receptors, ion channels, including hERG, and transporters to identify on- and off-target interactions. Any ligands with significant inhibition in primary binding were subjected to secondary binding assays to determine their Ki values. The newly synthesized imidazodiazepines were found to have variable affinities for the benzodiazepine site and negligible or no binding to any off-target profile receptors that could cause other physiological problems.

Alfalfa (Medicago sativa L.) is a widely grown and important forage crop. However, alkali stress is detrimental to alfalfa yield and nutritional quality. Gamma-aminobutyric acid (GABA) is a signaling molecule, it participates in and responds to metabolic regulation related to plant growth and development and stress. In this study, we clarify the effect of spraying alfalfa seedlings with GABA on the alkali tolerance of the seedlings. We determined that exogenous application of GABA at 75 mmol/L improved the resistance of alfalfa seedlings to alkali stress caused by exposure to 100 mmol/L NaHCO3, pH 8.5. Exogenous GABA significantly increased the chlorophyll content, the accumulation of soluble sugars in the plants, significantly decreased their relative electrical conductivity, malondialdehyde (MDA), superoxide anion (O2−) and hydrogen peroxide (H2O2) contents, and significantly increased the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD). Exogenous GABA increased the activities of GAD and GABA-T, increased the content of glutamate and endogenous GABA, and regulated the expression of the genes MsGAD, MsGABA-T and MsGDH. In alfalfa plants that survived for a long time, compared to the control group, root length and fresh weight were significantly higher. Exogenous GABA had a positive effect on the resistance of alfalfa seedlings to alkali stress, and the effect was closely associated with GAD and GABA-T activity, glutamate content and the levels of endogenous GABA and antioxidants. This work provides a new method for the cultivation of early-stage alfalfa seedlings under low or moderate alkali stress conditions through the application of 75 mmol/L GABA. [ABSTRACT FROM AUTHOR]

Summary: Germinated mung beans have been widely used as fresh vegetable or processed healthy food due to their high amounts of bioactive and nutritional compounds, including γ‐aminobutyric acid (GABA). The objectives of this study were to investigate the effects of different soaking conditions (temperature, ratios of seeds to water, soaking time, pH, addition of L‐glutamic acid (L‐Glu) or gibberellic acid (GA3)) and germination time on accumulation of GABA in the germinated mung bean seeds. The mung bean seeds, soaked at 40°C for 4 h with ratio of seeds to water of 1:4 (g mL−1) and then germinated for 7 h, accumulated higher amount of GABA than other soaking conditions and germination time. The addition of GA3 (0.30 mg L−1) or L‐glu (1,000 mg L−1) or acidifying to pH 5.5 of the soaking water had high impact on the GABA accumulation. Among them, the soaking water with pH 5.5 was more effective than adding with the L‐Glu or GA3 in the production of GABA (1677 mg/kg powder) and essential amino acids (16.56 g/100g powder) in the germinated mung bean seeds. The findings of this study provide useful information to produce GABA‐enriched and healthy foods from mung beans. [ABSTRACT FROM AUTHOR]

γ-Aminobutyric acid (GABA) is a non-protein amino acid with a variety of physiological functions. Recently, yeast Kluyveromyces marxianus strains involved in the catabolism and anabolism of GABA can be used as a microbial platform for GABA production. Okara, rich in nutrients, can be used as a low-cost fermentation substrate for the production of functional materials. This study first proved the advantages of the okara medium to produce GABA by K. marxianus C21 when l-glutamate (l-Glu) or monosodium glutamate (MSG) is the substrate. The highest production of GABA was obtained with 4.31 g/L at optimization condition of culture temperature 35 °C, fermentation time 60 h, and initial pH 4.0. Furthermore, adding peptone significantly increased the GABA production while glucose and vitamin B6 had no positive impact on GABA production. This research provided a powerful new strategy of GABA production by K. marxianus C21 fermentation and is expected to be widely utilized in the functional foods industry to increase GABA content for consumers as a daily supplement as suggested. [ABSTRACT FROM AUTHOR]

The antinociceptive activity of new synthesized short peptides of γ-aminobutyric acid (GABA) with pyroglutamate (pGlu) – pyroglutamyl GABA (pGlu-GABA), pyroglutamyl GABA ethyl ester (pGlu-GABA ethyl ester), and pyroglutamyl diGABA (pGlu-GABA-GABA) – has been investigated. The peptides were administered to rats in a dose of 20 mg/kg separately and in combination with pregabalin, in the same dose. Results of the tail flick test demonstrated that intraperitoneal administration of all the investigated substances exhibited antinociceptive activity, leading to increase in the tail flick latency time. The maximum value of the tail flick latency for all peptides was manifested after 90 min of administration and was higher compared to the same characteristics in the control group as follows: for pGlu-GABA, 20.5%; for pGlu-GABA ethyl ester, 40.99%; and for pGlu-diGABA, 33,23%. In addition to the own antinociceptive activity of investigated peptides, the ability to potentiate the analgesic efficacy of pregabalin was revealed. [ABSTRACT FROM AUTHOR]