المؤلفون: Yuexia Liao, Lijuan Fan, Peng Bin, Congrui Zhu, Qingyi Chen, Yepeng Cai, Jielin Duan, Qian Cai, Wei Han, Shizhen Ding, Xiangyu Hu, Yiran Zhang, Yulong Yin, Wenkai Ren

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 11/1/2022, Vol. 119 Issue 44, p1-11, 44p

مصطلحات موضوعية: B cell differentiation, GERMINAL centers, GABA, B cells, BUTYRIC acid

مستخلص: Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA⁺ B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA-mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling-mediated intestinal mucosal immunity as a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN. [ABSTRACT FROM AUTHOR]

: Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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.)

المؤلفون: Saori Yokoi^1,2 yokois@pharm.hokudai.ac.jp, Kiyoshi Naruse², Yasuhiro Kamei², Satoshi Ansai^2,3, Masato Kinoshita⁴, Mari Mito⁵, Shintaro Iwasaki^5,6, Shuntaro Inoue¹, Teruhiro Okuyama⁷, Shinichi Nakagawa¹, Larry J. Young^8,9,10, Hideaki Takeuchi^3,11 hideaki.takeuchi.a8@tohoku.ac.jp

المصدر: Proceedings of the National Academy of Sciences of the United States of America. 3/3/2020, Vol. 117 Issue 9, p4802-4808. 7p.

مصطلحات موضوعية: *ORYZIAS latipes, *BUTYRIC acid, *OXYTOCIN, *ADENOSINE triphosphatase

مستخلص: Oxytocin is a central neuromodulator required for facilitating mate preferences for familiar individuals in a monogamous rodent (prairie vole), irrespective of sex. While the role of oxytocin in mate choice is only understood in a few monogamous species, its function in nonmonogamous species, comprising the vast majority of vertebrate species, remains unclear. To address this issue, we evaluated the involvement of an oxytocin homolog (isotocin, referred herein as oxt) in mate choice in medaka fish (Oryzias latipes). Female medaka prefer to choose familiar mates, whereas male medaka court indiscriminately, irrespective of familiarity. We generated mutants of the oxt ligand (oxt) and receptor genes (oxtr1 and oxtr2) and revealed that the oxt-oxtr1 signaling pathway was essential for eliciting female mate preference for familiar males. This pathway was also required for unrestricted and indiscriminate mating strategy in males. That is, either oxt or oxtr1 mutation in males decreased the number of courtship displays toward novel females, but not toward familiar females. Further, males with these mutations exhibited enhanced mate-guarding behaviors toward familiar females, but not toward novel females. In addition, RNA-sequencing (seq) analysis revealed that the transcription of genes involved in gamma-amino butyric acid metabolism as well as those encoding ion-transport ATPase are upregulated in both oxt and oxtr1 mutants only in female medaka, potentially explaining the sex difference of the mutant phenotype. Our findings provide genetic evidence that oxt-oxtr1 signaling plays a role in the mate choice for familiar individuals in a sexspecific manner in medaka fish. [ABSTRACT FROM AUTHOR]

المؤلفون: Fernández-Solari, Javier, Scorticati, Camila, Mohn, Claudia, De Laurentiis, Andrea, Billi, Silvia, Franchi, Ana, McCann, Samuel M., Rettori, Valeria

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2004 Mar 01. 101(9), 3264-3268.

الوصول الحر: https://www.jstor.org/stable/3371190Test

المؤلفون: Absalom, Nathan¹, Eghorn, Laura F.², Villumsen, Inge S.², Karim, Nasiara¹, Bay, Tina², Olsen, Jesper V.³, Knudsen, Gitte M.⁴, Bräuner-Osborne, Hans², Frølund, Bente², Clausen, Rasmus P.², Chebib, Mary¹ mary.collins@sydney.edu.au, Wellendorph, Petrine² pw@farma.ku.dk

المصدر: Proceedings of the National Academy of Sciences of the United States of America. 8/14/2012, Vol. 109 Issue 33, p13404-13409. 6p.

مصطلحات موضوعية: *GABA receptors, *BUTYRIC acid, *PROTEIN binding, *PHARMACOLOGY, *XENOPUS laevis

مستخلص: γ-Hydroxybutyric acid (GHB) binding to brain-specific high-affinity sites is well-established and proposed to explain both physiological and pharmacological actions. However, the mechanistic links between these lines of data are unknown. To identify molecular targets for specific GHB high-affinity binding, we undertook photolinking studies combined with proteomic analyses and identified several GABAA receptor subunits as possible candidates. A subsequent functional screening of various recombinant GABAA receptors in Xenopus laevis oocytes using the two-electrode voltage clamp technique showed GHB to be a partial agonist at αβδ- but not αβγ-receptors, proving that the δ-subunit is essential for potency and efficacy. GHB showed preference for α4 over α(1,2,6)-subunits and preferably activated α4β1δ (EC50 = 140 nM) over α4β(2/3)δ (EC50 = 8.41/1.03 mM). Introduction of a mutation, α4F71L, in α4β1(δ)-receptors completely abolished GHB but not GABA function, indicating nonidentical binding sites. Radioligand binding studies using the specific GHB radioligand [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid showed a 39% reduction (P = 0.0056) in the number of binding sites in α4 KO brain tissue compared with WT controls, corroborating the direct involvement of the α4-subunit in high-affinity GHB binding. Our data link specific GHB forebrain binding sites with α4-containing GABAA receptors and postulate a role for extrasynaptic α4δ-containing GABAA receptors in GHB pharmacology and physiology. This finding will aid in elucidating the molecular mechanisms behind the proposed function of GHB as a neurotransmitter and its unique therapeutic effects in narcolepsy and alcoholism. [ABSTRACT FROM AUTHOR]

المؤلفون: Schmitt, Henri, Guyaux, Michel, Pochet, Roland, Kram, Raphael

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 1980 Jul 01. 77(7), 4065-4068.

الوصول الحر: https://www.jstor.org/stable/9036Test

المؤلفون: Yong-Jun Chen, Meng Zhang, Dong-Min Yin, Lei Wen, Annie Ting, Pu Wang, Yi-Sheng Lu, Xin-Hong Zhu, Shu-Ji Li, Cui-Ying Wi, Xue-Ming Wang, Lai, Cary, Wen-Cheng Xiong, Lin Mei, Tian-Ming Gao

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 12/14/2010, Vol. 107 Issue 50, p21818-21823, 6p, 5 Graphs

مصطلحات موضوعية: AMINOBUTYRIC acid, AMINO acids, BUTYRIC acid, AMINO acid neurotransmitters, INTERNEURONS

مستخلص: Neuregulin 1 (NRG1) is a trophic factor that acts by stimulating ErbB receptor tyrosine kinases and has been implicated in neural development and synaptic plasticity. In this study, we investigated mechanisms of its suppression of longterm potentiation (LTP) in the hippocampus. We found that NRG1 did not alter glutamatergic transmission at SC-CAl synapses but increased the GABAA receptormediated synaptic currents in CAl pyramidal cells via a presynaptic mechanism. Inhibition of GABAA receptors blocked the suppressing effect of NRG1 on LTP and prevented ecto-ErbB4 from enhancing LIP, implicating a role of GABAergic transmission. To test this hypothesis further, we generated parvalbumin (PV)-Cre;ErbB4^-/- mice in which ErbB4, an NRG1 receptor in the brain, is ablated specifically in PV-positive interneurons. NRG1 was no longer able to increase inhibitory postsynaptic currents and to suppress LTP in PV-Cre; ErbB4^-/- hippocampus. Accordingly, contextual fear conditioning, a hippocampus-dependent test, was impaired in PV-Cre;ErbB4^-/- mice. In contrast, ablation of ErbB4 in pyramidal neurons had no effect on NRG1 regulation of hippocampal LIP or contextual fear conditioning. These results demonstrate a critical role of ErbB4 in PV-positive interneurons but not in pyramidal neurons in synaptic plasticity and support a working model that NRG1 suppresses LIP by enhancing GABA release. Considering that NRG1 and ErbB4 are susceptibility genes of schizophrenia, these observations contribute to a better understanding of how abnormal NRG1/ErbB4 signaling may be involved in the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

: Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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.)

المؤلفون: Shuttle, C. G., Hamilton, R., O'Regan, B. C., Nelson, J., Durrant, J. R.

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 9/21/2010, Vol. 107 Issue 38, p16448-16452, 5p

مصطلحات موضوعية: ORGANIC electronics, ELECTRONIC equipment, BUTYRIC acid, OPTOELECTRONICS, SOLAR cells, ELECTRONIC circuits

مستخلص: A key challenge for organic electronics research is to develop device models that correctly account for the structural and energetic disorder typically present in such materials. In this paper we report an approach to analyze the electrical performance of an organic electronic device based upon charge extraction measurements of charge densities and transient optoelectronic measurements of charge carrier dynamics. This approach is applied to a poly(3-hexyl thiophene) (P3HT)/6,6 phenyl C61 butyric acid methyl ester (PCBM) blend photovoltaic device. These measurements are employed to determine the empirical rate law for bimolecular recombination losses, with the energetic disorder present in the materials being accounted for by a charge-density-dependent recombination coefficient. This rate law is then employed to simulate the current! voltage curve. This simulation assumes the only mechanism for the loss of photogenerated charges is bimolecular recombination and employs no fitting parameters. Remarkably the simulation is in good agreement with the experimental current/voltage data over a wide range of operating conditions of the solar cell. We thus demonstrate that the primary determinant of both the open-circuit voltage and fill factor of P3HT: PCBM devices is bimolecular recornbination. We go on to discuss the applicability of this analysis approach to other materials systems, and particularly to emphasize the effectiveness of this approach where the presence of disorder complicates the implementation of more conventional, voltagebased analyses such as the Shockley diode equation. [ABSTRACT FROM AUTHOR]

: Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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.)

المؤلفون: Rúźićka, Kamil, Strader, Lucia C., Bailly, Aurélien, Yang, Haibing, Blakeslee, Joshua, Łangowski, Łukasz, Nejedlá, Eliška, Fujita, Hironori, ltoh, Hironori, Syōno, Kunihiko, Hejátko, Jan, Gray, William M., Martinoia, Enrico, Geisler, Markus, Bartel, Bonnie, Murphy, Angus S., Friml, Jirl

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 6/8/2010, Vol. 107 Issue 23, p10749-10753, 5p

مصطلحات موضوعية: ARABIDOPSIS, AUXIN, BUTYRIC acid, CELL membranes, MULTIDRUG resistance, INDOLE, HOMEOSTASIS

مستخلص: Differential distribution of the plant hormone auxin within tissues mediates a variety of developmental processes. Cellular auxin levels are determined by metabolic processes including synthesis, degradation, and (de)conjugation, as well as by auxin transport across the plasma membrane. Whereas transport of free auxins such as naturally occurring indole-3-acetic acid (IAA) is well characterized, little is known about the transport of auxin precursors and metabolites. Here, we identify a mutation in the ABCG37 gene of Arabidopsis that causes the polar auxin transport inhibitor sensitive I (,pisl) phenotype manifested by hypersensitivity to auxinic compounds. ABCG37 encodes the pleiotropic drug resistance transporter that transports a range of synthetic auxinic compounds as well as the endogenous auxin precursor indole-3-butyric acid (IBA), but not free IAA. ABCG37 and its homolog ABCG36 act redundantly atoutermost root plasma membranes and, unlike established IAA transporters from the PIN and ABCB families, transport IBA out of the cells. Our findings explore possible novel modes of regulating auxin homeostasis and plant development by means of directional transport of the auxin precursor IBA and presumably also other auxin metabolites. [ABSTRACT FROM AUTHOR]

: Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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.)

المؤلفون: Lorena Arancibia-Cârcamo, I., Yuen, Eunice Y., Muir, James, Lumb, Michael J., Michels, Guido, Saliba, Richard S., Smart, Trevor G., Zhen Yan, Kittler, Josef T., Moss, Stephen J.

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 10/13/2009, Vol. 106 Issue 41, p17552-17557, 6p

مصطلحات موضوعية: UBIQUITIN, AMINO acids, BUTYRIC acid, NEURAL transmission, CEREBRAL ischemia, LYSOSOMES, ION channels

مستخلص: The strength of synaptic inhibition depends partly on the number of GABAA receptors (GABAARS) found at synaptic sites. The trafficking of GABAARS within the endocytic pathway is a key determinant of surface GABAAR number and is altered in neuropathologies, such as cerebral ischemia. However, the molecular mechanisms and signaling pathways that regulate this trafficking are poorly understood. Here, we report the subunit specific lysosomal targeting of synaptic GABAARs. We demonstrate that the targeting of synaptic GABAARs into the degradation pathway is facilitated by ubiquitination of a motif within the intracellular domain of the y2 subunit. Blockade of lysosomal activity or disruption of the trafficking of ubiquitinated cargo to lysosomes specifically increases the efficacy of synaptic inhibition without altering excitatory currents. Moreover, mutation of the ubiquitination site within the γ2 subunit retards the lysosomal targeting of GABAARs and is sufficient to block the loss of synaptic GABAARs after anoxic insult. Together, our results establish a previously unknown mechanism for influencing inhibitory transmission under normal and pathological conditions. [ABSTRACT FROM AUTHOR]

: Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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.)

المؤلفون: Chandra-Shekara, A. C., Venugopal, Srivathsa C., Barman, Subhankar Roy, Kachroo, Aardra, Kachroo, Pradeep

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 4/24/2007, Vol. 104 Issue 17, p7277-7282, 6p

مصطلحات موضوعية: ARABIDOPSIS, FATTY acids, ACETIC acid, GENE expression, CARBOXYLIC acids, BUTYRIC acid

مستخلص: In Arabidopsis, resistance to Turnip Crinkle Virus (TCV) depends on the resistance (R) gene, HRT, and the recessive locus rrt. Resistance also depends on salicylic acid (SA), EDS1, and PAD4. Exogenous application of SA confers resistance in RRT-containing plants by increasing HRT transcript levels in a PAD4-dependent manner. Here we report that reduction of oleic acid (18:1) can also induce HRT gene expression and confer resistance to TCV. However, the 18:1-regulated pathway is independent of SA, rrt, EDS1, and PAD4. Reducing the levels of 18:1. via a mutation in the SSI2-encoded stearoylacyl carrier protein-desaturase, or by exogenous application of glycerol, increased transcript levels of HRTas well as several other R genes. Second-site mutations in the ACT1-encoded glycerol-3-phosphate acyltransferase or GLY1-encoded glycerol-3- phosphate dehydrogenase restored 18:1 levels in HRT ssi2 plants and reestablished a dependence on rrt. Resistance to TCV and HRT gene expression in HRT act1 plants was inducible by SA but not by glycerol, whereas that in HRT pad4 plants was inducible by glycerol but not by SA. The low 18:1-mediated induction of R gene expression was also dependent on ACT1 but independent of EDS1, PAD4, and RAR1. Intriguingly, TCV inoculation did not activate this 18:1-regulated pathway in HRT plants, but instead resulted in the induction of several genes that encode 18:1-synthesizing isozymes. These results suggest that the 18:1-regulated pathway may be specifically targeted during pathogen infection and that altering 18:1 levels may serve as a unique strategy for promoting disease resistance. [ABSTRACT FROM AUTHOR]

: Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences 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.)