The non-protein amino acid γ-aminobutyric acid (GABA) has been proposed to be an ancient messenger for cellular communication conserved across biological kingdoms. GABA has well-defined signalling roles in animals; however, whilst GABA accumulates in plants under stress it has not been determined if, how, where and when GABA acts as an endogenous plant signalling molecule. Here, we establish endogenous GABA as a bona fide plant signal, acting via a mechanism not found in animals. Using Arabidopsis thaliana, we show guard cell GABA production is necessary and sufficient to reduce stomatal opening and transpirational water loss, which improves water use efficiency and drought tolerance, via negative regulation of a stomatal guard cell tonoplast-localised anion transporter. We find GABA modulation of stomata occurs in multiple plants, including dicot and monocot crops. This study highlights a role for GABA metabolism in fine tuning physiology and opens alternative avenues for improving plant stress resilience.

BackgroundElevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood.MethodsThe cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry.ResultsElevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment.ConclusionsSTAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0963-x) contains supplementary material, which is available to authorized users.

The theory of organizational justice has been supported by numerous empirical studies in the private sector. Although public administration scholars have investigated the fairness issue in pay and promotions, the main focus was confined to specific groups such as females and racial minorities. This research seeks to fill the gap by providing some generalizable findings. We investigate the justice issue by considering both individual-and organizational-level factors. By employing hierarchical linear modeling (HLM), the research examines whether the three dimensions of organizational justicedistributive, procedural, and informational justice-and several organizational-level factors affect four outcomes, including expectancy for career development, employee satisfaction, loyalty to senior leadership, and cooperation. The analysis confirms that the three dimensions of organizational justice are substantially associated with those employee attitudes, although organizational-level factors have little impact on them.

The elevated level of the amino acid metabolite homocysteine (Hcy) is known as a risk factor for ischemic stroke. The molecular mechanisms responsible for neurotoxicity of Hcy remain largely unknown in ischemic brains. The previous studies have shown that Hcy decreases the proliferation and viability of neural stem cells (NSCs) in vivo and in vitro. Autophagy is required for the maintenance of NSCs homeostasis. In the current study, we hypothesized that the toxic effect of Hcy on NSCs may involve the changes in autophagy level following cerebral ischemia/reperfusion injury. The results showed that Hcy reduced cell viability, increased LDH release, and induced nonapoptotic cell death in primary NSCs exposed to oxygen–glucose deprivation)/reoxygenation (OGD/R). Treatment with autophagy inhibitor 3-methyladenine (3MA) partly reversed the decrease in the viability and prevented LDH release triggered by Hcy combined with OGD/R. Increased punctate LC3 dots co-localizing with Nestin-stained NSCs were also observed in the subventricular zone of Hcy-treated MCAO animals, which were partially blocked by 3MA. In vitro studies further revealed that Hcy induced the formation of autophagosomes, markedly increased the expression of the autophagic markers and decreased p-ERK, p-PI3K, p-AKT, and p-mTOR levels. In addition, MHY1485, an activator of mTOR, reduced Hcy-induced increase in LC3 and Beclin 1 protein levels, meanwhile ERK and PI3K activators (TPA, curcumin for ERK and IGF-1 for PI3K, respectively) enhanced Hcy-triggered mTOR inhibition in OGD/R NSCs. Our findings suggest that Hcy may cause excessive autophagy by downregulation of both PI3K-AKT- and ERK- dependent mTOR signaling, thereby facilitates the toxicity of Hcy on NSCs in ischemic brains.