Role Of Signaling Research Articles

Role of BDNF Signaling in the Neuroprotective and Memory-enhancing Effects of Flavonoids in Alzheimer's Disease.

Foods rich in flavonoids are associated with a reduced risk of various chronic diseases, including Alzheimer's disease (AD). In fact, growing evidence suggests that consuming flavonoid- rich foods can beneficially affect normal cognitive function. Animal models have shown that many flavonoids prevent the development of AD-like pathology and improve cognitive deficits. Identifying the molecular causes underlying the memory-enhancing effect of flavonoid-rich foods makes it possible to provide the best diet to prevent cognitive decline associated with aging and Alzheimer's disease. Based on the most recent scientific literature, this review article critically examines the therapeutic role of dietary flavonoids in ameliorating and preventing the progression of AD and enhancement of memory with a focus on the role of the BDNF signaling pathway. The databases of PubMed, Web of Science, Google Scholar, and Scopus were searched up to March 2023 and limited to English language. Search strategies were using the following keywords in titles and abstracts: (Flavonoid-rich foods OR Flavonoids OR Polyphenols); AND (Brain-Derived Neurotrophic Factor OR BDNF OR CREB OR) AND (Alzheimer's disease OR memory OR cognition OR). Flavonoid-rich foods including green tea, berries, curcumin and pomegranate exert their beneficial effects on memory decline associated with aging and Alzheimer's disease mostly through the direct interaction with BDNF signaling pathway. The neuroprotective effects of flavonoid-rich foods through the CREB-BDNF mechanism have the potential to prevent or limit memory decline due to aging and Alzheimer's disease, so their consumption throughout life may prevent age-related cognitive impairment.

Improved ovarian adiponectin system expression in polycystic ovary syndrome treated with exenatide.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility. This experimental study was conducted to elucidate the role of adiponectin signaling in rats with PCOS treated with exenatide. Twenty-eight adult female Wistar rats were divided into four groups of seven. The normal group did not receive any drug. The PCOS+vehicle (Veh) group received estradiol valerate to induce PCOS, then was divided into PCOS +E50 and PCOS+E100 groups and treated with 50 or 100 mg/kg doses of exenatide, respectively. The mRNA expression of adiponectin and adiponectin receptor 1 (Adipo-R1) was evaluated using a semi-quantitative real-time polymerase chain reaction. The results indicated that the level of adiponectin diminished in the PCOS rats while exenatide increased adiponectin expression at both doses. Adiponectin receptor mRNA levels were higher in the PCOS rats than in the normal rats (p<0.05). In addition, exenatide decreased the levels of Adipo-R1 expression. Taken together, our results showed that exenatide may improve PCOS characteristics in rats through the molecular regulation of adiponectin and its receptor.

A maize semi-dwarf mutant reveals a GRAS transcription factor involved in brassinosteroid signaling.

Brassinosteroids (BR) and gibberellins (GA) regulate plant height and leaf angle in maize (Zea mays). Mutants with defects in BR or GA biosynthesis or signaling identify components of these pathways and enhance our knowledge about plant growth and development. In this study, we characterized three recessive mutant alleles of GRAS transcription factor 42 (gras42) in maize, a GRAS transcription factor gene orthologous to the DWARF AND LOW TILLERING (DLT) gene of rice (Oryza sativa). These maize mutants exhibited semi-dwarf stature, shorter and wider leaves, and more upright leaf angle. Transcriptome analysis revealed a role for GRAS42 as a determinant of BR signaling. Analysis of the expression consequences from loss of GRAS42 in the gras42-mu1021149 mutant indicated a weak loss of BR signaling in the mutant, consistent with its previously demonstrated role in BR signaling in rice. Loss of BR signaling was also evident by the enhancement of weak BR biosynthetic mutant alleles in double mutants of nana plant1-1 and gras42-mu1021149. The gras42-mu1021149 mutant had little effect on GA-regulated gene expression, suggesting that GRAS42 is not a regulator of core GA signaling genes in maize. Single-cell expression data identified gras42 expressed among cells in the G2/M phase of the cell cycle consistent with its previously demonstrated role in cell cycle gene expression in Arabidopsis (Arabidopsis thaliana). Cis-acting natural variation controlling GRAS42 transcript accumulation was identified by expression genome-wide association study (eGWAS) in maize. Our results demonstrate a conserved role for GRAS42/SCARECROW-LIKE 28 (SCL28)/DLT in BR signaling, clarify the role of this gene in GA signaling, and suggest mechanisms of tillering and leaf angle control by BR.

A genetic mouse model mimicking MET related human osteofibrous dysplasia is characterized by delays in fracture repair and defective osteogenesis.

Osteofibrous dysplasia (OFD) is a rare, benign, fibro-osseous lesion that occurs most commonly in the tibia of children. Tibial involvement leads to bowing and predisposes to the development of a fracture which exhibit significantly delayed healing processes, leading to prolonged morbidity. We previously identified gain-of-function mutations in the MET gene as a cause for OFD. In our present study, we test the hypothesis that gain-of-function MET mutations impair bone repair due to reduced osteoblast differentiation. A heterozygous Met exon 15 skipping (MetΔ15-HET) mouse was created to imitate the human OFD mutation. The mutation results in aberrant and dysregulation of MET-related signaling determined by RNA-seq in the murine osteoblasts extracted from the wide-type and genetic mice. Although no gross skeletal defects were identified in the mice, fracture repair was delayed in MetΔ15-HET mice, with decreased bone formation observed 2-week postfracture. Our data are consistent with a novel role for MET-mediated signaling regulating osteogenesis.

Alpha T-catenin: a crucial tumor suppressor in cancer pathogenesis.

Alpha T-catenin has recently been identified as a crucial tumor suppressor in various cancer types, with roles that go beyond just providing structural support in adherens junctions. This review brings together recent findings on alpha T-catenin's important involvement in key signaling pathways related to cancer progression. We present strong evidence of its regulatory role in Wnt signaling, a pathway often disrupted in colorectal cancer, and explain how it inhibits cell proliferation and tumor growth. We also discuss the significant downregulation of alpha T-catenin in colorectal cancers and its potential as a prognostic marker. Moreover, this review looks at how increasing alpha T-catenin levels can reduce tumor growth and spread, suggesting new therapeutic strategies. Additionally, we reveal alpha T-catenin's unexpected impact on NF-κB signaling in basal E-cadherin-negative breast cancer, expanding its importance across different cancer types. By bringing these findings together, we provide a thorough understanding of alpha T-catenin's tumor-suppressing actions, setting the stage for new targeted therapies and diagnostic tools in cancer treatment.

Oncostatin M-driven macrophage-fibroblast circuits as a drug target in autoimmune arthritis

BackgroundRecent single-cell RNA sequencing (scRNA-seq) analysis revealed the functional heterogeneity and pathogenic cell subsets in immune cells, synovial fibroblasts and bone cells in rheumatoid arthritis (RA). JAK inhibitors which ameliorate joint inflammation and bone destruction in RA, suppress the activation of various types of cells in vitro. However, the key cellular and molecular mechanisms underlying the potent clinical effects of JAK inhibitors on RA remain to be determined. Our aim is to identify a therapeutic target for JAK inhibitors in vivo.MethodsWe performed scRNA-seq analysis of the synovium of collagen-induced arthritis (CIA) mice treated with or without a JAK inhibitor, followed by a computational analysis to identify the drug target cells and signaling pathways. We utilized integrated human RA scRNA-seq datasets and genetically modified mice administered with the JAK inhibitor for the confirmation of our findings.ResultsscRNA-seq analysis revealed that oncostatin M (OSM) driven macrophage-fibroblast interaction is highly activated under arthritic conditions. OSM derived from macrophages, acts on OSM receptor (OSMR)-expressing synovial fibroblasts, activating both inflammatory and tissue-destructive subsets. Inflammatory synovial fibroblasts stimulate macrophages, mainly through IL-6, to exacerbate inflammation. Tissue-destructive synovial fibroblasts promote osteoclast differentiation by producing RANKL to accelerate bone destruction. scRNA-seq analysis also revealed that OSM-signaling in synovial fibroblasts is the main signaling pathway targeted by JAK inhibitors in vivo. Mice specifically lacking OSMR in synovial fibroblasts (Osmr∆Fibro) displayed ameliorated inflammation and joint destruction in arthritis. The JAK inhibitor was effective on the arthritis of the control mice while it had no effect on the arthritis of Osmr∆Fibro mice.ConclusionsOSM functions as one of the key cytokines mediating pathogenic macrophage-fibroblast interaction. OSM-signaling in synovial fibroblasts is one of the main signaling pathways targeted by JAK inhibitors in vivo. The critical role of fibroblast-OSM signaling in autoimmune arthritis was shown by a combination of mice specifically deficient for OSMR in synovial fibroblasts and administration of the JAK inhibitor. Thus, the OSM-driven synovial macrophage-fibroblast circuit is proven to be a key driver of autoimmune arthritis, serving as a crucial drug target in vivo.

The activation of TLR4-MyD88 signaling promotes hepatic dysfunction and fibrotic changes in SD rats resulting from prolonged exposure to sodium arsenite

Arsenic, a poisonous metalloid element, is linked to liver diseases, but the exactmechanisms for this process are not yet to be completely elucidated. Toll like receptor 4 (TLR4), acting as a pathogenic pattern recognition receptor, plays a pivotal role in various inflammatory diseases via the myeloid differentiation factor 88 (MyD88) pathway. This study aims to investigate the involvement of the TLR4-MyD88 signaling pathway in liver injury induced by prolonged exposure to sodium arsenite (NaAsO2) in Sprague-Dawley rats. Our research findings demonstratethe activation of TLR4-MyD88 signaling pathway in long-term NaAsO2-exposed rat liver tissues, leading to a significant release of inflammatory factors, which suggests its potential involvement in the pathogenesis of NaAsO2-induced liver injury. We further administered lipopolysaccharide (LPS), a natural ligand of TLR4, and TAK-242, a specific inhibitor of TLR4, to rats in order to validate the specific involvement of the TLR4-MyD88 signaling pathway in NaAsO2-induced liver injury. The results showed that, 1 mg/kg.bw LPS treatment significantly activated TLR4-MyD88 signalling pathway and its mediated pro-inflammatory factors, leading to up-regulation of activation indicators in hepatic stellate cells (HSCs) as well as increased secretion levels of extracellular matrix (ECM) in the liver, and ultimately induced liver fibrosis and dysfunction in rats. Relevantly, subsequent administration of 0.5 mg/kg.bw TAK-242 significantly attenuated the expression levels of TLR4 and its associated proteins, mitigated collagen deposition, and partially improved liver fibrosis and dysfunction caused by NaAsO2 in rats. Our study fully confirms the pivotal role of the TLR4-MyD88 signaling in promoting liver injury induced by NaAsO2, thereby providing a novel molecular target for preventing and treating patients with arsenic poisoning-related liver injury.

A review of TEC family kinases and their inhibitors in the treatment of alopecia areata.

The TEC (tyrosine kinase expressed in hepatocellular carcinoma) family kinases, an important class of protein kinases, play key roles in cell signaling and immune regulation. In this review, the association between the pathogenesis of alopecia areata and the structure and regulatory mechanisms of TEC family kinases in normal physiological processes, is explored. Furthermore, the potential clinical applications of TEC kinases and their inhibitors are highlighted by summarizing current insights into their mechanisms of action, clinical applications, and recent advancements in TEC kinase inhibitor research.

PKMζ alters oxycodone-taking in a dose- and sex-dependent manner

Opioid use disorder involves disruptions to glutamate homeostasis and dendritic spine density in the reward system. PKMζ is an atypical isoform of protein kinase C that is expressed exclusively in neurons and plays a role in postsynaptic glutamate signaling and dendritic spine maturation. As opioid use leads to alterations in glutamate transmission and dendritic spine density, we hypothesized that PKMζ deletion would alter opioid-taking behaviors. The current study examined two doses of oxycodone self-administration in male and female mice with constitutive deletion of PKMζ compared to wildtype controls. At a dose of 0.25 mg/kg/infusion, PKMζ deletion significantly potentiated oxycodone self-administration in both male and female mice. However, increases in motivation for oxycodone, as indicated by increased breakpoint on a progressive ratio schedule, were only seen in male PKMζ knockout mice and not females. When we examined a lower dose of oxycodone, 0.125 mg/kg/infusion, PKMζ knockout led to increases in oxycodone self-administration only in female mice. Additionally, female PKMζ knockout mice exhibited higher breakpoints on a progressive ratio schedule at this dose compared to all other groups. In addition to the self-administration studies, we also examined locomotor sensitization in response to experimenter administered oxycodone. PKMζ KO decreased oxycodone induced locomotion in males and potentiated oxycodone sensitization in females. Together, these results suggest that PKMζ acts to dampen oxycodone taking in both sexes, but females may be more sensitive to its effects.

TAX1BP1/A20 inhibited TLR2-NF-κB activation to induce tolerant expression of IL-6 in endothelial cells

The inflammatory cascadedriven by interleukin-6 (IL-6) plays a crucial role in the initiation and progression of chronic inflammatory conditions such as atherosclerosis. Research has demonstrated that prolonged exposure to inflammatory stimuli leads to the development of “immune tolerance” in specialized immune cells such as monocytes and macrophages, serving as a mechanism to prevent tissue damage and curb the inflammatory cascade. However, our recent investigation revealed that immune tolerance did not effectively regulate the production of IL-6 in human umbilical vein endothelial cells (HUVECs) when stimulated by a Toll-like receptor 2 (TLR2) ligand Pam3CSK4, which is a potent activator of the pro-inflammatory transcription factor NF-κB. Furthermore, the negative regulator of NF-κB signaling, A20, was ineffective in suppressing TLR2-induced IL-6 synthesis in this context. Notably, all A20 auxiliary molecules, with the exception of TAX1BP1, were found to be significantly expressed in HUVECs. DNA methylation in TAX1BP1 was confirmed in GEO database. According to the information provided, it is hypothesized that altered DNA methylation in HUVECs could potentially lead to decreased expression of TAX1BP1, thereby impeding A20′s capacity to modulate continuous activation of the TLR2-NF-κB pathway. This may consequently lead to unregulated production of IL-6, evading immune tolerance mechanisms. Subsequent investigations suggested that demethylating TAX1BP1 could enhance its expression, potentially reducing the endogenous IL-6 levels induced by repeated TLR2 stimulation and restoring A20′s inhibitory role in NF-κB signaling. Additionally, over-expression of TAX1BP1 coulddecrease the production of atherosclerosis-associated cytokines like IL-6, MCP-1, ICAM-1, and VCAM-1, while increasing NO release following repeated Pam3cks4 stimulation, along with enhanced co-localization of TAX1BP1 and A20. These findings indicate that inducing immune tolerance in endothelial cells may effectively suppress endogenous IL-6 production and halt the IL-6-mediated inflammatory cascade, with TAX1BP1/A20 identified as crucial components in this process.These insights provide novel perspectives and potential targets for therapeutic strategies in inflammatoryimmunological disorders involving the overproduction of IL-6.

The role of geographical distance for investment decisions in crowdinvesting

ABSTRACT Startups rely on alternative forms of financing, such as crowdinvesting, as they usually miss reliable credit ratings and bank loans. We explore the role of geographical distance between investors and startups, and analyze the role of signals and the investor-startup-relationship in investment decisions. Using a unique proprietary dataset from the largest crowdinvesting platform in Mexico, we show that distance between investors and startups negatively affects the investment probability and investment amount. An investor-startup-relationship only diminishes this correlation in specific instances while observable signals do in any case. Evidence is in line with the idea that investors with a close relationship to a startup should be used as fallback options instead of exclusive investors in startups’ early development stage. Furthermore, it underscores that signals are of high importance in modern forms of financing.

The role of fibrosis in endometriosis: a systematic review.

Fibrosis is an important pathological feature of endometriotic lesions of all subtypes. Fibrosis is present in and around endometriotic lesions, and a central role in its development is played by myofibroblasts, which are cells derived mainly after epithelial-to-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). Transforming growth factor-β (TGF-β) has a key role in this myofibroblastic differentiation. Myofibroblasts deposit extracellular matrix (ECM) and have contracting abilities, leading to a stiff micro-environment. These aspects are hypothesized to be involved in the origin of endometriosis-associated pain. Additionally, similarities between endometriosis-related fibrosis and other fibrotic diseases, such as systemic sclerosis or lung fibrosis, indicate that targeting fibrosis could be a potential therapeutic strategy for non-hormonal therapy for endometriosis. This review aims to summarize the current knowledge and to highlight the knowledge gaps about the role of fibrosis in endometriosis. A comprehensive literature overview about the role of fibrosis in endometriosis can improve the efficiency of fibrosis-oriented research in endometriosis. A systematic literature search was performed in three biomedical databases using search terms for 'endometriosis', 'fibrosis', 'myofibroblasts', 'collagen', and 'α-smooth muscle actin'. Original studies were included if they reported about fibrosis and endometriosis. Both preclinical in vitro and animal studies, as well as research concerning human subjects were included. Our search yielded 3441 results, of which 142 studies were included in this review. Most studies scored a high to moderate risk of bias according to the bias assessment tools. The studies were divided in three categories: human observational studies, experimental studies with human-derived material, and animal studies. The observational studies showed details about the histologic appearance of fibrosis in endometriosis and the co-occurrence of nerves and immune cells in lesions. The in vitro studies identified several pro-fibrotic pathways in relation to endometriosis. The animal studies mainly assessed the effect of potential therapeutic strategies to halt or regress fibrosis, for example targeting platelets or mast cells. This review shows the central role of fibrosis and its main cellular driver, the myofibroblast, in endometriosis. Platelets and TGF-β have a pivotal role in pro-fibrotic signaling. The presence of nerves and neuropeptides is closely associated with fibrosis in endometriotic lesions, and is likely a cause of endometriosis-associated pain. The process of fibrotic development after EMT and FMT shares characteristics with other fibrotic diseases, so exploring similarities in endometriosis with known processes in diseases like systemic sclerosis, idiopathic pulmonary fibrosis or liver cirrhosis is relevant and a promising direction to explore new treatment strategies. The close relationship with nerves appears rather unique for endometriosis-related fibrosis and is not observed in other fibrotic diseases. N/A.

A distinct protein posttranslational modifications-linked OsATL32-OsPPKL2-OsGSK2 loop modulates rice immunity against blast disease.

Protein posttranslational modifications play crucial roles in plant immunity through modulating a complicated signaling network mediated by different hormones. We previously demonstrated that OsATL32, an ATL-type E3 ligase, negatively contributes to rice immunity against Magnaporthe oryzae. Here, we show that OsATL32 forms a loop with OsPPKL2 and OsGSK2 through distinct protein posttranslational modifications to modulate rice immunity. OsATL32 ubiquitinates OsPPKL2, a protein phosphatase with Kelch-like repeat domains that exerts positive roles in regulating rice immunity against M. oryzae and chitin-triggered immune responses, for degradation. The glycogen synthase kinase 2 (OsGSK2), which acts as a negative regulator of rice immunity against M. oryzae and chitin-triggered immune responses, phosphorylates OsATL32 to elevate its protein stability and E3 ligase activity on OsPPKL2. Moreover, OsPPKL2 directly dephosphorylates OsGSK2, affecting its kinase activity on substrates including OsATL32 for phosphorylation. Like OsGSK2 as a BR signaling repressor, OsATL32 negatively regulates BR signaling; conversely, OsPPKL2 plays a positive role in BR signaling. These findings provide a molecular mechanism in which OsATL32 serves as a node connecting BR signaling and immunity by associating with OsPPKL2 and OsGSK2, assembling into a distinct protein posttranslational modifications-linked loop that functions in rice BR signaling and immunity.

A Novel NIR Fluorescent Probe for Rapid Response to Hydrogen Sulfide.

Hydrogen sulfide (H2S), as an important small molecule bioregulator, plays a key role in many physiological activities and signaling, and abnormal fluctuations in H2S concentration can lead to a variety of diseases. Therefore, it is of great significance to develop a near-infrared fluorescence probe to visualize fluctuations in H2S levels. This work is based on Sulfur-substituted dicyanomethylene-4H-chromene (DCM), A novel NIR fluorescent probe (E) -3 - (2 - (4 - (dicyanomethylene) -6-methyl-4H-Thiochromen-2-yl)vinyl-1-methylquinolin-1-ium (DMT) was synthesized successfully. Research has found that in weakly alkaline environments, the probe DMT reacts rapidly with H2S (only 10s), the fluorescence intensity at 684nm is enhanced by about 60 fold, the detection limit is as low as 0.1623 µM, the Stokes shift is large (94nm), and strong selectivity as well as anti-interference ability towards H2S. This will provide a new method for the rapid detection and further application of H2S.

The social and defensive function of olfactory behaviors in a pair-living sexually monogamous primate.

Olfactory behaviors serve a wide variety of social functions in mammals. Odor may signal information about attributes of individuals important for mating and reproduction. Olfactory behaviors, such as scent-marking, may also function as part of home range or resource defense strategies. We assessed the potential social and home range defense functions of olfactory behavior in a pair-living and sexually monogamous primate, Azara's owl monkey (Aotus azarae), in the Argentinian Chaco. This is the most extensive investigation of owl monkey olfactory behaviors in the wild. Individuals regularly performed olfactory behaviors (group mean + SD = 1.3 + 0.5 per hour). The patterns were generally comparable to those observed in studies of captive owl monkeys, except that urine washing was the most common behavior in the wild, as opposed to scent-marking and genital inspections. Most olfactory behaviors were performed by adults, and there were striking sex differences in genital inspections: almost all consisted of an adult male inspecting the paired adult female. These findings suggest that olfactory behaviors play an important role in signaling and coordinating reproduction among owl monkeys, particularly during periods of female conception and pregnancy. Additionally, our research indicates that these behaviors may also serve as a defense strategy for maintaining the core area of their home ranges. This study offers the first assessment of the role of olfactory behaviors in reproductive contexts and home range defense in pair-living, monogamous platyrrhine primates.

Role of STAT3-FOXO3 Signaling in the Modulation of Neuroplasticity by PD-L1-HGF-Decorated Mesenchymal Stem Cell-Derived Exosomes in a Murine Stroke Model.

The limited therapeutic strategies available for stroke leave many patients disabled for life. This study assessed the potential of programmed death-ligand 1 (PD-L1) and hepatocyte growth factor (HGF)-engineered mesenchymal stem cell-derived exosomes (EXO-PD-L1-HGF) in enhancing neurological recovery post-stroke. EXO-PD-L1-HGF, which efficiently endocytosed into target cells, significantly diminishes the H2O2-induced neurotoxicity and increased the antiapoptotic proteins in vitro. EXO-PD-L1-HGF attenuates inflammation by inhibiting T-cell proliferation and increasing the number of CD8+CD122+IL-10+ regulatory T cells. Intravenous injection of EXO-PD-L1-HGF could target stromal cell-derived factor-1α (SDF-1α+) cells over the peri-infarcted area of the ischemic brain through CXCR4 upregulation and accumulation in neuroglial cells post-stroke. EXO-PD-L1-HGF facilitates endogenous nestin+ neural progenitor cell (NPC)-induced neurogenesis via STAT3-FOXO3 signaling cascade, which plays a pivotal role in cell survival and neuroprotection, thereby mitigating infarct size and enhancing neurological recovery in a murine stroke model. Moreover, increasing populations of the immune-regulatory CD19+IL-10+ and CD8+CD122+IL-10+ cells, together with reducing populations of proinflammatory cells, created an anti-inflammatory microenvironment in the ischemic brain. Thus, innovative approaches employing EXO-PD-L1-HGF intervention, which targets SDF-1α+ expression, modulates the immune system, and enhances the activation of resident nestin+ NPCs, might significantly alter the brain microenvironment and create a niche conducive to inducing neuroplastic regeneration post-stroke.

Activation of the antioxidant system and transduction of the mediated by exogenous calcium improve drought resistance in tobacco

Drought stress is one of the most important stresses in plants. The important role of calcium signal as a second messenger in alleviating drought stress is still unclear. We used tobacco as test material to simulate drought stress with 20 % PEG concentration. Physiological and transcriptome techniques were used to study how the model plant tobacco protects itself from drought stress by examining the mechanism used by exogenous calcium ions to respond to the antioxidant and hormone signals that indicate drought stress. Exogenous calcium was shown to increase the levels of expression of the proteins CDPK, CBL/CIPK and AQPs that respond to signaling by calcium under drought stress. The cis-acting elements of the promoters of the genes related to signals primarily focused on hormone and drought-related elements, which suggests that the exogenous calcium may mediate the transduction of hormone signals in response to drought stress. The results of physiological and transcriptional data showed that oxidative damage occurred in the tobacco leaves under drought stress. Under drought stress, exogenous calcium can enhance the activities of SOD (4.75 %), POD (42.33 %) and APX (512.43 %), up-regulate the expression of the genes that encode antioxidant enzymes to eliminate excessive reactive oxygen species (ROS), and alleviate the oxidative damage to tobacco leaves under drought stress. The calcium produced during drought stress increased the content of auxin (IAA), decreased that of abscisic acid (ABA) and downstream gene expression, and prevented excessive amplification of the ABA signal. Exogenous calcium enhanced the crosstalk between cytokinin, gibberellin and ABA signals.In summary, exogenous calcium can stimulate the synergistic effect of calcium and hormone signals and the antioxidant system, eliminate ROS, improve the crosstalk between plant hormones, and improve the drought resistance of tobacco.

Synthesis, Characterization, and Reactivity of a Synthetic End-On Cobalt(II) Alkyl Persulfide Complex as a Model Platform for Thiolate Persulfidation.

Persulfides (RSS-) are ubiquitous source of sulfides (S2-) in biology, and interactions between RSS- and bioinorganic metal centers play critical roles in biological hydrogen sulfide (H2S) biogenesis, signaling, and catabolism. Here, we report the use of contact-ion stabilized [Na(15-crown-5)][tBuSS] (1) as a simple synthon to access rare metal alkyl persulfide complexes and to investigate the reactivity of RSS- with transition metal centers to provide insights into metal thiolate persulfidation, including the fundamental difference between alkyl persulfides and alkyl thiolates. Reaction of 1 with [CoII(TPA)(OTf)]+ afforded the η1-alkyl persulfide complex [CoII(TPA)(SStBu)]+ (2), which was characterized by X-ray crystallography, UV-vis spectroscopy, and Raman spectroscopy. RSS- coordination to the Lewis acidic Co2+ center provided additional stability to the S-S bond, as evidenced by a significant increase in the Raman stretching frequency for 2 (vS-S = 522 cm-1, ΔvS-S = 66 cm-1). The effect of persulfidation on metal center redox potentials was further elucidated using cyclic voltammetry, in which the Co2+ → Co3+ oxidation potential of 2 (Ep,a = +89 mV vs SCE) is lowered by nearly 700 mV when compared to the corresponding thiolate complex [CoII(TPA)(StBu)]+ (3) (Ep,a = +818 mV vs SCE), despite persulfidation being generally seen as an oxidative post-translational modification. The reactivity of 2 toward reducing agents including PPh3, BH4-, and biologically relevant thiol reductant DTT led to different S2- output pathways, including formation of a dinuclear 2Co-2SH complex [CoII2(TPA)2(μ2-SH)2]2+(4).

Presynaptic Rac1 in the hippocampus selectively regulates working memory

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Presynaptic Rac1 in the hippocampus selectively regulates working memory.

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.