Nitro-fatty acids (NO₂-FAs) are the product of the reaction between reactive nitrogen species derived of nitric oxide (NO) and unsaturated fatty acids. In animal systems, NO₂-FAs are considered novel ...signaling mediators of cell function based on a proven antiinflammatory response. Nevertheless, the interaction of NO with fatty acids in plant systems has scarcely been studied. Here, we examine the endogenous occurrence of nitro-linolenic acid (NO₂-Ln) in Arabidopsis and the modulation of NO₂-Ln levels throughout this plant’s development by mass spectrometry. The observed levels of this NO₂-FA at picomolar concentrations suggested its role as a signaling effector of cell function. In fact, a transcriptomic analysis by RNA-seq technology established a clear signaling role for this molecule, demonstrating that NO₂-Ln was involved in plant defense response against different abiotic-stress conditions, mainly by inducing heat shock proteins and supporting a conserved mechanism of action in both animal and plant defense processes. Bioinformatics analysis revealed that NO₂-Ln was also involved in the response to oxidative stress conditions, mainly depicted by H₂O₂, reactive oxygen species, and oxygen-containing compound responses, with a high induction of ascorbate peroxidase expression. Closely related to these results, NO₂-Ln levels significantly rose under several abiotic-stress conditions such as wounding or exposure to salinity, cadmium, and low temperature, thus validating the outcomes found by RNA-seq technology. Jointly, to our knowledge, these are the first results showing the endogenous presence of NO₂-Ln in Arabidopsis (Arabidopsis thaliana) and supporting the strong signaling role of these molecules in the defense mechanism against different abiotic-stress situations.
Post-translational modifications (PTMs) mediated by nitric oxide (NO)-derived molecules have become a new area of research, as they can modulate the function of target proteins. Proteomic data have ...shown that ascorbate peroxidase (APX) is one of the potential targets of PTMs mediated by NO-derived molecules. Using recombinant pea cytosolic APX, the impact of peroxynitrite (ONOO–) and S-nitrosoglutathione (GSNO), which are known to mediate protein nitration and S-nitrosylation processes, respectively, was analysed. While peroxynitrite inhibits APX activity, GSNO enhances its enzymatic activity. Mass spectrometric analysis of the nitrated APX enabled the determination that Tyr5 and Tyr235 were exclusively nitrated to 3-nitrotyrosine by peroxynitrite. Residue Cys32 was identified by the biotin switch method as S-nitrosylated. The location of these residues on the structure of pea APX reveals that Tyr235 is found at the bottom of the pocket where the haem group is enclosed, whereas Cys32 is at the ascorbate binding site. Pea plants grown under saline (150mM NaCl) stress showed an enhancement of both APX activity and S-nitrosylated APX, as well as an increase of H2O2, NO, and S-nitrosothiol (SNO) content that can justify the induction of the APX activity. The results provide new insight into the molecular mechanism of the regulation of APX which can be both inactivated by irreversible nitration and activated by reversible S-nitrosylation.
Mirth is elicited by the perception of humor, which requires the resolution of an incongruity in an unexpected and playful manner. Previous psychophysiological research using affective pictures is ...scarce, and did not elucidate the cognitive and affective components of the humor process. In this study, the passive viewing paradigm is applied to mirthful, incongruent, neutral and erotic pictures to characterize the emotional response of mirth. Physiological (zygomaticus major ZM activity, skin conductance response SCR and heart rate HR), behavioral (free viewing time) and subjective responses (mirthful ratings) were recorded from 63 participants. The presence of an inflection change in the ZM response and mirthfulness ratings were used as markers of humor comprehension. Participants showed the greatest ZM and HR in response to mirthful compared to incongruent, erotic and neutral pictures, as well as a stronger SCR response to mirthful compared to incongruent and neutral pictures. The overall results shed light on the temporal course of the humor process, suggesting that humor comprehension (cognitive component) occurred around 1000–1500 ms after picture onset, according to the ZM and SCR responses; and the humor appreciation stage (emotional component) occurred at around 3500 ms after stimulus onset, according to the HR and SCR changes. Moreover, marked interindividual variability was observed in the number of smiles, and in the pictures that provoked them. This points to the complexity of the humor process, and suggests the need to develop methods to elicit mirth and elucidate the factors potentially underlying individual differences in humor.
To characterize the emotional response of mirth, the passive viewing paradigm is applied to mirthful, incongruent, neutral and erotic pictures while recording physiological, behavioral and subjective responses. Our results showed increased zygomatic, heart rate and skin conductance responses to mirthful pictures. The latencies of these responses provide insight into the temporal course of the cognitive and emotional components of the humor process.
The ascorbate–glutathione cycle is a metabolic pathway that detoxifies hydrogen peroxide and involves enzymatic and non-enzymatic antioxidants. Proteomic studies have shown that some enzymes in this ...cycle such as ascorbate peroxidase (APX), monodehydroascorbate reductase (MDAR), and glutathione reductase (GR) are potential targets for post-translational modifications (PMTs) mediated by nitric oxide-derived molecules. Using purified recombinant pea peroxisomal MDAR and cytosolic and chloroplastic GR enzymes produced in Escherichia coli, the effects of peroxynitrite (ONOO⁻) and S-nitrosoglutathione (GSNO) which are known to mediate protein nitration and S-nitrosylation processes, respectively, were analysed. Although ONOO⁻ and GSNO inhibit peroxisomal MDAR activity, chloroplastic and cytosolic GR were not affected by these molecules. Mass spectrometric analysis of the nitrated MDAR revealed that Tyr213, Try292, and Tyr345 were exclusively nitrated to 3-nitrotyrosine by ONOO⁻. The location of these residues in the structure of pea peroxisomal MDAR reveals that Tyr345 is found at 3.3 Å of His313 which is involved in the NADP-binding site. Site-directed mutagenesis confirmed Tyr345 as the primary site of nitration responsible for the inhibition of MDAR activity by ONOO⁻. These results provide new insights into the molecular regulation of MDAR which is deactivated by nitration and S-nitrosylation. However, GR was not affected by ONOO⁻ or GSNO, suggesting the existence of a mechanism to conserve redox status by maintaining the level of reduced GSH. Under a nitro-oxidative stress induced by salinity (150 mM NaCl), MDAR expression (mRNA, protein, and enzyme activity levels) was increased, probably to compensate the inhibitory effects of S-nitrosylation and nitration on the enzyme. The present data show the modulation of the antioxidative response of key enzymes in the ascorbate–glutathione cycle by nitric oxide (NO)-PTMs, thus indicating the close involvement of NO and reactive oxygen species metabolism in antioxidant defence against nitro-oxidative stress situations in plants.
Nitric oxide (NO) is a biological messenger that orchestrates a plethora of plant functions, mainly through post-translational modifications (PTMs) such as S-nitrosylation or tyrosine nitration. In ...plants, hundreds of proteins have been identified as potential targets of these NO-PTMs under physiological and stress conditions indicating the relevance of NO in plant-signaling mechanisms. Among these NO protein targets, there are different antioxidant enzymes involved in the control of reactive oxygen species (ROS), such as H2O2, which is also a signal molecule. This highlights the close relationship between ROS/NO signaling pathways. The major plant antioxidant enzymes, including catalase, superoxide dismutases (SODs) peroxiredoxins (Prx) and all the enzymatic components of the ascorbate-glutathione (Asa-GSH) cycle, have been shown to be modulated to different degrees by NO-PTMs. This mini-review will update the recent knowledge concerning the interaction of NO with these antioxidant enzymes, with a special focus on the components of the Asa-GSH cycle and their physiological relevance.
MicroRNAs (miRNAs) are a class of small (20-24 nucleotides), highly conserved, non-coding RNA molecules whose main function is the post-transcriptional regulation of gene expression through ...sequence-specific manners, such as mRNA degradation or translational repression. Since these key regulatory molecules are implicated in several biological processes, their altered expression affects the preservation of cellular homeostasis and leads to the development of a wide range of pathologies. Over the last few years, relevant investigations have elucidated that miRNAs participate in different stages of bone growth and development. Moreover, the abnormal expression of these RNA molecules in bone cells and tissues has been significantly associated with the progression of numerous bone diseases, including osteoporosis, osteosarcoma, osteonecrosis and bone metastasis, among others. In fact, miRNAs regulate multiple pathological mechanisms, including altering either osteogenic or osteoblast differentiation, metastasis, osteosarcoma cell proliferation, and bone loss. Therefore, in this present review, aiming to impulse the research arena of the biological implications of miRNA transcriptome in bone diseases and to explore their potentiality as a theragnostic target, we summarize the recent findings associated with the clinical significance of miRNAs in these ailments.
Summary
During stem elongation, wheat (Triticum aestivum) increases its stem carbohydrate content before anthesis as a reserve for grain filling. Hydraulic functioning during this mobilization ...process is not well understood, and contradictory results exist on the direct effect of drought on carbohydrate mobilization.
In a dedicated experiment, wheat plants were subjected to drought stress during carbohydrate mobilization. Measurements, important to better understand stem physiology, showed some unexpected patterns that could not be explained by our current knowledge on water transport. Traditional water flow and storage models failed to properly describe the drought response in wheat stems during carbohydrate mobilization. To explain the measured patterns, hypotheses were formulated and integrated in a dedicated model for wheat.
The new mechanistic model simulates two hypothetical water storage compartments: one where water is quickly exchanged with the xylem and one that contains the carbohydrate storage. Water exchange between these compartments is turgor‐driven. The model was able to simulate the measured increase in stored carbohydrate concentrations with a decrease in water content and stem diameter.
Calibration of the model showed the importance of turgor‐driven apoplastic water flow during carbohydrate mobilization. This resulted in an increase in stem hydraulic capacitance, which became more important under drought stress.
This paper examines the persistent effects of eliminating tariffs on Mexican imports, following the implementation of the North American Free Trade Agreement (NAFTA), on Americans' human capital ...investment. We leverage quasi‐experimental changes in tariffs on Mexican imports across birth cohorts and within states. We show that NAFTA increases the probability of ever attending college and earning a degree. These results, however, mask important heterogeneous effects within the sample. We find white Americans drive these positive effects. In contrast, the educational attainment of racial and ethnic minorities, especially men, shrank under NAFTA, decreasing their probability of graduating from high school.
Objective
The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the ...disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis.
Methods
This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS‐D) at 5 years of follow‐up. Survival was analysed using the Kaplan–Meier method and Cox regression models.
Results
According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21–1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51–0.76), age (>70 years: HR = 3.78; 95% CI: 1.94–7.36), need for help (yes: HR = 1.43; 95% CI: 1.17–1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16–1.82), tumour size (T3–T4: HR = 1.56; 95% CI: 1.22–1.99), nodule staging (N1–N2: HR = 2.46; 95% CI: 2.04–2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55–0.91).
Conclusions
There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.
Exposure to heavy metals has been shown to cause damage to a variety of different tissues and cell types including hair cells, the sensory cells of our inner ears responsible for hearing and balance. ...Elevated levels of one such metal, cadmium, have been associated with hearing loss and shown to cause hair cell death in multiple experimental models. While the mechanisms of cadmium-induced cell death have been extensively studied in other cell types they remain relatively unknown in hair cells. We have found that calcium signaling, which is known to play a role in cadmium-induced cell death in other cell types through calmodulin and CaMKII activation as well as IP3 receptor and mitochondrial calcium uniporter mediated calcium flow, does not appear to play a significant role in cadmium-induced hair cell death. While calmodulin inhibition can partially protect hair cells this may be due to impacts on mechanotransduction activity. Removal of extracellular calcium, and inhibiting CaMKII, the IP3 receptor and the mitochondrial calcium uniporter all failed to protect against cadmium-induced hair cell death. We also found cadmium treatment increased pAkt levels in hair cells and pERK levels in supporting cells. This activation may be protective as inhibiting these pathways enhances cadmium-induced hair cell death rather than protecting cells. Thus cadmium-induced hair cell death appears distinct from cadmium-induced cell death in other cell types where calcium, Akt and ERK signaling all promote cell death.
•Calmodulin inhibition protects against cadmium-induced hair cell death.•Inhibition of CaMKII, and Mitochondrial or ER calcium flow fails to protect.•Cadmium activates Akt signaling in hair cells and ERK signaling in supporting cells.•Inhibiting Akt or ERK signaling increases cadmium-induced hair cell death.
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