S-nitrosylation of NADPH oxidase regulates cell death in plant immunity.

Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes, but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the latter generated by NADPH oxidases related to those responsible for the pathogen-activated respiratory burst in phagocytes. Both nitric oxide and reactive oxygen intermediates have been implicated in controlling the hypersensitive response, a programmed execution of plant cells at sites of attempted infection. However, the molecular mechanisms that underpin their function and coordinate their synthesis are unknown. Here we show genetic evidence that increases in cysteine thiols modified using nitric oxide, termed S-nitrosothiols, facilitate the hypersensitive response in the absence of the cell death agonist salicylic acid and the synthesis of reactive oxygen intermediates. Surprisingly, when concentrations of S-nitrosothiols were high, nitric oxide function also governed a negative feedback loop limiting the hypersensitive response, mediated by S-nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890 compromised S-nitrosothiol-mediated control of AtRBOHD activity, perturbing the magnitude of cell death development. This cysteine is evolutionarily conserved and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting that this mechanism may govern immune responses in both plants and animals.

AtGSNOR1 function is required for multiple developmental programs in Arabidopsis.

Nitric oxide (NO) has been proposed to regulate a diverse array of activities during plant growth, development and immune function. S-nitrosylation, the addition of an NO moiety to a reactive cysteine thiol, to form an S-nitrosothiol (SNO), is emerging as a prototypic redox-based post-translational modification. An ARABIDOPSIS THALIANA S-NITROSOGLUTATHIONE (GSNO) REDUCTASE (AtGSNOR1) is thought to be the major regulator of total cellular SNO levels in this plant species. Here, we report on the impact of loss- and gain-of-function mutations in AtGSNOR1 upon plant growth and development. Loss of AtGSNOR1 function in atgsnor1-3 plants increased the number of initiated higher order axillary shoots that remain active, resulting in a loss of apical dominance relative to wild type. In addition atgsnor1-3 affected leaf shape, germination, 2,4-D sensitivity and reduced hypocotyl elongation in both light and dark grown seedlings. Silique size and seed production were also decreased in atgsnor1-3 plants and the latter was reduced in atgsnor1-1 plants, which overexpress AtGSNOR1. Overexpression of AtGSNOR1 slightly delayed flowering time in both long and short days, whereas atgsnor1-3 showed early flowering compared to wild type. In the atgsnor1-3 line, FLOWERING LOCUS C (FLC) expression was reduced, whereas transcription of CONSTANS (CO) was enhanced. Therefore, AtGSNOR1 may negatively regulate the autonomous and photoperiod flowering time pathways. Both overexpression and loss of AtGSNOR1 function also reduced primary root growth, while root hair development was increased in atgsnor1-1 and reduced in atgsnor1-3 plants. Collectively, our findings imply that AtGSNOR1 controls multiple genetic networks integral to plant growth and development.

The Youngest Infant to Be Diagnosed with Autosomal Dominant Hypocalcemia Type 2 Harboring a Novel Variant of GNA11: A Case Study and Literature Review.

Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia and inappropriately low PTH concentrations. ADH type 2 (ADH2) is caused by a heterozygous gain-of-function mutation in GNA11 that encodes the subunit of G11, the principal G protein that transduces calcium-sensing receptor signaling in the parathyroid. Clinical features related to hypocalcemia in ADH2 range from asymptomatic to tetany and seizures. We report the clinical and molecular analysis of an infant with ADH2. Exome sequencing identified a de novo heterozygous missense variant, c. G548C (p. Arg183Pro) in GNA11. This is the youngest Korean case to be diagnosed with ADH 2. In addition, we summarized the literature related to eight mutations in GNA11 from 10 families.

The Effect of Labor and Relationship Exclusions on Older Korean Men with Depression.

To manage depression of older men, it is necessary to identify factors that influence depression and improve them. This study used the Korean Aging Longitude Research to understand the effects of labor exclusion and relationship exclusion on depression in Korean male seniors aged 65 and older. According to research on the effect of labor exclusion and relationship exclusion on depression, depression in the case where labor was excluded was 1.69 times higher in 2014, 1.65 times higher in 2016, and 1.93 times higher in 2018 compared to the case where labor was not excluded. Depression in the case where relationship was excluded was 2.94 times higher in 2014, 3.15 times higher in 2016, and 2.57 times higher in 2018 compared to the case where relationship was not excluded. Depression in the case where labor and relationship were both excluded was 3.00 times higher in 2014, 3.23 times higher in 2016, and 2.81 times higher in 2018 compared to the case where neither labor nor relationship was excluded. Since labor exclusion and relationship exclusion have a big influence on depression in older men, it is necessary to establish plans for job creation and for the formation of social relationships for the elderly.

The Effect of Additional Private Health Insurance on Mortality in the Context of Universal Public Health Insurance.

(1) Background: Korea operates its national health insurance (NHI) system as a form of public health insurance, and is commonly regarded as having achieved universal health coverage (UHC). However, many Korean households register for additional private health insurance (PHI) programs. Typically, registration rates for PHI are higher for individuals with a higher socioeconomic status (SES). A difference in mortality between those with and without additional PHI would indicate that there are health inequalities within the Korean NHI system under UHC. Therefore, this study aimed to confirm whether additional PHI affects mortality under the Korean NHI system. (2) Methods: We conducted a longitudinal study using the Korean Longitudinal Study of Aging data from the first to the sixth wave. The analysis included 8743 participants, who were divided into two groups: those who only had NHI and those who had both NHI and PHI. Differences in mortality between the two groups were compared using the Cox proportional hazard regression. (3) Results: The group with both NHI and PHI had lower mortality than the group with only NHI (hazard ratio = 0.53, 95% confidence interval: 0.41, 0.9). (4) Conclusions: The results of this study reveal that there are health disparities according to SES and PHI within the Korean NHI system under UHC. Therefore, relevant government institutions and experts should further improve the NHI system to reduce health disparities.

Nitric oxide function and signalling in plant disease resistance.

Nitric oxide (NO) is one of only a handful of gaseous signalling molecules. Its discovery as the endothelium-derived relaxing factor (EDRF) by Ignarro revolutionized how NO and cognate reactive nitrogen intermediates, which were previously considered to be toxic molecules, are viewed. NO is now emerging as a key signalling molecule in plants, where it orchestrates a plethora of cellular activities associated with growth, development, and environmental interactions. Prominent among these is its function in plant hypersensitive cell death and disease resistance. While a number of sources for NO biosynthesis have been proposed, robust and biologically relevant routes for NO production largely remain to be defined. To elaborate cell death during an incompatible plant-pathogen interaction NO functions in combination with reactive oxygen intermediates. Furthermore, NO has been shown to regulate the activity of metacaspases, evolutionary conserved proteases that may be intimately associated with pathogen-triggered cell death. NO is also thought to function in multiple modes of plant disease resistance by regulating, through S-nitrosylation, multiple nodes of the salicylic acid (SA) signalling pathway. These findings underscore the key role of NO in plant-pathogen interactions.

The effect of xylometazoline spray for expansion of nasal cavity.

BACKGROUND: During nasotracheal intubation it is important to have proper pretreatment for nasal mucosa constriction and nasal cavity expanding. Nasal packing of epinephrine gauze is widely used as well as xylometazoline. The aim of this study was to compare and evaluate the efficacy of prophylactic intranasal spray of xylometazoline against epinephrine gauze packing in expanding the nasal cavity. METHODS: Volunteers (n = 32) in their twenties without nasal disease such as septal deviation or rhinitis were enrolled in the study. The more patent nostril in each subject was measured by acoustic rhinometry as the base value. After intranasal spray of xylometazoline, the same nostril was remeasured by same method. Twenty four hours later, intranasal packing of epinephrine gauze was done and the same treatment was done. Subject preferences about the procedures were asked. RESULTS: THERE WERE SIGNIFICANT DIFFERENCE AMONG TREATMENTS (BASE VALUE: 0.582 ± 0.164 cm(2), xylometazoline spray: 0.793 ± 0.165 cm(2), epinephrine gauze packing: 0.990 ± 0.290 cm(2)) in acoustic rhinometry. While the epinephrine gauze packing showed more efficient mucosa constriction, subjects preferred xylometazoline spray. CONCLUSIONS: Even though xylometazoline spray was less effective than epinephrine gauze packing, the simplicity and convenience compensated. In patients undergoing nasotracheal intubation, xylometazoline spray can be an alternative to epinephrine gauze packing.

Cultured cambial meristematic cells as a source of plant natural products.

A plethora of important, chemically diverse natural products are derived from plants. In principle, plant cell culture offers an attractive option for producing many of these compounds. However, it is often not commercially viable because of difficulties associated with culturing dedifferentiated plant cells (DDCs) on an industrial scale. To bypass the dedifferentiation step, we isolated and cultured innately undifferentiated cambial meristematic cells (CMCs). Using a combination of deep sequencing technologies, we identified marker genes and transcriptional programs consistent with a stem cell identity. This notion was further supported by the morphology of CMCs, their hypersensitivity to γ-irradiation and radiomimetic drugs and their ability to differentiate at high frequency. Suspension culture of CMCs derived from Taxus cuspidata, the source of the key anticancer drug, paclitaxel (Taxol), circumvented obstacles routinely associated with the commercial growth of DDCs. These cells may provide a cost-effective and environmentally friendly platform for sustainable production of a variety of important plant natural products.

HD-ZIP III activity is modulated by competitive inhibitors via a feedback loop in Arabidopsis shoot apical meristem development.

Shoot apical meristem (SAM) development is coordinately regulated by two interdependent signaling events: one maintaining stem cell identity and the other governing the initiation of lateral organs from the flanks of the SAM. The signaling networks involved in this process are interconnected and are regulated by multiple molecular mechanisms. Class III homeodomain-leucine zipper (HD-ZIP III) proteins are the most extensively studied transcription factors involved in this regulation. However, how different signals are integrated to maintain stem cell identity and to pattern lateral organ polarity remains unclear. Here, we demonstrated that a small ZIP protein, ZPR3, and its functionally redundant homolog, ZPR4, negatively regulate the HD-ZIP III activity in SAM development. ZPR3 directly interacts with PHABULOSA (PHB) and other HD-ZIP III proteins via the ZIP motifs and forms nonfunctional heterodimers. Accordingly, a double mutant, zpr3-2 zpr4-2, exhibits an altered SAM activity with abnormal stem cell maintenance. However, the mutant displays normal patterning of leaf polarity. In addition, we show that PHB positively regulates ZPR3 expression. We therefore propose that HD-ZIP III activity in regulating SAM development is modulated by, among other things, a feedback loop involving the competitive inhibitors ZPR3 and ZPR4.

S-nitrosylation: an emerging redox-based post-translational modification in plants.

S-nitrosylation, the covalent attachment of a nitric oxide moiety to a cysteine thiol, is now established as a key post-translational modification in animals. This process has been shown to regulate the function of a wide variety of regulatory, structural, and metabolic proteins. The emerging evidence now suggests that S-nitrosylation may also have a central function in plant biology.

A central role for S-nitrosothiols in plant disease resistance.

Animal S-nitrosoglutathione reductase (GSNOR) governs the extent of cellular S-nitrosylation, a key redox-based posttranslational modification. Mutations in AtGSNOR1, an Arabidopsis thaliana GSNOR, modulate the extent of cellular S-nitrosothiol (SNO) formation in this model plant species. Loss of AtGSNOR1 function increased SNO levels, disabling plant defense responses conferred by distinct resistance (R) gene subclasses. Furthermore, in the absence of AtGSNOR1, both basal and nonhost disease resistance are also compromised. Conversely, increased AtGSNOR1 activity reduced SNO formation, enhancing protection against ordinarily virulent microbial pathogens. Here we demonstrate that AtGSNOR1 positively regulates the signaling network controlled by the plant immune system activator, salicylic acid. This contrasts with the function of this enzyme in mice during endotoxic shock, where GSNOR antagonizes inflammatory responses. Our data imply SNO formation and turnover regulate multiple modes of plant disease resistance.