Highlights d Dimedone Switch method is a versatile, chemoselective persulfide labeling approach d Protein persulfidation is an evolutionarily conserved modification of cysteine thiols d Persulfidation waves rescue cysteines from overoxidation caused by ROS d Persulfidation decreases with aging, increases with caloric restriction, and extends lifespan
Cysteine sulfinic acid or S-sulfinylation is an oxidative post-translational modification (OxiPTM) that is known to be involved in redox-dependent regulation of protein function but has been historically difficult to analyze biochemically. To facilitate the detection of S-sulfinylated proteins, we demonstrate that a clickable, electrophilic diazene probe (DiaAlk) enables capture and site-centric proteomic analysis of this OxiPTM. Using this workflow, we revealed a striking difference between sulfenic acid modification (S-sulfenylation) and the S-sulfinylation dynamic response to oxidative stress, which is indicative of different roles for these OxiPTMs in redox regulation. We also identified >55 heretofore-unknown protein substrates of the cysteine sulfinic acid reductase sulfiredoxin, extending its function well beyond those of 2-cysteine peroxiredoxins (2-Cys PRDX1-4) and offering new insights into the role of this unique oxidoreductase as a central mediator of reactive oxygen species-associated diseases, particularly cancer. DiaAlk therefore provides a novel tool to profile S-sulfinylated proteins and study their regulatory mechanisms in cells.
As a result of an author oversight in the originally published version of this article, the surname of author Bruno Gonzalez-Zorn was misspelled as ''Gonzales-Zorn.'' Additionally, the scheme in the Graphical Abstract contains a final product of proteinS -Sdimedone, rather than proteinS -dimedone. These errors have now been corrected in the article online. The authors apologize for the errors and any inconvenience that may have resulted.
Spirituality, purpose in life, and trait anxiety contribute to different levels of resilience in patients with depression and/or anxiety disorders. Our results would deepen the understanding of resilience and provide potential targets of resilience-focused intervention in these patients.
The Connor-Davidson Resilience Scale (CD-RISC) is a brief self-rating questionnaire for measuring resilience. The aims of the present study were to describe the development of a Korean version of the CD-RISC (K-CD-RISC) and to more firmly establish its psychometric properties in terms of reliability and validity. The participants consisted of a general population sample (n=194) and psychiatric outpatients (n=127) with non-psychotic mood or anxiety disorders. The K-CD-RISC score means (standard deviation) were 65.9 (13.6) in the general population and 50.4 (20.5) in the psychiatric outpatients. The mean score of the general population was significantly higher than that of the psychiatric outpatients. Exploratory factor analysis revealed five factors, and the obtained factor structure was verified through confirmatory factor analysis. In the general population, the Cronbach's α coefficient of the K-CD-RISC was found to be 0.92. Greater resilience was found to be associated with less perceived stress, anxiety and depression and with higher levels of positive affect and purpose in life. Taken together, our findings suggest that the K-CD-RISC has good psychometric properties and is a valid and reliable tool for assessing resilience.
Post-translational changes in the redox state of cysteine residues can rapidly and reversibly alter protein functions, thereby modulating biological processes. The nematode C. elegans is an ideal model organism for studying cysteine-mediated redox signaling at a network level. Here we present a comprehensive, quantitative, and site-specific profile of the intrinsic reactivity of the cysteinome in wild-type C. elegans. We also describe a global characterization of the C. elegans redoxome in which we measured changes in three major cysteine redox forms after H2O2 treatment. Our data revealed redox-sensitive events in translation, growth signaling, and stress response pathways, and identified redox-regulated cysteines that are important for signaling through the p38 MAP kinase (MAPK) pathway. Our in-depth proteomic dataset provides a molecular basis for understanding redox signaling in vivo, and will serve as a valuable and rich resource for the field of redox biology.
ObjectiveThe present study aimed to evaluate the efficacy of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (DLPFC) for the treatment of obsessive-compulsive disorder (OCD).MethodsTwenty-seven patients with treatment resistant OCD were randomly assigned to 3 week either active (n=14) or sham (n=13) rTMS. The active rTMS parameters consisted of 1 Hz, 20-minute trains (1,200 pulses/day) at 100% of the resting motor threshold (MT). OCD symptoms, mood, and anxiety were assessed at baseline and every week throughout the treatment period.ResultsA repeated-measures analysis of variance (ANOVA) was used to evaluate changes on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Our results revealed a significant reduction in YBOCS scores in the active group compared with the sham group after 3 weeks. Similarly, a repeated-measures ANOVA revealed significant effect of time and time×group interaction on scores on the Hamilton Depression Rating Scale and the Clinical Global Impression-Severity scale. There were no reports of any serious adverse effects following the active and sham rTMS treatments.ConclusionLF rTMS over the right DLPFC appeared to be superior to sham rTMS for relieving OCD symptoms and depression in patients with treatment-resistant OCD. Further trials with larger sample sizes should be conducted to confirm the present findings.
ERβ is regarded as a “tumor suppressor” in breast cancer due to its anti-proliferative effects. However, unlike ERα, ERβ has not been developed as a therapeutic target in breast cancer due to loss of ERβ in aggressive cancers. In a small molecule library screen for ERβ stabilizers, we identified Diptoindonesin G (Dip G) which significantly increases ERβ protein stability, while decreasing ERα protein levesl. Dip G enhances the transcription and anti-proliferative activities of ERβ, while attenuating the transcription and proliferative effects of ERα. Further investigation revealed that instead of targeting ER, Dip G targets the CHIP E3 ubiquitin ligase shared by ERα and ERβ. Thus, Dip G is a dual functional moiety that reciprocally controls ERα and ERβ protein stability and activities via an indirect mechanism. The ERβ stabilization effects of Dip G may enable the development of ERβ-targeted therapies for human breast cancers.
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