MYB30 integrates light signals with antioxidant biosynthesis to regulate plant responses during postsubmergence recovery.

Submergence is an abiotic stress that limits agricultural production world-wide. Plants sense oxygen levels during submergence and postsubmergence reoxygenation and modulate their responses. Increasing evidence suggests that completely submerged plants are often exposed to low-light stress, owing to the depth and turbidity of the surrounding water; however, how light availability affects submergence tolerance remains largely unknown. Here, we showed that Arabidopsis thaliana MYB DOMAIN PROTEIN30 (MYB30) is an important transcription factor that integrates light signaling and postsubmergence stress responses. MYB DOMAIN PROTEIN30 protein abundance decreased upon submergence and accumulated during reoxygenation. Under submergence conditions, CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), a central regulator of light signaling, caused the ubiquitination and degradation of MYB30. In response to desubmergence, however, light-induced MYB30 interacted with MYC2, a master transcription factor involved in jasmonate signaling, and activated the expression of the VITAMIN C DEFECTIVE1 (VTC1) and GLUTATHIONE SYNTHETASE1 (GSH1) gene families to enhance antioxidant biosynthesis. Consistent with this, the myb30 knockout mutant showed increased sensitivity to submergence, which was partially rescued by overexpression of VTC1 or GSH1. Thus, our findings uncover the mechanism by which the COP1-MYB30 module integrates light signals with cellular oxidative homeostasis to coordinate plant responses to postsubmergence stress.

Age Specific Risks of Uterine Cancer in Type 2 Diabetes and Associated Comorbidities in Taiwan.

Introduction: The global incidence of uterine cancer has increased substantially in recent decades. We evaluated if the trend of increasing prevalence of diabetes mellitus (DM) and obesity are attributed to the development of uterine cancer. Methods: Using data derived from the National Health Insurance database and Taiwan Cancer Registry, multivariate Cox proportional hazards regression models were adapted to analyze the risk factors of uterine cancer with potential confounding variables. Results: There were a total of 5,104,242 women aged 30−70 years enrolled in the study and 147,772 of them were diagnosed with DM during 2005−2007. In a total of 11 years of follow-up, 14,398 subjects were diagnosed with uterine cancer. An elevated risk of uterine cancer was observed in women with DM of all ages (HR 1.66, 95% CI 1.53−1.81, p < 0.0001). The effect of DM was highest at age 30−39 years (RR 3.05, 95% CI 2.35−3.96, p < 0.0001). In the group of <50 years old, DM patients had at least a twofold higher risk of developing uterine cancer (HR 2.39, 95% CI 2.09−2.74, p < 0.0001). Subjects among all ages diagnosed with polycystic ovary syndrome (PCOS) (HR 2.91, 95% CI 2.47−3.42, p < 0.0001), obesity (HR 2.13, 95% CI 1.88−2.41, p < 0.0001), and those undergoing hormone replacement therapy (HRT) (HR 1.60, 95% CI 1.33−1.93, p < 0.0001) were also positively associated with uterine cancer. Positive associations of hyperlipidemia (HR 1.33, 95% CI 1.22−1.46, p < 0.0001) and statin use (HR 1.27, 95% CI 1.12−1.44, p = 0.0002) on uterine cancer were only observed in subjects <50 years. On the contrary, hyperlipidemia was negatively associated with uterine cancer in subjects ≥50 years (HR 0.91, 95% CI: 0.84−0.98, p = 0.0122). Conclusions: DM is in general the most important risk factor for uterine cancer, especially in premenopausal women. Obesity, PCOS, HPL, statin use, and HRT were also associated with uterine cancer in subjects younger than 50 years. Premenopausal women with DM and respective comorbidities should be aware of the development of uterine cancer.

SINAT E3 Ubiquitin Ligases Mediate FREE1 and VPS23A Degradation to Modulate Abscisic Acid Signaling.

In plants, the ubiquitin-proteasome system, endosomal sorting, and autophagy are essential for protein degradation; however, their interplay remains poorly understood. Here, we show that four Arabidopsis (Arabidopsis thaliana) E3 ubiquitin ligases, SEVEN IN ABSENTIA OF ARABIDOPSIS THALIANA1 (SINAT1), SINAT2, SINAT3, and SINAT4, regulate the stabilities of FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING1 (FREE1) and VACUOLAR PROTEIN SORTING23A (VPS23A), key components of the endosomal sorting complex required for transport-I, to modulate abscisic acid (ABA) signaling. GFP-SINAT1, GFP-SINAT2, and GFP-SINAT4 primarily localized to the endosomal and autophagic vesicles. SINATs controlled FREE1 and VPS23A ubiquitination and proteasomal degradation. SINAT overexpressors showed increased ABA sensitivity, ABA-responsive gene expression, and PYRABACTIN RESISTANCE1-LIKE4 protein levels. Furthermore, the SINAT-FREE1/VPS23A proteins were codegraded by the vacuolar pathway. In particular, during recovery post-ABA exposure, SINATs formed homo- and hetero-oligomers in vivo, which were disrupted by the autophagy machinery. Taken together, our findings reveal a novel mechanism by which the proteasomal and vacuolar turnover systems regulate ABA signaling in plants.

Association between acrylamide exposure and sex hormones in males: NHANES, 2003-2004.

INTRODUCTION: Acrylamide is widely present in heat-processed food, cigarette smoke and environment. Reproductive toxicity was reported in animals treated with acrylamide, particularly in males. The reproductive toxicity of acrylamide and its active metabolite, glycidamide, was reported to be mainly mediated through DNA damage in spermatocytes. However, the effect of acrylamide on sex hormones in men is unknown. METHODS: There were 468 male subjects (age ≧ 12 years) enrolled to determine the relationships between hemoglobin adducts of acrylamide (HbAA) and hemoglobin adducts of glycidamide (HbGA) with several sex hormones using the National Health and Nutrition Examination Survey (NHANES), 2003 to 2004. All potential confounding variables in the data set were properly adjusted. RESULTS: We found that one unit increase in the natural log-transformed HbAA level was associated with an increase in natural log transformed serum inhibin B level by 0.10 (SE = 0.05; P = 0.046), and natural log transformed serum sex hormone binding globulin (SHBG) by 0.15 (SE = 0.15; P = 0.036). With respect to HbGA, one unit increase in the natural log-transformed HbGA level was associated with an increase in natural log transformed serum anti-Müllerian Hormone (AMH) level by 0.31 (SE = 0.00; P = 0.003). CONCLUSION: In this representative cohort, we identified positive associations between acrylamide exposure and several sex hormones in men. The HbAA is positively associated with inhibin B and SHBG, and HbGA is positively associated with AMH. Other than genotoxicity, our findings suggested that altered sex hormones might also play a role in acrylamide-related reproductive toxicity in males.

Association among total serum isomers of perfluorinated chemicals, glucose homeostasis, lipid profiles, serum protein and metabolic syndrome in adults: NHANES, 2013-2014.

Perfluorinated chemicals (PFCs) have been used widely in consumer products manufacture. Recent in vitro as well as animal studies have found that there are different toxicity and pharmacokinetic profiles between isomers of perfluorooctanoic acid (PFOA) and/or perfluorooctane sulfonate (PFOS). However, the differential effects of linear or branched PFOA/PFOS isomers on human beings have never been reported. Herein, we examined 1871 adult subjects (age older than 18 years) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to determine the association between the isomers of PFOA/PFOS and serum biochemistry profiles, including glucose, lipids, protein and components of metabolic syndrome (MS). The results showed that for PFOA, increased linear PFOA was associated with increases in total cholesterol, serum albumin and an enhancement of ß cell function as well as a decrease in the serum globulin. Increased branched PFOA was significantly associated with increased fasting glucose. All isomers of PFOA were positively associated with high-density lipoprotein-cholesterol (HDL-C) and negatively associated with glycohemoglobin (HbA1C). The branched PFOS was positively associated with ß cell function and inversely associated with serum globulin. Both linear and branched isomers of PFOS were positively associated with the total protein and albumin. The increased branched PFOA was associated with less HDL-C insufficiency defined by the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) MS criteria, whereas the increased concentrations of serum total and linear PFOS were associated with less hypertriglyceridemia by the NCEP-ATP III. In conclusion, serum isomers of PFOA and PFOS were associated with glucose homeostasis, serum protein as well as lipid profiles; they were also indicators of MS. This may suggest that there is a distinct difference in the toxicokinetics of the isomers of PFOA and PFOS. Further clinical and animal studies are warranted to clarify the putative causal relationships between isomers and biochemical alterations.