BRZ-INSENSITIVE-LONG HYPOCOTYL8 inhibits kinase-mediated phosphorylation to regulate brassinosteroid signaling.

Glycogen synthase kinase 3 (GSK3) is an evolutionarily conserved serine/threonine protein kinase in eukaryotes. In plants, the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) functions as a central signaling node through which hormonal and environmental signals are integrated to regulate plant development and stress adaptation. BIN2 plays a major regulatory role in brassinosteroid (BR) signaling and is critical for phosphorylating/inactivating BRASSINAZOLE-RESISTANT 1 (BZR1), also known as BRZ-INSENSITIVE-LONG HYPOCOTYL 1 (BIL1), a master transcription factor of BR signaling, but the detailed regulatory mechanism of BIN2 action has not been fully revealed. In this study, we identified BIL8 as a positive regulator of BR signaling and plant growth in Arabidopsis (Arabidopsis thaliana). Genetic and biochemical analyses showed that BIL8 is downstream of the BR receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and promotes the dephosphorylation of BIL1/BZR1. BIL8 interacts with and inhibits the activity of the BIN2 kinase, leading to the accumulation of dephosphorylated BIL1/BZR1. BIL8 suppresses the cytoplasmic localization of BIL1/BZR1, which is induced via BIN2-mediated phosphorylation. Our study reveals a regulatory factor, BIL8, that positively regulates BR signaling by inhibiting BIN2 activity.

BIL9 Promotes Both Plant Growth via BR Signaling and Drought Stress Resistance by Binding with the Transcription Factor HDG11.

Drought stress is a major threat leading to global plant and crop losses in the context of the climate change crisis. Brassinosteroids (BRs) are plant steroid hormones, and the BR signaling mechanism in plant development has been well elucidated. Nevertheless, the specific mechanisms of BR signaling in drought stress are still unclear. Here, we identify a novel Arabidopsis gene, BRZ INSENSITIVE LONG HYPOCOTYL 9 (BIL9), which promotes plant growth via BR signaling. Overexpression of BIL9 enhances drought and mannitol stress resistance and increases the expression of drought-responsive genes. BIL9 protein is induced by dehydration and interacts with the HD-Zip IV transcription factor HOMEODOMAIN GLABROUS 11 (HDG11), which is known to promote plant resistance to drought stress, in vitro and in vivo. BIL9 enhanced the transcriptional activity of HDG11 for drought-stress-resistant genes. BIL9 is a novel BR signaling factor that enhances both plant growth and plant drought resistance.

Form follows function: Nuclear morphology as a quantifiable predictor of cellular senescence.

Enlarged or irregularly shaped nuclei are frequently observed in tissue cells undergoing senescence. However, it remained unclear whether this peculiar morphology is a cause or a consequence of senescence and how informative it is in distinguishing between proliferative and senescent cells. Recent research reveals that nuclear morphology can act as a predictive biomarker of senescence, suggesting an active role for the nucleus in driving senescence phenotypes. By employing deep learning algorithms to analyze nuclear morphology, accurate classification of cells as proliferative or senescent is achievable across various cell types and species both in vitro and in vivo. This quantitative imaging-based approach can be employed to establish links between senescence burden and clinical data, aiding in the understanding of age-related diseases, as well as assisting in disease prognosis and treatment response.

Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

In obesity, several epigenetic modifications, including histones remodeling, DNA methylation, and microRNAs, could accumulate and determine increased expression of inflammatory molecules, the adipokines, that in turn might induce or accelerate the onset and development of cardiovascular and metabolic disorders. In order to better clarify the potential epigenetic mechanisms underlying the modulation of the inflammatory response by adipokines, the DNA methylation profile in peripheral leukocytes of the promoter region of IL-6 and NF-kB genes and plasma miRNA-21 levels were evaluated in 356 healthy subjects, using quantitative pyrosequencing-based analysis, and correlated with plasma adiponectin levels, body fat content and the primary pro-inflammatory markers. In addition, correlation analysis of DNA methylation profiles and miRNA-21 plasma levels with intima-media thickness (IMT), a surrogate marker for early atherosclerosis, left ventricular mass (LVM), left ventricular ejection fraction (LVEF), and cardiac performance index (MPI) was also performed to evaluate any potential clinical implication in terms of cardiovascular outcome. Results achieved confirmed the role of epigenetics in the obesity-related cardiovascular complications and firstly supported the potential role of plasma miRNA-21 and IL-6 and NF-kB DNA methylation changes in nucleated blood cells as potential biomarkers for predicting cardiovascular risk in obesity. Furthermore, our results, showing a role of adiponectin in preventing epigenetic modification induced by increased adipose tissue content in obese subjects, provide new evidence of an additional mechanism underlying the anti-inflammatory properties and the cardiovascular benefits of adiponectin. The exact mechanisms underlying the obesity-related epigenetic modifications found in the blood cells and whether similar epigenetic changes reflect adipose and myocardial tissue modifications need to be further investigated in future experiments.

miR-21 in Human Cardiomyopathies.

miR-21 is a 22-nucleotide long microRNA that matches target mRNAs in a complementary base pairing fashion and regulates gene expression by repressing or degrading target mRNAs. miR-21 is involved in various cardiomyopathies, including heart failure, dilated cardiomyopathy, myocardial infarction, and diabetic cardiomyopathy. Expression levels of miR-21 notably change in both heart and circulation and provide cardiac protection after heart injury. In the meantime, miR-21 also tightly links to cardiac dysfunctions such as cardiac hypertrophy and fibrosis. This review focuses on the miR-21 expression pattern and its functions in diseased-heart and further discusses the feasibility of miR-21 as a biomarker and therapeutic target in cardiomyopathies.