LN is a serious complication of systemic lupus erythematosus (SLE), affecting up to 60% of patients with SLE and may lead to end-stage renal disease (ESRD). Macrophages play multifaceted roles in the pathogenesis of LN, including clearance of immune complexes, antigen presentation, regulation of inflammation, and tissue repair. Macrophages are abundant in the glomeruli and tubulointerstitium of LN patients and are positively correlated with serum creatinine levels and the severity of renal pathology.
View Article and Find Full Text PDFPlant root systems play a pivotal role in plant physiology and exhibit diverse phenotypic traits. Understanding the genetic mechanisms governing root growth and development in model plants like maize is crucial for enhancing crop resilience to drought and nutrient limitations. This study focused on identifying and characterizing ZmPILS6, an annotated auxin efflux carrier, as a key regulator of various crown root traits in maize.
View Article and Find Full Text PDFStress-induced retrograde signal transmission from the plastids to the nucleus has long puzzled plant biologists. To address this, we performed a suppressor screen of the ceh1 mutant, which contains elevated 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate (MEcPP) levels, and identified the gain-of-function mutant impα-9, which shows reversed dwarfism and suppressed expression of stress-response genes in the ceh1 background despite heightened MEcPP. Subsequent genetic and biochemical analyses established that the accumulation of MEcPP initiates an upsurge in Arabidopsis SKP1-like 1 (ASK1) abundance, a pivotal component in the proteasome degradation pathway.
View Article and Find Full Text PDFKawasaki disease (KD) is one of the most challenging diseases that is defined as an acute vasculitis that affects the coronary arteries primarily in children. It causes complications if left untreated at early stages, ultimately leading to death. Corticosteroids have been recognized to treat and cause great impact on the patients with KD.
View Article and Find Full Text PDFTris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used, additive flame retardant that migrates from end-use products, leading to ubiquitous exposure of humans around the world. However, little is known about whether TDCIPP disrupts the physiology of human embryonic cells. Therefore, the objective of this study was to determine whether TDCIPP alters cell viability, cellular metabolism, cytosine methylation, and reactive oxygen species (ROS) levels within human embryonic kidney (HEK293) cells.
View Article and Find Full Text PDFPlant survival depends on dynamic stress-response pathways in changing environments. To uncover pathway components, we screened an ethyl methanesulfonate-mutagenized transgenic line containing a stress-inducible luciferase construct and isolated a constitutive expression mutant. The mutant is the result of an amino acid substitution in the seventh subunit of the hetero-octameric conserved oligomeric Golgi (COG) complex of Arabidopsis thaliana.
View Article and Find Full Text PDFJ Clin Hypertens (Greenwich)
July 2023
To assess the value of electrocardiogram (ECG) RV5/V6 criteria for diagnosing left ventricular hypertrophy (LVH) in marathons. A total of 112 marathon runners who met the requirements for "Class A1" events certified by the Chinese Athletics Association in Changzhou City were selected, and their general clinical information was collected. ECG examinations were performed using a Fukuda FX7402 Cardimax Comprehensive Electrocardiograph Automatic Analyser, whereas routine cardiac ultrasound examinations were performed using a Philips EPIQ 7C echocardiography system.
View Article and Find Full Text PDFObjective: To identify whether there exists a genetic correlation and causal relationship between 25(OH)D and autism spectrum disorder (ASD).
Methods: Based on large-scale genome-wide association studies, a series of genetic approaches were adopted to obtain summary statistics. Using linkage disequilibrium score regression, we assessed the shared polygenic structure between traits and performed pleiotropic analysis under composite null hypothesis (PLACO) to identify pleiotropic loci between complex traits.
Wheat, an essential crop for global food security, is well adapted to a wide variety of soils. However, the gene networks shaping different root architectures remain poorly understood. We report here that dosage differences in a cluster of monocot-specific 12-OXOPHYTODIENOATE REDUCTASE genes from subfamily III (OPRIII) modulate key differences in wheat root architecture, which are associated with grain yield under water-limited conditions.
View Article and Find Full Text PDFReconfiguration of the plastidial proteome in response to environmental cues is central to tailoring adaptive responses. To define the underlying mechanisms and consequences of these reconfigurations, we performed a suppressor screen, using a mutant () accumulating high levels of a plastidial retrograde signaling metabolite, MEcPP. We isolated a revertant partially suppressing the dwarf stature and high salicylic acid of and identified the mutation in a putative plastidial metalloprotease (VIR3).
View Article and Find Full Text PDFTranscriptional regulators of the general stress response (GSR) reprogram the expression of selected genes to transduce informational signals into cellular events, ultimately manifested in a plant's ability to cope with environmental challenges. Identification of the core GSR regulatory proteins will uncover the principal modules and their mode of action in the establishment of adaptive responses. To define the GSR regulatory components, we employed a yeast-one-hybrid assay to identify the protein(s) binding to the previously established functional GSR motif, termed the rapid stress response element (RSRE).
View Article and Find Full Text PDFPlants employ an array of intricate and hierarchical signaling cascades to perceive and transduce informational cues to synchronize and tailor adaptive responses. Systemic stress response (SSR) is a recognized complex signaling and response network quintessential to plant's local and distal responses to environmental triggers; however, the identity of the initiating signals has remained fragmented. Here, we show that both biotic (aphids and viral pathogens) and abiotic (high light and wounding) stresses induce accumulation of the plastidial-retrograde-signaling metabolite methylerythritol cyclodiphosphate (MEcPP), leading to reduction of the phytohormone auxin and the subsequent decreased expression of the phosphatase PP2C.
View Article and Find Full Text PDFGene transcription is counterbalanced by messenger RNA decay processes that regulate transcript quality and quantity. We show here that the evolutionarily conserved DHH1/DDX6-like RNA hellicases of Arabidopsis thaliana control the ephemerality of a subset of cellular mRNAs. These RNA helicases co-localize with key markers of processing bodies and stress granules and contribute to their subcellular dynamics.
View Article and Find Full Text PDFExquisitely regulated plastid-to-nucleus communication by retrograde signaling pathways is essential for fine-tuning of responses to the prevailing environmental conditions. The plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) has emerged as a stress signal transduced into a diverse ensemble of response outputs. Here, we demonstrate enhanced phytochrome B protein abundance in red light-grown MEcPP-accumulating mutant Arabidopsis () plants relative to wild-type seedlings.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2020
The methylerythritol phosphate (MEP) pathway is responsible for producing isoprenoids, metabolites with essential functions in the bacterial kingdom and plastid-bearing organisms including plants and Apicomplexa. Additionally, the MEP-pathway intermediate methylerythritol cyclodiphosphate (MEcPP) serves as a plastid-to-nucleus retrograde signal. A suppressor screen of the high MEcPP accumulating mutant plant () led to the isolation of 3 revertants (designated -) resulting from independent intragenic substitutions of conserved amino acids in the penultimate MEP-pathway enzyme, hydroxymethylbutenyl diphosphate synthase (HDS).
View Article and Find Full Text PDFPlant survival necessitates constant monitoring of fluctuating light and balancing growth demands with adaptive responses, tasks mediated via interconnected sensing and signaling networks. Photoreceptor phytochrome B (phyB) and plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) are evolutionarily conserved sensing and signaling components eliciting responses through unknown connection(s). Here, via a suppressor screen, we identify two phyB mutant alleles that revert the dwarf and high salicylic acid phenotypes of the high MEcPP containing mutant ceh1.
View Article and Find Full Text PDFInstruction: Several factors affect the in-stent intimal healing process after drug-eluting stents (DESs) implantation. We hope to investigate the influence of plaque characteristics on subsequent heterogeneous neointimal hyperplasia (NIH) using optical coherence tomography (OCT).
Methods: The study population consisted 217 patients with single-vessel de novo lesions who underwent both pre-procedural OCT scan and 12-month follow-up OCT examination.
The ancient morphoregulatory hormone auxin dynamically realigns dedicated cellular processes that shape plant growth under prevailing environmental conditions. However, the nature of the stress-responsive signal altering auxin homeostasis remains elusive. Here we establish that the evolutionarily conserved plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) controls adaptive growth by dual transcriptional and post-translational regulatory inputs that modulate auxin levels and distribution patterns in response to stress.
View Article and Find Full Text PDFBiochem Biophys Res Commun
June 2018
It was previously found that patients with symptom of myocardial dysfunction had increased levels of thrombin. Apixaban is one of the novel oral anticoagulant drugs widely used in clinic. As the inhibitor of FXa (prothrombin), it inhibits prothrombin conversion into thrombin leading to thrombin deficiency in vivo.
View Article and Find Full Text PDFPlants have evolved tightly regulated signaling networks to respond and adapt to environmental perturbations, but the nature of the signaling hub(s) involved have remained an enigma. We have previously established that methylerythritol cyclodiphosphate (MEcPP), a precursor of plastidial isoprenoids and a stress-specific retrograde signaling metabolite, enables cellular readjustments for high-order adaptive functions. Here, we specifically show that MEcPP promotes two Brassicaceae-specific traits, namely endoplasmic reticulum (ER) body formation and induction of indole glucosinolate (IGs) metabolism selectively, via transcriptional regulation of key regulators NAI1 for ER body formation and MYB51/122 for IGs biosynthesis).
View Article and Find Full Text PDFThe general stress response (GSR) is an evolutionarily conserved rapid and transient transcriptional reprograming of genes central for transducing environmental signals into cellular responses, leading to metabolic and physiological readjustments to cope with prevailing conditions. Defining the regulatory components of the GSR will provide crucial insight into the design principles of early stress-response modules and their role in orchestrating master regulators of adaptive responses. Overaccumulation of methylerythritol cyclodiphosphate (MEcPP), a bifunctional chemical entity serving as both a precursor of isoprenoids produced by the plastidial methylerythritol phosphate (MEP) pathway and a stress-specific retrograde signal, in ceh1 (constitutively expressing hydroperoxide lyase1)-mutant plants leads to large-scale transcriptional alterations.
View Article and Find Full Text PDFCdc42, a member of the Rho-family small GTP-binding proteins, is a pivotal signaling switch that cycles between active GTP-bound and inactive GDP-bound forms, controlling actin cytoskeleton organization and cell polarity. In this report, we show that MgCdc42, a Cdc42 ortholog in Magnaporthe grisea, is required for its plant penetration. Consequently, the deletion mutants show dramatically decreased virulence to rice due to the arrest of penetration and infectious growth, which may be attributed to the defect of turgor and superoxide generation during the appressorial development in Mgcdc42 deletion mutants.
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