Architecture of CTPS filament networks revealed by cryo-electron tomography.

The cytoophidium is a novel type of membraneless organelle, first observed in the ovaries of Drosophila using fluorescence microscopy. In vitro, purified Drosophila melanogaster CTPS (dmCTPS) can form metabolic filaments under the presence of either substrates or products, and their structures that have been analyzed using cryo-electron microscopy (cryo-EM). These dmCTPS filaments are considered the fundamental units of cytoophidia.

Structural Basis of Bifunctional CTP/dCTP Synthase.

The final step in the de novo synthesis of cytidine 5'-triphosphate (CTP) is catalyzed by CTP synthase (CTPS), which can form cytoophidia in all three domains of life. Recently, we have discovered that CTPS binds to ribonucleotides (NTPs) to form filaments, and have successfully resolved the structures of Drosophila melanogaster CTPS bound with NTPs. Previous biochemical studies have shown that CTPS can bind to deoxyribonucleotides (dNTPs) to produce 2'-deoxycytidine-5'-triphosphate (dCTP).

Dynamic Arabidopsis P5CS filament facilitates substrate channelling.

In plants, the rapid accumulation of proline is a common response to combat abiotic stress. Delta-1-pyrroline-5-carboxylate synthase (P5CS) is a rate-limiting enzyme in proline synthesis, catalysing the initial two-step conversion from glutamate to proline. Here we determine the first structure of plant P5CS.

Cytoophidia and filaments: you must unlearn what you have learned.

The nucleotide CTP can be synthesized de novo from UTP via the metabolic enzyme CTP synthase (CTPS). As a textbook enzyme, CTPS has been extensively studied for seven decades. However, it came as a surprise when CTPS was found to form snake-shaped mesoscale cytoophidia in fruit fly cells.

Structural basis of human PRPS2 filaments.

Background: PRPP synthase (PRPS) transfers the pyrophosphate groups from ATP to ribose-5-phosphate to produce 5-phosphate ribose-1-pyrophosphate (PRPP), a key intermediate in the biosynthesis of several metabolites including nucleotides, dinucleotides and some amino acids. There are three PRPS isoforms encoded in human genome. While human PRPS1 (hPRPS1) and human PRPS2 (hPRPS2) are expressed in most tissues, human PRPS3 (hPRPS3) is exclusively expressed in testis.

Exosome-mediated inhibition of microRNA-449a promotes the amplification of mouse retinal progenitor cells and enhances their transplantation in retinal degeneration mouse models.

Inherited and age-related retinal degenerations are the commonest causes of blindness without effective treatments. Retinal progenitor cells (RPCs), which have the multipotency to differentiate into various retinal cell types, are regarded as a promising source of cell transplantation therapy for retinal degenerative diseases. However, the self-limited expansion of RPCs causes difficulty in cell source supply and restrict its clinical treatment.

Nomogram for predicting overall survival time of patients with stage IV colorectal cancer.

Background: Prognosis varies among stage IV colorectal cancer (CRC). Our study aimed to build a robust prognostic nomogram for predicting overall survival (OS) of patients with stage IV CRC in order to provide evidence for individualized treatment.

Method: We collected the information of 16,283 patients with stage IV CRC in the Surveillance, Epidemiology, and End Results (SEER) database and then randomized these patients in a ratio of 7:3 into a training cohort and an internal validation cohort.

Filamentation modulates allosteric regulation of PRPS.

Phosphoribosyl pyrophosphate (PRPP) is a key intermediate in the biosynthesis of purine and pyrimidine nucleotides, histidine, tryptophan, and cofactors NAD and NADP. Abnormal regulation of PRPP synthase (PRPS) is associated with human disorders, including Arts syndrome, retinal dystrophy, and gouty arthritis. Recent studies have demonstrated that PRPS can form filamentous cytoophidia in eukaryotes.

GTP-Dependent Regulation of CTP Synthase: Evolving Insights into Allosteric Activation and NH Translocation.

Cytidine-5'-triphosphate (CTP) synthase (CTPS) is the class I glutamine-dependent amidotransferase (GAT) that catalyzes the last step in the de novo biosynthesis of CTP. Glutamine hydrolysis is catalyzed in the GAT domain and the liberated ammonia is transferred via an intramolecular tunnel to the synthase domain where the ATP-dependent amination of UTP occurs to form CTP. CTPS is unique among the glutamine-dependent amidotransferases, requiring an allosteric effector (GTP) to activate the GAT domain for efficient glutamine hydrolysis.

Structural basis of dynamic P5CS filaments.

The bifunctional enzyme Δ-pyrroline-5-carboxylate synthase (P5CS) is vital to the synthesis of proline and ornithine, playing an essential role in human health and agriculture. Pathogenic mutations in the P5CS gene (ALDH18A1) lead to neurocutaneous syndrome and skin relaxation connective tissue disease in humans, and P5CS deficiency seriously damages the ability to resist adversity in plants. We have recently found that P5CS forms cytoophidia in vivo and filaments in vitro.

Increased risk of colorectal neoplasia in inflammatory bowel disease patients with post-inflammatory polyps: A systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) patients with post-inflammatory polyps (PIPs) may carry an increased risk of colorectal neoplasia (CRN) including dysplasia and cancer. Current guidelines recommend active colonoscopy follow-up for these patients. However, the evidence for guidelines is still poor.

Structural basis for ligand binding modes of CTP synthase.

Cytidine triphosphate synthase (CTPS), which comprises an ammonia ligase domain and a glutamine amidotransferase domain, catalyzes the final step of de novo CTP biosynthesis. The activity of CTPS is regulated by the binding of four nucleotides and glutamine. While glutamine serves as an ammonia donor for the ATP-dependent conversion of UTP to CTP, the fourth nucleotide GTP acts as an allosteric activator.

The proline synthesis enzyme P5CS forms cytoophidia in Drosophila.

Compartmentation of enzymes via filamentation has arisen as a mechanism for the regulation of metabolism. In 2010, three groups independently reported that CTP synthase (CTPS) can assemble into a filamentous structure termed the cytoophidium. In searching for CTPS-interacting proteins, here we perform a yeast two-hybrid screening of Drosophila proteins and identify a putative CTPS-interacting protein, △-pyrroline-5-carboxylate synthase (P5CS).

Drosophila CTP synthase can form distinct substrate- and product-bound filaments.

Intracellular compartmentation is a key strategy for the functioning of a cell. In 2010, several studies revealed that the metabolic enzyme CTP synthase (CTPS) can form filamentous structures termed cytoophidia in prokaryotic and eukaryotic cells. However, recent structural studies showed that CTPS only forms inactive product-bound filaments in bacteria while forming active substrate-bound filaments in eukaryotic cells.

Stem cells: a promising candidate to treat neurological disorders.

Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system. Therefore, based on the regenerative capacity of stem cells, transplantation therapies of various stem cells have been tested in basic research and preclinical trials, and some have shown great prospects. This manuscript overviews the cellular and molecular characteristics of embryonic stem cells, induced pluripotent stem cells, neural stem cells, retinal stem/progenitor cells, mesenchymal stem/stromal cells, and their derivatives in vivo and in vitro as sources for regenerative therapy.

Exosomes derived from human umbilical vein endothelial cells promote neural stem cell expansion while maintain their stemness in culture.

The neural stem cell (NSC) niche in subventricular zone (SVZ) of adult mammalian brain contains dense vascular plexus, where endothelial cells (ECs) regulate NSCs by releasing plenty of angiocrine factors. However, the role of ECs-derived exosomes, a novel type of mediators of intercellular communications, in the regulation of NSCs remains unclear. In the current study, primary NSCs isolated from embryonic mouse brains form more neurospheres when cultured in the presence of human umbilical vein endothelial cells (HUVECs).

miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice.

Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted.

Endothelial nitric oxide synthase (eNOS) 4b/a polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus: A meta-analysis.

Many studies have accessed the association between eNOS-4b/a polymorphism and the risk of diabetic nephropathy (DN) among type 2 diabetic subjects. However, the results are conflicting and inconclusive. The aim of current meta-analysis was to more precisely estimate the relationship.

[Effects of comprehensive therapy on serum SPARC levels in ankylosing spondylitis patients accompanied with osteoporosis].

Objective: To observe the effects of comprehensive therapy on serum secreted protein acidic and rich in cysteine (SPARC) levels in ankylosing spondylitis (AS) patients accompanied with osteoporosis (OP), and to explore the possible mechanisms for SPARC in AS patients accompanied with osteoporosis.

Methods: Totally 48 AS patients accompanied with OP (Group A) were treated with massage, intravenous infusion of Cervus and Cucumis Polypeptide Injection, and Bushen Quhan Zhiwang Decoction (BQZD) for 3 months. At the same time, 45 normal healthy subjects were recruited as the normal control group (Group B).