Repulsive guidance molecule acts in axon branching in Caenorhabditis elegans

Repulsive guidance molecules (RGMs) are evolutionarily conserved proteins implicated in repulsive axon guidance. Here we report the function of the Caenorhabditis elegans ortholog DRAG-1 in axon branching. The axons of hermaphrodite-specific neurons (HSNs) extend dorsal branches at the region abutting the vulval muscles. The drag-1 mutants exhibited defects in HSN axon branching in addition to a small body size phenotype. DRAG-1 expression in the hypodermal cells was required for the branching of the axons. Although DRAG-1 is normally expressed in the ventral hypodermis excepting the vulval region, its ectopic expression in vulval precursor cells was sufficient to induce the branching. The C-terminal glycosylphosphatidylinositol anchor of DRAG-1 was important for its function, suggesting that DRAG-1 should be anchored to the cell surface. Genetic analyses suggested that the membrane receptor UNC-40 acts in the same pathway with DRAG-1 in HSN branching. We propose that DRAG-1 expressed in the ventral hypodermis signals via the UNC-40 receptor expressed in HSNs to elicit branching activity of HSN axons.

Repulsive Guidance Molecule Acts in Axon Branching in Caenorhabditis elegans

Repulsive guidance molecules (RGMs) are evolutionarily conserved proteins implicated in repulsive axon guidance. Here we report the function of the Caenorhabditis elegans ortholog DRAG-1 in axon branching. The axons of hermaphrodite-specific neurons (HSNs) extend dorsal branches at the region abutting the vulval muscles. The drag-1 mutants exhibited defects in HSN axon branching in addition to a small body size phenotype. DRAG-1 expression in the hypodermal cells was required for the branching of the axons. Although DRAG-1 is normally expressed in the ventral hypodermis excepting the vulval region, its ectopic expression in vulval precursor cells was sufficient to induce the branching. The C-terminal glycosylphosphatidylinositol anchor of DRAG-1 was important for its function, suggesting that DRAG-1 should be anchored to the cell surface. Genetic analyses suggested that the membrane receptor UNC-40 acts in the same pathway with DRAG-1 in HSN branching. We propose that DRAG-1 expressed in the ventral hypodermis signals via the UNC-40 receptor expressed in HSNs to elicit branching activity of HSN axons.

Impact of Different Durations of Fasting on Intestinal Autophagy and Serum Metabolome in Broiler Chicken

Fasting-induced autophagy in the intestine is beneficial for body health. This study was designed to explore the relationship between the host metabolism and intestinal autophagy. Broilers were randomly assigned into 48 cages. At 0 (CT), 12 (FH12), 24 (FH24), 36 (FH36), 48(FH48), and 72 h (FH72) before 09:00 a.m. on day 25, eight cages of birds were randomly allotted to each fasting time point using completely random design, and their food was removed. At 09:00 a.m. on day 25, the blood and jejunum were sampled for serum metabolome and autophagy gene analyses, respectively. The results showed that the autophagy gene Atg7 has a good quadratic fit with fasting duration (R2 = 0.432, p < 0.001). Serum phosphatidylethanolamine (PE) and lyso-PE were decreased in the birds that were fasted for 24 h or longer. Conversely, the serum phosphatidylcholine (PC) and lyso-PC were increased in the birds that were fasted for 36 h or longer. Metabolism pathway analysis showed that the serum glycerophospholipid, phenylalanine, and GnRH signaling pathways were downregulated with the extended fasting duration. The serum metabolites involved in glycosylphosphatidylinositol anchor biosynthesis, autophagy, and ferroptosis were upregulated in all of the fasted groups. Correlation analysis showed that serum PE (18:3(9Z,12Z,15Z)/P-18:0) was a potential biomarker for intestinal autophagy. Our findings provide a potential biomarker related to intestinal autophagy.

Antifungal Activity of Gepinacin Scaffold Glycosylphosphatidylinositol Anchor Biosynthesis Inhibitors with Improved Metabolic Stability

ABSTRACT The glycosylphosphatidylinositol anchor biosynthesis inhibitor gepinacin demonstrates broad-spectrum antifungal activity and negligible mammalian toxicity in culture but is metabolically labile. The stability and bioactivity of 39 analogs were tested in vitro to identify LCUT-8, a stabilized lead with increased potency and promising single-dose pharmacokinetics. Unfortunately, no antifungal activity was seen at the maximum dosing achievable in a neutropenic rabbit model. Nevertheless, structure-activity relationships identified here suggest strategies to further improve compound potency, solubility, and stability.

The Role of Glypicans in Cancer Progression and Therapy

Glypicans are a family of heparan sulfate proteoglycans that are attached to the cell membrane via a glycosylphosphatidylinositol anchor. Glypicans interact with multiple ligands, including morphogens, growth factors, chemokines, ligands, receptors, and components of the extracellular matrix through their heparan sulfate chains and core protein. Therefore, glypicans can function as coreceptors to regulate cell proliferation, cell motility, and morphogenesis. In addition, some glypicans are abnormally expressed in cancers, possibly involved in tumorigenesis, and have the potential to be cancer-specific biomarkers. Here, we provide a brief review focusing on the expression of glypicans in various cancers and their potential to be targets for cancer therapy.