Interactions between Lateral Hypothalamic Orexin and Dorsal Raphe Circuitry in Energy Balance.

Orexin/hypocretin terminals innervate the dorsal raphe nucleus (DRN), which projects to motor control areas important for spontaneous physical activity (SPA) and energy expenditure (EE). Orexin receptors are expressed in the DRN, and obesity-resistant (OR) rats show higher expression of these receptors in the DRN and elevated SPA/EE. We hypothesized that orexin-A in the DRN enhances SPA/EE and that DRN-GABA modulates the effect of orexin-A on SPA/EE.

Cyclin D1 extensively reprograms metabolism to support biosynthetic pathways in hepatocytes.

Cell proliferation requires metabolic reprogramming to accommodate biosynthesis of new cell components, and similar alterations occur in cancer cells. However, the mechanisms linking the cell cycle machinery to metabolism are not well defined. Cyclin D1, along with its main partner cyclin-dependent kinase 4 (Cdk4), is a pivotal cell cycle regulator and driver oncogene that is overexpressed in many cancers.

Neural anomalies during vigilance in schizophrenia: Diagnostic specificity and genetic associations.

Impaired vigilance is a core cognitive deficit in schizophrenia and may serve as an endophenotype (i.e., mark genetic liability).

A negative reciprocal regulatory axis between cyclin D1 and HNF4α modulates cell cycle progression and metabolism in the liver.

Hepatocyte nuclear factor 4α (HNF4α) is a master regulator of liver function and a tumor suppressor in hepatocellular carcinoma (HCC). In this study, we explore the reciprocal negative regulation of HNF4α and cyclin D1, a key cell cycle protein in the liver. Transcriptomic analysis of cultured hepatocyte and HCC cells found that cyclin D1 knockdown induced the expression of a large network of HNF4α-regulated genes.

Evidence for a Novel Regulatory Interaction Involving Cyclin D1, Lipid Droplets, Lipolysis, and Cell Cycle Progression in Hepatocytes.

During normal proliferation, hepatocytes accumulate triglycerides (TGs) in lipid droplets (LDs), but the underlying mechanisms and functional significance of this steatosis are unknown. In the current study, we examined the coordinated regulation of cell cycle progression and LD accumulation. As previously shown, hepatocytes develop increased LD content after mitogen stimulation.

Immune characteristics correlating with HSV-1 immune control and effect of squaric acid dibutyl ester on immune characteristics of subjects with frequent herpes labialis episodes.

Introduction: Differences in immune characteristics, including immune gene expression by peripheral blood mononuclear cells (PBMCs), correlating with herpes labialis and good or poor immune control of herpes simplex virus type 1 (HSV-1), and how these characteristics change after dosing with squaric acid dibutyl ester (SADBE), were investigated.

Methods: PBMCs were collected from persons positive for IgG against HSV-1 and having frequent, infrequent, or no herpes labialis outbreaks. The PBMCs were tested for proliferation against HSV-1 and a fungal antigen (Candida) and immune gene expression in the presence of HSV-1 and Candida.

Effect of systemic heparan sulfate haploinsufficiency on steady state hematopoiesis and engraftment of hematopoietic stem cells.

Heparan sulfate (HS) proteoglycans on stromal and hematopoietic stem/progenitor cells (HSPC) help form the stem cell niche, co-localize molecules that direct stem cell fate, and modulate HSPC homing and retention. Inhibition of HS function mobilizes marrow HSPC. In vitro, HSPC maintenance is influenced by stromal HS structure and concentration.

The effects of Gremlin1 on human umbilical cord blood hematopoietic progenitors.

Bone morphogenetic proteins (BMPs) support malignant hematopoiesis in CML. Conversely, the multi-functional BMP antagonist Gremlin1 supports self-renewing cancer stem cells of other malignancies. Inhibition of BMP signaling in CML, or of Gremlin1 in solid tumors, may therefore have therapeutic potential.

Intracerebroventricular transplantation of human bone marrow-derived multipotent progenitor cells in an immunodeficient mouse model of mucopolysaccharidosis type I (MPS-I).

Mucopolysaccharidosis type I (MPS-I; Hurler syndrome) is an inborn error of metabolism caused by lack of the functional lysosomal glycosaminoglycan (GAG)-degrading enzyme α-L-iduronidase (IDUA). Without treatment, the resulting GAG accumulation causes multisystem dysfunction and death within the first decade. Current treatments include allogeneic hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy.

Activity of recombinant cysteine-rich domain proteins derived from the membrane-bound MUC17/Muc3 family mucins.

Background: The membrane-bound mucins, MUC17 (human) and Muc3 (mouse), are highly expressed on the apical surface of intestinal epithelia and have cytoprotective properties. Their extracellular regions contain two EGF-like Cys-rich domains (CRD1 and CRD2) connected by an intervening linker segment with SEA module (L), and may function to stimulate intestinal cell restitution. The purpose of this study was to determine the effect of size, recombinant host source, and external tags on mucin CRD1-L-CRD2 protein activity.

Human intestinal MUC17 mucin augments intestinal cell restitution and enhances healing of experimental colitis.

Unlabelled: The membrane-bound mucins, MUC17 (human) and Muc3 (mouse), are highly expressed on the apical surface of intestinal epithelia and are thought to be cytoprotective. The extracellular regions of these mucins contain EGF-like Cys-rich segments (CRD1 and CRD2) connected by an intervening linker domain (L). The purpose of this study was to determine the functional activity of human MUC17 membrane-bound mucin.

Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing.

Background & Aims: Muc3 intestinal mucin contains an extracellular cysteine-rich domain with 2 epidermal growth factor (EGF)-like motifs. The aim of this study was to determine the functional properties of Muc3 proteins.

Methods: Glutathione S-transferase-fusion proteins containing both Muc3 EGF-like domains (m3EGF1,2) or truncated versions (m3EGF1 and m3EGF2) were purified from Escherichia coli.

Characterization of the mouse Muc3 membrane bound intestinal mucin 5' coding and promoter regions: regulation by inflammatory cytokines.

The mouse Muc3 mucin is a membrane-bound glycoprotein highly expressed in the intestinal tract. We have characterized the mouse Muc3 5' structure and regulation of its promoter by cytokines and growth factors. The first two exons of Muc3 are separated by an intron of over 8 kb.

Coordinated Muc2 and Muc3 mucin gene expression in Trichinella spiralis infection in wild-type and cytokine-deficient mice.

Mucin hypersecretion is an important component of the immune response to gastrointestinal nematode infection. Two discrete types of mucin proteins exist in the mouse intestine, secretory Muc2 and membrane-bound Muc3. We examined Muc2 and Muc3 expression in wild-type mice and mice lacking gamma interferon receptor (IFNgammaR-/-), tumor necrosis factor receptor 1 (TNFR1-/-) and interleukin 4 (IL4-/-) infected with Trichinella spiralis.

Altered mucin core peptide expression in acute and chronic cholecystitis.

Human mucin genes include membrane-bound mucins (MUC1, MUC3, MUC4) and secretory mucins (MUC2, MUC5AC, MUC5B, MUC6). Our aim was to determine mucin gene expression in human gallbladder cell lines, normal gallbladder from liver donors (N = 7) and surgical specimens with mild chronic cholecystitis (N = 29), chronic cholecystitis (N = 48), and acute and chronic cholecystitis (N = 27). MUC1 mRNA was ubiquitous; however, only rare MUC1 immunoreactivity was detected.

Mucin gene expression in the rat middle ear: an improved method for RNA harvest.

Mucins are heavily glycosylated proteins characterized by high molecular weight and heterogeneous structure. Mucin genes are expressed in a tissue- or epithelium-specific manner. Although mucins are known to be important structural components of the mucociliary transport system that protects epithelium against invading microorganisms, very little is known about mucin gene expression unique to the middle ear.

Cloning and characterization of mouse intestinal MUC3 mucin: 3' sequence contains epidermal-growth-factor-like domains.

Mucin glycoproteins are a heterogeneous family of high-molecular-mass, heavily glycosylated proteins differentially expressed in epithelial tissue of the gastrointestinal, reproductive and respiratory tracts. We report here the cloning of a mouse caecal mucin (MCM). Amino acid analysis of purified MCM revealed a high content of serine (10.

Bile acid-induced alterations of mucin production in differentiated human colon cancer cell lines.

Damage to the gastrointestinal tract mucous layer may render underlying cells susceptible to intraluminal toxins or carcinogens. Our aim was to determine the effect of bile acids on mucin, the primary constituent of mucous. Differentiated Caco-2 and HT29 cells were used as models of human colonic epithelial cells.

Tauroursodeoxycholic acid protects in vitro models of human colonic cancer cells from cytotoxic effects of hydrophobic bile acids.

Bile acids have been implicated as tumor promoters that enhance epithelial proliferation and the development of colonic tumors. This study investigated the effects of bile acids on the growth of in vitro models of human colonic epithelial cells. Cell lines with varying degrees of differentiation (Caco2, HT29, LS174T, and Lovo) were studied.

Mouse gastric mucin: cloning and chromosomal localization.

Mucins protect gastric epithelium by maintaining a favourable pH gradient and preventing autodigestion. The purpose of this study was to clone a mouse gastric mucin which would provide a foundation for analysis of mucin gene regulation. Mucin was purified from the glandular portion of gastric specimens and deglycosylated by HF solvolysis.

Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression.

Background & Aims: Secretory mucins play an important role in gastric cytoprotection and are derived from a heterogeneous family of genes. The aim of this study was to determine the specific type and location of mucin gene expression in the human stomach.

Methods: Expression cloning was performed by screening a human gastric complementary DNA expression library with antisera against deglycosylated gastric mucin.

Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium.

Mucins synthesized by malignant cells may contribute (via decreased cellular adhesion and immune recognition) to cancer invasion and metastases. Human mucins are derived from a heterogeneous family of genes, labeled MUC1-6. Our aim was to determine the pattern of mucin gene expression in normal, preneoplastic (intestinal metaplasia), and malignant gastric specimens.