Fibronectin contributes to notochord intercalation in the invertebrate chordate, Ciona intestinalis.

Background: Genomic analysis has upended chordate phylogeny, placing the tunicates as the sister group to the vertebrates. This taxonomic rearrangement raises questions about the emergence of a tunicate/vertebrate ancestor.

Results: Characterization of developmental genes uniquely shared by tunicates and vertebrates is one promising approach for deciphering developmental shifts underlying acquisition of novel, ancestral traits.

Heart genetics in a small package, exploiting the condensed genome of Ciona intestinalis.

Defects in the initial establishment of cardiogenic cell fate are likely to contribute to pervasive human congenital cardiac abnormalities. However, the molecular underpinnings of nascent cardiac fate induction have proven difficult to decipher. In this review we explore the participation of extracellular, cellular and nuclear factors in comprehensive specification networks.

A genome-wide association study of chronic otitis media with effusion and recurrent otitis media identifies a novel susceptibility locus on chromosome 2.

Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs).

Evaluation of 15 functional candidate genes for association with chronic otitis media with effusion and/or recurrent otitis media (COME/ROM).

DNA sequence variants in genes involved in the innate immune response and secondary response to infection may confer susceptibility to chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). We evaluated single nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99 SNPs were successfully genotyped on the Sequenom platform in 142 families (618 subjects) from the Minnesota COME/ROM Family Study.

Molecular evolution of the fibulins: implications on the functionality of the elastic fibulins.

The fibulins form a family of secreted proteins associated with the basement membrane, cell adhesive structures, and elastic fibers characterized by the presence of a unique fibulin-like C-terminal domain preceded by a rod-like tandem array of calcium-binding EGF modules. We traced the origin of the fibulin gene family to the base of the metazoans. In invertebrates, Fibulin-1 and Hemicentin comprise the fibulin gene set.

Glucose transporter 10 and arterial tortuosity syndrome: the vitamin C connection.

Arterial Tortuosity Syndrome (ATS) is a heritable disease characterized by twisting and lengthening of the major arteries, hypermobility of the joints, and laxity of skin. ATS is caused by mutations in SLC2A10, encoding Glucose Transporter 10 (GLUT10). The current model of ATS holds that loss of GLUT10 at the nuclear periphery induces a glucose-dependent increase in Transforming Growth Factor-beta (TGFbeta) that stimulates vessel wall cell proliferation.

Functional evolution of the microfibril-associated glycoproteins.

The microfibril-associated glycoproteins (MAGPs) are cysteine-rich low molecular weight components of the fibrillin-based microfibrillar complex. MAGPs are evolutionarily conserved in vertebrates and have important roles in microfibril and elastic fiber structure, homeostasis, and vascular development. Two MAGPs, designated MAGP1 and MAGP2, are encoded in the mammalian genome.

Deficiency in microfibril-associated glycoprotein-1 leads to complex phenotypes in multiple organ systems.

Microfibril-associated glycoprotein-1 (MAGP-1) is a small molecular weight component of the fibrillin-rich microfibril. Gene-targeted inactivation of MAGP-1 reveals a complex phenotype that includes increased body weight and size due to excess body fat, an altered wound healing response in bone and skin, and a bleeding diathesis. Elastic tissues rich in MAGP-1-containing microfibrils develop normally and show normal function.

The intracellular form of human MAGP1 elicits a complex and specific transcriptional response.

Microfibril-associated glycoprotein-1 (MAGP1) is found associated with microfibrils in the extracellular matrix (ECM). In humans, MAGP1 is expressed as two alternatively spliced isoforms: MAGP1A, the extracellular microfibril-associated form; and MAGP1B, an exclusively intracellular isoform derived from the skipping of exon 3. The biological function of MAGP1B is unknown.

Differential expression of facilitative glucose transporters in normal and tumour kidney tissues.

Objective: To investigate the differences in the pattern of glucose transporter (GLUT) gene expression between normal and tumour tissues and among histological subtypes of renal cell carcinomas (RCCs), as malignant cells are characterized by increased glucose uptake and use.

Materials And Methods: Enhanced glucose uptake probably depends on the overexpression of GLUT, usually GLUT1 and/or GLUT3, but there are few comprehensive studies to evaluate the relative expression pattern and level of GLUT in normal and tumour kidney tissues, especially of the recently identified GLUT genes. In all, 71 kidney surgical samples were evaluated using reverse transcriptase-polymerase chain reaction (RT-PCR) for GLUT1-14 in normal and tumour (clear cell, papillary and chromophobe RCC, and oncocytoma) tissues.

Association of the FBXO11 gene with chronic otitis media with effusion and recurrent otitis media: the Minnesota COME/ROM Family Study.

Objective: The FBXO11 gene is the human homologue of the gene mutated in the novel deaf mouse mutant jeff (Jf), a single gene model of otitis media. We have evaluated single nucleotide polymorphisms (SNPs) in the FBXO11 gene for association with chronic otitis media with effusion/recurrent otitis media (COME/ROM).

Design: A total of 13 SNPs were genotyped across the 98.

Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes.

Background: GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans.

Regulatory elements of microfibril-associated glycoprotein-1 gene expression in muscle cells.

The Mfap2 gene encodes the microfibril-associated glycoprotein-1 (MAGP1), an extracellular matrix protein of microfibrillar structures. The gene is transcribed from a major transcription start site embedded in a CpG island. Mapping of transcriptionally active regions in the 5' flanking sequence identified a region, located between nucleotides -339 and -109 as the Mfap2 basal promoter.

Functional characterization of the promoter of the human glucose transporter 10 gene.

The human SLC2A10 gene encodes the high-affinity glucose transporter 10 (GLUT10) and is widely expressed in adult tissues, including organs which play major roles in glucose homeostasis. Its function and genomic location in a region linked to Type 2 diabetes susceptibility are consistent with a potential role in Type 2 diabetes. Analysis of the CpG-rich promoter revealed the presence of two major transcription start points with differential use in tissues and cell lines.

Glucose transporters in the thyroid.

Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an essential role in cellular metabolism. Increased uptake of glucose compared to cells in normal tissue is a defining characteristic of malignant cells. This has been the basis for positron emission tomography imaging of thyroid tumor metastases using fluorodeoxyglucose uptake.

Differential expression of glucose transporters in normal and pathologic thyroid tissue.

Malignant cells demonstrate increased glucose uptake and utilization. Immunohistochemical studies have suggested that enhanced glucose uptake in cancer cells may be caused by the overexpression of glucose transporters (GLUTs), in most cases GLUT1 and/or GLUT3. The aim of this study was to examine in detail the expression pattern and levels of GLUT genes in normal and pathologic thyroid tissues and to evaluate the clinical significance of GLUT mRNA levels.

Chronic and recurrent otitis media: a genome scan for susceptibility loci.

Otitis media (OM) is the most common childhood disease. Almost all children experience at least one episode, but morbidity is greatest in children who experience chronic/recurrent OM (COME/ROM). There is mounting evidence that COME/ROM clusters in families and exhibits substantial heritability.

Identification of a major microfibril-associated glycoprotein-1-binding domain in fibrillin-2.

Using yeast two-hybrid, ligand blotting, and solid phase binding assays, we have shown that microfibril-associated glycoprotein-1 (MAGP-1) interacts with the 8-cysteine motif of fibrillin-2 encoded by exon 24. Binding to this sequence was demonstrated for full-length MAGP-1 as well as for the MAGP-1 matrix-binding domain encoded by exons 7 and 8. The matrix-binding domain, but not the full-length protein, also bound to regions of fibrillin-2 defined by exons 16 and 17, exon 20, and exons 23 and 24.

Identification of a matrix-binding domain in MAGP1 and MAGP2 and intracellular localization of alternative splice forms.

MAGP1 is a small molecular mass protein associated with microfibrils in the extracellular matrix (ECM). To identify the molecular basis of its interaction with other microfibrillar proteins, deletion constructs of MAGP1 were expressed in a mammalian cell system that served as a model for microfibril assembly. This study identified a 54-amino acid sequence in the carboxyl-terminal region of the protein that defines a matrix-binding domain that is sufficient to target MAGP1 to the ECM.