The present invention is directed to secreted and transmembrane polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Secreted and Transmembrane Polypeptides and Nucleic Acids Encoding the Same

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. Minute amounts of LPS released from infecting pathogens can initiate potent innate immune responses that prime the immune system against further infection. However, when the LPS response is not properly controlled it can lead to fatal septic shock syndrome. The common structural pattern of LPS in diverse bacterial species is recognized by a cascade of LPS receptors and accessory proteins, LPS binding protein (LBP), CD14 and the Toll-like receptor4 (TLR4)–MD-2 complex. The structures of these proteins account for how our immune system differentiates LPS molecules from structurally similar host molecules. They also provide insights useful for discovery of anti-sepsis drugs. In this review, we summarize these structures and describe the structural basis of LPS recognition by LPS receptors and accessory proteins.

/pdf/recognition-of-lipopolysaccharide-pattern-by-tlr4-complexes-3ggc78q9g4.pdf

Recognition of lipopolysaccharide pattern by TLR4 complexes

The per-generation mutation rate in humans is high. De novo mutations may compensate for allele loss due to severely reduced fecundity in common neurodevelopmental and psychiatric diseases, explaining a major paradox in evolutionary genetic theory. Here we used a family based exome sequencing approach to test this de novo mutation hypothesis in ten individuals with unexplained mental retardation. We identified and validated unique non-synonymous de novo mutations in nine genes. Six of these, identified in six different individuals, are likely to be pathogenic based on gene function, evolutionary conservation and mutation impact. Our findings provide strong experimental support for a de novo paradigm for mental retardation. Together with de novo copy number variation, de novo point mutations of large effect could explain the majority of all mental retardation cases in the population.

A de novo paradigm for mental retardation.

The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides gene expression profiles associated with solid tumor stem cells, as well as novel stem cell cancer markers useful for the diagnosis, characterization, and treatment of solid tumor stem cells.

Compositions and methods for treating and diagnosing cancer

Structures of the Toll-like Receptor Family and Its Ligand Complexes

We have identified three novel, rarely expressed human genes that encode new members of the lipid transfer/lipopolysaccharide binding protein (LT/LBP) gene family based on sequence homology. BPI and other members of the LT/LBP family are structurally related proteins capable of binding phospholipids and lipopolysaccharides. Real-time PCR studies indicate that BPIL1 and BPIL3 are highly expressed in hypertrophic tonsils. In situ hybridization analysis of BPIL2 shows prominent expression in skin specimens from psoriasis patients. BPIL1 and BPIL3 map to Chromosome 20q11; thus, these novel genes form a cluster with BPI and two other members of the LT/LBP gene family on the long arm of human Chr 20. BPIL2 maps to Chr 22q13. The exon/intron organization of all three genes is highly conserved with that of BPI, suggesting evolution from a common ancestor.

Three new human members of the lipid transfer/lipopolysaccharide binding protein family (LT/LBP)

Stem cell growth factor-like polypeptides

Method of promoting stem cell proliferation or survival by contacting a cell with a stem cell factor-like polypeptide

Antibodies specific for semaphorin-like polypeptides

Methods and materials relating to alpha-2-macroglobulin-like polypeptides and polynucleotides

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