Abstract: Methods for alleviating symptoms in a Smith Kingsmore Syndrome (SKS) patient using low doses of a mTOR inhibitor. Also provided herein are methods to determine suitable doses of a mTOR inhibitor for a SKS patient to alleviate at least one symptom associated with SKS with little or no negative impact on behavior features such as the sleep pattern of the SKS patient.

Abstract: Methods and compositions for diagnosis and prognosis of mammalian carcinoma or cancer derived from primary epithelial cells and tissue fibrosis are designed using newly identified epithelial cell-type specific splicing factors ESRP1 and ESRP2, which have roles in tumor suppression. Diagnostic reagents for the detection of these splicing factors in nucleotide or protein form are useful in such methods. Therapeutic compositions can provide epithelial cells with these factors to maintain FGFR2 and assist in suppressing metastasis. A high throughput splicing assay to identify compounds that change splicing events is described. RNCP1 is also identified as a splicing factor and a diagnostic for conditions characterized by inappropriate FGFR2-splicing.

Abstract: Methods and compositions for diagnosis and prognosis of mammalian carcinoma or cancer derived from primary epithelial cells and tissue fibrosis are designed using newly identified epithelial cell-type specific splicing factors ESRP1 and ESRP2, which have roles in tumor suppression. Diagnostic reagents for the detection of these splicing factors in nucleotide or protein form are useful in such methods. Therapeutic compositions can provide epithelial cells with these factors to maintain FGFR2 and assist in suppressing metastasis. A high throughput splicing assay to identify compounds that change splicing events is described. RNCP1 is also identified as a splicing factor and a diagnostic for conditions characterized by inappropriate FGFR2-splicing.

Abstract: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse CDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn IL Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.

Abstract: The present invention provides isolated nucleic acids and proteins that are new and distinct members of the bHLH-PAS superfamily of transcription regulators. These “MOPs” (members of PAS) are useful in a variety of research, diagnostic and therapeutic applications. Several of the MOPs of the present invention are ?-class hypoxia-inducible factors. Several other of the MOPs of the invention are involved in circadian signal transduction.

Abstract: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn II. Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.

Abstract: The present invention provides methods of identifying circadian rhythm modulators and methods of modulating circadian rhythm in animals.

Abstract: The present invention provides a transgenic non-human animals comprising a disruption in the melanopsin gene as well as methods for using the animals to identify agents useful for modulating circadian rhythm in animals.

Abstract: This invention provides novel Epo-modulating polypeptides. The invention also provides methods for screening modulators of Epo expression. The methods comprise first screening test agents for modulators of an Epo-modulating polypeptide and then further screening the identified modulating agents for modulators of Epo expression. The invention further provides methods and pharmaceutical compositions for modulating Epo expression in cells and for treating diseases and conditions due to Epo deficiency.