Abstract: Methods for treatment of insulin resistance and type II diabetes by administration of inhibitors of the PKI pathway are provided. In some aspects, inhibitors of the PKI pathway, such as inhibitors of PIKB, HIF1 and/or mTOR, can be used to treat subject having insulin resistance who are refractory to GLP1 agonist therapy.

Abstract: Methods for treatment of insulin resistance and type II diabetes by administration of inhibitors of the PKI pathway are provided. In some aspects, inhibitors of the PKI pathway, such as inhibitors of PIKB, HIF1 and/or mTOR, can be used to treat subject having insulin resistance who are refractory to GLP1 agonist therapy.

Abstract: In some aspects, methods for treating a bacterial infection in a mammalian subject are provided. In some embodiments, a class IIa HDAC inhibitor such as, e.g., a HDAC4 inhibitor, may be used to treat a bacterial infection such as, e.g., anthrax, pertussis, tuberculosis, or cholera.

Abstract: In some aspects, methods for treating a bacterial infection in a mammalian subject are provided. In some embodiments, a class IIa HDAC inhibitor such as, e.g., a HDAC4 inhibitor, may be used to treat a bacterial infection such as, e.g., anthrax, pertussis, tuberculosis, or cholera.

Abstract: The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors or activators of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1, Dach2, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach, or activates CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2.

Abstract: Disclosed herein are methods for identifying agents capable of affecting the expression, posttranslational modification, and/or an activity of TRB3, for example, in adipose tissue and/or adipocytes. Such agents are useful, for example, to mobilize fat stores and as prospective obesity therapeutics.

Abstract: Disclosed herein are methods for identifying agents capable of affecting the expression, posttranslational modification, and/or an activity of TRB3, for example, in adipose tissue and/or adipocytes. Such agents are useful, for example, to mobilize fat stores and as prospective obesity therapeutics.

Abstract: The present invention describes modulator of protein kinase B (PKB)/Akt proteins, exemplified by the Tribbles (TRB) family. An exemplary member of the TRB family, TRB-3, binds to Akt and inhibits its catalytic activity, in turn causing altered regulation of glucose metabolism pathways. TRB-3 expression is strongly induced in the fasting state, and upregulated in mouse models of type II, causing disruptions in insulin signaling. Accordingly, the present invention further provides compositions and methods for disrupting the interaction between such a modulator and PKB/Akt protein kinases. Also provided are methods of determining if a subject has a predisposition to impaired glucose regulation and methods for treating diabetes mellitus using invention compositions.

Abstract: In accordance with the present invention, it has been discovered that glucose and incretin hormones promote pancreatic islet cell survival via the calcium and cAMP dependent induction, respectively, of the transcription factor CREB. Specifically, a signaling module has been identified which mediates cooperative effects of calcium and cAMP on islet cell gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a cytoplasmic CREB coactivator. The module comprises a cAMP regulated snf1-like kinase called SIK2 and the calcium regulated phosphatase calcineurin, both of which associate with TORC2 in the cytoplasm. TORC2 is repressed under basal conditions through a phosphorylation dependent interaction with 14-3-3 proteins. cAMP and calcium signals stimulate CREB target gene expression via complementary effects on TORC2 dephosphorylation; cAMP disrupts TORC2-associated activity of SIK2 or related family members, whereas calcium induces TORC2 dephosphorylation via calcineurin.

Abstract: A method and apparatus for forming solder bumps by molten solder deposition into cavity arrays in a substrate immediately followed by solidification of molten solder such that precise replication of cavity volumes is consistently achieved in formed solder bump arrays. Various solder filling problems, such as those caused by surface tension and oxidation effects, are overcome by a combination of narrow molten Solder dispense slots and solidification of dispensed molten solder.

Abstract: The present invention relates to compositions which specifically bind to a multimeric protein complex but not to the individual and separate components of the complex, or alternatively, compositions which specifically bind to individual and separate components but not to any complex thereof. The present invention also relates to methods of using such compositions for identifying compounds that promote multimeric complex formation and/or disruption and for treating disorders associated with aberrant complex formation by modulating the formation and/or disruption of multimeric protein complexes.

Abstract: The present invention provides a method to design compounds that mimic the effects of Pbx in stabilizing STF-1 binding. Using well known DNA binding assays, a person having ordinary skill in this art would be able to screen compounds to determine drugs effective in promoting STF-1 binding to DNA. In this way, one will be able to discover new compounds useful in stimulating somatostatin and insulin production.