Distinct and redundant functions of histone deacetylases HDAC1 and HDAC2 in proliferation and tumorigenesis

Histone deacetylases (HDACs) are negative regulators of gene expression and have been implicated in tumorigenesis and tumor progression. Therefore, HDACs are promising targets for antitumor drugs. However, the relevant isoforms of the 18 members encompassing HDAC family have not been identified. Studies utilizing either gene targeting or knockdown approaches reveal both specific and redundant functions of the closely related class I deacetylases HDAC1 and HDAC2 in the control of proliferation and differentiation. Combined ablation of HDAC1 and HDAC2 in different cell types led to a severe proliferation defects or enhanced apoptosis supporting the idea that both enzymes are relevant targets for tumor therapy. In a recent study on the role of HDAC1 in teratoma formation we have reported a novel and surprising function of HDAC1 in tumorigenesis. In this tumor model HDAC1 attenuates proliferation during teratoma formation. In the present work we discuss new findings on redundant and unique functions of HDAC1 and HDAC2 as regulators of proliferation and tumorigenesis and potential implications for applications of HDAC inhibitors as therapeutic drugs

THE INTRINSIC HAND – A 22 DEGREE-OF-FREEDOM ARTIFICIAL HAND-WRIST REPLACEMENT

Now is an exciting time to be in the field of Upper-Limb Prosthetics. Due to the limited function of current commercially available upper-limb prosthetics and the increased incidence of amputation injuries being seen in Operation Enduring Freedom (OEF - Afghanistan) and Operation Iraqi Freedom (OIF) a number of new initiatives have been put into place to develop replacement arm/hand systems capable of replicating the function of the human arm and hand. In particular, the Defense Advanced Research Projects Agency (DARPA) has a four year initiative, “Revolutionizing prosthetics 2009”. The goal of this program is to develop a replacement arm/hand system capable of enabling soldiers with limb loss from OEF/OIF the capability of returning to service similar to the way those with lower ankle-foot disarticulation have been able to do for years. Led by the Johns Hopkins University Applied Physics Laboratory, the goal of this project is to design a fully functional biomechatronic analog to the human hand and arm. The device must be capable of duplicating the function of the original limb and withstand the rigors of daily living. Our involvement on this team is to develop robust and anthropomorphic hand-wrist prostheses capable of dexterous manipulation suitable for use by persons with all levels of trans-radial limb loss. Where as to date most anthropomorphic high degree of freedom hand manipulators place their actuators in the forearm [8, 9], this paper details the results of placing the actuators intrinsic to the hand