Coordination-directed self-assembly of nano-cages: metal ion-change, ligand-extending, shape-control and transdermal drug delivery.

The combination of different pyridyl ligands and metal ions has proven to be a very reliable strategy for controlling the coordination mode of the heterometallic coordination nano-cages. Adjusting the length of the ligands could result in the selective synthesis of several heterometallic coordination nano-cages, either [8Rh + 2M]-4L, [8Rh + 2M]-5L or [8Rh + 4M]-6L cages, derived from the very same precursors (LH3tzdc) through half-sandwich rhodium self-assembly. Moreover, a series of [8Rh + 4M]-6L cages was chosen to exemplify the preparation. The rigidity of various pyridyl donor ligands caused the vertical nano-cage to be energetically preferred and was able to change the self-assembly process through ligand flexibility to selectively give the inclined nano-cage and cross nano-cage.

Analysis of Meiotic Double-Strand Break Initiation in Mammals.

The repair of programmed DNA double-strand breaks (DSBs) physically tethers homologous chromosomes in meiosis to allow for accurate segregation through meiotic cell divisions. This process, known as recombination, also results in the exchange of alleles between parental chromosomes and contributes to genetic diversity. In mammals, meiotic DSBs occur predominantly in a small fraction of the genome, at sites known as hotspots. Studies of the formation and repair of meiotic DSBs in mammals are challenging, because few cells undergo meiotic DSB formation at a given time. To better understand the initiation and control of meiotic recombination in mammals, we have devised a highly sensitive method to map the sites of meiotic DSBs genome wide. Our method first isolates DNA bound to DSB repair proteins and then specifically sequences the associated single-stranded DNA. This protocol has generated the first meiotic DSB maps in several mammals and the only map of meiotic DSBs in humans.

The normal function of the cancer kinase Mirk/dyrk1B is to reduce reactive oxygen species.

Mirk kinase is a gene upregulated and sometimes amplified in pancreatic cancers and in ovarian cancers, but expressed at very low levels in most normal diploid cells except for skeletal muscle. The muscle cell function of Mirk kinase selected for by cancer cells is unknown. It is now shown that Mirk protein is expressed at low levels and is largely nuclear in cycling skeletal muscle C2C12 myoblasts, but is translocated to the cytoplasm and upregulated when myoblasts initiate differentiation, as shown by immunofluorescence staining and by cell fractionation. Either Mirk depletion or Mirk kinase inhibition increased ROS levels in cycling C2C12 myoblasts. However, Mirk protein is localized in the cytoplasm of mature muscle fibers, specifically in the fast twitch fibers of human skeletal muscle where toxic ROS levels are generated by muscle contraction. C2C12 myoblasts at high density in differentiation media fuse to form differentiated postmitotic myotubes that can contract. A Mirk kinase inhibitor induced a dose-dependent increase in ROS in this model for fast twitch fibers of human skeletal muscle. Efficient Mirk depletion in SU86.86 pancreatic cancer cells by an inducible shRNA decreased expression of eight antioxidant genes. Thus both cancer cells and differentiated myotubes utilize Mirk kinase to relieve oxidative stress.