Stability difference between DNA and RNA mini-hairpins containing two G-C pairs.

The deoxyribonucleotide fragments, d(GCGAAAGC) and d(GCGAAGC) form extraordinarily stable mini-hairpin structures containing only two G-C pairs. In contrast, the corresponding ribonucleotide fragments, r(GCGAAAGC) and r(GCGAAGC) are not so stable, although they also form mini-hairpin structures. The stability difference between these DNA and RNA mini-hairpins was examined by NMR studies and the molecular mechanics calculations, and by comparing with the stability of several sequence variants. Their stability was deduced to vary delicately depending on helical patterns formed by DNA (B form) and RNA (A form) structures.     

Pharmacokinetic Modelling of [2-13C]Uracil Metabolism in Normal and DPD-Deficient Dogs

A physiologically based pharmacokinetic (PBPK) model to simulate the plasma concentration and ¹³CO₂ exhalation after [2-¹³C]uracil administration to DPD-suppressed dogs was developed. Simulation using this PBPK model should be useful in clinical situations where DPD-deficient patients at risk are to be detected with [2-¹³C]uracil as an in vivo probe.     

Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer

Chk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity. Mus81(Δex3-4/Δex3-4) mice have increased cancer susceptibility that is exacerbated by p53 inactivation. In this study, we demonstrate that Chk2 inactivation impairs the development of Mus81(Δex3-4/Δex3-4) lymphoid cells in a cell-autonomous manner. Importantly, in contrast to its predicted tumor suppressor function, loss of Chk2 promotes mitotic catastrophe and cell death, and it results in suppressed oncogenic transformation and tumor development in Mus81(Δex3-4/Δex3-4) background. Thus, our data indicate that an important role for Chk2 is maintaining lymphocyte development and that dual inactivation of Chk2 and Mus81 remarkably inhibits cancer.     

Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells

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Highlights? LT-HSCs activate glycolysis and generate ATP in a HIF-1α-dependent manner ? Pdk overexpression in HIF-1α^Δ/Δ HSCs restored glycolysis and stem cell capacity ? Pdk2^?/?: Pdk4^?/? LT-HSCs show defective glycolysis and cell cycle quiescence ? Pdk mimetic promotes the survival and transplantation capacity of LT-HSCs     

Antifreeze Emulsions Produced from Linoleic Acid and Water Using Enzymatically Modified Gelatin

An enzymatically modified gelatin with covalently attached leucine dodecyl ester, referred to as EMG-12, was used as a surfactant to prepare emulsions with different properties by changing the surfactant concentration, oil volume fraction, and pH in the water phase. The emulsions generally resisted the freezing of their constituent bulk water at approximately ?10°C, but similar emulsions produced with soy protein isolate, casein, or Tween-80 as control agents were less resistant. The freezing (or unfreezing) of the bulk water in these emulsions depended on the kind of agent used, not on the emulsion properties such as average area of the oil/water interface, stability against coalescence, and stability against creaming. The emulsion produced with EMG-12, like that produced with polyglycerol stearate, tended to maintain its unfrozen state even in the presence of silver iodide crystals added as heterogeneous ice-nuclei. The significance of producing such an antifreeze emulsion is discussed from the standpoint of cryopreservation of cold-sensitive food and biological systems.     

Phylogenetic beta diversity reveals historical effects in the assemblage of the tree floras of the Ryukyu Archipelago

Quantifying the roles of historical versus contemporary constraints in determining species diversity is a central issue in island biogeography, and the phylogenetic beta diversity between islands is an essential measure specifying the influence of historical barriers on insular assemblages. In this study, using phylogenetic information for 513 tree species on 26 islands in the subtropical Ryukyu Archipelago, phylogenetic beta diversity between islands was calculated, and effects of historical factors (gaps as surrogate measures of historical barriers) and current ones (distance, area and elevation) on the phylogenetic structure of tree assemblages were examined. The pattern of phylogenetic beta diversity demonstrated that the Tokara Gap and geographical distance were consistently important for characterizing tree assemblages in the Ryukyus relative to other historical and current factors, which suggests that the Tokara Gap and distance‐limited dispersal from the two adjacent source islands have left a deep imprint on the phylogenetic structure of the current tree flora of the islands.