The complete mitochondrial genome sequence of the Kori salamander Hynobius yangi (Caudata: Hynobiidae)

The complete mitochondrial genome (JN415127) was sequenced and annotated newly from an individual of Hynobius yangi populations which were collected in Ulju-gun, Korea. The total length of the H. yangi genome is 16,403 bp, with a total base composition of 33.5% A, 32.3% T, 20.5% C, and 13.6% G.     

The complete mitochondrial genome of human parasitic roundworm, Ascaris lumbricoides

The genome length of the Ascaris lumbricoides, human parasitic roundworm, is 14,281 bp with a nucleotide composition of 22.1% A, 49.8% T, 7.8% C, and 20.3% G. The genome consists of 12 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 1 control region.     

Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy

Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously euploid. Here we report that normal hPSC--including induced pluripotent--lines are karyotypic mosaics of euploid cells intermixed with many cells showing non-clonal aneuploidies as identified by chromosome counting, spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic cells. This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that it is a normal, rather than pathological, feature of stem cell lines. The karyotypic heterogeneity generated by mosaic aneuploidy may contribute to the reported functional and phenotypic heterogeneity of hPSCs lines, as well as their therapeutic efficacy and safety following transplantation.     

Microfabricated particulate drug-delivery systems

Micro- and nanoparticulate drug-delivery systems (DDSs) play a significant role in formulation sciences. Most particulate DDSs are scaffold-free, although some particles are encapsulated inside other biomaterials for controlled release. Despite rapid progress in recent years, challenges still remain in controlling the homogenicity of micro-/nanoparticles, especially for two crucial factors in particulate DDSs: the size and shape of the particles. Recent approaches make use of microfabrication techniques to generate micro-/nanoparticles with highly controllable architectures free of scaffolds. This review presents an overview of a burgeoning field of DDSs, which can potentially overcome some drawbacks of conventional techniques for particle fabrication and offer better control of particulate DDSs.     

Conformational changes of pore helix coupled to gating of TRPV5 by protons

The transient receptor potential channel TRPV5 constitutes the apical entry pathway for transepithelial Ca2+ transport. We showed that TRPV5 was inhibited by both physiological intra- and extracellular acid pH. Inhibition of TRPV5 by internal protons was enhanced by extracellular acidification. Similarly, inhibition by external protons was enhanced by intracellular acidification. Mutation of either an extra- or an intracellular pH sensor blunted the cross-inhibition by internal and external protons. Both internal and external protons regulated the selectivity filter gate. Using the substituted cysteine accessibility method, we found that intracellular acidification of TRPV5 caused a conformational change of the pore helix consistent with clockwise rotation along its long axis. Thus, rotation of pore helix caused by internal protons facilitates closing of TRPV5 by external protons. This regulation by protons likely contributes to pathogenesis of disturbances of Ca2+ transport in many diseased states. Rotation of pore helix may be a common mechanism for cross-regulation of ion channels by extra- and intracellular signals.     

Striatal information signaling and integration in globus pallidus: timing matters

Advances in research on globus pallidus (GP) suggest that this 'long thought to be' relay in the 'indirect pathway' plays a unique and critical role in basal ganglia function. The traditional idea of parallel processing within the basal ganglia is also challenged by recent findings. It is now clear that axons of GP neurons form large, perisomatic baskets around target neurons in all major basal ganglia nuclei, thereby exerting a profound influence on the output of the entire basal ganglia. GP neurons are autonomously active both in vivo and in vitro. It is believed that temporal information carried along the corticostriatopallidal pathway is critical for proper motor execution. The importance of appropriately controlled discharge of GP neurons is highlighted by psychomotor disorders such as Parkinson's disease, in which alterations in the pattern and synchrony of discharge in GP neurons are thought to contribute to motor symptoms. Several lines of evidence suggest that the aberrant activity of GP neurons following dopamine depletion is caused by alteration in the synaptic input from both striatum and subthalamic nucleus. In normal subjects, the capability of striatal input in translating cortical input into precisely timed responses in GP neurons is mediated by (1) the expression of postsynaptic GABA(A) receptor composed of subunits with fast kinetic properties; (2) an effective GABA reuptake system in terminating the action of synaptically released GABA, and (3) the existence of dendritic HCN channels that actively abbreviate the time course of the inhibitory postsynaptic potentials and reset rhythmic discharge. Despite the rapid pace in uncovering the elements that shape the activity along the striatopallidosubthalamic pathway, the origin of rhythmic, synchronized bursting of GP neurons seen in parkinsonism has not been fully established experimentally. Further elucidation of the factors that control the information transfer in the striatopallidal synapses is thus critical to our understanding of basal ganglia function and establishing treatment for Parkinson's disease and other basal ganglia disorders.     

Antimitogenesis linked to regulation of Skp2 gene expression

Prostacyclin has many effects in the vasculature; one of the less well understood is the ability to block cell cycle progression through G(1) phase. We previously reported that the prostacyclin mimetic, cicaprost, selectively inhibits cyclin E-cyclin-dependent kinase-2 (Cdk2), and now we show that it acts by regulating the expression of Skp2, the F-box protein that targets p27(Kip1) for ubiquitin-mediated proteolysis. First, we show that cicaprost prevents the late G(1) phase down-regulation of p27(Kip1) and that the inhibitory effect of cicaprost on cyclin E-Cdk2 activity and S phase entry is eliminated by deleting p27(Kip1). Levels of the closely related Cdk2 inhibitor, p21(Cip1), are unaffected by cicaprost. Moreover, we show that cicaprost blocks the induction of Skp2 mRNA and that ectopic expression of a Skp2 cDNA overrides the effect of cicaprost on p27(Kip1) levels and S phase entry. Our data show that inhibition of F-box protein gene expression can underlie the effect of a potent antimitogen.