Doyeon Kim

General rules for functional microRNA targeting

The functional rules for microRNA (miRNA) targeting remain controversial despite their biological importance because only a small fraction of distinct interactions, called site types, have been examined among an astronomical number of site types that can occur between miRNAs and their target mRNAs. To systematically discover functional site types and to evaluate the contradicting rules reported previously, we used large-scale transcriptome data and statistically examined whether each of approximately 2 billion site types is enriched in differentially downregulated mRNAs responding to overexpressed miRNAs. Accordingly, we identified seven non-canonical functional site types, most of which are novel, in addition to four canonical site types, while also removing numerous false positives reported by previous studies. Extensive experimental validation and significantly elevated 3′ UTR sequence conservation indicate that these non-canonical site types may have biologically relevant roles. Our expanded catalog of functional site types suggests that the gene regulatory network controlled by miRNAs may be far more complex than currently understood.

Magnetothermopower of single wall carbon nanotube newtwork

Abstract We have measured the electrical resistivity and thermoelectric power (TEP) of single wall carbon nanotube (SWCN) network. The resistivity result can be fitted to the variable range hopping (VRH) type conduction formula. The room temperature TEP is about 30~60 μV/K and the overall temperature dependence of the TEP is similar to that of the disordered alloy which shows the electron-phonon enhancement of TEP. By applying the magnetic field up to 6 Tesla, the magnitude of the TEP is reduced by ~2 μV/K while the overall temperature dependence is more or less the same. The results are discussed by the heterogeneous model which was adapted to the conducting polymers.

High pressure synthesis and superconductivity of Ba1-xKxBiO3 (0.35 < x < 1)

The whole region of superconductivity in the Ba1−xKxBiO3 (BKBO) system (0.35<x<1) has been investigated by synthesizing the samples with the high pressure and high temperature technique. As the K doping ratio (x) increases, the superconducting transition temperature (Tc) of the BKBO system decreases from 30.4 K for x=0.37 to very low diamagnetic signal below 3 K for x=0.74. The synthesis of the samples without including any bariums in the starting composition (x=1) resulted in different Tc and lattice parameters from sample to sample with partial substitutions of Bi at the K site in final products. With detailed synthesis information of the BKBO samples which varies with x, the evolution of Tc by doping in the cubic BKBO system is compared with other superconducting bismuthates and discussed on a basis of its electronic band structure.

Real-Time GnRH Gene Transcription in GnRH Promoter-Driven Luciferase-Expressing Transgenic Mice: Effect of Kisspeptin

Pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) is indispensable for controlling proper pituitary gonadotrope functions; however, the mechanism underlying GnRH pulse generation remains largely unknown. It is important to understand the cellular oscillator in individual GnRH neurons and temporal synchronization among GnRH neurons. In this brief review, we summarize our recent findings on episodic GnRH gene transcription at the single GnRH neuron level and in synchronized multicellular burst in relation to the temporal pattern of GnRH secretion. We also detail the effects of kisspeptin on ultradian rhythmic GnRH gene transcription and secretion. We extend our discussion to the hierarchical interaction between circadian and ultradian rhythms. Taken together, the current review elucidates the genomic control of GnRH pulse generation in hypothalamic neurons.

Thermoelectric power of MgB2

Abstract Thermoelectric power (TEP) of MgB 2 and its changes with the superconducting transition temperature ( T c ) have been investigated. MgB 2 samples synthesized with different techniques––sample 1 by the encapsulation method and sample 2 by the high pressure and high temperature technique––showed different T c ( T c of sample 1= 38.7 K, and T c of sample 2 = 40.4 K). The characteristic features of the TEP of these samples––low temperature linear behavior, deviation from the low temperature linear behavior at a certain temperature, and an almost saturating value at ∼300 K––were found to vary systematically with T c , consistent with the previously reported TEP changes in Mg 1− x Al x B 2 . These changes of the TEP behaviors with T c in the superconducting diborides system are discussed in comparison with those of high T c cuprates and bismuthates. The common feature of the saturating TEP at high temperatures suggests the importance of an anharmonic electron–phonon interaction.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells.

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer.

Cooperative roles of the suprachiasmatic nucleus central clock and the adrenal clock in controlling circadian glucocorticoid rhythm

The mammalian circadian timing system consists of the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and subsidiary peripheral clocks in other tissues. Glucocorticoids (GCs) are adrenal steroid hormones with widespread physiological effects that undergo daily oscillations. We previously demonstrated that the adrenal peripheral clock plays a pivotal role in circadian GC rhythm by driving cyclic GC biosynthesis. Here, we show that the daily rhythm in circulating GC levels is controlled by bimodal actions of central and adrenal clockwork. When mice were subjected to daytime restricted feeding to uncouple central and peripheral rhythms, adrenal GC contents and steroidogenic acute regulatory protein expression peaked around zeitgeber time 00 (ZT00), consistent with shifted adrenal clock gene expression. However, restricted feeding produced two distinct peaks in plasma GC levels: one related to adrenal GC content and the other around ZT12, which required an intact SCN. Light pulse-evoked activation of the SCN increased circulating GC levels in both wild-type and adrenal clock-disrupted mutant mice without marked induction of GC biosynthesis. In conclusion, we demonstrate that adrenal clock-dependent steroidogenesis and a SCN-driven central mechanism regulating GC release cooperate to produce daily circulatory GC rhythm.

Global and local competition between exogenously introduced microRNAs and endogenously expressed microRNAs.

It has been reported that exogenously introduced micro-RNA (exo-miRNA) competes with endogenously expressed miRNAs (endo-miRNAs) in human cells, resulting in a detectable upregulation of mRNAs with endo-miRNA target sites (TSs). However, the detailed mechanisms of the competition between exo- and endo-miRNAs remain uninvestigated. In this study, using 74 microarrays that monitored the whole-transcriptome response after introducing miRNAs or siRNAs into HeLa cells, we systematically examined the derepression of mRNAs with exo- and/or endo-miRNA TSs. We quantitatively assessed the effect of the number of endo-miRNA TSs on the degree of mRNA derepression. As a result, we observed that the number of endo-miRNA TSs was significantly associated with the degree of derepression, supporting that the derepression resulted from the competition between exo- and endo-miRNAs. However, when we examined whether the site proficiency of exo-miRNA TSs could also influence mRNA derepression, to our surprise, we discovered a strong positive correlation. Our analysis indicates that site proficiencies of both exo- and endo-miRNA TSs are important determinants for the degree of mRNA derepression, implying that the derepression of mRNAs in response to exo-miRNA is more complex than that currently perceived. Our observations may lead to a more complete understanding of the detailed mechanisms of the competition between exo- and endo-miRNAs and to a more accurate prediction of miRNA targets. Our analysis also suggests an interesting hypothesis that long 3′-UTRs may function as molecular buffer against gene expression regulation by individual miRNAs.

X-ray absorption near-edge structure spectra study of the Ba1−xKxBiO3 (0.37⩽x⩽1.0) superconductor

Abstract X-ray absorption near-edge structure spectra (XANES) of the Ba 1− x K x BiO 3 (BKBO) (0.37⩽ x ⩽1.0) superconductor have been measured at the Bi L III edge. To estimate changes of the Bi valence state, and reveal its influence on the superconducting properties of this solid solution, quantitative spectral characteristics of the 2p 3/2 →6s transition in the series comprising different Ba/K ratios were determined. The superconducting transition T c of the BKBO samples, determined from dc magnetic susceptibility measurements, monotonously decreases from Ba 0.63 K 0.37 BiO 3 ( T c =30.4 K) to Ba 0.26 K 0.74 BiO 3 (a very low diamagnetic signal was detected at T ∼3 K). This corresponds to the increase of Bi valence determined from XANES data in the range +4.36⩽ ν ⩽+4.74. Further increase of the K content to x >0.8 results in reappearance of superconductivity with T c =9 K. The maximum value of formal Bi valence versus K content corresponds with the minimum in T c .

Rules for functional microRNA targeting

MicroRNAs (miRNAs) are ~22nt-long single-stranded RNA molecules that form a RNA-induced silencing complex with Argonaute (AGO) protein to post-transcriptionally downregulate their target messenger RNAs (mRNAs). To understand the regulatory mechanisms of miRNA, discovering the underlying functional rules for how miRNAs recognize and repress their target mRNAs is of utmost importance. To determine functional miRNA targeting rules, previous studies extensively utilized various methods including high-throughput biochemical assays and bioinformatics analyses. However, targeting rules reported in one study often fail to be reproduced in other studies and therefore the general rules for functional miRNA targeting remain elusive. In this review, we evaluate previously-reported miRNA targeting rules and discuss the biological impact of the functional miRNAs on gene-regulatory networks as well as the future direction of miRNA targeting research.