Multiple Access Protocols for a Multichannel Optical Fibre Local Area Network Using a Passive Star Topology and WDM

Hyong W. Lee,Jon W. Mark 대한전자공학회 1995 대한전자공학회 학술대회 Vol.1995 No.6

STAT3 promotes motor neuron differentiation by collaborating with motor neuron-specific LIM complex

Lee, Seunghee,Shen, Rongkun,Cho, Hyong-Ho,Kwon, Ryuk-Jun,Seo, So Yeon,Lee, Jae W.,Lee, Soo-Kyung National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.28

<P>The motor neuron (MN)–hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN–hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN–hexamer–bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN–hexamer, enhancing the transcriptional activity of the MN–hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN–hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord.</P>

Isl1 Directly Controls a Cholinergic Neuronal Identity in the Developing Forebrain and Spinal Cord by Forming Cell Type-Specific Complexes

Cho, Hyong-Ho,Cargnin, Francesca,Kim, Yujin,Lee, Bora,Kwon, Ryuk-Jun,Nam, Heejin,Shen, Rongkun,Barnes, Anthony P.,Lee, Jae W.,Lee, Seunghee,Lee, Soo-Kyung Public Library of Science 2014 PLoS genetics Vol.10 No.4

<▼1><P>The establishment of correct neurotransmitter characteristics is an essential step of neuronal fate specification in CNS development. However, very little is known about how a battery of genes involved in the determination of a specific type of chemical-driven neurotransmission is coordinately regulated during vertebrate development. Here, we investigated the gene regulatory networks that specify the cholinergic neuronal fates in the spinal cord and forebrain, specifically, spinal motor neurons (MNs) and forebrain cholinergic neurons (FCNs). Conditional inactivation of <I>Isl1</I>, a LIM homeodomain factor expressed in both differentiating MNs and FCNs, led to a drastic loss of cholinergic neurons in the developing spinal cord and forebrain. We found that Isl1 forms two related, but distinct types of complexes, the Isl1-Lhx3-hexamer in MNs and the Isl1-Lhx8-hexamer in FCNs. Interestingly, our genome-wide ChIP-seq analysis revealed that the Isl1-Lhx3-hexamer binds to a suite of cholinergic pathway genes encoding the core constituents of the cholinergic neurotransmission system, such as acetylcholine synthesizing enzymes and transporters. Consistently, the Isl1-Lhx3-hexamer directly coordinated upregulation of cholinergic pathways genes in embryonic spinal cord. Similarly, in the developing forebrain, the Isl1-Lhx8-hexamer was recruited to the cholinergic gene battery and promoted cholinergic gene expression. Furthermore, the expression of the Isl1-Lhx8-complex enabled the acquisition of cholinergic fate in embryonic stem cell-derived neurons. Together, our studies show a shared molecular mechanism that determines the cholinergic neuronal fate in the spinal cord and forebrain, and uncover an important gene regulatory mechanism that directs a specific neurotransmitter identity in vertebrate CNS development.</P></▼1><▼2><P><B>Author Summary</B></P><P>Neurons utilize various chemicals to transmit signals to a target cell. Distinct types of neurons in the spinal cord and forebrain, collectively termed cholinergic neurons, utilize the same chemical, acetylcholine, for signal transmission. These neurons play critical roles in controlling locomotion and cognition. In this study, we have found that the <I>Isl1</I> gene orchestrates the process to generate cholinergic neurons in the spinal cord and forebrain. Isl1 forms two different types of multi-protein complexes in the spinal cord and forebrain. Both complexes bind the same genomic regions in a group of genes critical for cholinergic signal transmission, and promote their simultaneous expression. These cholinergic genes include enzymes that synthesize acetylcholine and proteins required to package acetylcholine into vesicles. The Isl1-containing multi-protein complexes were able to trigger the generation of cholinergic neurons in embryonic stem cells and neural stem cells. Our study reveals crucial mechanisms to coordinate the expression of genes in the same biological pathway in different cell types. Furthermore, it suggests a new strategy to produce cholinergic neurons from stem cells.</P></▼2>

Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways

Byun, Sanguine,Lim, Semi,Mun, Ji Young,Kim, Ki Hyun,Ramadhar, Timothy R.,Farrand, Lee,Shin, Seung Ho,Thimmegowda, N. R.,Lee, Hyong Joo,Frank, David A.,Clardy, Jon,Lee, Sam W.,Lee, Ki Won American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.39

<P>Bioactive phytochemicals can suppress the growth of malignant cells, and investigation of the mechanisms responsible can assist in the identification of novel therapeutic strategies for cancer therapy. Ginger has been reported to exhibit potent anti-cancer effects, although previous reports have often focused on a narrow range of specific compounds. Through a direct comparison of various ginger compounds, we determined that gingerenone A selectively kills cancer cells while exhibiting minimal toxicity toward normal cells. Kinase array screening revealed JAK2 and S6K1 as the molecular targets primarily responsible for gingerenone A-induced cancer cell death. The effect of gingerenone A was strongly associated with relative phosphorylation levels of JAK2 and S6K1, and administration of gingerenone A significantly suppressed tumor growth <I>in vivo</I>. More importantly, the combined inhibition of JAK2 and S6K1 by commercial inhibitors selectively induced apoptosis in cancer cells, whereas treatment with either agent alone did not. These findings provide rationale for dual targeting of JAK2 and S6K1 in cancer for a combinatorial therapeutic approach.</P>

Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90 ^RSK2

Lim, Sung H,Jung, Sung K,Byun, Sanguine,Lee, Eun J,Hwang, Jung A,Seo, Sang G,Kim, Yeong A,Yu, Jae G,Lee, Ki W,Lee, Hyong J Blackwell Publishing Ltd 2013 Journal of cellular and molecular medicine Vol.17 No.5

<P>Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects <I>in vitro</I>. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. <I>In vitro</I> kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, <I>in vivo</I>. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects <I>in vitro</I> and <I>in vivo</I> and may have potential as a treatment for the prevention of skin ageing.</P>