• Title/Summary/Keyword: WDR

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Identification of WDR7 as a Novel Downstream Target of the EphA8-Odin Signaling Complex

  • Park, Eun-Jeong;Park, Soo-Chul
    • Animal cells and systems
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    • v.13 no.1
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    • pp.9-15
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    • 2009
  • Eph receptors and their ephrin ligands have been implicated in a variety of cellular processes such as cellular morphogenesis and motility. Our previous studies demonstrated that Odin, one of the Anks family proteins, functions as a scaffolding protein of the EphA8 signaling pathway leading to modulation of cell migration or axonal outgrowth. Here we show that WDR7 is associated with Odin and that it is possibly implicated in the EphA8 signaling pathway. WD40 repeats present in the COOH-terminal region of WDR7 appear to be crucial for its association with Odin, whereas the binding motif of Odin is located in between ankyrin repeats and PTB domain. Co-immunoprecipitation experiments revealed that association of WDR7 with Odin is enhanced by ephrin ligand treatment, possibly through forming large protein complexes including both EphA8 and ephrin-A5. Consistently, immunofluorescence staining experiments suggested that WDR7 constitute a component of the large protein complexes containing Odin, EphA8 and ephrin-A5. Taken together, our results suggest the WDR7-Odin complexes might be involved in the signaling pathway downstream of the EphA8 receptor.

Calcium Channel Blockers Suppress the Responses of Rat Dorsal Horn Cell to Nociceptive Input (쥐 척수후각세포의 유해자극 반응에 대한 칼슘이온통로 차단제의 억제작용)

  • Kang, Sok-Han;Kim, Kee-Soon;Shin, Hong-Kee
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.6
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    • pp.625-637
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    • 1997
  • Calcium ions are implicated in a variety of physiological functions, including enzyme activity, membrane excitability, neurotransmitter release, and synaptic transmission, etc. Calcium antagonists have been known to be effective for the treatment of exertional angina and essential hypertension. Selective and nonselective voltage-dependent calcium channel blockers also have inhibitory action on the acute and tonic pain behaviors resulting from thermal stimulation, subcutaneous formalin injection and nerve injury. This study was undertaken to investigate the effects of iontophoretically applied $Ca^{++}$ and its antagonists on the responses of WDR (wide dynamic range) cells to sensory inputs. The responses of WDR cells to graded electrical stimulation of the afferent nerve and also to thermal stimulation of the receptive field were recorded before and after iontophoretical application of $Ca^{++}$, EGTA, $Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA, ${\omega}-conotoxin$ MVIIC and ${\omega}-agatoxin$ IVA. Also studied were the effects of a few calcium antagonists on the C-fiber responses of WDR cells sensitized by subcutaneous injection of mustard oil (10%). Calcium ions and calcium channel antagonists ($Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA & ${\omega}-agatoxin$ IVA) current-dependently suppressed the C-fiber responses of WDR cells without any significant effects on the A-fiber responses. But ${\omega}-conotoxin$ MVIIC did not have any inhibitory actions on the responses of WDR cell to A-fiber, C-fiber and thermal stimulation. Iontophoretically applied EGTA augmented the WDR cell responses to C-fiber and thermal stimulations while spinal application of EGTA for about $20{\sim}30\;min$ strongly inhibited the C-fiber responses. The augmenting and the inhibitory actions of EGTA were blocked by calcium ions. The WDR cell responses to thermal stimulation of the receptive field were reduced by iontophoretical application of $Ca^{++}$, verapamil, ${\omega}-agatoxin$ IVA, and ${\omega}-conotoxin$ GVIA but not by ${\omega}-conotoxin$ MVIIC. The responses of WDR cells to C-fiber stimulation were augmented after subcutaneous injection of mustard oil (10%, 0.15 ml) into the receptive field and these sensitized C-fiber responses were strongly suppressed by iontophoretically applied $Ca^{++}$, verapamil, ${\omega}-conotoxin$ GVIA and ${\omega}-agatoxin$ IVA. These experimental findings suggest that in the rat spinal cord, L-, N-, and P-type, but not Q-type, voltage-sensitive calcium channels are implicated in the calcium antagonist-induced inhibition of the normal and the sensitized responses of WDR cells to C-fiber and thermal stimulation, and that the suppressive effect of calcium and augmenting action of EGTA on WDR cell responses are due to changes in excitability of the cell.

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Automatic Exposure Time Control of WDR Camera Adapting Neural Network (뉴럴 네트워크를 이용한 WDR 카메라 자동 노출 제어)

  • Yun, Se-Hwan;Kim, Jin-Hun
    • Proceedings of the KIEE Conference
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    • 2004.11c
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    • pp.364-366
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    • 2004
  • WDR(Wide Dynamic Range) camera has been recently introduced to provide good detailed information for the extremely dark or white area. The double shuttering camera acquires two pictures with different exposure time for the same scenes so that each image has its unique information as for the bright/dark area. Those images are combined internally to produce an image with enough details. This paper proposes a NN based method to control the exposure time of the WDR camera. Our goal is to develop a method to automatically control the exposure time like human decision. A neural model is trained to determine to increase/decrease shutter time for the given situation. The ability to adapt to unknown situation is shown for the sample cases.

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Comparison of Somatostatin and Morphine Action on the Responses of Wide Dynamic Range Cells in the Dorsal Horn to Peripheral Noxious Mechanical and Heat Stimulation in Cats

  • Jung, Sung-Jun;Choi, Young-In;Kim, Jun
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.2
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    • pp.155-163
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    • 1998
  • The purpose of present study was to compare the effects of somatostatin (SOM) and morphine (Mor) on the responses of wide dynamic range (WDR) cells to peripheral noxious stimulation. Single neuronal activity was recorded with a carbon-filament electrode at the lumbosacral enlargement of cat spinal cord. After identifying WDR cells, their responses to peripheral noxious mechanical or thermal stimuli were characterized and the effects of SOM and Mor, applied either iontophoretically or intrathecally, were studied. In most cells SOM and Mor suppressed noxious stimulus-evoked WDR neuronal activity, though a few WDR neurons showed no change or were excited by SOM and Mor. Systemically applied naloxone, a non-specific opioid antagonist, always reversed the Mor induced suppression of neuronal activity evoked by noxious mechanical stimuli, but did not always reverse the suppression of neuronal activity elicited by SOM. The suppressive effect of Mor on thermal stimulus-evoked neuronal activity was partially reversed by naloxone, while that of SOM were not reversed at all. The above results suggest that both Mor and SOM exert an inhibitory effect on thermal and mechanical stimulus-evoked WDR neuronal activity in cat spinal dorsal horn, but the mechanisms are dependent upon the functional populations of dorsal horn nociceptive neurons.

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Effects of Taurine and ${\beta}-Alanine$ on the Responses of Dorsal Horn Cell to Various Stimuli in Cats (Taurine 및 ${\beta}-alanine$이 고양이 척수후각세포의 Activity에 미치는 효과)

  • Koh, Young-Ik;Kang, Sok-Han;Kim, Jin-Hyuk;Shin, Hong-Kee;Kim, Kee-Soon
    • The Korean Journal of Physiology
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    • v.24 no.1
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    • pp.171-180
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    • 1990
  • In 19 cats anesthetized with ${\alpha}-chloralose$ effects of taurine and ${\beta}-alanine$ on the responses of wide dynamic range (WDR) cells to mechanical, chemical and thermal stimuli were investigated in the lumbar spinal cord of the cat. Also studied was an interaction of strychnine with taurine in affecting the activities of WDR cells. Following intravenous administration of taurine, the responses of WDR cells to all types of mechanical stimuli were markedly enhanced, demonstrating that the response to pressure was most sensitive to taurine action. When the receptive field was exposed to thermal stimuli ($50^{\circ}C$) for 20 sec. taurine increased activity of WDR cell to 169.5% of the control value. The $K^{+}$-induced activation of WDR cells was invariably suppressed after taurine administration. Intravenously administered strychnine remarkably reduced the enhanced response of WDR cell to natural stimuli resulting from intravenous administration of taurine. Also ${\beta}-alanine$ markedly activated the response of spinal dorsal horn cell to natural mechanical stimuli. These findings suggest that neutral amino acid and its derivative such as ${\beta}-alanine$ and taurine can enhance the response of WDR cells to different stimuli in cats.

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WD Repeat Domain 1 Deficiency Inhibits Neointima Formation in Mice Carotid Artery by Modulation of Smooth Muscle Cell Migration and Proliferation

  • Hu, JiSheng;Pi, ShangJing;Xiong, MingRui;Liu, ZhongYing;Huang, Xia;An, Ran;Zhang, TongCun;Yuan, BaiYin
    • Molecules and Cells
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    • v.43 no.8
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    • pp.749-762
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    • 2020
  • The migration, dedifferentiation, and proliferation of vascular smooth muscle cells (VSMCs) are responsible for intimal hyperplasia, but the mechanism of this process has not been elucidated. WD repeat domain 1 (WDR1) promotes actin-depolymerizing factor (ADF)/cofilin-mediated depolymerization of actin filaments (F-actin). The role of WDR1 in neointima formation and progression is still unknown. A model of intimal thickening was constructed by ligating the left common carotid artery in Wdr1 deletion mice, and H&E staining showed that Wdr1 deficiency significantly inhibits neointima formation. We also report that STAT3 promotes the proliferation and migration of VSMCs by directly promoting WDR1 transcription. Mechanistically, we clarified that WDR1 promotes the proliferation and migration of VSMCs and neointima formation is regulated by the activation of the JAK2/STAT3/WDR1 axis.

[$Zn^{2+}$ Modulates the Responses of Rat Dorsal Horn Neuron to C-Fiber Stimulation and Excitatory Amino Acids

  • Ahn, Chang-Hoon;Shin, Hong-Kee;Kim, Jin-Hyuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.6
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    • pp.455-461
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    • 2000
  • Zinc contained in the neurons of central nervous system is activity-dependently released and then attenuates NMDA (N-methyl-D-aspartate)-induced neurotoxicity while augmenting non-NMDA-induced neurodegeneration. Zinc also has been reported to produce antinociceptive action on the inflammation- and nerve injury-induced hyperalgesia in the behavioral test. In this study, we investigated the effects of zinc on the responses of dorsal horn cells to NMDA, kainate and graded electrical stimulation of C-fibers. In the majority of WDR cells (70.6%), zinc current-dependently inhibited WDR cell responses to NMDA and in the remaining cells, produced biphasic responses; excitation followed by inhibition. Zinc augmented the responses of WDR cells to iontophoretical application of kainate. The dominant effect of $Zn^{2+}$ on the responses of WDR cells to C-fiber stimulation was excitatory, but inhibition, excitation-inhibition and no change of the responses to C-fiber stimulation were induced. $Ca^{2+}-EDTA$ antagonized the excitatory or inhibitory effects of $Zn^{2+}$ on the WDR cell responses. These experimental findings suggest that $Zn^{2+}$ modulates the transmission of sensory information in the rat spinal cord.

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Effect of Clonidine on the Dorsal Horn Cell Activities in the Cat (Clonidine이 고양이 척수후각세포의 Activity에 미치는 효과)

  • Chi, Yong-Chul;Kim, Jin-Hyuk;Koh, Sang-Don;Shin, Hong-Kee;Kim, Kee-Soon
    • The Korean Journal of Physiology
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    • v.22 no.1
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    • pp.89-100
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    • 1988
  • Effect of clonidine on the dorsal horn cell responses to mechanical stimulations were studies in 3 spinalized cats and 10 cats with intact spinal cord. The type of dorsal horn cells was determined according to their response patterns to four graded mechanical stimulations (brush, pressure, pinch and squeeze) applied to the respective receptive fields. In the present study the results obtained only from the wide dynamic range (WDR) cells were included. The responses of the WDR cells to noxious mechanical stimuli were selectively suppressed following intravenous administration of clonidine into the experimental animals. The clonidine-induced changes in responses of the WDR cells to mechanical stimulation were not affected by naloxone or propranolol whereas effect of clonidine on WDR cell responses was almost completely abolished after intravenous administration of yohimbine. Also in the spinalized cats results parallel to those observed in cats with intact spinal cord were obtained. The results of present study strongly implies that analgesic action of clonidine can be mediated through excitation of ${\alpha}_{2}-adrenoceptor$ even at the spinal cord level without supraspinal mechanism.

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A case of Galloway-Mowat syndrome with novel compound heterozygous variants in the WDR4 gene

  • Kim, Hamin;Lee, Hyunjoo;Lee, Young-Mock
    • Journal of Genetic Medicine
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    • v.17 no.2
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    • pp.97-101
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    • 2020
  • The combination of central nervous system abnormalities and renal impairment is a notable characteristic of Galloway-Mowat syndrome (GAMOS), a disease which often accompanies microcephaly, developmental delay, and nephrotic syndrome. Many subtypes exist having various phenotypes and genotypes, and many genetic causes are still being identified. An 18-month-old boy first visited our clinic for seizure, delayed development, and microcephaly. During follow-up visits he developed proteinuria and nephrotic syndrome at the age of 6. Nephrotic syndrome became refractory to treatment. These phenotypes were suggestive of GAMOS. Next generation sequencing was performed for genetic analysis and revealed novel compound heterozygous variants in the WDR4 gene: c.494G>A (p.Arg165Gln) and c.540C>G (p.Ile180Met). This is the first case in Korea of GAMOS involving the WDR4 gene.

Characterization of Electroacupuncture Effects on the Responses of Rat Dorsal Horn Neurons to Noxious Stimulation (전침자극이 흰쥐척수후각세포의 유해자극반응에 미치는 효과의 특성)

  • Shin, Hong-kee;Park, Dong-suk;Lee, Seo-eun;Kim, Jin-hyuk
    • Journal of Acupuncture Research
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    • v.19 no.4
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    • pp.167-182
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    • 2002
  • This experiment was designed to investigate the effects of electroacupuncture (EA) on chronic pains and factors that affected EA effects. The responses of wide dynamic range (WDR) cells to electrical stimulation of $A{\delta}$ & C afferent fibers were used as an index of pain in rats with chronic pains induced by intraplantar injection of complete Freund's adjuvant or peripheral nerve injury. In rats with chronic pains, low (2Hz) and high (100Hz) frequency EA stimulation applied to zusanli caused the inhibition of WDR cell responses in about 60% of rats and the inhibitory actions were dependent on the stimulus strength. EA stimulation also induced an excitation of WDR cell responses in 23.9% of rats and no effect in 15.8% of rats. However, it seemed that in normal rats compared to the rat with chronic pains, the incidence of which EA stimulation caused the excitation or no effect was high. Reversible spinalization almost completely blocked EA-induced inhibitory or excitatory effects. EA stimulation more frequently induced the excitation of WDR cell responses in lightly anesthetized (0.6%) rats and the enhanced responses of WDR cells were inhibited by EA stimulation in the rat anesthetized with 1.5% enflurane. These experimental findings suggest that in rats with chronic pain, EA stimulation inhibited WDR cell responses to slow $A{\delta}$ and C fiber stimulation and EA-induced inhibitory action was under the control of descending inhibitory system and degree of anesthesia.

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