277 research outputs found

    Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory

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    Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory

    RACK1 mediates rewiring of intracellular networks induced by hepatitis C virus infection

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    Hepatitis C virus (HCV) is a positive-strand RNA virus replicating in a membranous replication organelle composed primarily of double-membrane vesicles (DMVs) having morphological resemblance to autophagosomes. To define the mechanism of DMV formation and the possible link to autophagy, we conducted a yeast two-hybrid screening revealing 32 cellular proteins potentially interacting with HCV proteins. Among these was the Receptor for Activated Protein C Kinase 1 (RACK1), a scaffolding protein involved in many cellular processes, including autophagy. Depletion of RACK1 strongly inhibits HCV RNA replication without affecting HCV internal ribosome entry site (IRES) activity. RACK1 is required for the rewiring of subcellular membranous structures and for the induction of autophagy. RACK1 binds to HCV nonstructural protein 5A (NS5A), which induces DMV formation. NS5A interacts with ATG14L in a RACK1 dependent manner, and with the ATG14L-Beclin1-Vps34-Vps15 complex that is required for autophagosome formation. Both RACK1 and ATG14L are required for HCV DMV formation and viral RNA replication. These results indicate that NS5A participates in the formation of the HCV replication organelle through interactions with RACK1 and ATG14L. Author summary All positive-strand RNA viruses replicate their genomes in distinct membrane-associated compartments designated replication organelles. The compartmentalization of viral replication machinery allows the enrichment and coordination of cellular and viral factors required for RNA replication and the evasion from innate host defense systems. Hepatitis C virus (HCV), a prototype member of the Flaviviridae family, rearranges intracellular membranes to construct replication organelles composed primarily of double-membrane vesicles (DMVs) which are morphologically similar to autophagosomes. Nonstructural protein 5A (NS5A), which is essential for HCV replication, induces DMV formation. Here, we report that NS5A triggers DMV formation through interactions with RACK1 and components of the vesicle nucleation complex acting at the early stage of autophagy. These results illustrate how a virus skews cellular machineries to utilize them for its replication by hijacking cellular proteins through protein-protein interactions. This research sheds light on the molecular basis of replication organelle formation by HCV and possibly other viruses employing organelles with DMV morphology.11Ysciescopu

    Hippocampal mossy cell involvement in behavioral and neurogenic responses to chronic antidepressant treatment

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    Most antidepressants, including selective serotonin reuptake inhibitors (SSRIs), initiate their drug actions by rapid elevation of serotonin, but they take several weeks to achieve therapeutic onset. This therapeutic delay suggests slow adaptive changes in multiple neuronal subtypes and their neural circuits over prolonged periods of drug treatment. Mossy cells are excitatory neurons in the dentate hilus that regulate dentate gyrus activity and function. Here we show that neuronal activity of hippocampal mossy cells is enhanced by chronic, but not acute, SSRI administration. Behavioral and neurogenic effects of chronic treatment with the SSRI, fluoxetine, are abolished by mossy cell-specific knockout of p11 or Smarca3 or by an inhibition of the p11/AnxA2/SMARCA3 heterohexamer, an SSRI-inducible protein complex. Furthermore, simple chemogenetic activation of mossy cells using Gq-DREADD is sufficient to elevate the proliferation and survival of the neural stem cells. Conversely, acute chemogenetic inhibition of mossy cells using Gi-DREADD impairs behavioral and neurogenic responses to chronic administration of SSRI. The present data establish that mossy cells play a crucial role in mediating the effects of chronic antidepressant medication. Our results indicate that compounds that target mossy cell activity would be attractive candidates for the development of new antidepressant medications. © 2019, Springer Nature Limited.1

    Small Bowel Volvulus Induced by Mesenteric Lymphangioma in an Adult: a Case Report

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    Mesenteric lymphangiomas are rare abdominal masses that are seldom associated with small bowel volvulus, and especially in adult patients. We report here on an unusual case of small bowel volvulus that was induced by a mesenteric lymphangioma in a 43-year-old man who suffered from repeated bouts of abdominal pain. At multidetector CT, we noticed whirling of the cystic mesenteric mass and the adjacent small bowel around the superior mesenteric artery. Small bowel volvulus induced by the rotation of the mesenteric lymphangioma was found on exploratory laparotomy. Lymphangioma should be considered as a rare cause of small bowel volvulus in adult patients

    Characteristics and efficacy of fish-derived gelatin microparticles as an embolic agent in a rabbit renal model: regulation of the degradation period by molecular weight

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    PURPOSE:To evaluate the embolic effect of fish-derived gelatin microparticles (GMPs) and compare the degradation periods and biocompatibilities of different molecular weight (MW) GMPs in a rabbit model.METHODS:GMPs were designed to degrade within 21 days (high MW GMP, 15-30 kDa) and 2 days (low MW GMP, 5-15 kDa) in vivo. Renal arteries of 24 rabbits were embolized using both high and low MW GMPs (155-350 µm). Rabbits were sacrificed either immediately after embolization, or after follow-up (F/U) angiogram on days 2 and 21 of embolization, respectively (4 rabbits in each of the 6 subgroups). Pathological changes of recanalized vessels were evaluated using the Banff classification. For the in vitro study, each type of GMP was mixed with normal saline and morphological changes were compared for 14 days.RESULTS:Fish-derived GMPs showed effective embolization. On 2-day F/U angiography, occluded vessels were more recanalized to the peripheral branches in low MW group. On day 21, a parenchymal perfusion defect recovered to a greater extent in low MW group than that in high MW group. Mean Banff scores for intimal arteritis on 2-day F/U and interstitial fibrosis on 21-day F/U were higher in high MW group (1.75 ± 0.58 vs. 0.19 ± 0.4 and 2.56 ± 0.63 vs. 0.88 ± 0.89; P < .001). On in vitro assessment, low MW GMP lost the spherical shape and degraded, and was invisible on microscopy on day 6, whereas high MW GMP was only partially degraded after 2 weeks.CONCLUSION:Fish-derived GMPs showed effective embolization in a rabbit model. Low MW GMPs degraded within 2 days with a low inflammatory response

    Efficient Photoelectrochemical Water Oxidation by Metal-Doped Bismuth Vanadate Photoanode with Iron Oxyhydroxide Electrocatalyst

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    Intensive attention has been currently focused on the discovery of semiconductor and proficient cocatalysts for eventual applications to the photoelectrochemical water splitting system. A W-Mo-doped BiVO4 semiconductor was prepared by the surfactant-assisted thermal decomposition method on a fluorine-doped tin oxide conductive film. The W-Mo-doped BiVO4 films showed a porous morphology with the grain sizes of about 270 nm. Because the hole diffusion length of BiVO4 is about 100 nm, the W-Mo-doped BiVO4 film in this study is an ideal candidate for the photoelectrochemical water oxidation. Iron oxyhydroxide (FeOOH) electrocatalyst was chemically deposited on the W-Mo-doped BiVO4 to investigate the effect of the electrocatalyst on the semiconductor. The W-Mo-doped BiVO4/FeOOH composite electrode showed enhanced activity compared to the pristine W-Mo-doped BiVO4 electrode for water oxidation reaction. The chemical deposition is a promising method for the deposition of FeOOH on semiconductor

    Severe hypotension and water intoxication developed after an accidental oxytocin overdose in a morbidly obese patient undergoing cesarean section -A case report-

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    We present a 32-year-old, extremely obese, pregnant woman who developed severe hypotension and water intoxication after an accidental injection of large bolus of oxytocin during cesarean section under general anesthesia. The patient was initially thought to have an amniotic fluid embolism because of the abrupt hemodynamic changes developed immediately after fetal delivery and lack of recognition of medication error. It is highly recommended that careful attention should be paid not only to the possibility of hemodynamic deterioration and water intoxication if oxytocin is given rapidly in excessive doses, but to the confirmation of the proper use of the drug before it is injected

    Enhancement of hole injection using ozone treated Ag nanodots dispersed on indium tin oxide anode for organic light emitting diodes

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    The authors report the enhancement of hole injection using an indium tin oxide (ITO) anode covered with ultraviolet (UV) ozone-treated Ag nanodots for fac tris (2-phenylpyridine) iridium Ir(ppy)3-doped phosphorescent organic light-emitting diodes (OLEDs). X-ray photoelectron spectroscopy and UV-visible spectrometer analysis exhibit that UV-ozone treatment of the Ag nanodots dispersed on the ITO anode leads to formation of Ag2O nanodots with high work function and high transparency. Phosphorescent OLEDs fabricated on the Ag2O nanodot-dispersed ITO anode showed a lower turn-on voltage and higher luminescence than those of OLEDs prepared with a commercial ITO anode. It was thought that, as Ag nanodots changed to Ag2O nanodots by UV-ozone treatment, the decrease of the energy barrier height led to the enhancement of hole injection in the phosphorescent OLEDs.This work was supported by Korea Research Foundation grant funded by Korean Government (MOEHRD: Basic Research Promotion Fund)(KRF-2006-003-D00243) and Ministry of Commerce, Industry, and Energy

    Detection Rates of Bacteria in Chronic Otitis Media with Effusion in Children

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    This study was performed to investigate polymerase chain reaction-based detection of bacterial DNA in middle ear fluid and assess the correlation between the PCR-positive rate with several factors associated with middle ear effusion. The purpose was to gain a further understanding of bacterial infection as a major cause of otitis media with effusion. Of the 278 specimens of middle ear fluid, 39 (14%) tested positive by ordinary culture. The overall detection rate of bacterial DNA using the PCR method was 36.7% for middle ear effusion, and bacterial DNA detection rates of Hemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis in the middle ear effusion were 29.1%, 4.7% and 10.8%, respectively. The bacterial DNA detection rate was higher in ears with a history of acute otitis media than those without the history. High detection rates were observed in patients younger than 48 months who have had a higher tendency to present with acute otitis media. We concluded that PCR is a more sensitive method for the detection of bacteria in middle ear effusion than ordinary culture, and acute otitis media is a major contributor to the pathogenesis of otitis media with effusion
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