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  • 1
    Publication Date: 2012-06-16
    Description: Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Won, Hyejung -- Lee, Hye-Ryeon -- Gee, Heon Yung -- Mah, Won -- Kim, Jae-Ick -- Lee, Jiseok -- Ha, Seungmin -- Chung, Changuk -- Jung, Eun Suk -- Cho, Yi Sul -- Park, Sae-Geun -- Lee, Jung-Soo -- Lee, Kyungmin -- Kim, Daesoo -- Bae, Yong Chul -- Kaang, Bong-Kiun -- Lee, Min Goo -- Kim, Eunjoon -- England -- Nature. 2012 Jun 13;486(7402):261-5. doi: 10.1038/nature11208.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22699620" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Antimetabolites/pharmacology ; *Autistic Disorder/genetics/metabolism ; Behavior, Animal/*drug effects/physiology ; Benzamides/*pharmacology ; Cycloserine/*pharmacology ; Disease Models, Animal ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/*genetics ; Pyrazoles/*pharmacology ; Receptors, N-Methyl-D-Aspartate/*agonists/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Chromoblastomycosis is a cutaneous and subcutaneous mycotic disease caused by the dematiaceous (black) fungi. Five species of fungi are known generally to be the cause: Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, F. compacta and Rhinocladiella cerphilum. In infected tissue they can appear as pigmented sclerotic bodies, commonly called ‘copper pennies’, which are pathognomonic of chromoblastomycosis. The infection usually occurs through traumatic skin inoculation, with the majority of lesions occurring on the feet and legs of outdoor workers. We report a patient in whom the lesions had begun on the right breast, which is an unexposed area, without a history of trauma. A uniform, reliable treatment does not exist but our patient was mycologically cured with the use of amphotericin B and the subsequent combination of 5-flucytosine and itraconazole.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We have successfully grown δ-doped AlGaAs structures and δ-doped AlGaAs/InGaAs pseudomorphic high electron mobility transistor (HEMT) structures by atmospheric pressure metalorganic chemical vapor deposition (MOCVD). Capacitance-voltage (C-V) profiles with full-width at half-maximum as small as 32 A(ring) demonstrate very narrow doping profiles of δ-doped AlGaAs layers grown at 650–700 °C. Theoretical C-V profiles of δ-doped AlGaAs have been self-consistently calculated with the L valley taken into account and compared with the experimental results. A δ-doped AlGaAs/InGaAs pseudomorphic HEMT structure with a 30 A(ring) spacer layer yields a sheet carrier concentration of 2.25×1012 cm−2 with an electron mobility of 20 300 cm2/V s at 77 K.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 75 (1994), S. 1764-1770 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The thermal oxidation of polycrystalline GexSi1−x (0.10≤x≤0.47) and pseudomorphic Ge0.2Si0.8 has been studied in wet ambient at 550 to 900 °C. A uniform GexSi1−xO2 oxide is observed by backscattering spectrometry for a high Ge content at low oxidation temperatures; a SiO2 oxide is obtained for a low Ge content at high temperatures; a GeySi1−yO2 oxide with reduced Ge content (y〈x) is found in between. Ge piles up behind the oxide when SiO2 or GeySi1−yO2 form. The transition between these three types of oxides also depends on the crystallinity of the GeSi alloy. When a uniform GexSi1−xO2 oxide grows, its thickness is proportional to the square root of the oxidation duration, which indicates that the rate-limiting process is the diffusive transport across the oxide of, most probably, the oxidant. The rate increases with the Ge content in the alloys. The proportionality constant, B, for this process is B(T)=[(1.0±0.2)×1011 nm2/h]exp[(−1.1±0.2 eV)/kT] for Ge0.47Si0.53. It is proposed that, in general, the oxidation behavior is determined by the competition between the speed of the diffusive process in the unoxidized GeSi alloy and the velocity at which the oxidation front progresses. The controlling factors are the oxidation temperature, the composition, and the structure of the GexSi1−x alloy. A model is proposed that is based on these three factors. Analogies with this system exist where all three elements are solid.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1468-2494
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A human Cu,Zn-superoxide dismutase was fused with a transcriptional transactivator protein transduction domain of HIV-1 to produce a novel anti-aging ingredient for cosmeceuticals, transcriptional transactivator superoxide dismutase (Tat-SOD). Stability tests and evaluation of the transduction efficacy and enzymatic activity suggest Tat-SOD is an effective active ingredient for anti-aging treatment.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2018-02-02
    Description: Purpose: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC). Experimental Design and Results: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN–PARP–DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro. ChIP-PCR assay revealed that N-MYC transcriptionally activates PARP1, PARP2, BRCA1, RMI2, and TOPBP1 through binding to the promoters of these genes. MYCN or PARP1 gene knockdown significantly reduced the expression of MYCN–PARP–DDR pathway genes and NED markers, and inhibition with MYCNsi and/or PARPsi, BRCA1si, or RMI2si significantly suppressed malignant activities, including cell viability, colony formation, and cell migration, in C4-2b4 and NCI-H660 cells. Targeting this pathway with AURKA inhibitor PHA739358 and PARP inhibitor olaparib generated therapeutic effects similar to those of gene knockdown in vitro and significantly suppressed tumor growth in both C4-2b4 and MDACC PDX144-13C subcutaneous models in vivo . Conclusions: Our results identify a novel MYCN–PARP–DDR pathway that is driven by N-MYC in a subset of CRPC-Adeno and in NEPC. Targeting this pathway using in vitro and in vivo CRPC-Adeno and CRPC-Neuro models demonstrated a novel therapeutic strategy for NEPC. Further investigation of N-MYC–regulated DDR gene targets and the biological and clinical significance of MYCN–PARP–DDR signaling will more fully elucidate the importance of the MYCN–PARP–DDR signaling pathway in the development and maintenance of NEPC. Clin Cancer Res; 24(3); 696–707. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 8
    Publication Date: 2018-04-14
    Description: We report a general strategy for obtaining high-quality, large-area metal-chalcogenide semiconductor films from precursors combining chelated metal salts with chalcoureas or chalcoamides. Using conventional organic solvents, such precursors enable the expeditious formation of chalco-gels, which are easily transformed into the corresponding high-performance metal-chalcogenide thin films with large, uniform areas. Diverse metal chalcogenides and their alloys (MQ x : M = Zn, Cd, In, Sb, Pb; Q = S, Se, Te) are successfully synthesized at relatively low processing temperatures (〈400°C). The versatility of this scalable route is demonstrated by the fabrication of large-area thin-film transistors (TFTs), optoelectronic devices, and integrated circuits on a 4-inch Si wafer and 2.5-inch borosilicate glass substrates in ambient air using CdS, CdSe, and In 2 Se 3 active layers. The CdSe TFTs exhibit a maximum field-effect mobility greater than 300 cm 2 V –1 s –1 with an on/off current ratio of 〉10 7 and good operational stability (threshold voltage shift 〈 0.5 V at a positive gate bias stress of 10 ks). In addition, metal chalcogenide–based phototransistors with a photodetectivity of 〉10 13 Jones and seven-stage ring oscillators operating at a speed of ~2.6 MHz (propagation delay of 〈 27 ns per stage) are demonstrated.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 9
    Publication Date: 2018-04-19
    Description: Predation is considered a major selective pressure in the evolution of fear, but the neurophysiology of predator-induced fear is unknown. We simultaneously recorded lateral amygdala (LA) and prelimbic (PL) area neuronal activities as rats exited a safe nest to search for food in an open space before, during, and after encountering a "predator" robot programmed to surge from afar. Distinct populations of LA neurons transiently increased spiking as rats either advanced or fled the robot, whereas PL neurons showed longer-lasting spike trains that preceded and persisted beyond LA activity. Moreover, discrete LA-PL cell pairs displayed correlated firings only when the animals either approached or fled the robot. These results suggest a general fear function of the LA-PL circuit where the PL participates in the initial detection of potential threats, the LA signals the occurrence of real threats, and the dynamic LA-PL interaction optimizes defensive readiness for action.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 10
    Publication Date: 2018-07-04
    Description: Background/Aim: Dendropanax morbifera (DM) and Commersonia bartramia (CB) are possible candidates for immunotherapy. In this study, the cytotoxicity and chemical sensitization of DM and CB extracts on gynecologic and colon cancers were evaluated. Materials and Methods: The malignant cell lines were cultured and analyzed for cytotoxicity and chemical sensitization. A mouse model was also constructed to make the condition similar to in vivo. Reverse transcription-polymerase chain reaction was conducted to determine alterations in drug-resistant genes. Results: The extracts from DM and CB showed specific cytotoxicity to malignant cell lines. DM increased chemical sensitivity to cervical and ovarian cancer, while CB showed improved sensitization to endometrial cancer. The effects of the extracts were confirmed using a mouse model. The extracts induced differences in the expression levels of a number of genes related to drug resistance. Conclusion: DM and CB extracts could be novel agents for immunotherapy and chemical sensitization in gynecologic and colon cancers.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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