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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2018-08-17
    Description: RNA tails play integral roles in the regulation of messenger RNA (mRNA) translation and decay. Guanylation of the poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, the most common of which is guanosine. A single guanosine residue is sufficient to impede the deadenylase CCR4-NOT complex, which trims the tail and exposes guanosine at the 3' end. Consistently, depletion of TENT4A and TENT4B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of posttranscriptional gene regulation.
    Keywords: Molecular Biology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-09-02
    Description: Transcriptional coactivator PPAR coactivator (PGC)-1α and its splice variant N-terminal (NT)-PGC-1α mediate transcriptional regulation of brown adipose tissue (BAT) thermogenesis in response to changes in ambient temperature. PGC-1α is dispensable for cold-induced BAT thermogenesis as long as NT-PGC-1α is present. However, the functional significance of NT-PGC-1α in BAT has not been determined. In the present study, we generated NT-PGC-1α –/– mice to investigate the effect of NT-PGC-1α deficiency on adaptive BAT thermogenesis. At thermoneutrality, NT-PGC-1α –/– mice exhibited abnormal BAT phenotype with increased accumulation of large lipid droplets concomitant with marked downregulation of FA oxidation (FAO)-related genes. Consistent with transcriptional changes, mitochondrial FAO was significantly diminished in NT-PGC-1α –/– BAT. This alteration, in turn, enhanced glucose utilization within the NT-PGC-1α –/– BAT mitochondria. In line with this, NT-PGC-1α –/– mice had higher reliance on carbohydrates. In response to cold or β 3 -adrenergic receptor agonist, NT-PGC-1α –/– mice transiently exhibited lower thermogenesis but reached similar thermogenic capacities as their WT littermates. Collectively, these findings demonstrate that NT-PGC-1α is an important contributor to the maintenance of FAO capacity in BAT at thermoneutrality and provide deeper insights into the relative contributions of PGC-1α and NT-PGC-1α to temperature-regulated BAT remodeling.
    Print ISSN: 0022-2275
    Electronic ISSN: 1539-7262
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Plant Science 100 (1994), S. 171-178 
    ISSN: 0168-9452
    Keywords: Electroporation ; Festuca arundinacea Schreb ; Protoplasts ; Transient expression assay
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    ISSN: 0584-8539
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Human skin colour shows variations throughout life, and many extrinsic and intrinsic factors influence melanogenesis. Facultative pigmentation of sun-exposed skin has been suggested to reflect cumulative lifetime ultraviolet (UV) exposure in caucasians. However, pigmentary changes due to various regulatory factors may be different in dark-skinned peoples. Objectives  To observe the variations in skin colour due to ageing, gender differences and seasonal changes in Koreans with skin type IV or V. Methods  Skin pigmentation was measured at five body sites (buttock, glabella, the V of the neck area, inner arm and dorsal forearm) using skin reflectance spectroscopy in 497 subjects (age range 0–87 years) in winter and 311 subjects (age range 0–84 years) in summer. Among these subjects, 110 were assessed in both seasons. Three independent measurements at each site were done and the average value was used as the pigmentation level. Results  Constitutive pigmentation of the buttock was highest in the first decade of life. It then decreased during the second decade and this decreased level was maintained after the third decade. In contrast to caucasians, facultative pigmentation and sun exposure index did not increase with ageing. Gender differences were significant at all body sites after the first decade. Seasonal changes were apparent in dorsal forearm pigmentation. Little difference was seen in forehead pigmentation between summer and winter. Conclusions  Basal melanogenic regulation might not be different between Asians and caucasians. However, the sun exposure index may not represent lifelong cumulative UV exposure in Koreans. Age-, gender- and season-related characteristics of skin pigmentation in Koreans imply that genetically determined basal skin colour plays an important part in characterizing later responsiveness to UV radiation and sex hormones. Understanding differences between races will be helpful in studying the regulatory mechanisms of melanogenesis.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    British journal of dermatology 140 (1999), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Atopic dermatitis has been seen to result from multifactorial inheritance, with interaction between genetic and environmental factors. The genetic association may differ according to the ethnic backgrounds.Objective The purpose of this study was to investigate the genetic factors in Korean atopic dermatitis patients by studying the human leucocyte antigen (HLA) class I association and polymorphisms of transporters associated with antigen presentation (TAP) and low-molecular-weight polypeptide (LMP) genes.Methods HLA-A and B genotyping was performed in 53 atopic dermatitis patients and 184 healthy controls using the standard microlymphocytotoxicity technique. TAP1, TAP2, LMP2, and LMP7 gene polymorphisms were anaylzed using the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP), PCR-amplification refractory mutation system (ARMS), and PCR-restriction fragment length polymorphism (RFLP).Results Allele frequency of HLA-A24 was significantly increased in patients with atopic dermatitis compared to controls (P 〈 0.05). HLA-B alleles showed no differences in distribution between patients and controls. Genotype, phenotype, and allele frequencies of TAP1 gene also revealed no differences in distribution between patients and controls. Analysis of TAP2 gene polymorphisms showed increased frequencies of the TAP2*C allele and TAP2*A/TAP2*C genotype in atopic dermatitis patients compared to controls (P 〈 0.05). Distribution of LMP2 and LMP7 gene polymorphisms was similar for patients and controls.Conclusion This study demonstrates an association of atopic dermatitis with HLA-A24 and TAP2*C alleles in Korean patients. Discrepancy with the previous reports might be related to different patient characteristics and ethnic variations.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-3040
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Much attention has been paid to the signal sequences of eukaryotic protoporphyrinogen oxidases (protoxes); both the organelles targeted by protoxes and the role of protoxes in conferring resistance against protox-inhibiting herbicides, such as oxyfluorfen, have been examined. However, there have been no reports on the translocation of prokaryotic protoxes. This study investigated the targeting ability of Myxococcus xanthus protox in vitro and in vivo. In an in vitro translocation assay using a dual import system, M. xanthus protein was detected in chloroplasts and mitochondria, suggesting that the M. xanthus protox protein was targeted into both organelles. In order to confirm the in vitro dual targeting ability of M. xanthus, we used a stable transgenic strategy to investigate dual targeting in vivo. In transgenic rice plants overexpressing M. xanthus protox, M. xanthus protox antibody cross-reacted with proteins with predicted molecular masses of 50 kDa from both chloroplasts and mitochondria, and this in vivo transgene expression corresponded to a prominent increase in chloroplastic and mitochondrial protox activity. Seeds from the transgenic lines M4 and M7 germinated in solid Murashige and Skoog media of up to 500 µm of oxyfluorfen, whereas wild-type seeds did not germinate in 1 µm. After 4-week-old-rice plants were treated with oxyfluorfen for 3 d, lines M4 and M7 exhibited normal growth, whereas the wild-type line was severely bleached and necrotized. The herbicidal resistance is attributed to the insignificant accumulation of photodynamic protoporphyrin IX in cytosol because the high chloroplastic and mitochondrial protox activity in oxyfluorfen-treated transgenic lines, compared with that in oxyfluorfen-treated and untreated wild-type plants, metabolizes protoporphyrinogen IX to chlorophyll and heme. A practical application of the dual targeting of M. xanthus protox for obtaining outstanding resistance to peroxidizing herbicides is discussed.
    Type of Medium: Electronic Resource
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