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141.
Background
Germ-cell nuclear factor (GCNF, NR6AI) is an orphan nuclear receptor. Its expression pattern suggests it functions during embryogenesis, in the placenta and in germ-cell development. Mouse GCNF cDNA codes for a protein of 495 amino acids, whereas the four reported human cDNA variants code for proteins of 454 to 480 amino acids. Apart from this size difference, there is sequence conservation of up to 98.7%. To elucidate the genomic structure that gives rise to the different human GCNF mRNAs, the sequence information of the human GCNF locus is compared to the previously reported structure of the mouse locus. 相似文献142.
Raimund W Kinne Thomas Liehr Volkmar Beensen Elke Kunisch Thomas Zimmermann Heidrun Holland Robert Pfeiffer Hans-Detlev Stahl Wolfgang Lungershausen Gert Hein Andreas Roth Frank Emmrich Uwe Claussen Ursula G Froster 《Arthritis research & therapy》2001,3(5):1-20
Chromosomal aberrations were comparatively assessed in nuclei extracted from synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases. Peripheral blood lymphocytes (PBL) and skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n = 4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centromere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 RA patients (19%), with involvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 21 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomies of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were detected in SFB of OA and spondylarthropathy patients. No aberrations were detected in i) PBL or skin FB from the same patients (except for one OA patient with a karyotype 45,X[10]/46,XX[17] in PBL and variable polysomies in long-term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joints or of patients with joint trauma. In conclusion, qualitatively comparable chromosomal aberrations were observed in synovial tissue and early-passage SFB of patients with RA, OA, and other inflammatory joint diseases. Thus, although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic inflammatory stress in rheumatic diseases. 相似文献
143.
Phytopharmaceuticals and dietary supplements containing valerian are used as mild sleep-inducing agents. An in vitro radioligand binding assay at A(1) and A(2A) adenosine receptors (ARs) was conducted with a fixed extract combination of valerian and hop (Ze 91019) to investigate a possible mechanism for the pharmacological activity of the extract. Component extracts of valerian and hop were also individually investigated. The fixed combination Ze 91019 as well as the valerian extracts therein exhibited selective affinity to A(1)ARs (K(i) = 0.15-0.37 mg/mL vs [(3)H]CCPA). The same extracts exhibited partial agonist activity at the A(1) adenosine receptor as indicated by a lower degree of stimulation of [35S]GTP gamma S binding in membrane preparations of CHO-hA(1) cells as compared to the full A(1) AR agonist N(6)-cyclopentyladenosine (CPA). In addition valerian extract inhibited cAMP accumulation in CHO-hA(1) cell membranes. The partial agonistic activity at A(1)ARs may thus play a role in the sleep inducing effect of Ze 91019 and the valerian extract therein. 相似文献
144.
Myosin VIIa,harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle 总被引:14,自引:0,他引:14
Boëda B El-Amraoui A Bahloul A Goodyear R Daviet L Blanchard S Perfettini I Fath KR Shorte S Reiners J Houdusse A Legrain P Wolfrum U Richardson G Petit C 《The EMBO journal》2002,21(24):6689-6699
Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia. 相似文献
145.
High-level production of the non-cariogenic sucrose isomer palatinose in transgenic tobacco plants strongly impairs development 总被引:6,自引:0,他引:6
Palatinose (isomaltulose, 6-O-alpha-D-glucopyranosyl-D-fructose) is a structural isomer of sucrose which is produced from sucrose by some bacterial strains as a reserve material during periods of low carbon availability. The ability to synthesise palatinose is not only advantageous for the bacteria but is also of industrial interest since palatinose is used as a sucrose substitute in food production. To explore the possibility of palatinose production in plants a recently isolated sucrose isomerase gene (palI; EC 5.4.99.11) from Erwinia rhapontici [F. B?rnke et al. (2001) J Bacteriol 183: 2425-2430] was cloned into a plant expression vector between the constitutive 35S CaMV promoter and the octopine synthase polyadenylation signal. To allow secretion of the protein into the apoplast the signal peptide of the potato proteinase inhibitor II was N-terminally fused to the pall coding region. Expression of the protein was verified by northern and western blot analyses. Efficient secretion of the protein was demonstrated by palI detection in intercellular fluids. Transgenic plants expressing palI accumulated high levels of palatinose. As a consequence, transgenic plants showed severe phenotypic alterations. Young leaves were curled and developed bleached areas during maturation. Flowers were misshapen and sterile. Based on nonaqueous fractionation experiments palatinose was found in several subcellular compartments, indicating limited membrane transport of the sugar. In contrast to results obtained with short-term feeding experiments, no evidence for palatinose-mediated regulation of photosynthetic or defence genes could be obtained in the transgenic palI-expressing tobacco plants. Based on our results we conclude that plants can efficiently be used as bioreactors for the production of palatinose. Furthermore, tissue-specific expression of palI should allow carbon allocation to specific tissues and/or cell-types to be modulated. 相似文献
146.
Multiple nicotinic acetylcholine receptor α-subunits are expressed in the arterial system of the rat
Brüggmann D Lips KS Pfeil U Haberberger RV Kummer W 《Histochemistry and cell biology》2002,118(6):441-447
Neuronal nicotinic acetylcholine receptors (nAChRs) are hetero- and homopentamers built up by nine different alpha-subunits and three different beta-subunits. The subtype composition within the receptor determines ligand specificity, affinity and cation permeability. In this study we focused on the distribution of the ligand binding alpha-subunits in the rat arterial system by means of RT-PCR and immunohistochemistry. Subtypes alpha3, alpha5, alpha7 and alpha10 were found to be expressed by endothelial cells, suggesting that they are equipped both with calcium-preferring (alpha7 homopentamers) and monovalent cation-preferring (heteropentamers containing alpha3- and alpha5-subunits) nAChR channels. All alpha-subtypes except alpha9 were expressed by vascular smooth muscle cells with a highly specific distribution pattern along the vascular tree. While every alpha-subunit except alpha9 was detected in the thoracic aorta, intrapulmonary arterial branches contained only alpha7 immunoreactivity, and other vascular beds held intermediate positions with respect to the extent of alpha-subunit expression. Current knowledge does not allow to correlate these distribution patterns to specific functions, but it can be anticipated that at least some components of nAChR-mediated signalling in the arterial wall are highly specific for individual arteries. 相似文献
147.
Construction of a 'unigene' cDNA clone set by oligonucleotide fingerprinting allows access to 25 000 potential sugar beet genes 总被引:1,自引:0,他引:1
148.
149.
To gain further knowledge about rare genetic diseases, a world wide method for data collection via the Internet has been established. This new approach will improve collecting valuable data from single case reports. Ramedis saves standardised patient data which will be usable for statistics, longitudinal examinations and cooperative studies in future time. Embedded in the scene of the German Human Genome Project, Ramedis directly will enable phenotype-genotype correlations. Beside the better characterisation of clinical heterogeneity of rare metabolic diseases, there may be a great benefit for the treatment of these patients in whom prospective studies are otherwise expensive and difficult to perform. This contribution presents the motivation for this system, introduces features, current state and the future of the project. Additionally, first experiences of using Ramedis by health professionals are explained. 相似文献
150.
Quantitation of the tumor-targeting properties of antibody fragments conjugated to cell-permeating HIV-1 TAT peptides 总被引:5,自引:0,他引:5
Niesner U Halin C Lozzi L Günthert M Neri P Wunderli-Allenspach H Zardi L Neri D 《Bioconjugate chemistry》2002,13(4):729-736
Human monoclonal antibodies are promising agents for the development of more selective anticancer therapeutics. However, the tumor-targeting efficiency of most anticancer antibodies is severely limited by their poor penetration into the tumor mass. Recent studies have shown that a peptide derived from the HIV TAT protein could improve the distribution of cytoplasmic reporter proteins when administered systemically as fusion proteins or cross-linked chimeras. In this article, we tested by quantitative biodistribtution analysis whether conjugation to TAT peptides could improve the tumor targeting properties of scFv(L19)-Cys: an engineered human antibody fragment specific for the ED-B domain of fibronectin, a marker located in the modified extracellular matrix surrounding tumor neovasculature. Our results show that TAT peptides, consisting either of L-amino acids or D-amino acids, can efficiently transduce target cells when conjugated to fluorophores and/or antibody fragments, suggesting a receptor-independent cell entry mechanism. However, conjugation of scFv(L19)-Cys to TAT peptides resulted in a severely reduced tumor targeting performance compared to the unconjugated antibody, as measured in murine F9 teratocarcinoma-bearing mice, after intravenous injection of the radiolabeled antibody preparations. Our results outline the usefulness of TAT peptides for the efficient in vitro transduction of cells with globular proteins. In particular, the use of TAT peptides composed of D-amino acids may significantly reduce proteolytic degradation. At the same time, the poor biodistribution properties of antibody-TAT conjugates cast doubts over the applicability of this methodology for the delivery of biopharmaceuticals in vivo. 相似文献