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  • 1
    Keywords: CELLS ; CELL ; POPULATION ; GENE ; PROTEIN ; transcription ; TRANSCRIPTION FACTOR ; REDUCTION ; animals ; cell cycle ; CELL-CYCLE ; CYCLE ; MOUSE ; MUTANT ; NERVOUS-SYSTEM ; etiology ; REGION ; REGIONS ; EMBRYO ; PHENOTYPE ; PROGENITOR CELLS ; REGULATOR ; LAYER ; EMBRYOS ; DENTATE GYRUS ; ADULT ; CORTEX ; NEURONS ; FOREBRAIN DEVELOPMENT ; BETA-TUBULIN ISOTYPE ; BrdU ; DEVELOPING MOUSE NEOCORTEX ; lamination ; limbic system ; MURINE CEREBRAL WALL ; NEURAL STEM-CELLS ; neurogenesis ; PROLIFERATIVE EPITHELIUM ; tailless ; VENTRICULAR ZONE
    Abstract: The tailless (tlx) gene is a forebrain-restricted transcription factor. Tlx mutant animals exhibit a reduction in the size of the cerebral hemispheres and associated structures ( Monaghan et al., 1997). Superficial cortical layers are specifically reduced, whereas deep layers are relatively unaltered ( Land and Monaghan, 2003). To determine whether the adult laminar phenotype has a developmental etiology and whether it is associated with a change in proliferation/differentiation decisions, we examined the cell cycle and neurogenesis in the embryonic cortex. We found that there is a temporal and regional requirement for the Tlx protein in progenitor cells (PCs). Neurons prematurely differentiate at all rostrocaudal levels up to mid-neurogenesis in mutant animals. Heterozygote animals have an intermediate phenotype indicating there is a threshold requirement for Tlx in early cortical neurogenesis. Our studies indicate that PCs in the ventricular zone are sensitive to loss of Tlx in caudal regions only; however, PCs in the subventricular zone are altered at all rostrocaudal levels in tlx-deficient animals. Furthermore, we found that the cell cycle is shorter from embryonic day 9.5 in tlx(-/-) embryos. At mid-neurogenesis, the PC population becomes depleted, and late PCs have a longer cell cycle in tlx-deficient animals. Consequently, later generated structures, such as upper cortical layers, the dentate gyrus, and the olfactory bulbs, are severely reduced. These studies indicate that tlx is an essential intrinsic regulator in the decision to proliferate or differentiate in the developing forebrain
    Type of Publication: Journal article published
    PubMed ID: 15385616
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  • 2
    Keywords: GENE ; GENES ; PATIENT ; COMPLEX ; COMPLEXES ; kidney ; RAT-KIDNEY ; SEQUENCES ; TRANSPORT ; MUTATION ; genetics ; MUTATIONS ; methods ; AMINO-ACID-TRANSPORT ; CANADA ; cystinuria ; SLC3A1 ; SLC7A9 ; amino acid ; EXPRESSION CLONING ; inherited disorder ; KIDNEY CDNA ; microcrystals ; stone
    Abstract: Background. Cystinuria is an inherited disorder of cystine and dibasic amino acid transport in kidney. Subtypes are defined by the urinary cystine excretion patterns of the obligate heterozygous parents: Type I/N (fully recessive or silent); Type II/N (high excretor); Type III/N (moderate excretor). The first gene implicated in cystinuria (SLC3A1 ) is associated with the Type I urinary phenotype. A second cystinuria gene (SLC7A9 ) was recently isolated, and mutations of this gene were associated with dominant (non-Type I) cystinuria alleles. Here we report genotype-phenotype studies of SLC7A9 mutations in a cohort of well-characterized cystinuria probands and their family members. Methods. Individual exons of the SLC7A9 gene were screened by single strand conformation polymorphism (SSCP) analysis and sequencing of abnormally migrating fragments. Results. Seven mutations were identified. A single bp insertion (799insA) was present in four patients: on Type III alleles in two patients and on Type II alleles in two patients. These results suggest that Type II and Type III may be caused by the same mutation and, therefore, other factors must influence urinary cystine excretion. A 4bp deletion in intron 12 (IVS12+4delAGTA) and a missense mutation (1245G--〉A, A354T) were identified on Type III alleles. A nonsense codon (1491G--〉T, E436X) and a possible splicing mutation (IVS9-17G--〉A) were seen in a Type I/III patient, but the mutations could not be assigned to particular alleles. Of additional interest were two missense mutations (316T--〉C, I44T and 967C--〉T, P261L) linked to Type I alleles. Conclusion. Our results provide evidence that some SLC7A9 mutations may be associated with fully recessive (Type I) forms of cystinuria. We also demonstrate SLC7A9 mutations in dominant Types II and III cystinuria. The finding of SLC7A9 mutations in all three subtypes underscores the complex interactions between specific cystinuria genes and other factors influencing cystine excretion. A simpler phenotypic classification scheme (recessive and dominant) for cystinuria is warranted
    Type of Publication: Journal article published
    PubMed ID: 12371955
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC); 20130526-20130529; Düsseldorf; DOCP 024 /20130521/
    Publication Date: 2013-05-22
    Keywords: Cavernous malformation ; CCM genes ; Endothelial function ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 4
    Keywords: EXPRESSION ; IN-VIVO ; MODEL ; SITES ; STEM-CELLS ; SAFETY ; INTEGRATION ; INFUSION ; LENTIVIRAL VECTOR ; ENHANCE
    Abstract: "Ex vivo" regional gene therapy using lentiviral (LV) vectors to over-express bone morphogenetic protein 2 (BMP-2) is an effective way to enhance bone healing in animal models. Here, we evaluated two different "ex vivo" approaches using either "same day" rat bone marrow cells (SDRBMCs) or cultured rat bone marrow cells (C-RBMCs), both transduced with a LV based two-step transcriptional activation system overexpressing GFP (LV-TSTA-EGFP), to assess the fate of the transduced cells and the safety of this approach. The transduced cells were implanted in femoral defects of syngeneic rats. Animals were sacrificed at 4, 14, 28 and 56 days after surgery (n=5 per group). Viral copies were detectable in the defect site of SD-RBMC group and gradually declined at 8w (5 log decrease compared to 4d). In the C-RBMC animals, there was a 2-4 log decline in the viral copy numbers at 2w and 4w, but at 8w there was a relative rise (about 100 fold) in the number of the viral vectors in the defect site of 4 (out of 5) animals compared to the previous time points. For both gene transfer approaches, the pattern of tissue distribution was non-specific and no histological abnormalities were noted in either group. In summary, we demonstrated that the LV-TSTA transduced cells remain in the defect site for at least 56 days, though the numbers decreased over time. There were no consistent findings of viral copies in internal organs which is encouraging with respect to the development of this strategy for use in humans.
    Type of Publication: Journal article published
    PubMed ID: 26264707
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch); 20080601-20080604; Würzburg; DOCP 058 /20080530/
    Publication Date: 2008-05-30
    Keywords: CCM genes ; cavernous malformation ; gene expression ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract A study of the immobilization for226Ra waste has been carried out. Cement-based concrete was used as a matrix for the solidification of radium waste. The experimental results show that the cement mixture with water/cement between 0.46–0.54 has higher strengh (above 20 MPa), and the compressive strength was not reduced by addition of 1% barite or the radium waste (RaSO4) into the concrete solid.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1612-1112
    Keywords: Micellar electrochromatography ; Electroosmotic flow ; Column coatings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary An investigation was carried out to study the electroosmotic flow (EOF) in micellar electrokinetic capillary chromatography (MECC). Fused silica capillaries were treated with various reagents to investigate the parameters influencing the magnitude and reproducibility of the EOF. The results for untreated and treated columns were collected and compared under the same experimental conditions. Furthermore, experiments with and without sodium dodecylsulfate (SDS) addition to the buffer were carried out to elucidate the influence of this surfactant on the EOF. The mechanisms behind the effects of these modifications on the EOF and the stability of the coatings on the column wall are discussed.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1612-1112
    Keywords: Electrokinetic capillary chromatography ; Micellar agents ; Chlorophenoxy acids ; Herbicides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A method for the separation of a number of herbicides consisting of chlorophenoxy acids by micellar electrokinetic capillary chromatography (MECC) was developed. Sodium dodecyl sulphate (SDS), Brij 35, cetyltrimethylammonium bromide (CTAB) and methanol were introduced into the buffers to investigate their effects on the separation of the herbicides. SDS combined with Brij 35 as the micellar agent was found to provide the best overall separation of these components.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The aim of this paper is to consider using effective natural minerals in studying the retardation and migration of radium under the influence of groundwater in the far-field of a radioactive waste repository. The properties of adsorbing radium by minerals are studied by adopting the static and dynamic adsorption method. Preliminary experimental results give confidence in the validity of using Maifanshih and barite to adsorb radium in water and to serve as effective retarding materials in radioactive waste repositories, their Kd values being 3815 and 2955, respectively. The study on a certain number of conditions of adsorbing radium by the promissing material Maifanshih is reported for the first time. The mechanism of radium adsorption has been discussed and modeling of migration of radium in the minerals has been presented to establish a rational basis for the longterm prediction required for safety assessment of underground disposal of radioactive waste.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-8752
    Keywords: Treatment planning ; optimization ; skeleton ; medial axis transformation ; radiosurgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is recognized that multiple-shot radiosurgery using the Leksell Gamma Knife (LGK) can result in larger penumbra dose and less target dose homogeneity compared with a single shot treatment. In addition, the number of shots used increases significantly with increasing volume, which makes planning and optimization time consuming and complex. Although such complexity may not affect the accuracy of treatment delivery itself, it is difficult to assess the dosimetrical merits of a given plan. To deal with this complicated process, we have studied shot-related effects and target shape as separate issues. Shot-related effects include homogeneity, penumbra, shot weight, and prescription isodose line “shift.” Target shape is analyzed using morphological tools. Target volume and shape, as represented by the three-dimensional (3-D) medial axis transform or skeleton, are used to determine optimal shot positions, sizes, and number. These parameters are determined from successive 3-D skeletons of the unplanned target volume. Essentially, target shape is replicated by the arrangement of shots compromising the 3-D skeleton, forcing a conformal dose distribution. This planning process has been automated for multishot treatment. A clinical case in 3-D demonstrates this approach as a replacement for manual planning when a plan with multiple shots is required.
    Type of Medium: Electronic Resource
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