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  • Articles  (622)
  • Saccharomyces cerevisiae  (233)
  • bioavailability  (223)
  • 42.55
  • Chemical Engineering
  • Electronic structure and strongly correlated systems
  • Springer  (622)
  • 1985-1989  (321)
  • 1980-1984  (301)
  • 1
    Electronic Resource
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    Springer
    Journal of industrial microbiology and biotechnology 4 (1989), S. 49-53 
    ISSN: 1476-5535
    Keywords: l-Phenylacetyl carbinol ; Saccharomyces cerevisiae ; Yeast ; Benzaldehyde ; Biotransformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary The rate of production ofl-phenylacetyl carbinol bySaccharomyces cerevisiae in reaction mixtures containing benzaldehyde with sucrose or pyruvate as cosubstrate was investigated in short 1 h incubations. The effect of yeast dose rate, sucrose and benzaldehyde concentration and pH on the rate of reaction was determined. Maximum biotransformation rates were obtained with concentrations of benzaldehyde, sucrose and yeast of 6 g, 40 g and 60 g/l, respectively. Negligible biotransformation rates were observed at a concentration of 8 g/l benzaldehyde. The reaction had a pH optimum of 4.0–4.5. Rates of bioconversion of benzaldehyde and selected substituted aromatic aldehydes using both sucrose and sodium pyruvate as cosubstrate were compared. The rate of aromatic alcohol production was much higher when sucrose was used rather than pyruvate.o-Tolualdehyde and 1-chlorobenzaldehyde were poor substrates for aromatic carbinol formation although the latter produced significant aromatic alcohol in sucrose-containing media. Yields of 2.74 and 3.80 g/l phenylacetyl carbinol were produced from sucrose and pyruvate, respectively, in a 1 h reaction period.
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  • 2
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    Journal of industrial microbiology and biotechnology 4 (1989), S. 81-84 
    ISSN: 1476-5535
    Keywords: Ethanol fermentation ; Wheat starch ; Saccharomyces cerevisiae ; immobilization ; Continuous dynamic immobilized biocatalyst bioreactor ; Biocatalyst bioreactor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary A simple and efficient method of conversion of wheat starch B to ethanol was investigated. Employing a two-stage enzymatic saccharification process, 95% of the wheat starch was converted to fermentable sugars in 40 h. From 140 g/l total sugars in the feed solution, 63.6 g/l ethanol was produced continuously with a residence time of 3.3 h in a continuous dynamic immobilized biocatalyst bioreactor by immobilized cells ofSaccharomyces cerevisiae. The advantages and the application of this bioreactor to continuous alcoholic fermentation of industrial substrates are presented.
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  • 3
    ISSN: 1572-8773
    Keywords: Manganese ; Electron spin resonance ; Superoxide dismutase ; Saccharomyces cerevisiae ; Yeast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Manganese accumulation was studied by room-temperature electron spin resonance (ESR) spectroscopy inSaccharomyces cerevisiae grown in the presence of increasing amounts of MnSO4. Mn2+ retention was nearly linear in intact cells for fractions related to both low-molecular-mass and macromolecular complexes (‘free’ and ‘bound’ Mn2+, respectively). A deviation from linearity was observed in cell extracts between the control value and 0.1 mM Mn2+, indicating more efficient accumulation at low Mn2+ concentrations. The difference in slopes between the two straight lines describing Mn2+ retention at concentrations lower and higher than 0.1 mM, respectively, was quite large for the free Mn2+ fraction. Furthermore it was unaffected by subsequent dialyses of the extracts, showing stable retention in the form of low-molecular-mass complexes. In contrast, the slope of the line describing retention of ‘bound’ Mn2+ at concentrations higher than 0.1 mM became less steep after subsequent dialyses of the cell extracts. This result indicates that the macromolecule-bound Mn2+ was essentially associated with particulate structures. In contrast to Cu2+, Mn2+ had no effect on the major enzyme activities involved in oxygen metabolism except for a slight increase of cyanide-resistant Mn-superoxide dismutase activity, due to dialyzable Mn2+ complexes.
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  • 4
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    Applied physics 49 (1989), S. 29-32 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60B
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Design and characteristics of an “external cavity single mode GaAs diode laser” are described which allow continuous wavelength tuning over 50 GHz without mode hops. Tuning is achieved by synchronous tilting of both a thin solid etalon and a Brewster plate inside the laser resonator. Stabilizing the laser frequency to an external Fabry-Perot interferometer yields a frequency stability of ≦1 MHz at output powers up to 20 m W.
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  • 5
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    Applied physics 49 (1989), S. 377-381 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We have studied the Doppler-broadened 11.76 μm 15NH3 emission line optically pumped in a ring resonator by a cw CO2 laser operating on the 10R(42) line. In the pure ammonia, even if the pumping occurs inside the Doppler width, the two-photon Raman process seems to be responsible for the laser emission. Both in the pure 15NH3 and in the 15NH3, N2, and He mixture we demonstrate the possibility of obtaining a unidirectional laser amplifier.
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  • 6
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    Applied physics 48 (1989), S. 305-309 
    ISSN: 1432-0649
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The optically pumped FIR laser lines at 119 μm from CH3OH and at 127 μm from13CD3OH are known to be the most powerful in the far infrared spectral region. We report on efficiency measurements for our waveguide laser system. The effect of various parameters was investigated, resulting in the highest efficiency ever reported for the 119 μm line. The Stark effect and others parameters of the 127 μm were measured, and a new13CD3OH laser line at 175 μm discovered, with the same pump transition. These measurements are helpful for completing the assignment already proposed for the 127 μm line.
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  • 7
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    Applied physics 49 (1989), S. 91-97 
    ISSN: 1432-0649
    Keywords: 7.65G ; 42.55 ; 86.70G ; 86.70L
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The paper describes a photoacoustic spectrometer for detection of NH3 in power plant emission with a detection limit below 1 ppm. The radiation source is a tunable CO2 waveguide laser, and detection is performed at reduced pressure, where the vibration-rotation lines of NH3 are essentially Doppler broadened. Immunity against interference is ensured by recording a characteristic spectral profile, and problems associated with the high concentration of CO2, and the associated line center absorption are eliminated by utilizing the effect of kinetic cooling on the photoacoustic phase. A computerized spectrometer has been constructed and tested under realistic conditions at a Danish power plant operating a test facility for selective non-catalytic reduction of NO x . Results of this field test are given.
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  • 8
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    Applied physics 49 (1989), S. 269-273 
    ISSN: 1432-0649
    Keywords: 42.55 ; 78.45 ; 78.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We report on room-temperature cw laser action of Er3+: Yttrium-aluminum-garnet (YAG) and Er3+: Yttrium-gallium-garnet (YGG) crystals at 1.64 μm. The laser operates from the metastable4 I 13/2 manifold into an upper Stark level of the4 I 15/2 ground-state manifold of Er3+. Due to reabsorption losses, the Er3+ concentration of the laser crystals must be low. Laser pumping at a wavelength of 647.1 nm yields lowest thresholds around 30 mW and slope efficiencies up to 12.7% for Er:YAG. Laser operation in Er:YGG is achieved with higher thresholds of about 200 mW and smaller slope efficiencies of 0.9%. The effective emission cross section in YAG is estimated to be σe≈5×10−21 cm2.
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  • 9
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    Applied physics 49 (1989), S. 541-544 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A simplified analysis of the small-signal gain in the presence of a Gaussian mode is presented for several undulator designs. For a filamentary electron beam, an analytical expression of the gain is obtained and found to be in agreement with previous work and with computer simulations. A general expression of the small-signal gain for the optical klystron FEL is given.
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  • 10
    ISSN: 1432-0649
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract This work reports 83 new optically pumped far infrared laser lines, using deuterated methyl alcohol, CHD2OH, as active medium. For each line we list the measured wavelength, its polarization relative to the pump line, the optimum gas pressure and the CO2 laser pump power at the maximum absorption.
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  • 11
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    Applied physics 48 (1989), S. 299-304 
    ISSN: 1432-0649
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The12CH3 18OH molecule has been investigated for new far-infrared laser lines by optically pumping it with a cw waveguide CO2 laser. The larger tunability (318 MHz) with respect to a conventional CO2 laser permits the pumping of many12CH3 18OH lines. As a consequence 100 new laser lines have been discovered, ranging from 34.6 μm to 653.2 μm in wavelength. The infrared spectrum of12CH3 18OH has been observed and all the fundamental vibration energies measured.
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  • 12
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Vector ; Glyphosate resistance ; Transformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The E. coli aroA gene was inserted between yeast promoter and terminator sequences in different shuttle expression plasmids and found to confer enhanced EPSP synthase activity as well as resistance to glyphosate toxicity. Subsequently, a transformation system using these newly constructed vectors in yeast was characterized. The efficiency of the glyphosate resistance marker for transformation and selection with plasmid pHR6/20-1 in S. cerevisiae laboratory strain SHY2 was found to be relatively high when compared with selection for LEU2 prototrophy. The fate of the recombinant plasmid pHR6/20-1 in the transformants, the preservation of the aroA E. coli DNA fragment in yeast, mitotic stability, EPSP synthase activity, and growth on glyphosate-containing medium have been investigated. As this plasmid also allows direct selection for glyphosate resistant transformants on rich media, the glyphosate resistance marker was used for transforming both S. cerevisiae laboratory strain SHY2 and brewer's yeast strains S. cerevisiae var. “uvarum” BHS5 and BHS2. In all cases, the vector pHR6/20-1 was maintained as an autonomously replicating plasmid. The resistance marker is, therefore, suitable for transforming genetically unlabeled S. cerevisiae laboratory, wild, and industrial yeast strains.
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  • 13
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Chromosome V ; Ty elements ; tRNA genes ; Transposition hot-spots ; Yeast polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Ty4 is a novel transposable element in the yeast, Saccharomyces cerevisiae, which is present in only a few copies in the genome (Stucka et al. 1989). In strain C836 one of the three copies (Ty4-90) is contained in cosmid clone c90, where it resides on chromosome V. Analysis of this region reveals a “hot-spot” of transposition: in addition to Ty4-90, the locus contains a complete Ty3 element and seven singular delta, sigma and tau elements. Three tRNA genes (for His, Lys, and Ile) are located in this region, and these are closely associated with one or the other of the elements, a phenomenon commonly observed in yeast. A comparison of c90 with corresponding regions from other strains shows that the locus is highly polymorphic and that this polymorphism is explicitly associated with Ty transposition and recombination events.
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  • 14
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    Current genetics 16 (1989), S. 315-321 
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Antisuppressor ; ADE3 ; Translation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Mutations in a known yeast gene, ADE3, were shown to act as an antisuppressor, reducing the efficiency of the omnipotent suppressor, sup45-2. The ADE3 locus encodes the trifunctional enzyme C1-tetrahydrofolate synthase, which is required for the biosynthesis of purines, thymidylate, methionine, histidine, pantothenic acid and formylmethionyl-tRNAfmet. The role of this enzyme in translational fidelity had not previously been suspected.
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  • 15
    ISSN: 1432-0983
    Keywords: Yeast ; Saccharomyces cerevisiae ; Nonsense suppression ; Omnipotent suppressors ; Gene mapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Ten dominant omnipotent suppressors of Saccharomyces cerevisiae, which were previously shown to be different from SUP46, have been examined. Nine are mapped in a region between lys5 and cyh2 on the left arm of chromosome VII. These suppressors, like SUP46, manifest sensitivity to increased temperature and the antibiotics paromomycin and hygromycin B. In addition, they have an identical action spectrum. These results strongly suggest that they are allelic to each other and they are designated SUP138. The tenth is mapped to a position between his1 and arg6 on the right arm of chromosome V. This suppressor, named SUP139, does not manifest temperature sensitivity nor antibiotic sensitivity. SUP139 and SUP138, which are clearly distinguished by means of action spectrum, act on much fewer nonsense mutations than SUP46. It is now clear that dominant omnipotent suppressors arising at a single locus are homogeneous and that their efficiency is locus-dependent. The order of efficiency is SUP46〉SUP138〉SUP139.
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  • 16
    ISSN: 1432-0983
    Keywords: Yeast ; Repair ; Complementation ; Saccharomyces cerevisiae ; Schizosaccharomyces pombe ; Gene cloning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Two Saccharomyces cerevisiae genes necessary for excision repair of UV damage in DNA, RAD1 and RAD2, were introduced individually, on a yeast shuttle vector, into seven Schizosaccharomyces pombe mutants — rads1, 2, 5, 13, 15,16 and 17. The presence of the cloned RAD1 gene did not affect survival of any of the S. pombe mutants. The RAD2 gene increased survival of S. pombe rad13 to near the wild-type level after UV irradiation and had no effect on any of the other mutants tested. S. pombe rad13 mutants are somewhat defective in removal of pyrimidine dimers so complementation by the S. cerevisiae RAD2 gene suggests that the genes may code for equivalent proteins in the two yeasts.
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  • 17
    ISSN: 1432-0983
    Keywords: DNA transformation ; Saccharomyces cerevisiae ; Site-specific recombination ; 2μ DNA plasmid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The 2μ DNA plasmid of the yeast Saccharomyces cerevisiae does not confer any known selectable phenotype to the host cell carrying it. Selection of cells transformed with purified 2μ DNA therefore cannot be achieved, and the intracellular presence of 2μ can only be assessed by molecular analysis of the DNA complement. In addition, 2μ alone does not replicate in bacterial hosts, thus rendering its amplification by conventional methods impossible. We have isolated a shuttle plasmid, pBH-2L, generated by in vivo sites-pecific recombination between the endogenous 2μ DNA plasmid and pRL, a pBR322 derivative containing the yeast LEU2 gene and one 2μ repeat sequence associated with the origin of replication. This new shuttle plasmid has the property, when transformed into yeast, of undergoing site-specific recombinational resolution between its two direct repeat sequences. This releases 2μ plasmid and pRL as individual molecules. The latter can undergo progressive mitotic loss during growth in nonselective medium, ultimately leaving leucine auxotrophic transformants that contain only 2μ DNA plasmid. This system can be utilized to introduce 2μ DNA alone into cells lacking it, thereby providing a novel means to study the biology and the molecular genetics of the plasmid and its potential practical applications as a vector.
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  • 18
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    Current genetics 15 (1989), S. 113-120 
    ISSN: 1432-0983
    Keywords: Calmodulin mutant ; Nuclear division ; Chromosome stability ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The coding region of a yeast calmodulin gene was fused to a galactose-inducible GAL1 promoter, and a conditional-lethal mutant of Saccharomyces cerevisiae, in which the expression of calmodulin was regulated by galactose, was constructed. The mutant grew normally in galactose medium, but in glucose medium, in which the promoter was repressed, it ceased growing after 12–15 h. The growth arrest was associated with a decrease in intracellular calmodulin levels: after 12h, no intracellular calmodulin protein was detectable. Analysis of the terminal phenotype showed that when the cell stopped growing, it had a bud, a nucleus after S-phase and a short mitotic spindle. Thus, the defect was mainly in nuclear division. Bud growth was partially inhibited in these cells: 27% of the cells stopped growing with a small bud. Furthermore, calmodulin-deficient cells showed elevated rates of chromosome loss, possibly as the result of a defect in the precise segregation of chromosomes.
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  • 19
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    Current genetics 15 (1989), S. 235-237 
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Mitochondrial DNA ; Method of extraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A rapid method for the extraction of yeast mitochondrial DNA (mtDNA) is described. In comparison with previous methods, it simplifies several steps, does not require either the isolation of mitochondria or phenol treatment and is less time consuming. This protocol gives a high yield of pure mtDNA (50–120 μg from a 100-ml culture), which can be directly used in various molecular applications: restriction enzyme digestion, electrophoresis, blotting, labeling, cloning and sequencing.
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  • 20
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Mutagen hyperresistance ; Southern, Northern analysis ; Gene transplacement ; Transposon mapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The genes SNQ and SFA confer hyperresistance to 4-NQO and FA when present on a multi-copy plasmid in yeast. Both are non-essential genes since transplacement of SNQ by a disrupted snq-0::LEU2 yielded stable and viable haploid integrants. Southern analysis revealed that SNQ and SFA are single-loci genes, and OFAGE analysis showed that they are located on chromosome XIII and IV, respectively. Northern blot analysis of SNQ and SFA revealed poly(A)+ RNA transcripts of 2 kb and 1.7 kb, respectively. Nuclease S 1 mapping showed SNQ to have a coding region of 1.6 kb and SFA, one of 1.3 kb. The 5′ coding regions were determined for both genes, while the 3′ end could only be determined for gene SNQ. Both genes do not appear to contain introns. The SFA locus was also mapped by transposon mutagenesis. Tn10-LUK integrants disrupted the SFA gene function at sites that were determined by subcloning to lie within the SFA transcription unit.
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  • 21
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; SKI3 ; SKI5 ; M1 dsRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We have identified a mutant strain of the yeast Saccharomyces cerevisiae which overproduces killer toxin. This strain contains a single mutation which fails to complement defects in both the SKI3 and SKI5 genes, while a cloned copy of this gene complements both the ski3 and ski5 defects. The level of secreted toxin from a cDNA based plasmid is not increased in a ski3 strain, showing that the overproduction phenotype is dependent upon an increased level of M1 dsRNA.
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  • 22
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Psoralen photoaddition ; Interstrand cross-link ; Repair deficiency ; Genotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Two different UVA irradiation systems were initially biologically calibrated with two haploid yeast strains proficient and deficient, respectively, in nucleotide excision repair. The number of DNA lesions introduced into the cell's genome by the photoactivated bifunctional furocoumarin 8-MOP was then calculated by means of the applied UVA exposure doses. At LD37 the repair-proficient wild type had about 14 ICL and 34 furan-side monoadducts in its DNA, while doubly blocked repair mutant rad3-12 pso1-1 had 2 ICL and 3 monoadducts. Locus-specific reversion of lys1-1 followed two-hit kinetics in the repair-proficient wild type and one-hit kinetics in an excision-deficient rad2-20 mutant, as would be expected if ICL was the main type of mutagenic lesion in the wild type and monoadducts the main mutagenic lesion type in the excision-deficient strain. Quantitative comparison of 8-MOP + UVA-induced ICL with those induced by bifunctional mustard revealed the former to have a much higher genotoxicity.
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  • 23
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Protoplast fusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The percentage of hybrids formed during protoplast fusion in Saccharomyces cerevisiae is determined by the percentage of protoplasts at the GI/S boundary of the cell cycle.
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  • 24
    ISSN: 1432-0983
    Keywords: Peroxisomes ; Protein import ; Saccharomyces cerevisiae ; Hansenula polymorpha
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The DAS gene of Hansenula polymorpha was expressed in Saccharomyces cerevisiae under the control of different promoters. The heterologously synthesized dihydroxyacetone synthase (DHAS), a peroxisomal enzyme in H. polymorpha, shows enzymatic activity in baker's yeast. The enzyme was imported into the peroxisomes of S. cerevisiae not only under the appropriate physiological conditions for peroxisome proliferation (oleic acid media), but also in glucose-grown cells where it induced the enlargement of the few peroxisomes present. This growth process was not accompanied by an increase in the number of microbodies, which suggests a separate control mechanism for peroxisomal proliferation.
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  • 25
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    Current genetics 15 (1989), S. 399-401 
    ISSN: 1432-0983
    Keywords: Saccharomyces exiguus ; Saccharomyces cerevisiae ; HO gene ; MAT gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The DNA of Saccharomyces exiguus was analyzed by Southern hybridization using cloned MATa, MATα, and HO genes of Saccharomyces cerevisiae as probes. It was shown that S. exiguus has a DNA sequence homologous with the HO gene of S. cerevisiae and that this DNA sequence is on a chromosome of about 940 kb of DNA in S. exiguus. However, there is no DNA sequence in S. exiguus that is homologous with the MAT genes of S. cerevisiae.
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  • 26
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    European journal of nutrition 28 (1989), S. 130-141 
    ISSN: 1436-6215
    Keywords: bioavailability ; folic acid ; pharmaceutical preparation ; Bioverfügbarkeit ; Folsäure ; Arzneimittelzubereitung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Untersuchungen zur Bioverfügbarkeit essentieller Mikronährstoffe (Vitamine, Mineralstoffe, Spurenelemente) aus Lebensmitteln wie auch aus Arzneimittelzubereitungen sind von entscheidender Bedeutung bei der Beurteilung des jeweiligen Beitrages zur Nährstoffversorgung bzw. zur Abschätzung eines möglichen Therapieerfolges. Die Durchführung derartiger Prüfungen erfolgt in der Praxis nicht selten nach unterschiedlichen Kriterien. Deshalb werden zunächst die Grundsätze erläutert, die bei entsprechenden Prüfungen für eine valide Bewertung von Nähr- bzw. Wirkstoffgemischen oder Monopräparaten bedeutsam sind. Abschließend wird die Ermittlung der Bioverfügbarkeit von Folsäure an einem Beispiel demonstriert. Zur Testung werden die postresorptiven Kurvenintegrale ermittelt, wobei die Daten auf das basale Ausgangsniveau bezogen werden. Zur Beurteilung der Bioverfügbarkeit findet neben dem maximalen Vitaminanstieg im Serum sowie der Zeit bis zum Konzentrationsmaximum insbesondere der Bioverfügbarkeitsquotient von Test- und Referenzzubereitung mit seinem 95%-VB Berücksichtigung. Die Ergebnisse zeigen, daß die exemplarisch eingesetzte Testsubstanz, 5-Formyl-Tetrahydrofolsäure, eine sehr gute Bioverfügbarkeit aufweist und daß unter Anwendung der beschriebenen Rahmenbedingungen eine objektive Bewertung der Bioverfügbarkeit möglich ist.
    Notes: Summary Bioavailability studies of micronutrients (vitamins, minerals) from different food stuffs, as well as from pharmaceutical preparations are of great importance for the calculation of nutrient intake and/or the evaluation of the therapeutic value. In practice, bioavailability studies are not generally performed on a standardized level. For this reason basic criterions are presented and discussed. Finally, the investigation of the bioavailability of folate is demonstrated by an example. The parameters investigated are: the maximal concentration (cmax), the time to reach this maximum (tmax), and especially the bioavailability ratio determined from the area under the curve (AUC) after administration of the folic acid containing test and reference preparation. The results indicate that 5-formyl-tetrahydrofolic acid given in the tested form has nearly the same bioavailability (ratio: 1.02) as folic acid (pteroylmonoglutamic acid) in aqueous solution.
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  • 27
    ISSN: 1420-9071
    Keywords: Saccharomyces cerevisiae ; growth conditions ; kinaseless mutant ; plasma membrane vesicles ; glucose transport ; kinetics and computer simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In this study experimental data on the kinetic parameters investigated by other authors1–5, 11 together with own data on plasma membrane vesicles, have been subjected to a computer simulation based on the equations describing facilitated diffusion. The simulation led to an ideal fit describing the above data. From this it can be concluded that glucose is transported by facilitated diffusion, and not by active transport as was postulated by Van Steveninck14, 15. The simulation method also demonstrates that the fast sampling technique used by these authors1–5,11 underestimates the fluxes. Thus, the parameters given do not contribute to the understanding of glucose transport under different metabolic conditions. The K value of plasma membrane vesicles prepared from glucose-repressed cells is around 7 mM. Derepression, particularly by galactose, causes a highly significant increase in affinity as shown by a decrease in the K value to 2 mM. The highest affinity was measured in a triple kinaseless mutant grown on glycerol with a K value of 1 mM. If seems, therefore, that the kinetic parameters derived from initial uptake rates of glucose in intact cells1–5,11 using single flux analysis, such as Eadie-Hofstee- or Lineweaver-Burk-plots, are in error.
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  • 28
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    European journal of clinical pharmacology 37 (1989), S. 409-410 
    ISSN: 1432-1041
    Keywords: cimetidine ; metoclopramide ; antacids ; absorption ; bioavailability ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma cimetidine levels were determined in 9 normal subjects after a single oral dose of cimetidine 400 mg under control conditions, 2 h before metoclopramide 20 mg and 2 h after a potent antacid. The bioavailability of cimetidine was not significantly affected by metoclopramide and it was marginally reduced by the antacid.
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  • 29
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    European journal of clinical pharmacology 37 (1989), S. 419-421 
    ISSN: 1432-1041
    Keywords: N-Acetylcysteine ; oral administration ; bioavailability ; healthy subjects ; suckable formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of suckable tablets and granules of N-acetylcysteine (NAC) have been compared after oral administration of 400 mg doses to 10 healthy volunteers. The oral bioavailability of the NAC tablets was 103%. In a multiple dosing study of the same tablets in the same subjects, a high maintenance plasma level of NAC was revealed.
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  • 30
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    European journal of clinical pharmacology 37 (1989), S. 423-426 
    ISSN: 1432-1041
    Keywords: prednisolone ; food intake ; enteric-coated tablets ; pharmacokinetics ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prednisolone absorption and bioavailability of 10 mg enteric-coated (EC) and plain (uncoated) tablets were investigated after fasting and heavy meals (EC only) consumed to satiety in normal healthy volunteers. The same volunteers had also received 16 mg of prednisolone intravenously. In fasted subjects, the absolute bioavailability fraction, as normalised for intravenous doses, of prednisolone from plain tablets was 1.055 and from EC tablets was 0.996. The peak concentrations after plain and EC tablets were 309 and 249 ng/ml attained at 0.98 and 5.14 h, respectively. The means plasma elimination half-lives following the plain, EC tablets and intravenous administration in fasting conditions were 3.73, 3.89 and 3.78 h, respectively. Food interfered with both the absorption and the pharmacokinetics of prednisolone after EC tablets resulting in variability in its plasma levels. In some cases absorption of prednisolone was delayed for 12 h and remained at a measurable level for 24 h. In other cases, a normal absorption pattern was observed. This inter- and intrasubject variability of the effect of food appears to be related to its quantity, constituents and also the subjects physiological characteristics. It is concluded that enteric-coated prednisolone tablets should be administered at least 2 h between meals. However, for more predictable corticosteroid absorption (perhaps thus avoiding the therapeutic failure), plain prednisolone tablets are preferable.
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  • 31
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    European journal of clinical pharmacology 36 (1989), S. 383-388 
    ISSN: 1432-1041
    Keywords: naproxen ; sustained-release formulation ; pharmacokinetics ; bioavailability ; efficacy ; tolerability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and clinical efficacy of a once-daily sustained-release formulation of naproxen (sodium salt) have been compared with those of conventional-release agents. In a single dose pharmacokinetic study, the rate of absorption of the sustained-release preparation was less than that of a conventional-release preparation but the extent of absorption was the same. As is the case with conventional-release naproxen, food decreased the rate but not the extent of absorption of the sustained-release formulation. On multiple dose administration for 7 days, the AUC and average concentrations of the sustained release preparation (1 g daily) were the same as those for conventional release preparations of naproxen sodium (250 mg four times daily) and naproxen free acid (500 mg daily). The conventional-release sodium salt was absorbed more quickly with no differences in bioavailability. A double-blind clinical comparison in patients with osteoarthritis showed the sustained-release preparation (1 g daily) to be equivalent in efficacy to conventional naproxen capsules (500 mg twice daily) but to have a significantly lower incidence of gastrointestinal side-effects. The results suggest that sustained-release naproxen sodium has potential for use as a once-daily treatment for inflammatory disease.
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  • 32
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    European journal of clinical pharmacology 37 (1989), S. 313-316 
    ISSN: 1432-1041
    Keywords: diprafenone ; pharmacokinetics ; bioavailability ; first-pass metabolism ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the antiarrhythmic drug diprafenone have been investigated in 6 healthy volunteers following single intravenous (50 mg) and oral doses (50 and 150 mg). Diprafenone was mainly eliminated by metabolism in the liver. Following i.v. infusion of 50 mg diprafenone, the terminal half-life of elimination was 1.50 h, the volume of distribution at steady-state was 1.23 l·kg−1, and the free fraction in plasma was 1.68%. Mean total plasma clearance was 741 ml·min−1·70 kg−1, which approaches normal liver blood flow after correction for the blood/plasma concentration ratio. Thus, diprafenone can be classified as a high extraction drug. Following oral administration, a dose-dependent increase in bioavailability from 10.9 (50 mg dose) to 32.5% (150 mg dose) was observed. The data suggest that diprafenone is subject to saturable hepatic first-pass metabolism.
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  • 33
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    European journal of clinical pharmacology 37 (1989), S. 85-90 
    ISSN: 1432-1041
    Keywords: theophylline ; sustained-release formulation ; bioavailability ; fatty food ; dumping effect ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A cross-over study of kinetics has been undertaken in 12 healthy adults volunteers using two sustained-release theophylline products that allow once a day dosing (Theo-Dur tablets and Dilatrane A.P. bead filled capsules) to compare the i.v. pharmacokinetic profiles when taken with an hyperlipidic meal and a balanced standard meal. Each subject took part in four phases in randomised order, corresponding to all possible combinations of the products and the types of meal. Each phase involved a single dose of 9 to 11 mg·kg−1 theophylline administered at 20.00 h, at the beginning of the meal, with 100 ml water. The two formulations were found to be bioequivalent with both types of meal. Taken with a balanced meal, the mean parameters were similar; for Theo-Dur and Dilatrane A.P. they were respectively: Cmax: 11.32 mg·l−1 which plateaued from 8 to 10 h after dosing and 10.9 mg·l−1, which plateaued after 6 to 10 h; AUC 230 mg·h·l−1 and 220 mg·h·l−1; and MRT 18.2 h and 17.7 h. After the hyperlipidic meal the values for Theo-Dur and Dilatrane A.P. respectively, were: Cmax 10.9 mg·l−1 at 12 h and 11.3 mg·l−1 at 10 h; AUC 237 mg·h·l−1 and 227 mg·h·l−1; and MRT 19.2 h and 18.9 h. In spite of a decrease in the absorption rate, which led to a shift to the right of about 2 h of the plasma concentration-time curve, the bioavailability of both formulations were not significantly modified by a hyperlipidic meal as compared to a balanced meal. The shift of the curve with fatty food was not clinically important, as there was no dumping effect. The main difference between the two formulations was seen during the absorption phase, which was linear and less variable with Dilatrane A.P. and sigmoidal with Theo-Dur. This was observed with both types of meal.
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  • 34
    ISSN: 1432-072X
    Keywords: Saccharomyces cerevisiae ; Yeast ; Phospholipase B ; Lysophospholipase ; Enzyme inhibition ; AMP ; Unesterified fatty acids
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    Topics: Biology
    Notes: Abstract Divalent cations activate the lysophospholipase and transacylase reactions catalyzed by the same enzymes in the yeast Saccharomyces cerevisiae. The activation was observed at neutral pH, but not at the pH optimum of lysophospholipase/transacylase, near 3.5. Adenine nucleotides, especially AMP and ADP, are strong inhibitors of the same group of enzymes. Half maximal inhibition by AMP was found at a concentration of about 20 μM. The inhibition by nucleotides in low concentrations is enhanced by divalent cations.
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  • 35
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    Archives of microbiology 151 (1989), S. 198-202 
    ISSN: 1432-072X
    Keywords: Sexual agglutination ; Mating ; Saccharomyces cerevisiae ; Yeast
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    Topics: Biology
    Notes: Abstract Genetic regulation of the inducibility of sexual agglutination ability in the yeast Saccharomyces cerevisiae was studied. Detailed analysis of the degree of sexual agglutination was carried out; it showed that a greater number of genes are involved in the regulation of inducible sexual agglutination in strain H1-0 than previously assumed. Although dominancy of inducible phenotype over constitutive was confirmed, the effectiveness of one gene changing the constitutive phenotype to the inducible seemed to be somewhat low. Quantity per cell of agglutination substances responsible for sexual agglutination increased as the agglutination ability became greater.
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  • 36
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    Archives of microbiology 151 (1989), S. 391-398 
    ISSN: 1432-072X
    Keywords: Saccharomyces cerevisiae ; Exoglucanases ; Purification ; Protein moieties ; Tunicamycin
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    Topics: Biology
    Notes: Abstract Exoglucanase (exo-1,3-β-D-glucan glycohydrolase, EC 3.2.1.56) activity secreted by Saccharomyces cerevisiae into the culture medium was separated by ion exchange chromatography into two glycoprotein isoenzymes which contributed 10% (exoglucanase I) and 90% (exoglucanase II) towards the total activity. Analysis of the “in vitro” deglycosylated products by polyacrylamide gel electrophoresis under native or denaturing conditions indicated that the protein portions of both exoglucanases exhibited identical mobility, each one consisting of two polypeptides with M r of 47000 and 48000. The same profile was shown by the exoglucanase secreted in the presence of tunicamycin. Antibodies raised against the protein portion of exoglucanase II did react with both native exoglucanases and their deglycosylated products with a pattern indicative of immunological identity. Digestion of the “in vitro” deglycosylated products of both exoglucanases with Staphylococcus aureus V-8 protease or trypsin generated the same proteolytic fragments in each case. Only exoglucanase II was secreted by protoplasts. These and previously reported results indicate that the protein portions of both isoenzymes may be the product of the same gene (or a family of related genes), and that exoglucanase I is a product of enzyme II, modified by a process occurring beyond the permeability barrier of the cell.
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  • 37
    ISSN: 1432-072X
    Keywords: Saccharomyces cerevisiae ; Recombination ; Tryptophan cluster ; Yeast vectors ; Plasmid copy number
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    Topics: Biology
    Notes: Abstract We describe a convenient method for the in vivo construction of large plasmids that possess a multitude of restriction sites. A large (23 kbases) circular self-replicating plasmid carrying a partial LEU2-d gene was cotransformed with a circular non-replicating plasmid carrying the entire LEU2 gene. In vivo recombination results preferentially in a plasmid that carries both the LEU2-d and the entire LEU2 gene. In addition we also found one plasmid with a tandem LEU2 insertion and one plasmid where the LEU2-d gene was replaced by the entire LEU2 gene.
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  • 38
    ISSN: 1617-4623
    Keywords: Meiosis ; Saccharomyces cerevisiae ; Sporulation ; Inessential genes ; Meiosis
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    Notes: Summary SPR3 is one of at least nine genes which are expressed in sporulating Saccharomyces cerevisiae cells at the time of meiosis I. We show below that strains homozygous for null alleles of SPR3 are capable of normal meiosis and the production of viable ascospores. We have also monitored SPR3 expression in a series of strains that are defective in meiotic development, using an SPR3: lacZ fusion carried on a single copy plasmid. β-Galactosidase activity occurred at wild-type levels in diploid strains homozygous for mutations in spo13, rad50, rad57 and cdc9, but was greatly reduced in strains carrying cdc8 or spo7 defects. We conclude that SPR3 expression is a valid monitor of early meiotic development, even though the gene is inessential for the sporulation process.
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  • 39
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    Molecular genetics and genomics 217 (1989), S. 149-154 
    ISSN: 1617-4623
    Keywords: Saccharomyces cerevisiae ; HOM2 gene ; Aspartic semi-aldehyde ; General control
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    Topics: Biology
    Notes: Summary In Saccharomyces cerevisiae the HOM2 gene encodes aspartic semi-aldehyde dehydrogenase (ASA DH). The synthesis of this enzyme had been shown to be derepressed by growth in the presence of high concentrations of methionine. In the present work we have cloned and sequenced the HOM2 gene and found that the promoter region of this gene bears one copy of the consensus sequence for general control of amino acid synthesis. This prompted us to study the regulation of the expression of the HOM2 gene. We have found that ASA DH is the first reported enzyme of the related threonine and methionine pathway to be regulated by the general control of amino acid synthesis.
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  • 40
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    Molecular genetics and genomics 217 (1989), S. 464-470 
    ISSN: 1617-4623
    Keywords: Nucleosome positioning ; LEU2 gene ; Saccharomyces cerevisiae ; tRNA3 Leu gene ; Chromatin
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    Topics: Biology
    Notes: Summary The chromatin structure of theLEU2 gene and its flanks has been studied by means of nuclease digestion, both with micrococcal nuclease and DNase I. The gene is organized in an array of positioned nucleosomes. Within the promoter region, the nucleosome positioning places the regulatory sequences, putative TATA box and upstream activator sequence outside the nucleosomal cores. The tRNA3 Leu gene possesses a characteristic structure and is protected against nucleases. Most of the 5′ flank is sensitive to DNase I digestion, although no clear hypersensitive sites were found. The chromatin structure is independent of either the transcriptional state of the gene or the chromosomal or episomal location. Finally, in the plasmid pJDB207, which lacks most of the promoter, we have found that the chromatin structure of the coding region is similar to that of the wild-type allele.
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  • 41
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    Molecular genetics and genomics 216 (1989), S. 511-516 
    ISSN: 1617-4623
    Keywords: Nonsense mutation ; Read-through ; Saccharomyces cerevisiae
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    Topics: Biology
    Notes: Summary The yeast invertase structural gene SUC2 has two naturally occurring alleles, the active one and a silent allele called suc2°. Strains carrying suc2° are unable to ferment sucrose and do not show detectable invertase activity. We have isolated suc2° and found an amber codon at position 232 of 532 amino acids. However, transformants carrying suc2° on a multicopy plasmid were able to ferment sucrose and showed detectable invertase activity. Full-length invertase was found in gels stained for active invertase and in immunoblots. Therefore we concluded that the amber codon is occasionally read as an amino acid. The calculated frequency of read-through is about 4% of all translation events.
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  • 42
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    Molecular genetics and genomics 218 (1989), S. 293-301 
    ISSN: 1617-4623
    Keywords: Sporulation ; DNA sequence ; Saccharomyces cerevisiae ; Meiosis ; Chromosome segregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Genetic studies have previously demonstrated that the RED1 gene of Saccharomyces cerevisiae is required for chromosome segregation at the first meiotic division. Northern blot hybridization analysis indicates that the RED1 gene produces two transcripts of 2.75 and 3.2 kilobases. The major 2.75 kb transcript is not present in mitotic cells and is meiotically induced to accumulate maximally just prior to the meiosis I division. The DNA sequence of the RED1 gene was determined and used to predict the amino acid sequence of the encoded gene product. The RED1 protein is 827 amino acids in length and has a molecular weight of 95.5 kilodaltons. There is no significant homology between the RED1 amino acid sequence and other known protein sequences, including those encoded by genes essential for meiosis.
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  • 43
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    Molecular genetics and genomics 215 (1989), S. 401-406 
    ISSN: 1617-4623
    Keywords: Protein secretion ; Saccharomyces cerevisiae ; Invertase ; Endoplasmic reticulum ; Secretion mutants
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    Topics: Biology
    Notes: Summary Intercompartmental transport of secreted proteins in yeast was analysed using invertase mutants. Deletions and insertions at the BamHI (position +787) or the Asp718 (position +1159) sites of the SUC2 gene led to mutant proteins with different behaviour regarding secretion, localization and enzyme activity. The deletion mutants showed accumulation of core glycosylated material in the endoplasmic reticulum (ER) a decrease of secreted protein by 5%–30% and loss of enzyme activity. The secreted material was localized in the culture medium and not — as is normal for invertase-in the cell wall. No delay in transport from the Golgi to the cell surface was observed, indicating that the rate-limiting step for secretion is at the ER-Golgi stage. Two insertion mutants, pIPA and pIPB, retained enzyme activity. Mutant pIPB showed 10% secretion, while 60%–70% secretion was observed for pIPA. While the non-secreted material accumulated in the ER, the secreted material was present in the cell wall. The results suggest that the presence of structures incompatible with secretion leads to ER accumulation of mutated invertase.
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  • 44
    ISSN: 1617-4623
    Keywords: RNA splicing ; Maturase ; Recombinase ; Mitochondria ; Saccharomyces cerevisiae
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    Notes: Summary When the bI4 RNA maturase, encoded by the fourth intron of the mitochondrial cytochrome b gene of Saccharomyces cerevisiae, was expressed in Escherichia coli, formation of intra-chromosomal Lac+ recombinants was stimulated threefold. This “hyper-rec” phenotype was recA as well as recBCD dependent. The most active form of the bI4 maturase stimulated homologous recombination whereas splicing deficient mutants of bI4 maturase were either deficient in or unable to stimulate homologous recombination.
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  • 45
    ISSN: 1617-4623
    Keywords: Nucleotide sequence ; PET gene ; Mitochondrial import ; Saccharomyces cerevisiae
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    Notes: Summary Translation of mitochondrial cytochrome b mRNA in yeast is activated by the product of the nuclear gene CBS1. CBS1 encodes a 27 kDa precursor protein, which is cleaved to a 24 kDa mature protein during the import into isolated mitochondria. The sequences required for mitochondrial import reside in the amino-terminal end of the CBS1 precursor. Deletion of the 76 amino-terminal amino acids renders the protein incompetent for mitochondrial import in vitro and non-functional in vivo. When present on a high copy number plasmid and under the control of a strong yeast promoter, biological function can be restored by this truncated derivative. This observation indicates that the CBS1 protein devoid of mitochondrial targeting sequences can enter mitochondria in vivo, possibly due to a bypass of the mitochondrial import system.
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  • 46
    ISSN: 1617-4623
    Keywords: Mitochondrial introns ; Reverse transcriptase ; Saccharomyces cerevisiae
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    Notes: Summary Some pet- (or mit-) mutations impeding the splicing of one or several intron(s) of the yeast mitochondrial pre-mRNA(s) are suppressed in vivo by the DNA deletion of these introns. We have genetically demonstrated that introns aI1 and/or aI2 of the cytochrome c oxidase subunit 1 gene are necessary for this deletion process. The facts that adjacent introns are simultaneously deleted and that, in the pet- (or mit-) mutants which easily revert by intron deletion, the splicing of the introns they affect is only partially blocked, suggest that the intron encoded proteins aI1 and/or aI2 could intervene by means of their putative reverse transcriptase activity.
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  • 47
    ISSN: 1615-6102
    Keywords: Microtubule neoformation ; Nocodazole ; Protoplasts ; Saccharomyces cerevisiae
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    Notes: Summary By following microtubule neoformation after their complete destruction by nocodazole, we analyzed the pattern of microtubule nucleation in protoplasts ofSaccharomyces cerevisiae. Using immunofluorescence, the drug was shown to induce rapid and complete disassembly of both cytoplasmic and spindle microtubules and to selectively block protoplast nuclear division at a defined stage of the cell cycle. Treated protoplasts placed in a drug-free environment recovered a more abundant microtubular system. The majority of microtubules re-formed at SPBs whereas a minority of free-ended microtubules nucleated in the cytoplasm of the protoplasts without any detectable association with recognizable nucleation sites. Random nucleation of free microtubules might be induced by high amounts of unpolymerized tubulin likely to be present in the protoplasts at the moment of drug release.
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  • 48
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    Molecular genetics and genomics 218 (1989), S. 531-535 
    ISSN: 1617-4623
    Keywords: Origin of replication ; Promoter ; Saccharomyces cerevisiae
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    Notes: Summary In an attempt to devise a new assay for ARS-binding proteins we have inserted the HO ARS between the upstream activation site and the TATA region of the yeast CYC1 promoter. A marked reduction in promoter activity is observed. Inactivation of the HO ARS element by point mutation does not restore promoter activity to its original level, although a modest activation is seen. We have also inserted the HO ARS into the intron of the yeast actin gene; although there is no apparent deleterious effect on transcription, the activity of the ARS is abolished in this new environment.
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  • 49
    ISSN: 1617-4623
    Keywords: Saccharomyces cerevisiae ; Heavy metal resistance ; DNA sequence ; Membrane
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    Notes: Summary A DNA fragment conferring resistance to zinc and cadmium ions in the yeast Saccharomyces cerevisiae was isolated from a library of yeast genomic DNA. Its nucleotide sequence revealed the presence of a single open reading frame (ORF; 1326 bp) having the potential to encode a protein of 442 amino acid residues (molecular mass of 48.3 kDa). A frameshift mutation introduced within the ORF abolished resistance to heavy metal ions, indicating the ORF is required for resistance. Therefore, we termed it the ZRC1 (zinc resistance conferring) gene. The deduced amino acid sequence of the gene product predicts a rather hydrophobic protein with six possible membrane-spanning regions. While multiple copies of the ZRC1 gene enable yeast cells to grow in the presence of 40 mM Zn2+, a level at which wild-type cells cannot survive, the disruption of the chromosomal ZRC1 locus, though not a lethal event, makes cells more sensitive to zinc ions than are wild-type cells.
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  • 50
    ISSN: 1617-4623
    Keywords: Saccharomyces cerevisiae ; a-factor ; Conjugation ; G1 arrest ; ssl mutations
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    Notes: Summary Nine independent mutants which are supersensitive (ssl −) to G1 arrest by the mating hormone a-factor were isolated by screening mutagenized Saccharomyces cerevisiae MATα cells on solid medium for increased growth inhibition with a-factor. These mutants carried lesions in two complementation groups, ssl1 and ssl2. Mutations at the ssl1 locus were mating type specific: MATα ssl1 − cells were supersensitive to α-factor but MATα ssl1 − were not supersensitive to α-factor. In contrast, mutations at the ssl2. locus conferred supersensitivity to the mating hormone of the opposite mating type on both MATα, and MATa cells. The α-cell specific capacity to inactivate externally added a-factor was shown to be lacking in MATα ssl1 − mutants whereas MATα ssl2. cells were able to inactivate a-factor. Complementation analysis showed that ssl2 and sst2, a mutation originally isolated as conferring supersensitivity to α-factor to MATa cells, are lesions in the same gene. The ssl1 gene was mapped 30.5 centi-Morgans distal to ilv5 on chromosome XII.
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  • 51
    ISSN: 1617-4623
    Keywords: Aspergillus oryzae ; Alkaline protease ; Prepro sequence ; Heterologous expression ; Saccharomyces cerevisiae
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    Notes: Summary We have cloned and determined the nucleotide sequence of a cDNA fragment for the entire coding region of the alkaline protease (Alp) from a filamentous ascomycete Aspergillus oryzae. According to the deduced amino acid sequence, Alp has a putative prepro region of 121 amino acids preceding the mature region, which consists of 282 amino acids. A consensus sequence of a signal peptide consiting of 21 amino acids is found at the N-terminus of the prepro region. The primary structure of the mature region shares extensive homology (29%–44%) with those of subtilisin families, and the three residues (Asp 32, His 64 and Ser 221 in subtilisin BPN′) composing the active site are preserved. The entire cDNA, coding for prepro Alp, when introduced into the yeast Saccharomyces cerevisiae, directed the secretion of enzymatically active Alp into the culture medium, with its N-terminus and specific activity identical to native Aspergillus Alp.
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  • 52
    ISSN: 1617-4623
    Keywords: Gene conversion ; Crossing-over ; Mismatch repair ; Saccharomyces cerevisiae ; Psoralens
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    Notes: Summary The induction of gene conversion and mitotic crossing-over by photoaddition of psoralens, 254 nm ultraviolet radiation, and nitrogen mustards was determined in diploid cells homozygous for the pso3-1 mutation and in the corresponding wild type of Saccharomyces cerevisiae. For these different agents, the frequency of non-reciprocal events (conversion) is reduced in the pso3-1 mutant compared to the wild type. In contrast, the frequency of reciprocal events (crossing-over) is increased at a range of doses. These observations, together with the block in induced mutagenesis for both reverse and forward mutations previously reported for the pso3-1 mutant, suggest that the PS03 gene product plays a role in mismatch repair of short patch regions. The block in gene conversion in the pso3 homozygous diploid leads, in the case of nitrogen mustards, to specific repair intermediates which are lethal to the cells.
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  • 53
    ISSN: 1617-4623
    Keywords: Enhanced secretion ; Human lysozyme production ; Protease mutant ; Protein processing ; Saccharomyces cerevisiae
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    Notes: Summary Yeast mutant strains which secrete large amounts of human lysozyme were screened using an agar medium containing bacterial cells. Nine mutants secreted over 10 times more lysozyme than the wild-type parent strain. The mRNA levels for lysozyme in the mutants were not higher than that of the wild-type strain. Three of the mutant strains were deficient in carboxypeptidase Y activity. It was found that the protease deficiency was caused by a deficiency in conversion of proenzyme to mature enzyme in ssl1 mutant cells. The ssl1 gene was found to be closely linked to the centromere and determine both the efficiency of secretion of lysozyme and the processing of carboxypeptidase Y.
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  • 54
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    Molecular genetics and genomics 219 (1989), S. 495-498 
    ISSN: 1617-4623
    Keywords: ARS1 ; Plasmid multimerization ; RAD52 ; Saccharomyces cerevisiae ; Eukaryotic recombination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A mutant plasmid, pX, derived from the 1453 base pair small plasmid, YARp1 (or TRP1 RI circle), consists of 849 base pairs of DNA bearing the TRP1 gene and the ARS1 sequence of Saccharomyces cerevisiae and, unlike YARp1 and other commonly used yeast plasmids, highly multimerizes in a S. cerevisiae host. The multimerization of pX was dependent on RAD52, which is known to be necessary for homologous recombination in S. cerevisiae. Based upon this observation, a regulated system of multimerization of pX with GAL1 promoter-driven RAD52 has been developed. We conclude that the regulated multimerization of pX could provide a useful model system to study genetic recombination in the eukaryotic cell, in particular to investigate recombination intermediates and the effects of various trans-acting mutations on the multimerization and recombination of plasmids.
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  • 55
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    Molecular genetics and genomics 215 (1989), S. 455-462 
    ISSN: 1617-4623
    Keywords: Saccharomyces cerevisiae ; Orotate phosphoribosyl transferase ; Nucleotide sequence ; Transcription ; Regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The URA5 gene of Saccharomyces cerevisiae encodes orotate phosphoribosyl transferase (EC 2.4.2.10; OPRTase) which catalyses the transformation of orotate to OMP in the pyrimidine pathway. We present in this paper the cloning and the sequencing of this gene, the last in the yeast pyrimidine pathway to be cloned. We have deduced the protein sequence of the OPRTase of S. cerevisiae from the DNA sequence and compared it to that of Escherichia coli, Podospora anserina and Dictyostelium discoideum. Some important similarities in the structure of these four proteins have been found. Finally, we have quantified the transcription of the URA5 gene in different physiological conditions and confirmed that it was not under the control of UTP or any intermediary product of the pathway.
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  • 56
    ISSN: 1617-4623
    Keywords: DNA sequence ; PET gene ; Saccharomyces cerevisiae ; Mitochondrial import ; cytochrome c oxidase
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    Notes: Summary The yeast nuclear SCO1 gene is required for accumulation of the mitochondrially synthesized cytochrome c oxidase subunits I and II (COXI and COXII). We cloned and characterized the SCO1 gene. It codes for a 0.9 kb transcript. DNA sequence analysis predicts a 33 kDa protein. As shown by in vitro transcription and translation experiments in combination with import studies on isolated mitochodria, this protein is matured into a 30 kDa polypeptide which is tightly associated with a mitochondrial membrane. The possible function of the SCO1 gene product in the assembly of cytochrome c oxidase is discussed.
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  • 57
    ISSN: 1617-4623
    Keywords: Saccharomyces cerevisiae ; GLN1 ; Glutamine synthetase ; Regulatory systems ; Transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary TheGLN1 gene ofSaccharomyces cerivisiae was cloned by complementation of agln1 auxotroph. AGLN1-lacZ fusion was constructed to assayGLN1 promoter activity. β-Galactosidase and glutamine synthetase expression in chromosomally integratedGLN1-lacZ fusion strains were co-regulated in response to a shift from glutamine to glutamate as the nitrogen source, purine limitation, and 3-aminotriazole-induced histidine starvation. Regulation ofGLN1 expression by each of the three pathways occurred at the transcriptional level. Increased accumulation ofGLN1 mRNA was observed within 5 min after a shift from glutamine to glutamate as the nitrogen source. After 5 min following glutamine addition to the cells growing with glutamate as nitrogen source. This indicates that theGLN1 message is unstable and has a half-life of approximately 3 min. Deletion analysis indicated that the sequences required forGLN1 expression are located within approximately 350 bp upstream from the transcriptional initiation site.
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  • 58
    ISSN: 1617-4623
    Keywords: Saccharomyces cerevisiae ; DNA repair ; Cross-link ; Transposon mapping ; Nitrogen mustard
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We have isolated yeast gene SNM1 via complementation of sensitivity towards bi- and tri-functional alkylating agents in haploid and diploid yeast DNA repair-deficient snm1-1 mutants. Four independent clones of plasmid DNA containing the SNM1 locus were isolated after transformation with a YEp24-based yeast gene bank. Subcloned SNM1-containing DNA showed (i) complementation of the repair-deficiency phenotype caused by either one of the two different mutant alleles snm1-1 and snm1-2 ts; (ii) complementation in haploid and diploid yeast snm1-1 mutants by either single or multiple copies of the SNM1 locus; and (iii) that the SNM1 gene is at most 2.4 kb in size. Expression of SNM1 on the smallest subclone, however, was under the control of the GAL1 promotor. Gene size and direction of transcription was further verified by mutagenesis of SNM1 by Tn10-LUK transposon insertion. Five plasmids containing Tn10-LUK insertions at different sites of the SNM1-containing DNA were able to disrupt function of genomic SNM1 after gene transplacement. Correct integration of the disrupted SNM1::Tn10-LUK at the genomic site of SNM1 was verified via tetrad analysis of the sporulated diploid obtained after mating of the SNM1::Tn10-LUK transformant to a haploid strain containing the URA3 SNM1 wild-type alleles. The size of the poly(A)+ RNA transcript of the SNM1 gene is 1.1 kb as determined by Northern analysis.
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  • 59
    ISSN: 1617-4623
    Keywords: pso4-1 mutation ; Saccharomyces cerevisiae ; Error-prone recombinational repair ; Mitotic recombination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The induction of mitotic gene conversion and crossing-over inSaccharomyces cerevisiae diploid cells homozygous for thepso4-1 mutation was examined in comparison to the corresponding wild-type strain. Thepso4-1 mutant strain was found to be completely blocked in mitotic recombination induced by photoaddition of mono- and bifunctional psoralen derivatives as well as by mono- (HN1) and bifunctional (HN2) nitrogen mustards or 254 nm UV radiation in both stationary and exponential phases of growth. Concerning the lethal effect, diploids homozygous for thepso4-1 mutation are more sensitive to all agents tested in any growth phase. However, this effect is more pronounced in the G2 phase of the cell cycle. These results imply that the ploidy effect and the resistance of budding cells are under the control of thePSO4 gene. On the other hand, thepso4-1 mutant is mutationally defective for all agents used. Therefore, thepso4-1 mutant has a generalized block in both recombination and mutation ability. This indicates that thePSO4 gene is involved in an error-prone repair pathway which relies on a recombinational mechanism, strongly suggesting an analogy between thepso4-1 mutation and theRecA orLexA mutation ofEscherichia coli.
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  • 60
    ISSN: 1617-4623
    Keywords: GC clusters ; Mobile elements ; Target sites ; mtDNA ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary GC clusters constitute the major repetitive elements in the mitochondrial (mt) genome of the yeast Saccharomyces cerevisiae. Many of these clusters are optional and thus contribute much to the polymorphism of yeast mtDNAs. We have made a systematic search for polymorphic sites by comparing mtDNA sequences of various yeast strains. Most of the 26 di- or polymorphic sites found differ by the presence or absence of a GC cluster of the majority class, here referred to as the M class, which terminate with an AGGAG motif. Comparison of sequences with and without the GC clusters reveal that elements of the subclasses M1 and M2 are inserted 3′ to a TAG, flanked by A+T rich sequences. M3 elements, in contrast, only occur in tandem arrays of two to four GC clusters; they are consistently inserted 3′ to the AGGAG terminal sequence of a preexisting cluster. The TAG or the terminal AGGAG, therefore, are regarded as being part of the target sites for M1 and M2 or M3 elements, respectively. The dinucleotide AG is in common to both target sites; it also occurs at the 3′ terminus (AGGAG). This suggests its duplication during GC cluster insertion. This notion is supported by the observation that GC clusters of the minor classes G and V similarily repeat at their 3′ terminus a GT or an AA dinucleotide, respectively, from their putative target sites.
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  • 61
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    Molecular genetics and genomics 218 (1989), S. 57-63 
    ISSN: 1617-4623
    Keywords: Saccharomyces cerevisiae ; PET gene ; Transcriptional regulation ; Anaerobiosis ; 5′ mapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Translation of mitochondrial cytochrome b RNA in yeast requires the product of the nuclear gene CBS1, a 27.5 kDa soluble mitochondrial protein. In this paper we show that the CBS1 gene is located on chromosome IV immediately adjacent to COX9, the gene coding for cytochrome c oxidase subunit VIIa. CBS1 is transcribed as a very low abundant 900 b RNA. Transcription starts at a single position 101 bp upstream of the CBS1 initiation codon. At positions-39 to-27 of its leader sequence it contains a small open reading frame of 4 codons. By monitoring the β-galactosidase activity of a CBS1/lacZ fusion construct we show that expression of CBS1 is subjected to regulation by oxygen and by glucose: the β-galactosidase activity is elevated threefold in glycerol or galactose grown cells compared to that in glucose grown cells. A further threefold reduction of the activity is observed in anaerobically grown cells. In accordance with this result is the observation that the steady-state level of CBS1 mRNA of anaerobically grown cells is ninefold lower than that of aerobically cultured cells.
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  • 62
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    Hydrobiologia 188-189 (1989), S. 149-153 
    ISSN: 1573-5117
    Keywords: bacterial assays ; toxicity assessment ; microtox test ; oxygen consumption assay ; glucose mineralization assay ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Three differing bacterial toxicity assays were compared: the ‘Microtox’ test, (Photobacterium phosphoreum luminescence inhibition assay), the ‘oxygen consumption of activated sludge’ assay (ISO 8192), and the ‘Glucose U-14C mineralization’ assay (the rate of release of 14CO2 by ‘Escherichia coli’ ). Metals, amines, halogenated alcans, chlorophenols, aromatic hydrocarbons, surfactants, and pesticides were screened for their toxic activity. Results showed satisfactory repeatability of the three bacterial assays with variation coefficients between 5 and 32%. The ‘Microtox’ assay was the most sensitive test evaluated under our conditions. The lower sensitivity of the ‘oxygen consumption’ assay may have been due to high concentrations of substrates which modify toxicant bioavailability, and also to a high biomass/toxic substances ratio. The ‘Glucose U-14C mineralization’ assay was selective, and low in sensitivity; but the specific species used in this test — Escherichia coli — may have been responsible for this selectivity. The ‘Microtox’ test appears to be well adapted to the detection of aquatic environmental pollution, and to the toxicity screening of complex solid waste effluents and/or leachates. The ‘oxygen consumption’ assay can be advantageously used to measure the impact of sewage on activated sludge in biological treatment plants. The ‘Glucose U-14C mineralization’ assay, which does not require high biomass, can be useful for in situ studies using field microorganisms.
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  • 63
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    Hydrobiologia 176-177 (1989), S. 491-495 
    ISSN: 1573-5117
    Keywords: metal uptake ; dialysis with receiving resins ; bioavailability ; urban stormwaters
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    Topics: Biology
    Notes: Abstract Bioavailable metal uptake rates have been determined in urban stormwater by dialysis with receiving resins. Values at outfalls reflect the sporadic and variable nature of discharges of bioavailable metals with stormwater. Variations in the uptake rates may be explained in terms of hydrochemical processes affecting bioavailable metal mobilisation and transport in the stormwater system, including rainfall volume, rainfall acidity and gullypot interstitial water mobilisation.
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  • 64
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    Hydrobiologia 188-189 (1989), S. 487-496 
    ISSN: 1573-5117
    Keywords: heavy metals ; sediment ; speciation ; bioavailability ; tubificid worms
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    Topics: Biology
    Notes: Abstract The bioavailability of heavy metals in sediment to freshwater tubificid worms was compared with measures of chemical extractability using a sequential extraction procedure. In order to provide a range of test sediments of different quality, various mineral phases were prepared, in which the metals were spiked by adsorption or coprecipitation and these were then mixed with a bulk base sediment in known proportions. Results indicated good correlation between worm metal burden and metal mobilised from the sediments in the first (‘exchangeable’) sequential extraction step for Cd, Cu and Pb. Of the other metals tested, Zn levels in the worms were found to be constant, suggesting regulation, and Ni uptake was too small for accurate measurement. In general, metals spiked to the sediment directly, or adsorbed on the clay mineral phase were found to be much more available than those bound to sewage sludge, carbonate or hydrous ferric oxide phases.
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  • 65
    ISSN: 1573-5117
    Keywords: bioavailability ; bioaccumulation ; hydrophobicity ; fish ; chlorobenzenes
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    Topics: Biology
    Notes: Abstract In this study the uptake by guppies (Poecilia reticulata) of 1,2,3-trichlorobenzene (TCB) and hexachlorobenzene (HCB) from sediment-free water was compared with uptake in the presence of suspended sediment. The results show that the influence of suspended sediment on the uptake of chlorobenzenes varies with test compound. For TCB uptake was not influenced by the presence of suspended sediment. This is probably due to the large amount of the chemical which is dissolved relative to the amount which is present in the sorbed state. For the more hydrophobic HCB, the concentration found in the fish from the system with suspended sediment was significantly higher than in fish from the control experiment.
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  • 66
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    Journal of bioenergetics and biomembranes 21 (1989), S. 589-603 
    ISSN: 1573-6881
    Keywords: Vacuolar membrane H+ATPase ; vacuoles ; Saccharomyces cerevisiae ; catalytic cooperativity of ATP hydrolysis ; VMA genes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Our current work on a vacuolar membrane proton ATPase in the yeastSaccharomyces cerevisiae has revealed that it is a third type of H+-translocating ATPase in the organism. A three-subunit ATPase, which has been purified to near homogeneity from vacuolar membrane vesicles, shares with the native, membrane-bound enzyme common enzymological properties of substrate specificities and inhibitor sensitivities and are clearly distinct from two established types of proton ATPase, the mitochondrial F0F1-type ATP synthase and the plasma membrane E1E2-type H+-ATPase. The vacuolar membrane H+-ATPase is composed of three major subunits, subunita (M r =67 kDa),b (57kDa), andc (20 kDa). Subunita is the catalytic site and subunitc functions as a channel for proton translocation in the enzyme complex. The function of subunitb has not yet been identified. The functional molecular masses of the H+-ATPase under two kinetic conditions have been determined to be 0.9–1.1×105 daltons for single-cycle hydrolysis of ATP and 4.1–5.3×105 daltons for multicycle hydrolysis of ATP, respectively.N,N′-Dicyclohexylcarbodiimide does not inhibit the former reaction but strongly inhibits the latter reaction. The kinetics of single-cycle hydrolysis of ATP indicates the formation of an enzyme-ATP complex and subsequent hydrolysis of the bound ATP to ADP and Pi at a 7-chloro-4-nitrobenzo-2-oxa-1,3-diazolesensitive catalytic site. Cloning of structural genes for the three subunits of the H+-ATPase (VMA1, VMA2, andVMA3) and their nucleotide sequence determination have been accomplished, which provide greater advantages for molecular biological studies on the structure-function relationship and biogenesis of the enzyme complex. Bioenergetic aspects of the vacuole as a main, acidic compartment ensuring ionic homeostasis in the cytosol have been described.
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    Journal of bioenergetics and biomembranes 21 (1989), S. 621-632 
    ISSN: 1573-6881
    Keywords: ATPase ; [H+]-ATPase ; proton transport ; Neurospora crassa ; Saccharomyces cerevisiae ; Schizosaccharomyces pombe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract The fungal plasma membrane contains a proton-translocating ATPase that is closely related, both structurally and functionally, to the [Na+, K+]-, [H+, K+]-, and [Ca2+]-ATPases of animal cells, the plasma-membrane [H+]-ATPase of higher plants, and several bacterial cation-transporting ATPases. This review summarizes currently available information on the molecular genetics, protein structure, and reaction cycle of the fungal enzyme. Recent efforts to dissect structure-function relationships are also discussed.
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  • 68
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    Plant foods for human nutrition 39 (1989), S. 3-11 
    ISSN: 1573-9104
    Keywords: protein quality ; amino acids ; digestibility ; bioavailability ; rats ; in vitro enzyme assays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The USDA's collaborative study of methods of protein quality evaluation is introduced. It was intended primarily to provide a basis for the evaluation of possibly improved procedures for the labelling of foods as a source of dietary protein. In general, the usefulness of in vitro digestibility procedures has been confirmed, but problems remained for the in vitro evaluation of heat-damaged materials and of some types of pinto beans.
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  • 69
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    Plant foods for human nutrition 39 (1989), S. 85-91 
    ISSN: 1573-9104
    Keywords: protein quality ; amino acids ; rats ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Tryptophan bioavailabilities were estimated in 16 protein sources using 10 day rat growth assays with casein as the reference protein. Growth responses of rats fed test food diets were compared to growth responses of rats fed basal diets with graded levels of tryptophan ranging from 50 to 100 mg of tryptophan/100 g diet. Estimates of tryptophan availabilities were 85–100% for all products except whole wheat cereal (73%) and pinto beans (59%). Results of a previous study on lysine availability indicated that poor response to pinto beans was due either to poor digestibility or to the presence of some unidentified growth inhibitor.
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  • 70
    ISSN: 1573-904X
    Keywords: mean residence time ; moment analysis ; Michaelis–Menten elimination ; compartmental models ; bioavailability ; mean absorption time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Equations describing the mean residence time (MRT) of drugs in the body are derived for drugs that are administered by first-and zero-order rates into systems with Michaelis–Menten elimination. With computer simulations, the validity of these equations, the differences between them, and the conventional approach using the AUMC/AUC or the summation of mean times are demonstrated by examining calculations of the percentage of the administered dose eliminated at the MRT and AUMC/AUC. The effects of the absorption rate on the AUC and on the approximate and true MRT values in a nonlinear pharmacokinetic system are also illustrated with computer simulations. It was previously found that the true MRTiv = V ss · AUCiv/dose for an iv bolus. The total MRT (sum of input and disposition) of a drug after noninstantaneous administration was found to be a function of the MRTiv, two values of AUC (iv and non-iv), and exactly how the drug is administered expressed as the mean absorption time (MAT). In addition, a theoretical basis is proposed for calculation of the bioavailability of drugs in both linear and nonlinear pharmacokinetic systems.
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  • 71
    ISSN: 1573-904X
    Keywords: bioavailability ; scintigraphy ; gastrointestinal transit ; controlled release ; phenylpropanolamine ; hydroxypropylmethylcellulose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two controlled-release hydroxypropylmethylcellulose (HPMC) matrix formulations, a single-unit and a multiple-unit system, have been evaluated in human volunteers. Both formulations contained the sympathomimetic drug phenylpropanolamine hydrochloride and each was radiolabeled with 111Inbound Amberlite IR 120 ion-exchange resin. The formulations were administered to each of six healthy male volunteers and gastrointestinal (GI) transit was monitored using a gamma camera. Serum samples were taken at set time intervals and assayed for phenylpropanolamine content, thus allowing blood drug levels to be correlated with the position of the dosage form in the GI tract. The multiple-unit system emptied from the stomach gradually over a period of about 180 min, when administered after a light breakfast, whereas the single-unit dosage forms had extremely variable gastric emptying times (range, 60 to 〉570 min). However, both formulations provided prolonged phenylpropanolamine blood levels. The differences in the blood profiles obtained with the two formulations were attributed to variations in their in vitro release rates and not to any differences in their GI transit times.
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  • 72
    ISSN: 1573-904X
    Keywords: insulin ; collagen ; injection ; subcutaneous injection ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present study was undertaken to develop an agent that stabilizes insulin injected subcutaneously. 125I-Porcine insulin with 0.2 U/kg unlabeled porcine insulin was subcutaneously injected with or without collagen in the rat under the depilated skin of the back. At various times, the radioactivity in subcutaneous tissue was assayed for insulin and its metabolites by gel filtration. The degradation and absorption rate constants of insulin at the subcutaneous injection site were estimated according to a one-compartment model. The degradation rate constant of insulin in the presence of collagen at the injection site was less than half of the control rate. The inhibition was confirmed by increases in the immunoreactive insulin plasma levels and the hypoglycemic effect in rats and healthy volunteers. We postulate that collagen prevents insulin from being degraded by inhibiting proteolytic enzymes, mainly collagenase-like peptidase, in subcutaneous tissue.
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  • 73
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    Pharmaceutical research 6 (1989), S. 817-821 
    ISSN: 1573-904X
    Keywords: bioavailability evaluation ; absorption ; intraindividual variability ; bioavailability ; intraperitoneal ; lithium pharmacokinetics in rats
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A method for determination of absorption rate and bioavailability was developed to reduce the influence of intraindividual variability and applied to the absolute intraperitoneal availability of lithium in the rat. In this method the test and the reference doses are given with a few hours' interval, and the resulting concentration–time data are analyzed by nonlinear regression. The bioavailability estimation by this approach was compared to that of the traditional method, with test and reference doses given on separate days. The mean estimates of availability were 1.035 ± 0.109 (N = 7) and 0.984 ± 0.052 (N = 11) for the traditional and the alternative method, respectively. Thus, the precision was better in the latter. Major influences of dose- or time-dependent kinetics of lithium on the availability estimates were excluded by the design used. The estimation of bioavailability was robust with respect to the choice of absorption and disposition model and the duration of sampling. The plasma clearance of lithium was 169 ± 15 ml/hr/kg, with a terminal half-life of 5.0 ± 0.5 hr (N = 5).
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  • 74
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    Applied physics 45 (1988), S. 279-284 
    ISSN: 1432-0649
    Keywords: 07.65 ; 33 ; 42.55 ; 82.50
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    Topics: Physics
    Notes: Abstract The photophysical properties such as singlet absorption and fluorescence spectra, the fluorescence quantum yield and fluorescence decay time as well as the laser performance data such as the tuning range, the conversion efficiency, and the photochemical stability of 12 sterically hinderedp-quaterphenyls have been measured in ethanol and/or dioxane at room temperature. The sterically hinderedp-quaterphenyls exhibit shorter laser dye emissions in the 330–380 nm range than the parent compoundp-quaterphenyl. The conversion efficiencies of the sterically hinderedp-quaterphenyls range between 1 and 21%. The photochemical stability of the sterically hinderedp-quaterphenyls is by a factor of 10 to 20 better in dioxane than in ethanol. 2-Methyl-5-tert. butyl-p-quaterphenyl and 2,5,2‴,5‴-tetramethyl-p-quaterphenyl are among the most stable UV laser dyes known today.
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    Applied physics 47 (1988), S. 149-157 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60 ; 42.80
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    Topics: Physics
    Notes: Abstract We report the successful operation of a novel automatic impedance matching technique (AIMing) and observations of the opto-Hertzian effect. The AIMing system is capable of maintaining efficient RF power delivery to a CO2 waveguide laser over a wide range of operating conditions. The opto-Hertzian signal, produced by circulating laser power fluctuations and detected in the RF reflected power, has some interesting properties and may be used for laser frequency stabilisation.
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    Applied physics 46 (1988), S. 139-140 
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.55
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    Topics: Physics
    Notes: Abstract Pulses of 170 fs duration have been obtained by compression of 220–250 fs pulses of a hybrid excimer-dye laser setup.
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    Applied physics 46 (1988), S. 43-60 
    ISSN: 1432-0649
    Keywords: 42.55
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    Topics: Physics
    Notes: Abstract The passive and hybrid Q-switching and mode-locking of solid-state lasers, dye lasers, semiconductor lasers and gas lasers is reviewed. The dynamics of saturable absorbers and reverse saturable absorbers is illustrated. The nanosecond pulse generation by passive and hybrid Q-switching of low-gain active media is described. The picosecond and femtosecond pulse generation by passive and hybrid mode-locking in low-gain and high-gain active media is analysed. The performance data of passively and hybridly mode-locked cw femtosecond dye lasers are collected. The pulse shortening of ultra-fast pulses with saturable absorbers in intra-cavity and extra-cavity configurations is discussed.
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    Applied physics 45 (1988), S. 191-195 
    ISSN: 1432-0649
    Keywords: 42.65 ; 42.55
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    Topics: Physics
    Notes: Abstract A device exhibiting a power-dependent reflection coefficient with fast time response and no frequency shift is proposed and analysed. It utilizes a combination of a nonlinear crystal for second harmonic generation and a dichroic mirror with high reflectivity for the second harmonic and partial transmission for the fundamental wavelenth. This device has been successfully used in a preliminary experiment to modelock a Nd:YAG laser.
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    Applied physics 47 (1988), S. 101-105 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60 ; 42.65
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    Topics: Physics
    Notes: Abstract An XeCl laser beam has been used to investigate stimulated Raman scattering in H2 and in various H2-foreign gas mixtures. Helium, neon, argon, and nitrogen have been tested as foreign gases. In all the investigated mixtures with 50% of H2, the energy conversion efficiency to the first Stokes (353 nm) was more than 70% higher than that obtained in H2 at the same total pressure (40 bar) and pump energy (60 mJ). The dependence of the energy conversion efficiency on pump beam divergence has also been investigated.
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  • 80
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Site specific recombination ; 2 μ DNA plasmid
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    Topics: Biology
    Notes: Summary The purpose of this work is to identify and quantitate in vivo 2 μ plasmid FLP-independent recombination in yeast, using a nonselective assay system for rapid detection of phenotypic expression of the recombination events. A tester plasmid was constructed such that in vivo recombination between 2 μ direct repeat sequences produces the resolution of the plasmid into two circular DNA molecules. This recombinational event is detected as a phenotypic shift from red to white colonies, due to the mitotic loss of the plasmid portion containing the yeast ADE8 gene in a recipient ade1 ade2 ade8 genetic background. In the absence of the 2 μ FLP recombinase and/or its target DNA sequence, recombination is not abolished but rather continues at a high frequency of about 17%. This suggests that the FLP-independent events are mediated by the chromosomally-encoded general homologous recombination system. We therefore conclude that the totality of 2 μ DNA recombination events occurring in FLP+ cells is the contribution of both FLP-mediated and FLP-independent events.
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  • 81
    ISSN: 1432-0983
    Keywords: Schizosaccharomyces pombe ; Saccharomyces cerevisiae ; Argininosuccinate lyase ; Gene cloning
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    Topics: Biology
    Notes: Summary A gene bank of Sau3A partially restricted Schizosaccharomyces pombe DNA in YEp13 was used to transform an arg4 mutant of Saccharomyces cerevisiae. One colony was recovered which contained the YEp13 plasmid bearing a large insert complementing the argininosuccinate lyase (ASL) mutation. As shown by restriction mapping and subcloning experiments, the DNA sequence required for complementation is localized on a 2 kb BamHI-BamHI fragment. The plasmid complemented several S. cerevisiae arg4 mutants of independent origin and a S. pombe arg7 mutant lacking ASL. Low but significant ASL activities were detected in crude extracts of these transformants. No complementation of the E. coli argH mutant was observed. Southern blot hybridizations showed that the insert originates from the S. pombe genome. No cross-hybridization was found between this sequence and S. cerevisiae DNA. It can be concluded that the cloned DNA fragment bears the S. pombe ARG7 gene coding for ASL.
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    Current genetics 14 (1988), S. 413-418 
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Chromosome length polymorphisms ; FIGE ; OFAGE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Although Saccharomyces cerevisiae strains generally have similar chromosomal band patterns as revealed by pulsed field gel electrophoresis, individual bands often move slightly differently from one strain to the other. Surveying strains from our stock collection, we found that nearly all the bands of a certain pair of strains differed in their mobility. Some of these chromosome length polymorphisms segregated in a 2:2 ratio, indicating that they resulted from single structural alterations (i.e. additions or deletions). One of these was mapped on the right arm of chromosome 1. Others did not segrate in a simple 2:2 ratio. That is, there were progenies which had bands not present in either parent. We suggest that these new bands are the products of recombination between homologous chromosomes having two or more structural alterations.
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  • 83
    ISSN: 1432-0983
    Keywords: ARS ; Saccharomyces cerevisiae ; Schizosaccharomyces pombe ; Tetrahymena thermophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We have isolated several Tetrahymena thermophila chromosomal DNA fragments which function as autonomously replicating sequences (ARS) in the heterologous Saccharomyces cerevisiae and Schizosaccharomyces pombe selection systems. The Tetrahymena ARS sequences were first isolated in S. cerevisiae and were derived from non-ribosomal micro- and macronuclear DNA. Sequence analysis of the ARS elements identified either perfect or close matches with the 11 by S. cerevisiae ARS core consensus sequence. Subcloning studies of two Tetrahymena ARS elements defined functional regions ranging in size from 50 to 300 bp. Testing of the ARS elements in S. pombe revealed that most of the T. thermophila inserts confer ARS function in both yeasts, at least in the sense of promoting a high transformation frequency to plasmids which contain them. However, the actual sequences responsible for ARS activity were not always identical in the two yeasts.
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  • 84
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Ribosomal protein genes ; CYH2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A diploid strain of the yeast Saccharomyces cerevisiae has been constructed that has one copy of the ribosomal protein gene CYH2 completely deleted and replaced with the TRP1 gene using the method of Rothstein (1983). There are only small differences in growth rate and no detectable difference in steady state level of CYH2 mRNA between the diploid that is heterozygous for the CYH2 deletion and the parent diploid with two normal copies of this gene. This suggests that the diploid must partially compensate for the loss of one CYH2 gene. Tetrad dissection shows that haploid spores lacking the CYH2 gene cannot germinate. The lethality of this deletion can be rescued by a CYH2 cDNA on a low copy vector. Haploids which lack the genomic copy of the CYH2 gene, but contain a plasmid copy of the CYH2 cDNA are able to grow normally. These CYH2 deleted yeast haploids should be useful to analyze mutationally altered CYH2 genes and genes homologous to CYH2 from other organisms without interference from a genomic copy.
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  • 85
    ISSN: 1432-0983
    Keywords: Yeast ; Gene regulation ; Saccharomyces cerevisiae ; PDCI promoter
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    Topics: Biology
    Notes: Summary A 870 by promoter fragment of the PDC1 gene that includes the carbon source dependent regulatory regions was investigated using 5′ and 3′ promoter deletions. The results indicate that glucose and ethanol regulation of PDC1 transcription are independently controlled by distinct cis-acting regions. The consensus sequence AAATCGATA may play a role in this regulation, while the sequence (ATCA)AACCT may be important in transcription initiation.
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  • 86
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    Current genetics 13 (1988), S. 21-23 
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Transformation ; Plasmid ; Colony ; Polyethylene glycol
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    Topics: Biology
    Notes: Summary A rapid and simple yeast transformation procedure has been developed using colonies on agar plates. Saccharomyces cerevisiae SHY3 cells were picked up from colonies on YPD plates grown freshly or stored at 4 °C and incubated with M13RK9-T DNA at 30 °C for 1–2 h in a solution of Li+, Ca2+, Mg2+, triacetin and polyethylene glycol. About 3,500 transformants were obtained per µg of double stranded M13RK9-T DNA. Unlike the existing spheroplast techniques, single stranded M13RK9-T DNA transformed intact cells below one-hundredth frequency of the duplex form.
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  • 87
    ISSN: 1432-0983
    Keywords: Aspergillus terreus clonotheque ; Saccharomyces cerevisiae ; Homologous integration ; 2 μ circledirected chromosome destabilization
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    Topics: Biology
    Notes: Summary A genome clonotheque consisting of 25- to 40-kb Sau3A1 fragments of Aspergillus terreus DNA was constructed in the episomal cosmid vector pES33 containing the yeastARG4 gene. From the 475 transformants of cir° yeast strain ESH-0, 23 stable Arg + transformants were independently selected. Genetic and Southern analysis of these stable transformants showed that 39% arose as a result of recombination between cloned A. terreus DNA sequences and yeast chromosome XII. The recombination events most likely occurred in the regions of homology within the rDNA clusters of A. terreus and Saccharomyces cerevisiae.
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  • 88
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    Current genetics 13 (1988), S. 283-289 
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Inducible antisense gene ; Acetolactate synthase ; Bradytrophic phenocopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We report for the first time on the regulation of gene expression in yeast by antisense RNA. Chimaeric genes were constructed containing the 5′ upstream and partial coding sequence of SMR1 — a sulfometuron methyl resistant allele of the ILV2 locus. Such fragments were placed 5′ to 3′ and 3′ to 5′ under control of the GAL10 promoter and CYCl terminator in a high copy YEp plasmid. Following galactose induction only transformants containing antisense RNA genes showed biological activity against SMR1 gene expression. Antisense RNA inhibited synthesis of the SMR1 gene product acetolactate synthase and thus repressed cellular growth which resulted in a bradytrophic auxotroph revertable by addition of isoleucine and valine. Antisense RNA inhibition was enhanced in galactose medium containing sulfometuron methyl and in gcn4 cells deficient for positive regulation of the ILV2 locus. This system can be used to study factors that interfere with antisense RNA function and to assign biological function to randomly cloned DNA fragments.
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  • 89
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    Current genetics 14 (1988), S. 331-335 
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Meiosis ; Deletion mutations ; Sequence dissimilarities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A diploid yeast strain with extensive sequence dissimilarity in homologous regions near the LYS2 locus was sporulated, and spontaneous lys2 and lys5 mutant spores, selected on α-amino adipate, were analyzed. As many as 50% of the mutant spores contained a deletion in LYS2. These deletions occurred at a frequency of 5.0 × 10−7. While deletions of various sizes and endpoints were obtained, all the deletions recovered in this study included the border between homologous and non-homologous sequences located 4 kb upstream of LYS2. Large lys2 deletions that extended into an adjacent CYH2 duplication occurred at a frequency of 2.0 × 10−7, more than 1,000 times the frequency of the CYH2-LYS2 deletions found in a related haploid strain. This high frequency of CYH2-LYS2 deletions was observed only after sporulation of the diploid strain, and was dependent upon extensive sequence dissimilarity near the LYS2 locus.
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  • 90
    ISSN: 1432-0983
    Keywords: Saccharomyces cerevisiae ; Allosuppressor ; Translation ; Fidelity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Allosuppressor (sal) mutations enhance the efficiency of the yeast ochre suppressor SUQ5 and define five unlinked loci, SALT-SALS. A number of sal4 mutants were isolated and found to have pleiotropic, allele;specific phenotypes, including hypersensitivity in vivo to paromomycin and other antibiotics that stimulate translational errors in yeast. To examine further the nature of the SAL4 gene product, the wild type SAL4 gene was isolated by complementation of a conditional lethal allele sal4-2, and demonstrated to be a single copy gene encoding a single 1.6 kb transcript. Restriction mapping and DNA hybridisation analysis were used to demonstrate that the SAL4 gene is identical to the previously identified omnipotent suppressor gene SUP45 (SUPT). Our results implicate the SAL4 gene product as playing a major role in maintaining translational accuracy in yeast.
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  • 91
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    European journal of clinical pharmacology 34 (1988), S. 77-82 
    ISSN: 1432-1041
    Keywords: N-acetylcysteine ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of N-acetylcysteine (NAC) have been determined after its intravenous and oral administration to 6 healthy volunteers. According to a randomized cross-over design each subject received NAC 200 mg i.v. and 400 mg p.o., and blood samples were collected for 30 h. Reduced NAC had a volume of distribution (VSS) of 0.59 l·kg−1 and a plasma clearance of 0.84 l·h−1·kg−1. The terminal half-life after intravenous administration was 1.95 h. The oral bioavailability was 4.0%. Based on total NAC concentration, its volume of distribution (VSS) was 0.47 l·kg−1 and its plasma clearance was 0.11 l·h−1·kg−1. The terminal half-life was 5.58 h after intravenous administration and 6.25 h after oral administration. Oral bioavailability of total NAC was 9.1%.
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  • 92
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    European journal of clinical pharmacology 34 (1988), S. 315-317 
    ISSN: 1432-1041
    Keywords: albendazole ; echinococcosis ; bioavailability ; food intake ; fatty meal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the systemic availability of oral albendazole in 6 patients with echinococcosis either fasting or with breakfast. Albendazole sulphoxide, the pharmacologically active principle, was assayed by HPLC. Mean plasma concentrations and AUCs were 4.5 times higher when albendazole was given with breakfast than when administered in the fasting state. We conclude that therapy of echinococcosis with albendazole requires the drug to be taken with meals and that administration on an empty stomach might be more appropriate when intraluminal effects are desired, e.g. for intestinal parasites.
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  • 93
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    European journal of clinical pharmacology 34 (1988), S. 469-473 
    ISSN: 1432-1041
    Keywords: xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of xamoterol, a β-adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design. After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml·min−1 and the volume of distribution at steady-state (Vss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose. Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation.
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  • 94
    ISSN: 1432-0983
    Keywords: Formaldehyde ; DNA-protein cross-links ; Repair ; Saccharomyces cerevisiae ; Hyperresistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The formation and removal of formaldehyde-mediated DNA protein cross-linking was measured by CsCI density gradient analysis in yeast strains of differing resistance to formaldehyde. Wild-type cells and transformants made hyperresistant to formaldehyde by a multi-copy vector containing the yeast SFA gene were specifically labeled in their DNA and incubated in the presence of formaldehyde. Treatment with formaldehyde lead to the formation of equal amounts of DNA protein cross-links; subsequent liquid holding of cells for 24 h resulted in the removal of nearly all DNA protein crosslinks regardless of the original formaldehyde resistance status of the strains.
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  • 95
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    European journal of clinical pharmacology 34 (1988), S. 211-212 
    ISSN: 1432-1041
    Keywords: diclofenac ; sulglicotide ; bioavailability ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of diclofenac (D) was assessed in 12 healthy volunteers treated orally with single doses of 100 mg (retard formulation) and subsequently retreated with the same dose of (D) plus sulglicotide (S) 200 mg. (D) blood levels were measured by GLC in samples collected after 1, 2, 4, 6, 8, 12, 24 h. No relevant difference was seen in (D) bioavailability after (S) administration; after 8 h plasma levels of (D) were slightly higher after (S) (p〈0.05), but this difference can be considered incidental only. Thus, sulglicotide does not interfere with the bioavailability of diclofenac, and can be administered concurrently with the latter to prevent possible gastric injury by the antiinflammatory drug.
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  • 96
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    European journal of clinical pharmacology 35 (1988), S. 21-24 
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
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  • 97
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    European journal of clinical pharmacology 35 (1988), S. 69-75 
    ISSN: 1432-1041
    Keywords: L-carnitine ; pharmacokinetics ; intravenous and oral doses ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 and 6 g was studied in 6 healthy subjects on a low-carnitine diet. Carnitine was more rapidly eliminated from plasma after the 6 g dose. Comparing the doses, the t1/2β of the elimination phase (β) was 6.5 h vs 3.9 h, the elimination constant 0.40 vs 0.50 h−1 and the plasma carnitine clearance was 5.4 vs 6.11 · h−1 for the 2 g and 6 g doses, respectively, showing dose-related elimination. Saturable kinetics were not found. The apparent volumes of distribution after the two doses were not significantly different and were of the same order as the total body water. Urinary recoveries of the 2 g and 6 g doses were 70% and 82%, respectively, during the first 24 h. Following the oral doses, there was no significant difference between the areas under the plasma carnitine concentration-time curves. Urinary recovery was 8% and 4% for the 2 g and 6 g doses during the first 24 h. Oral bioavailability was 16% for the 2 g dose and 5% for the 6 g dose. The results suggest that the mucosal absorption of carnitine was already saturated by the 2 g dose.
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  • 98
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    European journal of clinical pharmacology 35 (1988), S. 89-91 
    ISSN: 1432-1041
    Keywords: flecainide acetate ; Wolff-Parkinson-White syndrome ; rectal absorption ; suppository ; micro enema ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The rectal absorption of flecainide from an aqueous solution, a fatty suppository and a polyethyleneglycol suppository was studied in one patient with supraventricular tachycardia (Wolff-Parkinson-White syndrome) refractory for oral anti-arrhythmic treatment. Rectal absorption was found to be fast (t1/2abs=1 h) and complete when flecainide was administered as a solution (relative bioavailability 100%). Flecainide was poorly absorbed from a fatty suppository. The polyethyleneglycol suppository gave absorption with a relative bioavailability of 80% and t1/2 abs=1.2 h.
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  • 99
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    European journal of clinical pharmacology 35 (1988), S. 183-185 
    ISSN: 1432-1041
    Keywords: xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of xamoterol, a β-adrenergic partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 8 cardiac failure patients (NYHA Class II) of mean age 62 years. After i.v. dosing, the elimination half-life was 7.4±0.4 h, the total body clearance was 228±30 ml·min−1 and the volume of distribution at steady-state was 56±91. 72.5±4.3% of the dose was recovered unchanged in urine. After the oral dose, the absolute bioavailability of xamoterol was shown to be 5.9%. Peak plasma concentrations occurred 1 to 2.5 h after the oral dose. The apparent elimination half-life was significantly longer after oral doses (16±2 h) compared to that observed after an intravenous dose. Renal clearance of xamoterol exceeded glomerular filtration rate as measured by creatinine clearance. The pharmacokinetics of xamoterol in cardiac failure patients with good renal function (creatinine clearance 〉90 ml·min−1) were similar to published data in young healthy male volunteers.
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  • 100
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    European journal of clinical pharmacology 35 (1988), S. 423-425 
    ISSN: 1432-1041
    Keywords: ketorolac tromethamine ; non-narcotic analgesic ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketorolac tromethamine, a potent non-narcotic analgesic agent used for relief of moderate to severe pain, has been studied in 15 healthy volunteers who received single 10 mg doses intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.) in a three-way cross-over design. The kinetics of i.v. ketorolac were characterized by a terminal half-life of 5.09 h, a small plasma clearance (CL = 0.35 ml·min−1·kg−1) and a small tissue distribution (Vss=0.111·kg−1, Vβ=0.17 l·kg−1; mean (SD). Following i.m. and p.o. administration, peak levels of approximately 0.8 µg/ml were rapidly attained (tmax = 0.8 and 0.9 h, respectively) and the systemic bioavailability was essentially complete.
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