Prodromal features for Parkinson's disease--baseline data from the TREND study.

BACKGROUND AND PURPOSE: A number of non-motor features are known to precede motor manifestations of Parkinson's disease (PD). They are supposed to already represent the prodromal neurodegenerative state in those who later develop PD and are thus called prodromal markers. In this study, three prodromal markers, depression, rapid eye movement behaviour disorder (RBD) and hyposmia, were selected and were related to other prodromal features in elderly individuals without PD. METHODS: From the Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration (TREND) study, 698 healthy individuals aged 50-80 years reporting one or more of the selected prodromal markers (SPMs), but without neurodegenerative disorders, were evaluated and classified according to the status of prodromal markers. Other prodromal PD-related features were assessed with a 23-item questionnaire and compared between participants with and without the three SPMs. RESULTS: Individuals with the SPMs for PD endorsed more of the additional possible prodromal features of PD than those without; of 23 possible prodromal features, the median number identified amongst participants with no SPMs was two, compared with four with one marker, five with two and seven with three (P < 0.001). Regarding individual SPMs, participants with depression and RBD endorsed five of 23 markers, compared with three for those with hyposmia (P = 0.001). There was no significant increase in the number of prodromal features amongst those with two SPMs compared with those with only one marker. CONCLUSIONS: Individuals with the SPMs for PD report a higher prevalence of other prodromal PD symptoms. This may indicate that these markers can identify individuals at risk for PD.

Aqueous-phase photochemical formation of peroxides in authentic cloud and fog waters.

Gas-to-drop partitioning of hydrogen peroxide and its precursor, the hydroperoxyl radical (HO2.), has been considered the predominant or sole source of hydrogen peroxide in atmospheric water drops. However, atmospheric water can absorb solar ultraviolet radiation, which initiates the photoformation of peroxides (primarily hydrogen peroxide). Measurements of peroxide photoformation rates in authentic atmospheric water samples demonstrate that aqueous-phase photochemical reactions are a significant, and in some cases dominant, source of hydrogen peroxide to cloud and fog drops. This additional source could significantly change the current understanding, and hence, the models, of sulfuric acid deposition because hydrogen peroxide is the limiting reagent in the dominant pathway for the oxidation of sulfur dioxide to sulfuric acid in the troposphere over eastern North America.

The NDP-sugar co-substrate concentration and the enzyme expression level influence the substrate specificity of glycosyltransferases: cloning and characterization of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster.

BACKGROUND: Streptomyces fradiae is the principal producer of urdamycin A. The antibiotic consists of a polyketide-derived aglycone, which is glycosylated with four sugar components, 2x D-olivose (first and last sugar of a C-glycosidically bound trisaccharide chain at the 9-position), and 2x L-rhodinose (in the middle of the trisaccharide chain and at the 12b-position). Limited information is available about both the biosynthesis of D-olivose and L-rhodinose and the influence of the concentration of both sugars on urdamycin biosynthesis. RESULTS: To further investigate urdamycin biosynthesis, a 5.4 kb section of the urdamycin biosynthetic gene cluster was sequenced. Five new open reading frames (ORFs) (urdZ3, urdQ, urdR, urdS, urdT) could be identified each one showing significant homology to deoxysugar biosynthetic genes. We inactivated four of these newly allocated ORFs (urdZ3, urdQ, urdR, urdS) as well as urdZ1, a previously found putative deoxysugar biosynthetic gene. Inactivation of urdZ3, urdQ and urdZ1 prevented the mutant strains from producing L-rhodinose resulting in the accumulation of mainly urdamycinone B. Inactivation of urdR led to the formation of the novel urdamycin M, which carries a C-glycosidically attached D-rhodinose at the 9-position. The novel urdamycins N and O were detected after overexpression of urdGT1c in two different chromosomal urdGT1c deletion mutants. The mutants lacking urdS and urdQ accumulated various known diketopiperazines. CONCLUSIONS: Analysis of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster revealed a widely common biosynthetic pathway leading to D-olivose and L-rhodinose. Several enzymes responsible for specific steps of this pathway could be assigned. The pathway had to be modified compared to earlier suggestions. Two glycosyltransferases normally involved in the C-glycosyltransfer of D-olivose at the 9-position (UrdGT2) and in conversion of 100-2 to urdamycin G (UrdGT1c) show relaxed substrate specificity for their activated deoxysugar co-substrate and their alcohol substrate, respectively. They can transfer activated D-rhodinose (instead of D-olivose) to the 9-position, and attach L-rhodinose to the 4A-position normally occupied by a D-olivose unit, respectively.

Cloning and characterization of a gene cluster from Streptomyces cyanogenus S136 probably involved in landomycin biosynthesis.

From a cosmid library of Streptomyces cyanogenus S136, DNA fragments encompassing approximately 35 kb of the presumed landomycin biosynthetic gene cluster were identified and sequenced, revealing 32 open reading frames most of which could be assigned through data base comparison.

Granular cell tumors of biliary ducts. Report of two cases and review of the literature.

There were two cases of granular cell tumor of the extrahepatic biliary system; to our knowledge, 17 have previously been reported. The initial symptoms most often are those of biliary colic. The majority of the patients are black and female. The cystic duct and the common bile duct are most commonly involved. Additional biliary pathologic disorder is present in more than half of the patients.

Low-cost wavemeter with a solid Fizeau interferometer and fiber-optic input.

A wavemeter suitable for measuring the wavelength of pulsed and continuous laser light has been constructed on the basis of a solid Fizeau interferometer (SFI). An accuracy of 1 part in 10(6) has been demonstrated in a range extending from 563 to 613 nm. The use of the SFI and of a combination of a single-mode optical fiber and an achromatic lens as a beam collimating system substantially simplifies the optical layout and reduces cost. The difficulties connected with the dispersion of the SFI have been overcome by an analytical description of the characteristics of the interferometer and accurate temperature stabilization.

[DNA distribution and mitotic index in Ehrlich ascites tumor after colchicine administration]. / DNA-Verteilung und Mitosehäufigkeit beim Ehrlich-Aszites-Tumor nach Colchicin.

Additional information like the type of growth is efficient for the interpretation of single parameter DNA distribution curves of tumors. The consideration of mitotic indices leads to further insights. The different growth phases of the Ehrlich ascites tumor are characterized by reproducible DNA histograms. The mitotic index and the frequency of the four mitotic phases turn out to be independent of the growth phase. Colchicine exerts an obvious effect on the prophases and metaphases. In the histogram an accumulation of cells in the G2M phase is evident, also on a higher ploidy level. Nearly identical DNA histograms result in different growth phases. The mitotic index of prophases and metaphases is found to be nearly twice at the 11th and 15th day of growth in comparison with the 8th day. This indicates a higher sensitivity of the Ehrlich ascites tumor to colchicine in steady state which is not expressed in the histogram.

S-adenosylhomocysteine-hydrolase from bovine kidney: enzymatic and binding properties.

In the present study S-adenosylhomocysteine (SAH) hydrolase from the bovine kidney has been purified to apparent homogeneity by standard chromatographic procedures. The purified enzyme was free from adenosine deaminase activity and showed a one-banded pattern in SDS-PAGE with a monomer molecular mass of 47,500. The molecular mass of the native enzyme estimated by gel filtration was about 190,000. The pI was 5.5. For hydrolysis of SAH we found a Km of 5.0 +/- 1.2 microM and a V of 0.25 mumol/min/mg. In the direction of synthesis the Km for adenosine was 5.6 microM and V 0.53 mumol/min/mg. The enzyme activity was inhibited in the presence of adenosine with a Ki = 3 microM. In a second set of experiments we determined the binding characteristics of [3H]-adenosine to purified enzyme. The enzyme bound [3H]-adenosine with three apparent affinities: Kd1 = 6.8 +/- 0.7 nM and Bmax1 = 0.24 +/- 0.04 nmol/mg protein; Kd2 = 387 +/- 41 nM and Bmax2 = 1.4 nmol/mg protein, and Kd3 = 7.05 +/- 0.9 microM and Bmax3 = 9 nmol/mg protein. Binding of 25 nM [3H]-adenosine obeyed a monophasic reaction with a k+1 value of 0.025 min/nM. Dissociation of [3H]-adenosine-SAH hydrolase complex was markedly temperature dependent. After a 240-min incubation at 0 degrees C only 5-10% and at 20 degrees C 75% were displaceable. A fraction of 25% bound [3H]-adenosine was not displaceable by unlabeled adenosine. Our data show that the renal SAH hydrolase exhibits similar enzyme kinetics as the well-characterized SAH hydrolase from liver. The amount of SAH hydrolase present in renal tissues (1.4 nmol/g wet weight) could account almost entirely for the binding of renal tissue adenosine. Finally, we report for the first time a high affinity binding site of SAH hydrolase for adenosine, which remains unexplained at present.

Kinetics of the removal of iron pyrite from coal by microbial catalysis.

Different strains of Thiobacillus ferrooxidans and Thiobacillus thiooxidans were used to catalyze the oxidative dissolution of iron pyrite, FeS(2), in nine different coal samples. Kinetic variables and parametric factors that were determined to have a pronounced effect on the rate and extent of oxidative dissolution at a fixed Po(2) were: the bacterial strain, the nitrogen/phosphorus molar ratio, the partial pressure of CO(2), the coal source, and the total reactive surface area of FeS(2). The overall rate of leaching, which exhibited a first-order dependence on the total surface area of FeS(2), was analyzed mathematically in terms of the sum of a biochemical rate, nu(1), and a chemical rate, nu(2). Results of this study show that bacterial desulfurization (90 to 98%) of coal samples which are relatively high in pyritic sulfur can be achieved within a time-frame of 8 to 12 days when pulp densities are

Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae Tü2717.

Urdamycin A, the principal product of Streptomyces fradiae Tu2717, is an angucycline-type antibiotic and anticancer agent containing C-glycosidically linked D-olivose. To extend knowledge of the biosynthesis of urdamycin A the authors have cloned further parts of the urdamycin biosynthetic gene cluster. Three new ORFs (urdK, urdJ and urdO) were identified on a 3.35 kb fragment, and seven new ORFs (urdL, urdM, urdJ2, urdZl, urdGT2, urdG and urdH) on an 8.05 kb fragment. The deduced products of these genes show similarities to transporters (urdJ and urdJ2), regulatory genes (urdK), reductases (urdO), cyclases (urdL) and deoxysugar biosynthetic genes (urdG, urdH and urdZ1). The product of urdM shows striking sequence similarity to oxygenases (N-terminal sequence) as well as reductases (C-terminal sequence), and the deduced amino acid sequence of urdGT2 resembles those of glycosyltransferases. To determine the function of urdM and urdGT2, targeted gene inactivation experiments were performed. The resulting urdM deletion mutant strains accumulated predominantly rabelomycin, indicating that UrdM is involved in oxygenation at position 12b of urdamycin A. A mutant in which urdGT2 had been deleted produced urdamycin I, urdamycin J and urdamycin K instead of urdamycin A. Urdamycins I, J and K are tetracyclic angucyclinones lacking a C-C connected deoxysugar moiety. Therefore UrdGT2 must catalyse the earliest glycosyltransfer step in the urdamycin biosynthetic pathway, the C-glycosyltransfer of one NDP-D-olivose.