191 research outputs found
Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds
AbstractEne-reductases from the âOld Yellow Enzymeâ family of flavoproteins catalyze the asymmetric reduction of various α,ÎČ-unsaturated compounds at the expense of a nicotinamide cofactor. They have been applied to the synthesis of valuable enantiopure products, including chiral building blocks with broad industrial applications, terpenoids, amino acid derivatives and fragrances. The combination of these highly stereoselective biocatalysts with a cofactor recycling system has allowed the development of cost-effective methods for the generation of optically active molecules, which is strengthened by the availability of stereo-complementary enzyme homologues
Controlling the fatty acid hydroxylation regioselectivity of CYP152A1 (P450Bsb) by active site engineering
Regioselective hydroxylation on inactivated C-H bonds is among the dream reactions of organic chemists. Cytochrome P450 enzymes (CYPs) perform this reaction in general with high regio- and stereoselectivity (e.g. for steroids as substrates). Furthermore, enzyme engineering may allow to tune the regioselectivity of the enzyme. Regioselective in-chain hydroxylation of shorter or linear molecules (fatty acids), however, remains challenging even with this enzyme class, due to the high similarity of the substrateâs backbone carbons and their conformational flexibility. CYPs are well described for hydroxylating fatty acids selectively in the chemically more distinct a- or w-position. In contrast, selective in-chain hydroxylation of fatty acids lacks precedence. The peroxygenase CYP152A1 (P450Bsb) is a family member that displays fatty acid hydroxylation at both, the a- and b-position.
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The Locations of Gamma-Ray Bursts Measured by COMPTEL
The COMPTEL instrument on the Compton Gamma Ray Observatory is used to
measure the locations of gamma-ray bursts through direct imaging of MeV
photons. In a comprehensive search, we have detected and localized 29 bursts
observed between 1991 April 19 and 1995 May 31. The average location accuracy
of these events is 1.25\arcdeg (1), including a systematic error of
\sim0.5\arcdeg, which is verified through comparison with Interplanetary
Network (IPN) timing annuli. The combination of COMPTEL and IPN measurements
results in locations for 26 of the bursts with an average ``error box'' area of
only 0.3 deg (1). We find that the angular distribution of
COMPTEL burst locations is consistent with large-scale isotropy and that there
is no statistically significant evidence of small-angle auto-correlations. We
conclude that there is no compelling evidence for burst repetition since no
more than two of the events (or 7% of the 29 bursts) could possibly have
come from the same source. We also find that there is no significant
correlation between the burst locations and either Abell clusters of galaxies
or radio-quiet quasars. Agreement between individual COMPTEL locations and IPN
annuli places a lower limit of 100~AU (95% confidence) on the distance to
the stronger bursts.Comment: Accepted for publication in the Astrophysical Journal, 1998 Jan. 1,
Vol. 492. 33 pages, 9 figures, 5 table
Rational Engineering of a Flavoprotein Oxidase for Improved Direct Oxidation of Alcohols to Carboxylic Acids
The oxidation of alcohols to the corresponding carbonyl or carboxyl compounds represents a convenient strategy for the selective introduction of electrophilic carbon centres into carbohydrate-based starting materials. The O2-dependent oxidation of prim-alcohols by flavin-containing alcohol oxidases often yields mixtures of aldehyde and carboxylic acid, which is due to âover-oxidationâ of the aldehyde hydrate intermediate. In order to directly convert alcohols into carboxylic acids, rational engineering of 5-(hydroxymethyl)furfural oxidase was performed. In an attempt to improve the binding of the aldehyde hydrate in the active site to boost aldehyde-oxidase activity, two active-site residues were exchanged for hydrogen-bond-donating and -accepting amino acids. Enhanced over-oxidation was demonstrated and MichaelisâMenten kinetics were performed to corroborate these findings
A multifunctional mutagenesis system for analysis of gene function in zebrafish
Since the sequencing of the human reference genome, many human disease-related genes have been discovered. However, understanding the functions of all the genes in the genome remains a challenge. The biological activities of these genes are usually investigated in model organisms such as mice and zebrafish. Large-scale mutagenesis screens to generate disruptive mutations are useful for identifying and understanding the activities of genes. Here, we report a multifunctional mutagenesis system in zebrafish using the maize Ds transposon. Integration of the Ds transposable element containing an mCherry reporter for protein trap events and an EGFP reporter for enhancer trap events produced a collection of transgenic lines marking distinct cell and tissue types, and mutagenized genes in the zebrafish genome by trapping and prematurely terminating endogenous protein coding sequences. We obtained 642 zebrafish lines with dynamic reporter gene expression. The characterized fish lines with specific expression patterns will be made available through the European Zebrafish Resource Center (EZRC), and a database of reporter expression is available online (http://fishtrap.warwick.ac.uk/). Our approach complements other efforts using zebrafish to facilitate functional genomic studies in this model of human development and disease
Probing quantum phases of ultracold atoms in optical lattices by transmission spectra in cavity QED
Studies of ultracold atoms in optical lattices link various disciplines,
providing a playground where fundamental quantum many-body concepts, formulated
in condensed-matter physics, can be tested in much better controllable atomic
systems, e.g., strongly correlated phases, quantum information processing.
Standard methods to measure quantum properties of Bose-Einstein condensates
(BECs) are based on matter-wave interference between atoms released from traps
which destroys the system. Here we propose a nondestructive method based on
optical measurements, and prove that atomic statistics can be mapped on
transmission spectra of a high-Q cavity. This can be extremely useful for
studying phase transitions between Mott insulator and superfluid states, since
various phases show qualitatively distinct light scattering. Joining the
paradigms of cavity quantum electrodynamics (QED) and ultracold gases will
enable conceptually new investigations of both light and matter at ultimate
quantum levels, which only recently became experimentally possible. Here we
predict effects accessible in such novel setups.Comment: 6 pages, 3 figure
Radioactive 26Al and massive stars in the Galaxy
Gamma-rays from radioactive 26Al (half life ~7.2 10^5 yr) provide a
'snapshot' view of ongoing nucleosynthesis in the Galaxy. The Galaxy is
relatively transparent to such gamma-rays, and emission has been found
concentrated along the plane of the Galaxy. This led to the conclusion1 that
massive stars throughout the Galaxy dominate the production of 26Al. On the
other hand, meteoritic data show locally-produced 26Al, perhaps from spallation
reactions in the protosolar disk. Furthermore, prominent gamma-ray emission
from the Cygnus region suggests that a substantial fraction of Galactic 26Al
could originate in localized star-forming regions. Here we report high spectral
resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that
the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide
origin. We determine a present-day equilibrium mass of 2.8 (+/-0.8) M_sol of
26Al. We use this to estimate that the frequency of core collapse (i.e. type
Ib/c and type II) supernovae to be 1.9(+/- 1.1) events per century.Comment: accepted for publication in Nature, 24 pages including Online
Supplements, 11 figures, 1 tabl
Trametes versicolor carboxylate reductase uncovered
ABSTRACT: The first carboxylate reductase from Trametes versicolor was identified, cloned, and expressed in Escherichia coli. The enzyme reduces aromatic acids such as benzoic acid and derivatives, cinnamic acid, and 3-phenylpropanoic acid, but also aliphatic acids such as octanoic acid are reduced. GRAPHICAL ABSTRACT: [Image: see text
The Role of Environmental and Technology Policies in the Transition to a Low-Carbon Energy Industry
In a dynamic general equilibrium model we study the interplay between gradual and structural change in the transition to a low-carbon energy industry. We focus on the welfare-theoretic consequences of diverging social and private rates of time preference and a time-to-build feature in capital accumulation. Both features are particularly important in the transformation of energy systems. We show that only a combination of environmental and technology policies can achieve a socially optimal transition. We thus provide a new reason for environmental regulation to be complemented by technology policy such as a non-distortionary investment subsidy
Frequency, course and correlates of alcohol use from adolescence to young adulthood in a Swiss community survey
BACKGROUND: Few studies have analyzed the frequency of alcohol use across time from adolescence to young adulthood and its outcome in young adulthood. A Swiss longitudinal multilevel assessment project using various measures of psychopathology and psychosocial variables allowed for the study of the frequency and correlates of alcohol use so that this developmental trajectory may be better understood. METHOD: Alcohol use was studied by a questionnaire in a cohort of N = 593 subjects who had been assessed at three times between adolescence and young adulthood within the Zurich Psychology and Psychopathology Study (ZAPPS). Other assessment included questionnaire data measuring emotional and behavioural problems, life events, coping style, self-related cognitions, perceived parenting style and school environment, and size and efficiency of the social network. RESULTS: The increase of alcohol use from early adolescence to young adulthood showed only a few sex-specific differences in terms of the amount of alcohol consumption and the motives to drink. In late adolescence and young adulthood, males had a higher amount of alcohol consumption and were more frequently looking for drunkenness and feeling high. Males also experienced more negative consequences of alcohol use. A subgroup of heavy or problem drinkers showed a large range of emotional and behavioural problems and further indicators of impaired psychosocial functioning both in late adolescence and young adulthood. CONCLUSION: This Swiss community survey documents that alcohol use is problematic in a sizeable proportion of youth and goes hand in hand with a large number of psychosocial problems
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