Increased biosynthesis of acetyl-CoA in the yeast Saccharomyces cerevisiae by overexpression of a deregulated pantothenate kinase gene and engineering of the coenzyme A biosynthetic pathway.

Coenzyme A (CoA) and its derivatives such as acetyl-CoA are essential metabolites for several biosynthetic reactions. In the yeast S. cerevisiae, five enzymes (encoded by essential genes CAB1-CAB5; coenzyme A biosynthesis) are required to perform CoA biosynthesis from pantothenate, cysteine, and ATP.

Mutations in PPCS, Encoding Phosphopantothenoylcysteine Synthetase, Cause Autosomal-Recessive Dilated Cardiomyopathy.

Coenzyme A (CoA) is an essential metabolic cofactor used by around 4% of cellular enzymes. Its role is to carry and transfer acetyl and acyl groups to other molecules. Cells can synthesize CoA de novo from vitamin B5 (pantothenate) through five consecutive enzymatic steps.

Opi1 mediates repression of phospholipid biosynthesis by phosphate limitation in the yeast Saccharomyces cerevisiae.

Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are transcribed when precursor molecules inositol and choline (IC) are limiting. Gene expression is stimulated by the heterodimeric activator Ino2/Ino4, which binds to ICRE (inositol/choline-responsive element) promoter sequences. Activation is prevented by repressor Opi1, counteracting Ino2 when high concentrations of IC are available.

Measurement of the proton-air cross section at √s=57 TeV with the Pierre Auger Observatory.

We report a measurement of the proton-air cross section for particle production at the center-of-mass energy per nucleon of 57 TeV. This is derived from the distribution of the depths of shower maxima observed with the Pierre Auger Observatory: systematic uncertainties are studied in detail. Analyzing the tail of the distribution of the shower maxima, a proton-air cross section of [505±22(stat)(-36)(+28)(syst)] mb is found.

Multiple histone deacetylases are recruited by corepressor Sin3 and contribute to gene repression mediated by Opi1 regulator of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae.

Yeast genes of phospholipid biosynthesis are negatively regulated by repressor protein Opi1 when precursor molecules inositol and choline (IC) are available. Opi1-triggered gene repression is mediated by recruitment of the Sin3 corepressor complex. In this study, we systematically investigated the regulatory contribution of subunits of Sin3 complexes and identified Pho23 as important for IC-dependent gene repression.

Measurement of the depth of maximum of extensive air showers above 10{18} eV.

We describe the measurement of the depth of maximum, X{max}, of the longitudinal development of air showers induced by cosmic rays. Almost 4000 events above 10;{18} eV observed by the fluorescence detector of the Pierre Auger Observatory in coincidence with at least one surface detector station are selected for the analysis. The average shower maximum was found to evolve with energy at a rate of (106{-21}{+35}) g/cm{2}/decade below 10{18.

Quantitative analysis of D-24851, a novel anticancer agent, in human plasma and urine by liquid chromatography coupled with tandem mass spectrometry.

The development of a liquid chromatography/tandem mass spectrometric assay for the quantitative analysis of the novel tubulin inhibitor D-24851 in human plasma and urine is described. D-24851 and the deuterated internal standard were extracted from 250 microL of plasma or urine using hexane/ether (1:1, v/v). Subsequently, 10-microL aliquots of reconstituted extracts were injected onto an Inertsil ODS analytical column (50 x 2.

Ovarian stimulation for assisted reproduction with HMG and concomitant midcycle administration of the GnRH antagonist cetrorelix according to the multiple dose protocol: a prospective uncontrolled phase III study.

A total of 346 women with normal ovulatory function was stimulated with human menopausal gonadotrophins (HMG) to attain ovarian stimulation for IVF or intracytoplasmic sperm injection (ICSI). Stimulation with HMG started on cycle day 2 or 3. After 6 days of stimulation, Cetrorelix in its minimum effective multiple dose of 0.

Contribution of L-type calcium channels to epileptiform activity in hippocampal and neocortical slices of guinea-pigs.

The aim of the present investigation was to compare the antiepileptic efficacy of the specific L-type calcium channel blocker nifedipine in hippocampal and neocortical slice preparations in the Mg2+-free model of epilepsy. The main findings were as follows. (1) In hippocampal slices, in general, nifedipine (20-80 micromol/l) exerted a suppressive effect both on repetition rate and on area under epileptiform field potentials.

[MR tomography of astrocytic tumors (I-III)].

Magnetic resonance (MR) imaging was performed on 37 patients with histologically confirmed astrocytomas (I-III). In addition, the MR tissue parameters T1, T2 and proton density (RHO) were analysed by an interlaced CPMG spin echo sequence. Characteristic morphologic tumour patterns which subdivide astrocytomas into each different tumour grade are presented.

Information processing in nuclear magnetic resonance imaging.

An extended image analysis and classification system is presented to discuss the principal composition of the components as well as the methods of its realization in the field of reference based NMR diagnostics and tissue characterization.

[Gadolinium dimeglumine gadopentetate compared to CPMG sequencing and image synthesis].

The skulls of 46 patients were examined by means of ordinary scans and after contrast. 24 of these patients with cerebral abnormalities had scans, using identical planes, with and without contrast and with CPMG sequences. Contrast in intracranial, but extracerebral (extra-axial), tumours (meningiomas, neurinomas) was much better after using contrast, but intracerebral (intra-axial) tumours were mostly shown as well on T2-rated CPMG sequences.

[Reference substance for initialling the marker space in NMR tomography].

Dimethylsiloxane polymers are tested to serve as a reference medium in quantitative MR imaging. Simultaneously measured during the patient's examination, the reference data are used to normalize the intrinsic MR tissue parameters. This method helps to achieve interindividual comparability of tissue vectors which are defined by proton density, spin-spin and spin-lattice relaxation times, thus leading to a remarkable improvement in tissue classification.

[MR tomography in intracranial meningiomas].

The typical findings of intracranial meningiomas seen in 24 patients are described. The signal intensities at different acquisition parameters are analysed and optimal pulse sequences derived from these data. In 90% of the patients MR-tissue parameters were measured and correlated with the histological findings.

[Initial clinical results of tissue characterization by T1, T2 and proton density in nuclear magnetic resonance tomography].

The NMR parameters (proton density, relaxation times T1 and T2) have been assessed by Carr-Purcell-Meiboom-Gill (CPMG) spin echo sequences. A computer assisted analysis of the data of 21 patients with cerebral tumours allowed a classification of tumour tissue in different tumours. The use of quantitative procedures for tissue characterisation allows the differentiation of benign and malignant brain tissue by characteristic colour coding demonstrating morphological details like tumour, edema and necrosis as well as indicating the histological types of the tumours of the central nervous system.

[Plain imaging of meningioma in NMR tomography--retrospective contrast optimization by image synthesis].

Synthetic images of the tumour region were computed in the case of ten meningiomas for the purpose of determining retrospectively pulse sequences and sequence parameters supplying an optimal contrast between tumour and adjacent tissue in plain imaging. It was found that best results were obtained via the partial saturation/spin-echo sequence with a long recovery time (TR approximately greater than 2,000 msec) and a long maximum echo delay (TE max approximately greater than 200 msec). A comparable contrast quality can be attained by using the inversion-recovery sequence with an inversion time T1 approximately 450 msec.