The interplay of theory and experiment in the study of phenylnitrene

The intra- and intermolecular chemistry of phenylnitrene (PhN), its singlet-triplet energy separation, and its electronic spectra are interpreted with the aid of ab initio molecular orbital theory. The key to understanding singlet PhN is the recognition that this species has an open-shell electronic structure, in contrast to the related species, phenylcarbene, which has a closed-shell electronic structure. The thermodynamics of nitrenes, benzazirines, dehydroazepines, aminyl radicals, and their hydrocarbon analogues are also discussed.     

Transient expression of Dp140, a product of the Duchenne muscular dystrophy locus, during kidney tubulogenesis

Dystroglycan is a cell surface complex which in muscle links the extracellular matrix protein laminin-2 to the membrane associated cytoskeletal protein dystrophin. Recently it was found that dystroglycan is also expressed in developing epithelial cells. Moreover, antibodies against dystroglycan can perturb epithelial cell development in kidney organ culture. Dystroglycan could provide a link between the basement membrane and the intracellular space also in epithelial cells. However, there is no dystrophin in epithelial cells. By in situ hybridization here we show prominent expression of a shorter isoform of dystrophin, Dp140, in embryonic kidney tubules. In addition, another isoform, Dp71, is expressed by all studied embryonic epithelial cells. Both isoforms share the dystroglycan-binding region of dystrophin but lack the region known to bind to actin. Here we also characterized monoclonal antibodies against different domains of dystrophin and used these to study the distribution of Dp140 protein. In embryonic kidney tubules the dystrophin antibody VIA4(2)A3 stained an intracellular antigen close to the basal cells. In contrast, no staining was observed in adult kidney. We suggest that Dp140 is a structural component during kidney tubulogenesis but it may also be involved in signal transduction.     

Hypofrontality revisited: a high resolution single photon emission computed tomography study in schizophrenia

Hypofrontality or reduced activity in the prefrontal cortex, measured as reduced frontal perfusion or glucose uptake, has gained the status of an established finding in the medical literature on schizophrenia. Many relevant studies, however, have potential sources of bias, such as small subject numbers, or unreliable performance of activation tasks by the patients during the scanning procedure. Seventy patients with non-affective and non-organic psychoses were recruited--most qualifying for DSM III-R schizophrenia or schizophreniform psychosis (n = 60)--together with 20 healthy volunteers. They underwent single photon emission computed tomography with 99mTc-exametazime, carried out at rest. Tracer uptake was normalised to the occipital cortex. Group differences in tracer uptake were predicted in anterior regions of interest (prefrontal cortex and mesial frontal/cingulate cortex). Actively psychotic (including schizophrenic) patients not taking any drugs showed increased uptake in the prefrontal cortex. Reduced tracer uptake occurred in the mesial frontal cortex of schizophrenic patients, particularly if they were taking drugs. Relatively increased prefrontal tracer uptake associated with relatively decreased mesial frontal uptake characterised the patients in comparison with the controls. Generalised hypofrontality is, therefore, not a feature of schizophrenic patients at rest whether taking drugs or not.     

The Ketosynthase Domain Controls Chain Length in Mushroom Oligocyclic Polyketide Synthases

The nonreducing iterative type I polyketide synthases (NR-PKSs) CoPKS1 and CoPKS4 of the webcap mushroom Cortinarius odorifer share 88 % identical amino acids. CoPKS1 almost exclusively produces a tricyclic octaketide product, atrochrysone carboxylic acid, whereas CoPKS4 shows simultaneous hepta- and octaketide synthase activity and also produces the bicyclic heptaketide 6-hydroxymusizin. To identify the region(s) controlling chain length, four chimeric enzyme variants were constructed and assayed for activity in Aspergillus niger as heterologous expression platform. We provide evidence that the β-ketoacyl synthase (KS) domain determines chain length in these mushroom NR-PKSs, even though their KS domains differ in only ten amino acids. A unique proline-rich linker connecting the acyl carrier protein with the thioesterase domain varies most between these two enzymes but is not involved in chain length control.