Wild-Type Strain of Staphylococcus aureus Containing Two Genetic Linkage Groups for Penicillinase Production

Staphylococcus aureus strain 55C1, isolated from a patient in 1955, contained two genetic linkage groups for penicillinase formation. One was linked to genes that control resistance to cadmium and mercuric ions; it had properties of a plasmidborne gene. The other was not linked to resistance to these metal ions; it had properties of a chromosomal gene. Penicillinase formation by cells that contained either linkage group was inducible by penicillins. Induced penicillinase in cells that contained both linkage groups equalled the sum of that produced in cells containing each group singly. Exopenicillinase produced by cells containing either gene was serological type A. Constitutive penicillinase formation resulting from regulator gene mutations in either linkage group was repressed to differing extents by a wild-type determinant in the trans position. The genetic structure and the regulation of penicillinase formation in strain 55C1 resembled in general those for penicillinase linkage groups which Asheshov and Dyke described for diploid mutant strains of S. aureus PS 80. There were differences in detail, however.     

Cognitive disturbances in the cuprizone model of multiple sclerosis

Cognitive problems frequently accompany neurological manifestations of multiple sclerosis (MS). However, during screening of preclinical candidates, assessments of behaviour in mouse models of MS typically focus on locomotor activity. In the present study, we analysed cognitive behaviour of 9 to 10-week-old female C57Bl/6J mice orally administered with the toxin cuprizone that induces demyelination, a characteristic feature of MS. Animals received 400 mg/kg cuprizone daily for 2 or 4 weeks, and their performance was compared with that of vehicle-treated mice. Cuprizone-treated animals showed multiple deficits in short touchscreen-based operant tasks: they responded more slowly to visual stimuli, rewards and made more errors in a simple rule-learning task. In contextual/cued fear conditioning experiments, cuprizone-treated mice showed significantly lower levels of contextual freezing than vehicle-treated mice. Diffusion tensor imaging showed treatment-dependent changes in fractional anisotropy as well as in axial and mean diffusivities in different white matter areas. Lower values of fractional anisotropy and axial diffusivity in cuprizone-treated mice indicated developing demyelination and/or axonal damage. Several diffusion tensor imaging measurements correlated with learning parameters. Our results show that translational touchscreen operant tests and fear conditioning paradigms can reliably detect cognitive consequences of cuprizone treatment. The suggested experimental approach enables screening novel MS drug candidates in longitudinal experiments for their ability to improve pathological changes in brain structure and reverse cognitive deficits.     

Formation of amino acids by cobalt-60 irradiation of hydrogen cyanide solutions.

Aqueous solutions of hydrogen cyanide (0.004-0.1 M) were exposed to cobalt-60 gamma rays. Among the products formed on hydrolysis of the irradiated solution; glycine, alanine, valine, serine, threonine, aspartic acid, and glutamic acid have been identified.     

The lack of a solvent accessible hydroxide or water ligand to iron at the 3Fe center of Azotobacter vinelandii ferredoxin I

The X-ray crystal structure of Azotobacter vinelandii ferredoxin I (FdI) describes a planar 3Fe-3S center in which one of the iron atoms is ligated to a solvent accessible oxo ligand, presumably from water or hydroxide (Ghosh et al., (1982) J. Mol. Biol. 158, 73-109). Efforts to displace the proposed oxo ligand with cyanide were unsuccessful, even in 80% dimethylsulfoxide. In addition, comparison of the electron spin echo envelopes for H2O- and D2O-equilibrated samples of FdI showed only a slight deuterium modulation, far less than would be expected were water to be bound as an iron ligand. These results do not support the presence of a solvent accessible oxo ligand to the 3Fe center as described in the X-ray crystal structure.     

Decrease in hepatic cytochrome P-450 and catalase following allylisopropylacetamide: The effect of concomitant hemin administration

It is known that administration of allylisopropylacetamide (AIA) to rats increases δ-aminolevulinic acid synthetase (ALA-S), urine ascorbic acid excretion and decreases hepatic hemoproteins cytochrome P-450 and catalase. Hemin has been shown to inhibit induction of ALA-S by AIA. To investigate further the regulatory role of hemin, AIA was administered to rats over a 5 day period with and without hemin. Hemin did not prevent the decrease in P-450 or catalase caused by AIA but partially inhibited induction of ALA-S and the increase in ascorbic acid excretion. It is unlikely that the hemin is replacing endogenous heme in hemoprotein synthesis and we conclude that the role of hemin in suppressing induction phenomena that follow AIA treatment reflects a regulatory function not related to a role in hemoprotein synthesis.