Mode of Action of Pesticin

The mode of action of pesticin, a bacteriocin produced by many strains of Pasturella pestis, was studied. Pesticin action on macromolecular synthesis of a sensitive strain of Escherichia coli, strain , was found to have features similar to those of colicin E2-317 acting on the same strain. After exposure to pesticin, deoxyribonucleic acid synthesis was arrested and ribonucleic acid was degraded, but little effect was observed on protein synthesis. Pesticin, like colicin E2-317, induced lysogenic E. coli (P1), but, unlike the colicin, was active in the presence of dinitrophenol. Trypsin was found to reverse pesticin action up to 15 min after its addition at 40 C to E. coli . Pesticin action was studied on three sensitive bacterial strains, P. pestis 2C, P. pseudotuberculosis, and E. coli strain , which vary widely in their optimal growth temperature. P. pestis grows best at 29 C, P. pseudotuberculosis at 37 C, and E. coli at 40 C. It was found that pesticin action on all three strains was optimal at 40 C. Whereas the titer of pesticin was the same on all three strains when determined on agar, E. coli was the most sensitive to pesticin action in broth. No action of pesticin in broth on P. pseudotuberculosis was observed unless Ca ions were added. The effect was not immediate; that is, the cells had to be grown in a medium containing Ca⁺⁺ before they displayed sensitivity to pesticin.     

New antibiotic substance produced by Salmonella typhimurium LT2

Salmonella typhimurium LT2 excreted under certain conditions an antibiotic substance designated typhimuricin. It is suggested that the LT2 “cryptic” plasmid is involved in its production and in the immunity to it. Preliminary characterization of typhimuricin is presented.     

Modelling the Efficiency of Codon–tRNA Interactions Based on Codon Usage Bias

The tRNA adaptation index (tAI) is a widely used measure of the efficiency by which a coding sequence is recognized by the intra-cellular tRNA pool. This index includes among others weights that represent wobble interactions between codons and tRNA molecules. Currently, these weights are based only on the gene expression in Saccharomyces cerevisiae. However, the efficiencies of the different codon–tRNA interactions are expected to vary among different organisms. In this study, we suggest a new approach for adjusting the tAI weights to any target model organism without the need for gene expression measurements. Our method is based on optimizing the correlation between the tAI and a measure of codon usage bias. Here, we show that in non-fungal the new tAI weights predict protein abundance significantly better than the traditional tAI weights. The unique tRNA–codon adaptation weights computed for 100 different organisms exhibit a significant correlation with evolutionary distance. The reported results demonstrate the usefulness of the new measure in future genomic studies.     

Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury

In this study, using two different injury models in two different species, we found that early post-injury treatment with N-Acetyl Cysteine (NAC) reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting [1], to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI). For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30–60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man.     

Tumor necrosis factor-α synthesis inhibitor, 3,6'-dithiothalidomide, reverses behavioral impairments induced by minimal traumatic brain injury in mice

Mild traumatic brain injury (mTBI) patients do not show clear structural brain defects and, in general, do not require hospitalization, but frequently suffer from long-lasting cognitive, behavioral and emotional difficulties. Although there is no current effective treatment or cure for mTBI, tumor necrosis factor-alpha (TNF-α), a cytokine fundamental in the systemic inflammatory process, represents a potential drug target. TNF-α levels increase after mTBI and may induce or exacerbate secondary damage to brain tissue. The present study evaluated the efficacy of the experimental TNF-α synthesis inhibitor, 3,6'-dithiothalidomide, on recovery of mice from mTBI in a closed head weight-drop model that induces an acute elevation in brain TNF-α and an impairment in cognitive performance, as assessed by the Y-maze, by novel object recognition and by passive avoidance paradigms at 72 h and 7 days after injury. These impairments were fully ameliorated in mice that received a one time administration of 3,6'-dithiothalidomide at either a low (28 mg/kg) or high (56 mg/kg) dose provided either 1 h prior to injury, or at 1 or 12 h post-injury. Together, these results implicate TNF-α as a drug target for mTBI and suggests that 3,6'-dithiothalidomide may act as a neuroprotective drug to minimize impairment.     

Essential virulence determinants of different Yersinia species are carried on a common plasmid

Plasmids of 44.4–46 Mdal were identified in conditional virulent Yersinia species. All virulent strains studied are unable to grow on oxalate-containing plates at 37 °C (OX^? phenotype) which is a characteristic property of strains producing the essential virulence VW antigens. The phenotopic transition from OX^? to OX⁺ in these strains is concomitant with loss of virulence and loss of this plasmid. The similarity in size and in the DNA fragmentation patterns, generated by HindIII, of the plasmids isolated from either Y. pseudotuberculosis or two conditional virulent Y. pestis strains, suggests that a common plasmid—pSB2—is carried by these strains. A plasmid of a similar size, ~42 Mdal, and function was recently identified (P. Gemski, J. R. Lazere, and T. Casey, 1980, Infect. Immunity27, 682–685; D. L. Zink, J. C. Feeley, J. G. Wells, C. Vanderzant, J. C. Vickery, W. D. Roof, and G. A. O'Donovan, 1980, Nature (London)283, 224–225) in virulent Y. enterocolitica. We conclude that pSB2 in Y. pseudotuberculosis and Y. pestis and its counterpart in Y. enterocolitica carry genetic information essential for virulence common to the Yersinia species, probably related to VW antigen production. Several additional plasmids were identified in several strains of Y. pestis. One of these plasmids, designated pSB3 (12.5 Mdal), appears to be associated with pesticin production.     

Backbone <Superscript>1</Superscript>H, <Superscript>13</Superscript>C and <Superscript>15</Superscript>N chemical shift assignment of full-length human uracil DNA glycosylase UNG2

Human uracil N-glycosylase isoform 2—UNG2 consists of an N-terminal intrinsically disordered regulatory domain (UNG2 residues 1–92, 9.3 kDa) and a C-terminal structured catalytic domain (UNG2 residues 93–313, 25.1 kDa). Here, we report the backbone ¹H, ¹³C, and ¹⁵N chemical shift assignment as well as secondary structure analysis of the N-and C-terminal domains of UNG2 representing the full-length UNG2 protein.     

Mutagenic and colicine-inducing activity of two antioxidants: pyrogallol and purpurogallin.

The antioxidants pyrogallol and its oxidative derivative, purpurogallin, both induce colicine E2 as well as base substitution and frameshift mutations. Because of the bactericidal effect of purpurogallin, its mutagenicity could be best demonstrated by short-term exposure followed by dilution on the test plates. The colicine-inducing potential of purpurogallin was also observed when tested directly on the plates.