Streptococcus pneumoniae: the evolution of antimicrobial resistance to beta-lactams, fluoroquinolones and macrolides

Multi drug resistant Streptococcus pneumoniae constitute a major public health concern worldwide. In this review we discuss how the transformable nature of the pneumococcus, in parallel with antimicrobial induced stress, contributes to the evolution of antimicrobial resistance; and how the introduction of the pneumococcal conjugate vaccine has affected the situation.     

Random drift versus selection in academic vocabulary: an evolutionary analysis of published keywords

The evolution of vocabulary in academic publishing is characterized via keyword frequencies recorded in the ISI Web of Science citations database. In four distinct case-studies, evolutionary analysis of keyword frequency change through time is compared to a model of random copying used as the null hypothesis, such that selection may be identified against it. The case studies from the physical sciences indicate greater selection in keyword choice than in the social sciences. Similar evolutionary analyses can be applied to a wide range of phenomena; wherever the popularity of multiple items through time has been recorded, as with web searches, or sales of popular music and books, for example.     

Structural and functional characterization of a monoclonal antibody specific for the preS1 region of hepatitis B virus.

The monoclonal antibody 5a19, raised against the ay serotype of hepatitis B virus, binds to the segment of the preS1 region comprising residues 37-43, which is implicated in attachment of the virus to hepatocytes. The dissociation constant, derived from kinetic studies using surface plasmon resonance techniques, is in the low nanomolar range. The nucleotide sequence of the variable domains has been determined and the corresponding germ-line genes have been identified. The three-dimensional structure of the Fab fragment has been determined by X-ray crystallography to 2.6 A resolution.     

Menaquinone (vitamin K2) biosynthesis in Escherichia coli: synthesis of o-succinylbenzoate does not require the decarboxylase activity of the ketoglutarate dehydrogenase complex

The committed step in menaquinone biosynthesis is the formation of o-succinylbenzoate (OSB). It is presumed to require the reaction of a seven-carbon intermediate of the shikimate pathway with a succinic semialdehyde-thiamin pyrophosphate (TPP) anion, derived by decarboxylation of 2-ketoglutarate. The following evidence indicates that the decarboxylation is not a function of the ketoglutarate dehydrogenase complex but is carried out by a separate activity. (A) Cell-free extracts of Escherichia coli K12 without added TPP lose OSB synthase activity but retain all of the ketoglutarate dehydrogenase complex activities. (B) OSB synthase activity is inhibited by addition of tetrahydro-TPP (th-TPP) to the incubations. The ketoglutarate dehydrogenase complex activities are only inhibited by this analogue after an initial preincubation period. (C) The high molecular weight ketoglutarate dehydrogenase complex can be separated from OSB synthase activity by gel-permeation chromatography on Sepharose CL-6B. Experiment series A and B also provide supporting evidence that TPP does play an important role in menaquinone biosynthesis.     

Residual morphogenetic competence in the proximal core region of stage 25 chick limbs: Zwilling's hypothesis revisited

Morphogenetic competence (MC) exists in embryonic limb tissue once thought to have lost this property as a consequence of cytodifferentiation. By stage 25 of chick embryonic development, cells in the proximal core of the limb have committed to the cartilage phenotype and are producing their characteristic extracellular matrix. Recombinant limb-bud grafts constructed using isolated fragments of this tissue produce outgrowths with a limb-like skeletal pattern. Inclusion of proximal peripheral tissue in the grafts (with or without the polarizing tissue) inhibits outgrowth and skeletal morphogenesis, explaining the failure of earlier studies to reveal the MC of the proximal core (chondrogenic) cells. Since definitive chondroblasts express MC in more permissive surroundings, it appears that Zwilling's assertion, that the onset of cytodifferentiation causes the loss of MC, is an oversimplification and that complex tissue interactions are probably involved.     

Porcine-specific hemoglobin saturation measurements.

The determination of O(2) consumption by using arteriovenous O(2) content differences is dependent on accurate oxyhemoglobin saturation measurements. Because swine are a common experimental species, we describe the validation of CO-oximeter for porcine-specific oxyhemoglobin saturation. After developing a nonlinear mathematical model of the porcine oxyhemoglobin saturation curve, we made 366 porcine oxyhemoglobin saturation determinations with a calibrated blood-gas analyzer and a porcine-specific CO-oximeter. There was a high degree of correlation with minimal variability (r(2) = 0.99, SE of the estimate = 5.2%) between the mathematical model and the porcine-specific CO-oximeter measurements. Bland-Altman comparison showed that the CO-oximeter measurements were biased slightly lower (-0.4 vol%), and the limits of agreement (+/-2 SD) were 0.7 and -1.5 vol%. This is in contrast to a 10-20 vol% error if human-specific methods were used. The results show excellent agreement between the nonlinear model and CO-oximeter for porcine-specific oxyhemoglobin saturation measurements. In contrast, comparison of the porcine-specific oxyhemoglobin saturations with saturations obtained by using human methods highlights the necessity of species-specific measurement methodology.