Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link between Enzyme Superfamilies

Mandelate racemase (MR), a member of the enolase superfamily, catalyzes the Mg2+-dependent interconversion of the enantiomers of mandelate. Several α-keto acids are modest competitive inhibitors of MR [e.g., mesoxalate (Ki = 1.8 ± 0.3 mM) and 3-fluoropyruvate (Ki = 1.3 ± 0.1 mM)], but, surprisingly, 3-hydroxypyruvate (3-HP) is an irreversible, time-dependent inhibitor (kinact/KI = 83 ± 8 M–1 s–1). Protection from inactivation by the competitive inhibitor benzohydroxamate, trypsinolysis and electrospray ionization tandem mass spectrometry analyses, and X-ray crystallographic studies reveal that 3-HP undergoes Schiff-base formation with Lys 166 at the active site, followed by formation of an aldehyde/enol(ate) adduct. Such a reaction is unprecedented in the enolase superfamily and may be a relic of an activity possessed by a promiscuous progenitor enzyme. The ability of MR to form and deprotonate a Schiff-base intermediate furnishes a previously unrecognized mechanistic link to other α/β-barrel enzymes utilizing Schiff-base chemistry and is in accord with the sequence- and structure-based hypothesis that members of the metal-dependent enolase superfamily and the Schiff-base-forming N-acetylneuraminate lyase superfamily and aldolases share a common ancestor

Risks Vs. Benefits: The Ethics Of Radiography

Dr. Perle's article on radiology and ethics.http://dynamicchiropractic.com/mpacms/dc/article.php?id=5331

Irony and the dogma of force and sense

Frege’s distinction between force and sense is a central pillar of modern thinking about meaning. This is the idea that a self-standing utterance of a sentence S can be divided into two components. One is the proposition P that S’s linguistic meaning and context associates with it. The other is S’s illocutionary force. The force/sense distinction is associated with another thesis, the embedding principle, that implies that the only content that embeds in compound sentences is propositional content. We argue that both the Force/Sense distinction and the principle of embedding are seriously challenged by figurative language, and irony in particular. We conclude that theorists need to go back to the drawing board about the nature of illocutionary act

Splendid Hybrids: The Effects of a Tiger Beetle Hybrid Zone on Apparent Species Diversity

Nonexpert citizen groups are being used to monitor species to track ecosystem changes; however, challenges remain for proper identification, especially among diverse groups such as beetles. Tiger beetles, Cicindela spp., have been used for biological diversity monitoring because of their diversity and the ease of recognition. The finding of an apparent hybrid zone among Cicindela denverensis Casey, Cicindela limbalis Klug, and Cicindela splendida Hentz in central Nebraska prompted a detailed study of the biogeography of this species group within Nebraska, a test of characteristics that could be used by citizen scientists, and limited breeding experiments. This study suggests that while C. denverensis appears to hybridize with both C. limbalis and C. splendida within the hybrid zone, all three species maintain their integrity across most of their ranges, largely occupy unique geographic regions, and at least C. denverensis and C. splendida cooccur in many areas with no evidence of hybridization. Evidence of hybridization between C. limbalis and C. splendida was found at only two sites. Furthermore, breeding experiments with virgin C. splendida and C. denverensis showed that they are capable of producing hybrid larvae in the laboratory. The presence of morphological intergrades serves as a cautionary note when using biological indicator species

Splendid Hybrids: The Effects of a Tiger Beetle Hybrid Zone on Apparent Species Diversity

Nonexpert citizen groups are being used to monitor species to track ecosystem changes; however, challenges remain for proper identification, especially among diverse groups such as beetles. Tiger beetles, Cicindela spp., have been used for biological diversity monitoring because of their diversity and the ease of recognition. The finding of an apparent hybrid zone among Cicindela denverensis Casey, Cicindela limbalis Klug, and Cicindela splendida Hentz in central Nebraska prompted a detailed study of the biogeography of this species group within Nebraska, a test of characteristics that could be used by citizen scientists, and limited breeding experiments. This study suggests that while C. denverensis appears to hybridize with both C. limbalis and C. splendida within the hybrid zone, all three species maintain their integrity across most of their ranges, largely occupy unique geographic regions, and at least C. denverensis and C. splendida cooccur in many areas with no evidence of hybridization. Evidence of hybridization between C. limbalis and C. splendida was found at only two sites. Furthermore, breeding experiments with virgin C. splendida and C. denverensis showed that they are capable of producing hybrid larvae in the laboratory. The presence of morphological intergrades serves as a cautionary note when using biological indicator species

The necessary future of chiropractic education: a North American perspective

The chiropractic educational system in North America is currently in a state of flux. The attempted conversion of some chiropractic schools into "universities" and the want of university affiliation for chiropractic schools suggests that we are searching for a better alternative to the present system. In the early 20(th )century, the Flexner Report helped transform modern medical education into a discipline that relies on scientific and clinical knowledge. Some have wondered if it is time for a Flexner-type report regarding the education of doctors of chiropractic. This article outlines the current challenges within the chiropractic educational system and proposes positive changes for that system