Electron Transfer-oxy Radical Mechanism for Anti-cancer Agents: 9-anilinoacridines

A possible mode of action involving electron transfer is advanced for the 9- anilinoacridines. The mechanism entails formation of toxic oxy radicals which destroy the neoplasm. Cyclic voltammetry was performed on iminium type ions derived by protonation of the acridines. Reductions were generally reversible with potentials of about - 0.60 V. Involvement of quinoidal metabolites is also a possibility. The relationship of electrochemical behavior to structure and physiological activity is addressed

The morphology of the syrinx in passerine birds

The syrinx, for more than a century an important organ in determining the subdivisions of the avian order Passeriformes (perching birds), was examined in 983 specimens, representing 65 of the 67 families recognized by most modern authorities….https://elischolar.library.yale.edu/peabody_museum_natural_history_bulletin/1036/thumbnail.jp

Anti-cancer Action of Metal Complexes: Electron Transfer and Oxidative Stress?

Evidence is presented in support of an electron transfer mechanism for various metal complexes possessing anti-neoplastic properties. Cyclic voltammetry was performed on several metallocenes, bis(acetato)bis(imidazole)Cu(II), and coordination compounds (Cu or Fe) of the anti-tumor agents, bipyridine, phenanthroline, hydroxyurea, diethyldithiocarbamate, and α, α1-bis(8-hydroxyquinolin-7-yl)-4-methoxytoluene. The favorable reduction potentials ranged from +0.5 to -0.5 V. Electrochemical behavior is correlated in some cases with structure and physiological activity. Relevant literature data are discussed

HAMP domain structural determinants for signalling and sensory adaptation in Tsr, the E. coli serine chemoreceptor

pre-printMotile Escherichia coli cells track chemical gradients with high sensitivity over wide concentration ranges [recently reviewed in (Hazelbauer et al., 2008; Hazelbauer & Lai, 2010)]. Stimulus detection, amplification, and integration occur in an arrayed network of signaling complexes that contain transmembrane chemoreceptors (methyl-accepting chemotaxis proteins or MCPs), the signaling histidine kinase CheA, and CheW, which couples CheA activity to chemoreceptor control. In the absence of chemoattractant gradients, MCPs activate CheA, promoting frequent episodes of clockwise (CW) flagellar rotation and random changes in swimming direction. Binding of an attractant ligand to the periplasmic sensing domain of a receptor molecule down-regulates CheA bound to the cytoplasmic tip of the receptor (Fig. 1), promoting counter-clockwise (CCW) flagellar rotation and forward swimming. Subsequent sensory adaptation restores pre-stimulus behavior through changes in MCP methylation state, catalyzed by a dedicated methyltransferase (CheR) and methylesterase (CheB)

Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

Variation in the sternal notches of suboscine passeriform birds

The present study was undertaken to record the variations of the posterior border of the sternum of the New World suboscines, in an attempt to determine the reliability of this area of the sternum as a taxonomic character. The conclusions drawn from this survey (of 993 specimens) are that, within a broad range of variants, two basic kinds of sternal configuration are found: two-notched (Types 2-3-4, as defined), and four-notched (Types 5-6). The four-notched sternum is not confined to genera in the Rhinocryptidae and Conopophaga, as previously believed. Variations within the twoand four-notched sterna may not be considered taxonomically significant unless they can be shown to be consistent in a large series of specimens. In no case should a single specimen of a species be assumed to show the only sternal configuration of the species. The possible adaptive significance of the observed range of variation is briefly discussed, but no conclusions may be drawn until a functional analysis of the passerine sternum can be made

Fermentation of Cottonseed and Other Feedstuffs in Cattle Rumen Fluid

Bovine rumen fluid was fermented anaerobically over 48 h with cottonseed, corn, alfalfa, or a mixture of these substrates in anaerobic mineral buffer. Samples taken at different incubation times were derivatized with n-butanol and subjected to gas chromatography and mass spectroscopy. No unusual fermentation end-products from the cottonseed substrate were detected. Cottonseed supported rumen fermentation at levels comparable to those of the other substrates. Major components were usually found in the decreasing order of acetate, propionate, butyrate, and valerate, although acetate and propionate concentrations decreased late in the alfalfa and mixed-feed fermentations, eventually allowing butyrate concentrations to exceed those of propionate. As expected, lactate was produced in high concentrations when corn was fermented. The minor components 2-methylpropionate, 2- and 3-methylbutyrate, phenylacetate, phenylpropionate, and caproate also accumulated, with their relative concentrations varying with the substrate. Succinate was produced in substantial amounts only when corn and alfalfa were fermented; it did not accumulate when cottonseed was the substrate. Samples containing cottonseed were derivatized and subjected to reversed-phase high-performance liquid chromatography, revealing that gossypol concentrations did not change during fermentation

The anatomy and systematic position of the antpipits Conopophaga and Corythopis

The anatomical characters of the passerine family Conopophagidae have been reexamined. The sternum, syrinx, tarsus, antorbital osteology and pterylosis of Conopophaga and Corythopis were compared with a broad sample of other suboscines, with particular attention to the Formicariidae and Rhinocryptidae. Conopophaga was found to lie well within the range of variation of the Formicariidae in the principal characters (sternum and syrinx) used by Forbes in describing the Conopophagidae. The key character was the apparent presence in Conopophaga of a four-notched sternum. In nearly all specimens of Conopophaga, however, we found the sternum to have two notches and two large medial fenestrae. The four-notched condition is found in some species of Grallaria and Pittasoma, both considered to be formicariid. In most of the other characters studied also, Conopophaga strongly resembles Grallaria. The genus Corythopis differs from Conopophaga and all other furnarioids in the major diagnostic characters examined. In several respects, particularly the pterylosis and syringeal structure, it shows strong affinities with the Tyrannidae. It is recommended that Conopophaga be returned to its former position, near Grallaria in the Formicariidae. Corythopis must be moved from the Furnarioidea to the Tyrannoidea; its proper position appears to be in the family Tyrannidae

Structural and functional conservation of key domains in InsP3 and ryanodine receptors.

Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6 Å) and without (3.0 Å) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore