The Identity of “Chromium Malate”

Recently, several studies on the effects of a compound named “chromium malate,” with the proposed formula “Cr₂malate₃·xH₂O” where x = 3.5 or 5, on the health of healthy and diabetic rats have appeared. However, the compound is poorly characterized, and knowing the identity of this material could be important in the interpretation of the previous and of future studies on the effects of this compound in animals. Consequently, the synthesis, characterization, and identity of this material were explored. A combination of spectroscopic, magnetic, and elemental analyses and mass spectral studies reveal that the compound is probably a polymer, not a discrete molecule, and does not have the composition previously reported. The repeating unit of the polymer possesses an antiferromagnetically coupled trinuclear Cr(III) core. The current study suggests that previous reports on chromium malate and its effects in animals must be viewed with caution.

     

An artificial peptide with corticotropin-releasing factor receptor-2 (CRF-R2) selective properties: the role of primary structure in the induction of signal transduction pathways.

Considerable plasticity can occur within the amino acid sequence of amphiphilic peptide hormones. This is particularly evident within the corticotropin-releasing factor (CRF) family of peptides where, despite less than 15% sequence similarity among the four paralogous lineages, all are capable of acting as high affinity ligands to members of the CRF receptor family. This suggests that these peptides could undergo many mutational changes and remain as high affinity ligands to their receptors as long as the functional motifs do not change radically. Because paralogous peptide lineages are a product of genome duplications, additional genes encoding peptide-like sequences, which through mutation have lost their functional integrity, may exist. Function to these sequences may be restored if the appropriate motifs are reinserted into the primary structure. We screened rat genomic DNA with highly degenerate polymerase chain reaction (PCR) primers targeted to hybridize with the termini of CRF-related sequences. One set of sauvagine-based primers hybridized with a 120-bp sequence. The theoretical peptide sequence (SV4) showed similarity to the CRF family of peptides at the primary structure level. The encoded sequence was prepared by solid-phase synthesis and its activity assayed against mouse R1 and human R1/R2 receptors. SV4 did not bind to either mouse or human variants of the R1 receptor, but did bind to the R2 receptor with an affinity comparable to human CRF. SV4 exhibited a similar efficacy of cellular activation as CRF in trials quantifying the acidification rate of human R2alpha-transfected Chinese hamster ovary (CHO) cells, but not R1-transfected cells. SV4 utilizes adenylate cyclase as the principal secondary messenger of R2 signal transduction but, unlike urocortin or sauvagine, does not activate guanylate cyclase-, calcium- or mitogen-activated protein (MAP) kinase-mediated pathways. These data suggest that this artificial peptide may be useful to understand the cyclic adenosine monophosphate (cAMP)-dependent component of the CRF-R2 signal transduction cascade, and that additional sequences in the genome may be used to engineer bioactive peptides.     

The Ring Nematode,Criconemoides ornatus,on Peach and Centipede Grass

Criconemoides ornatus at 500, 1,000, and 10,000 specimens per 15-cm pot containing 1,500 cc of soil was not pathogenic or parasitic on "Loveli'' peach. The number of nematodes recovered was always less than the inoculum. Inocula of 1,000 and 10,000 specimens were pathogenic to centipede grass, but the 500 inoculum level was not. The number of nematodes recovered from parasitized centipede grass was considerably higher than the inoculum.     

The molecular economics of the long neuron

Summary 1. Nerve cells grow by progressively changing their nucleo-cytoplasmic ratio, whereas growth in other cell types is associated with an increase in number of nuclei or degree of ploidy of a single nucleus in such a way that the nucleo-cytoplasmic ratio is maintained within its original order of magnitude.2. Reasons are given for supposing that the primary factor in maintaining the nucleo-cytoplasmic ratio within its usual order of magnitude lies in the peculiar nature of protein metabolism which is keyed to a fixed number of DNA molecules.3. An input-output model was constructed of a molecular system operating under similar limitations and its properties examined.4. By altering the values under which the system operated it was possible to examine the ways in which the system could grow. Patterns emerged for both limited and indefinite growth, both ultimately depending on the supply of molecules with a short half-life.5. The pattern of indefinite growth which most nearly resembled that of the long neuron was one in which the deficiencies in labile molecules encountered by an extending system were met by transfer of similar molecules from adjacent unextended systems. The extended system, however, became liable to contract molecular debts whose magnitude was related to the degree of extension of the system.6. A series of comparisons were drawn between the properties of the model and the observed morphological, biochemical and physiological characteristics of neural tissue. The coincidences were found to be sufficiently numerous to suggest that models of this type may be useful in correlating morphological and biochemical findings in the nervous system and in the design of experiments.

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Die molekulare Ökonomie der langen Neuronen

Kurzfassung Im Gegensatz zu anderen Zellen ist ein Neuron in der Lage, durch Veränderung der Kern-Plasma-Relation progressiv zu wachsen. Dieses Phänomen wurde untersucht, wobei der Eiweißstoffwechsel einer Zelle als limitierender Faktor für die Erhaltung der normalen Kern-Plasma-Relation angesehen wurde. Es wurde ein Modell eines Systems konstruiert, mit voneinander abhängigen Molekülen verschiedener Halblebenszeiten, welche unter den Bedingungen molekularen Austausches operieren, die den Proteinstoffwechsel zu beherrschen und einzuschränken scheinen. Dann wurde geprüft, auf welche Weise dieses System sich durch Anstieg der Molekülzahlen auszudehnen vermag. In einer weitgehend dem Muster des unbeschränkten Wachstums der langen Neuronen ähnelnden Situation wurde dem Mangel an Molekülen mit kurzer Halblebenszeit (diese wurden in sich ausdehnenden Systemen gefunden) durch Überführung ähnlicher Moleküle aus benachbarten, nicht ausgedehnten Systemen begegnet. Das ausgedehnte System neigte aber dazu, Molekülschulden auf sich zu laden, deren Höhe abhing von dem Ausmaß der Systemausdehnung. Diese Sachverhalte stimmten überein mit vielen beobachteten histologischen, biochemischen und physiologischen Charakteristika der Nervengewebe. Es wurde daher gefolgert, daß Modelle dieser Art nützlich sein können hinsichtlich einer Korrelation morphologischer und biochemischer Befunde und der Planung geeigneter Experimente.

     

Hyperglycemia: cell death in a cave

Mitochondria play a central role in mediating high glucose-induced apoptosis. A recent study has shown that increases in glucose levels induce significant alterations in caveolae components, suggesting that high glucose may affect apoptotic signaling initiated in caveolae.     

Bacterial adhesion at synthetic surfaces.

A systematic investigation into the effect of surface chemistry on bacterial adhesion was carried out. In particular, a number of physicochemical factors important in defining the surface at the molecular level were assessed for their effect on the adhesion of Listeria monocytogenes, Salmonella typhimurium, Staphylococcus aureus, and Escherichia coli. The primary experiments involved the grafting of groups varying in hydrophilicity, hydrophobicity, chain length, and chemical functionality onto glass substrates such that the surfaces were homogeneous and densely packed with functional groups. All of the surfaces were found to be chemically well defined, and their measured surface energies varied from 15 to 41 mJ. m(-2). Protein adsorption experiments were performed with (3)H-labelled bovine serum albumin and cytochrome c prior to bacterial attachment studies. Hydrophilic uncharged surfaces showed the greatest resistance to protein adsorption; however, our studies also showed that the effectiveness of poly(ethyleneoxide) (PEO) polymers was not simply a result of its hydrophilicity and molecular weight alone. The adsorption of the two proteins approximately correlated with short-term cell adhesion, and bacterial attachment for L. monocytogenes and E. coli also correlated with the chemistry of the underlying substrate. However, for S. aureus and S. typhimurium a different pattern of attachment occurred, suggesting a dissimilar mechanism of cell attachment, although high-molecular-weight PEO was still the least-cell-adsorbing surface. The implications of this for in vivo attachment of cells suggest that hydrophilic passivating groups may be the best method for preventing cell adsorption to synthetic substrates provided they can be grafted uniformly and in sufficient density at the surface.