2-(Trimethylammonium) Ethyl (R)-3-Methoxy-3-oxo-2-Stearamidopropyl Phosphate Suppresses Osteoclast Maturation and Bone Resorption by Targeting Macrophage-Colony Stimulating Factor Signaling

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.     

Adenylate kinase isoenzymes in Aspergillus nidulans

Multiple HindIII-restriction fragments of Salmonella typhimurium and Salmonella typhi chromosomal DNA exhibited homology with the heat-labile enterotoxin (LT1) gene of Escherichia coli as determined by Southern blot analysis. A 9.4 kb HindIII restriction fragment identified in S. typhimurium and S. typhi chromosomal DNA reacted with both eltA and eltB gene probes. However, the homology of the 9.4 kb DNA fragment from these Salmonella species was greater with eltB than eltA. In addition, a synthetic oligonucleotide probe, made to a portion of the putative GM1-ganglioside binding region of cholera toxin (CT) and LT1, hybridized with the 9.4 kb DNA fragment of S. typhimurium but not with the 9.4 kb fragment found in S. typhi isolates. The hybridization of multiple restriction fragments of Salmonella DNA with eltA and eltB gene sequences further suggests duplication of the stx operon on the chromosome of these bacteria.     

Cub growth and maternal care in cheetahs

Using cub growth as an index, I examine the influence of maternalnutrition, litter size, and cub sex on maternal care in cheetahs(Acinonyx jubatus) and compare cub and litter growth rates withthose of other large feilds. Seventy-nine free-living cheetahcubs in 21 litters from 15 mothers were weighed at least oncebetween 6 and 48 days of age. Eleven litters were weighed atthe beginning and end of a 5-day observation of their mothers.The mean cub growth rate varied significantly between litters,due primarily to differences in maternal food intake. Growthdeclined sharply when maternal food intake was less than 1.5kg/ day, but did not increase with greater levels of food intake.Lower limits of growth rates may therefore have been set bythe mother's food intake, whereas upper limits may be set bythe intrinsic physiological ability of cubs to grow. Althoughmale cubs were heavier than female cubs in the same litter whenfirst weighed, major differences in growth rate between thesexes were not apparent at this stage. Both cheetah cubs andlitters grow fast relative to other large felids, and I arguethat this may be an adaptation to the high rate of cheetah juvenilemortality from predation.     

Temperature gradient gel electrophoresis: detection of a single base substitution in the cattle β-lactoglobulin gene

An A in equilibrium with G transition in exon III is known to differentiate alleles A and B of the cattle beta-lactoglobulin (BLG) gene. A BLG exon III fragment containing the transition site was amplified by the polymerase chain reaction. Temperature gradient gel electrophoresis (TGGE) was then used to detect this transition and hence to genotype cattle: the AT base-pair in allele A was readily distinguished from the GC base-pair of allele B. TGGE can be used to detect any single base-pair substitution, and thus is a powerful method of detecting genetic variability.     

The structure and function of phytochrome A: the roles of the entire molecule and of its various parts

Phytochrome A is readily cleavable by proteolytic agents to yield an amino-terminal fragment of 66 kilodalton (kDa), which consists of residues 1 to approximately 600, and a dimer of the carboxy-terminal 55-kDa fragment, from residue 600 or so to the carboxyl terminus. The former domain, carrying the tetrapyrrole chromophore, has been studied extensively because of its photoactivity, while less attention has been paid to the non-chromophoric portion until quite recently. However, the evidence gathered to date suggests that this domain is also of great improtance. We present here a review of the structure and the biochemical and physiological functions of the two domains, of parts of these domains, and of the cooperation between them.