Relationship between FTC 'tar' and urine mutagenicity in smokers of tobacco-burning or Eclipse cigarettes

The US Federal Trade Commission (FTC) classifies domestic cigarettes into one of three 'tar' categories based on 'tar' and nicotine levels. The objective of the present study was to determine urine mutagenicity in groups of smokers of ultra-low 'tar' (ULT), full-flavor low 'tar' (FFLT) and full-flavor 'tar' (FF) filtered cigarettes after switching to primarily tobacco-heating Eclipse cigarettes. Sixty-seven smokers maintained a specified diet and consumed ad libitum their usual brands of cigarettes, switched to Eclipse, and switched back to their usual brands. Twenty-four hour urine samples were collected weekly, concentrated on XAD-2 resin, and tested in the Ames mutagenicity assay using bacterial strains TA98 and YG1024 with S9 metabolic activation. Daily consumption of cigarettes was not significantly different (at P<0.05) between FTC 'tar' categories and average daily cigarette consumption did not change significantly in any smoker group after switching to Eclipse cigarettes. Average urine mutagenicity was 47% less (P<0.05) for ULT than for FFLT usual brand smokers as measured by the more sensitive strain YG1024, although no significant differences (P<0.05) were observed in urine mutagenicity between usual brand FTC 'tar' categories as measured by strain TA98. The reduction in urinary mutagens in the more sensitive strain, YG1024, observed in ULT smokers as compared with higher 'tar' categories suggest reduced exposure to mutagens. Usual brand salivary cotinine in the ULT group was significantly lower (P<0.05) than the FF group and the FFLT group. Salivary cotinine did not differ significantly (at P<0.05) among the smoker groups when smoking Eclipse compared to usual brand. After switching to Eclipse, the following reductions in urinary mutagenicity were observed: ULT, 70.1+/-6.4% (TA98), 70.9+/-6.2% (YG1024); FFLT, 77.1+/-2.4% (TA98), 73.6+/-2.0% (YG1024); and FF, 76.1+/-3.5% (TA98), 71.4+/-4.0% (YG1024). Across all 'tar' categories, cigarette smokers experienced significant reductions (P<0.05) in urine mutagenicity, but not salivary cotinine, upon switching to Eclipse. The reduction in urine mutagenicity when smoking Eclipse provides supporting evidence that Eclipse may present less risk of cancer compared to cigarettes currently in the market.     

Ingestion of plant secondary compounds causes diuresis in desert herbivores

Plant secondary compounds are recognized deterrents and toxins to a variety of herbivores. The effect of secondary compounds on water balance of herbivores is virtually unexplored, yet secondary compounds could potentially cause a decrease in an animal's ability to maintain water balance. We investigated the effects of secondary compounds, alpha-pinene and creosote resin, on water balance in three species of herbivorous woodrats (Neotoma stephensi, N. albigula, N. lepida). In separate experiments, we measured the effect of these secondary compounds on voluntary water consumption, urine volume and urine osmolarity. In both experiments, water intake and urine volume increased and urine osmolarity decreased compared to controls. Water balance of specialist or experienced woodrats was less affected than generalists and woodrats with less prior experience with particular secondary compounds. Our results suggest that secondary compounds have diuretic-like effects on herbivores. Woodrats live in arid habitats with limited access to freestanding water; thus an increase in water requirements may have profound consequences on foraging behavior and fitness.     

Can we infer peptide recognition specificity mediated by SH3 domains?

Protein interaction domain families that modulate the formation of macromolecular complexes recognize specific sequence or structural motifs. For instance SH3 and WW domains bind to polyproline peptides while SH2 and FHA domains bind to peptides phosphorylated in Tyr and Thr respectively. Within each family, variations in the chemical characteristics of the domain binding pocket modulate a finer peptide recognition specificity and, as a consequence, determine the selection of functional protein partners in vivo. In the proteomic era there is the need for reliable inference methods to help restricting the sequence space of the putative targets to be confirmed experimentally by more laborious experimental approaches. Here we will review the published data about the peptide recognition specificity of the SH3 domain family and we will propose a classification of SH3 domains into eight classes. Finally, we will discuss whether the available information is sufficient to infer the recognition specificity of any uncharacterized SH3 domain.     

The pam1 gene is required for meiotic bouquet formation and efficient homologous synapsis in maize (Zea mays L.)

The clustering of telomeres on the nuclear envelope (NE) during meiotic prophase to form the bouquet arrangement of chromosomes may facilitate homologous chromosome synapsis. The pam1 (plural abnormalities of meiosis 1) gene is the first maize gene that appears to be required for telomere clustering, and homologous synapsis is impaired in pam1. Telomere clustering on the NE is arrested or delayed at an intermediate stage in pam1. Telomeres associate with the NE during the leptotene-zygotene transition but cluster slowly if at all as meiosis proceeds. Intermediate stages in telomere clustering including miniclusters are observed in pam1 but not in wild-type meiocytes. The tight bouquet normally seen at zygotene is a rare event. In contrast, the polarization of centromeres vs. telomeres in the nucleus at the leptotene-zygotene transition is the same in mutant and wild-type cells. Defects in homologous chromosome synapsis include incomplete synapsis, nonhomologous synapsis, and unresolved interlocks. However, the number of RAD51 foci on chromosomes in pam1 is similar to that of wild type. We suggest that the defects in homologous synapsis and the retardation of prophase I arise from the irregularity of telomere clustering and propose that pam1 is involved in the control of bouquet formation and downstream meiotic prophase I events.     

A Genomewide Search for Type 2 Diabetes–Susceptibility Genes in Indigenous Australians

The prevalence of type 2 diabetes among Australian residents is 7.5%; however, prevalence rates up to six times higher have been reported for indigenous Australian communities. Epidemiological evidence implicates genetic factors in the susceptibility of indigenous Australians to type 2 diabetes and supports the hypothesis of the "thrifty genotype," but, to date, the nature of the genetic predisposition is unknown. We have ascertained clinical details from a community of indigenous Australian descent in North Stradbroke Island, Queensland. In this population, the phenotype is characterized by severe insulin resistance. We have conducted a genomewide scan, at an average resolution of 10 cM, for type 2 diabetes-susceptibility genes in a large multigeneration pedigree from this community. Parametric linkage analysis undertaken using FASTLINK version 4.1p yielded a maximum two-point LOD score of +2.97 at marker D2S2345. Multipoint analysis yielded a peak LOD score of +3.9 <1 cM from marker D2S2345, with an 18-cM 3-LOD support interval. Secondary peak LOD scores were noted on chromosome 3 (+1.8 at recombination fraction [theta] 0.05, at marker D3S1311) and chromosome 8 (+1.77 at theta=0.0, at marker D8S549). These chromosomal regions are likely to harbor novel susceptibility genes for type 2 diabetes in the indigenous Australian population.     

The energetics of ion distribution: the origin of the resting electric potential of cells

The relation between the energies of ion movement and ATP hydrolysis is unknown in tissues with widely varying electric potentials. Consequently, we measured the concentration of the nine major inorganic ions in the extra- and intracellular phases in heart, liver, and red cells with resting electrical potentials, E(N), of -86, -28, and -6 mV, respectively, under six different physiological conditions. We calculated the Nernst electric potential and the energy of ion movement between the phases. We found that the energy of ATP hydrolysis was essentially constant, between -54 and -58 kJ/mol, in all tissues and conditions. In contrast, as E(N) decreased, the energies of the Na+ and K+ gradients decreased, with slopes approximating their valence. The difference between the energies of Na+ and K+ gradients remained constant at 17 kJ/mol, which is approximately one third of the energy of ATP hydrolysis, demonstrating near-equilibrium of the Na+/K+ ATPase in all tissues under all conditions. All cations, except K+, were pumped out of cells and all anions, except Cl- in liver and red cell, were pumped into cells. We conclude that the energy of ATP was expressed in Na+/K+ ATPase and its linked inorganic ion transporters to create a Gibbs-Donnan near-equilibrium system, an inherent part of which was the electric potential.     

High-efficiency gene transfer into adult fish: a new tool to study fin regeneration

Zebrafish represents an excellent model to study the function of vertebrate genes (e.g., well-developed genetics, large number of mutants, and genomic sequencing in progress), inasmuch as we have tools to manipulate gene expression. Recent use of injected morpholinos in eggs provides a good method to " knockdown " gene expression in early development (Nasevicius and Ekker, 2000), and the "caged" RNA injected in eggs allows to overexpress a gene in a specific set of cells (Ando et al., 2001). However, a method to specifically modify gene expression in the juvenile or in the adult is still missing. Such a method would be a very powerful tool to understand gene function in differentiated tissues. We describe here an electroporation-based approach, which allows gene transfer in adult tissues. Its efficiency was assessed using a GFP (green fluorescent protein) dependent assay. We then used this method to disrupt the Fgf signalling pathway during the process of regeneration.     

Fifteen minutes of fim: control of type 1 pili expression in E. coli

Pili are used by Escherichia coli to attach to and invade mammalian tissues during host infection and colonization. Expression of type 1 pili, believed to act as virulence factors in urinary tract infections, is under control of the 'firm' genetic network. This network is able to sense the environment and actuate phase variation control. It is a prime exemplar of an integrative regulatory system because of its role in mediating a complex infection process, and because it instantiates a number of regulatory motifs, including DNA inversion and stochastic variation. With the help of a mathematical model, we explore the mechanisms and architecture of the fim network. We explain (1) basic network operation, including the roles of the recombinase and global regulatory protein concentrations, their DNA binding affinities, and their switching rates in observed phase variation behavior; (2) why there are two recombinases when one would seem to suffice; (3) the source of on-to-off switching specificity of FimE; (4) the role of fimE orientational control in switch dynamics; and (5) how temperature tuning of piliation is achieved. In the process, we identify a general regulatory motif that tunes phenotype to an environmental variable, and explain a number of apparent experimental inconsistencies.