Heterogeneity, nucleation, shrinkage and bloating in sol–gel glass ceramics (the case of lithium aluminosilicate compositions)

Sintering of sol–gel powders often leads to porous samples despite the high reactivity of such powders. The influence of heterogeneity coming firstly from the use of different reagents as gel formers (Si and Al alkoxides) or of a mixed nature (Si–Al ester) and secondly from the hydrolysis–polycondensation route (mixing in anhydrous condition or pre-hydrolysis of the reagents) was studied for a lithium aluminum silicate composition using differential thermal analysis, expansion-shrinkage measurements and X-ray diffraction. The effects of the synthesis conditions on the microstructures is discussed from optical microscopy, scanning electron microscopy and metallurgical observations.     

Chromosome association of minichromosome maintenance proteins in Drosophila endoreplication cycles

Minichromosome maintenance (MCM) proteins are essential eukaryotic DNA replication factors. The binding of MCMs to chromatin oscillates in conjunction with progress through the mitotic cell cycle. This oscillation is thought to play an important role in coupling DNA replication to mitosis and limiting chromosome duplication to once per cell cycle. The coupling of DNA replication to mitosis is absent in Drosophila endoreplication cycles (endocycles), during which discrete rounds of chromosome duplication occur without intervening mitoses. We examined the behavior of MCM proteins in endoreplicating larval salivary glands, to determine whether oscillation of MCM-chromosome localization occurs in conjunction with passage through an endocycle S phase. We found that MCMs in polytene nuclei exist in two states: associated with or dissociated from chromosomes. We demonstrate that cyclin E can drive chromosome association of DmMCM2 and that DNA synthesis erases this association. We conclude that mitosis is not required for oscillations in chromosome binding of MCMs and propose that cycles of MCM-chromosome association normally occur in endocycles. These results are discussed in a model in which the cycle of MCM-chromosome associations is uncoupled from mitosis because of the distinctive program of cyclin expression in endocycles.     

Increase of formation of methylamine and formaldehyde in vivo after administration of nicotine and the potential cytotoxicity

Methylamine is a constituent of cigarette smoke and the major end product of nicotine metabolism. Smoking or nicotine can induce the release of adrenaline, which is in turn deaminated by monoamine oxidase, also producing methylamine. We found that the urinary level of methylamine was significantly elevated following administration of nicotine (25 mg/Kg, i.p.). Semicarbazide-sensitive amine oxidase (SSAO) inhibitors further increased the excretion of methylamine induced by nicotine. Following administration of L-(-)-[N-methyl-3H]nicotine long-lasting irreversible radioactive adducts were detected in different mouse tissues and such adduct formation could be blocked by selective SSAO inhibitors. These adducts are probably cross-linked oligoprotein complexes cross-linked by formaldehyde. The findings support the idea that nicotine can enhance SSAO/methylamine-mediated increase of formaldehyde and oxidative stress and this could in part contribute the adverse effect of health associated with smoking.     

Physical activity, obesity, and the incidence of type 2 diabetes in a high-risk population

This study, examining the longitudinal relation among physical activity, body mass index, and development of type 2 diabetes in a high-risk population, is unique because diabetes was determined by oral glucose tolerance testing rather than by self-report. A physical activity questionnaire assessing past year leisure and occupational activity was administered to 1,728 nondiabetic Pima individuals aged 15-59 years as part of a series of clinic examinations in the Gila River Indian Community from 1987 to 2000. During an average follow-up period of 6 years, 346 subjects developed diabetes. Using time-dependent Cox proportional hazards modeling adjusting for age, the authors found that total activity was related to diabetes incidence in women and men (p < 0.05 in women only). After additional adjustment for body mass index, the relation between activity and diabetes incidence was weakened in both men and women. When the age-adjusted diabetes incidence rates were examined by levels of activity stratified by tertile of body mass index, the diabetes incidence rate remained lower in more active than in less active men and women from all body mass index groups, with the exception of the middle body mass index tertile in men (p < 0.05 in women only). These results suggest that the adoption and maintenance of a physically active lifestyle can play a significant role in preventing type 2 diabetes.     

Are we facing a 'post-antibiotic era'?--a review of the literature regarding antimicrobial drug resistance

Since the introduction of antibiotics in the 1940s, antibiotic resistance has become an increasing problem. Today, multiple-antibiotic resistance is commonly associated with a number of clinically important pathogens and is therefore an important issue in clinical nursing practice. Epidemiological studies identify a number of important factors associated with increases in antimicrobial resistance. These include patterns of antimicrobial use, changes in medical and veterinary care and social practices affecting the transmission of microbes. Bacterial mechanisms of antibiotic resistance and the genetics of resistance-gene transfer are explored, with the intention of developing nurses' knowledge and understanding of control measures.     

Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages

Mycobacterium avium (MAC) organisms multiply in phagosomes that have restricted fusigenicity with lysosomes, do not acidify due to a paucity of vacuolar proton-ATPases, yet remain accessible to recycling endosomes. During the course of mycobacterial infections, IFN-gamma-mediated activation of host and bystander macrophages is a key mechanism in the regulation of bacterial growth. Here we demonstrate that in keeping with earlier studies, cytokine activation of host macrophages leads to a decrease in MAC viability, demonstrable by bacterial esterase staining with fluorescein diacetate as well as colony-forming unit counts from infected cells. Analysis of the pH of MAC phagosomes demonstrated that the vacuoles in activated macrophages equilibrate to pH 5.2, in contrast to pH 6.3 in resting phagocytes. Biochemical analysis of MAC phagosomes from both resting and activated macrophages confirmed that the lower intraphagosomal pH correlated with an increased accumulation of proton-ATPases. Furthermore, the lower pH is reflected in the transition of MAC phagosomes to a point no longer accessible to transferrin, a marker of the recycling endosomal system. These alterations parallel the coalescence of bacterial vacuoles from individual bacilli in single vacuoles to communal vacuoles with multiple bacilli. These data demonstrate that bacteriostatic and bactericidal activities of activated macrophages are concomitant with alterations in the physiology of the mycobacterial phagosome.     

Folding of beta-sheet membrane proteins: a hydrophobic hexapeptide model

Beta-sheets, in the form of the beta-barrel folding motif, are found in several constitutive membrane proteins (porins) and in several microbial toxins that assemble on membranes to form oligomeric transmembrane channels. We report here a first step towards understanding the principles of beta-sheet formation in membranes. In particular, we describe the properties of a simple hydrophobic hexapeptide, acetyl-Trp-Leu5 (AcWL5), that assembles cooperatively into beta-sheet aggregates upon partitioning into lipid bilayer membranes from the aqueous phase where the peptide is strictly monomeric and random coil. The aggregates, containing 10 to 20 monomers, undergo a relatively sharp and reversible thermal unfolding at approximately 60 degreesC. No pores are formed by the aggregates, but they do induce graded leakage of vesicle contents at very high peptide to lipid ratios. Because beta-sheet structure is not observed when the peptide is dissolved in n-octanol, trifluoroethanol or sodium dodecyl sulfate micelles, aggregation into beta-sheets appears to be an exclusive property of the peptide in the bilayer membrane interface. This is an expected consequence of the hypothesis that a reduction in the free energy of partitioning of peptide bonds caused by hydrogen bonding drives secondary structure formation in membrane interfaces. But, other features of interfacial partitioning, such as side-chain interactions and reduction of dimensionality, must also contribute. We estimate from our partitioning data that the free energy reduction per residue for aggregation is about 0.5 kcal mol-1. Although modest, its aggregate effect on the free energy of assembling beta-sheet proteins can be huge. This surprising finding, that a simple hydrophobic hexapeptide readily assembles into oligomeric beta-sheets in membranes, reveals the potent ability of membranes to promote secondary structure in peptides, and shows that the formation of beta-sheets in membranes is more facile than expected. Furthermore, it provides a basis for understanding the observation that membranes promote self-association of beta-amyloid peptides. AcWL5 and related peptides thus provide a good starting point for designing peptide models for exploring the principles of beta-sheet formation in membranes.