Gene by smoking interaction: evidence for effects on low-density lipoprotein size and plasma levels of triglyceride and high-density lipoprotein cholesterol

We seek to determine whether significant gene x smoking interaction effects exist on plasma triglyceride (TG) levels, HDL cholesterol (HDL-C) level, and median LDL particle diameter (LDL-MPD) in Mexican American families enrolled in the San Antonio Family Heart Study. The sample consisted of 1,392 individuals distributed in 42 extended pedigrees, ranging in age from 16 years to 92 years. Separate quantitative genetic analyses were carried out for TG and HDL-C level and LDL-MPD using a maximum-likelihood-based variance decomposition approach while simultaneously adjusting for age and sex. Initial heritability estimates demonstrated significant (p < 0.001) additive genetic contributions to all three traits (h2 range 0.50 - 0.54). To test for a gene x smoking interaction, we included in the model additional smoking-status-specific variance terms and a genetic correlation term between smokers and nonsmokers. Comparisons of nested models revealed significant evidence (p < 0.01) for a gene X smoking interaction effect on TG level and LDL-MPD and possible evidence for an effect on HDL-C level. These results indicate that the gene or suite of genes regulating each of these phenotypes is likely the same in smokers and non-smokers but that smoking may alter the expression of genes, particularly those influencing TG level and LDL-MPD.     

A new, versatile field immunosensor for environmental pollutants: development and proof of principle with TNT, diuron, and atrazine

This paper presents a new, versatile, portable miniaturized flow-injection immunosensor which is designed for field analysis. The temperature-controlled field prototype can run for 6h without external power supply. The bio-recognition element is an analyte-specific antibody immobilized on a gold surface of pyramidal structures inside an exchangeable single-use chip, which hosts also the enzyme-tracer and the sample reservoirs. The competition between the enzyme-tracer and the analyte for the antigen-binding sites of the antibodies yields in the final step a chemiluminescence signal that is inversely proportional to the concentration of analyte in the given range of detection. A proof of principle is shown for nitroaromatics and pesticides. The detection limits (DL; IC20) reached with the field prototype in the laboratory was below 0.1 microg l(-1) for 2,4,6-trinitrotoluene (TNT), and about 0.2 microg l(-1) for diuron and atrazine, respectively. Important aspects in this development were the design of the competition between analyte and enzyme-tracer, the unspecific signal due to unspecific binding and/or luminescence background signal, and the flow pattern inside the chip.     

Reinstitutionalisation in mental health care: comparison of data on service provision from six European countries

Objective To establish whether reinstitutionalisation is occurring in mental health care and, if so, with what variations between western European countries.Design Comparison of data on changes in service provision.Setting Six European countries with different traditions of mental health care that have all experienced deinstitutionalisation since the 1970s—England, Germany, Italy, the Netherlands, Spain, and Sweden.Outcome measures Changes in the number of forensic hospital beds, involuntary hospital admissions, places in supported housing, general psychiatric hospital beds, and general prison population between 1990-1 and 2002-3.Results Forensic beds and places in supported housing have increased in all countries, whereas changes in involuntary hospital admissions have been inconsistent. The number of psychiatric hospital beds has been reduced in five countries, but only in two countries does this reduction outweigh the number of additional places in forensic institutions and supported housing. The general prison population has substantially increased in all countries.Conclusions Reinstitutionalisation is taking place in European countries with different traditions of health care, although with significant variation between the six countries studied. The precise reasons for the phenomenon remain unclear. General attitudes to risk containment in a society, as indicated by the size of the prison population, may be more important than changing morbidity and new methods of mental healthcare delivery.     

Twintrons are not unique to the Euglena chloroplast genome: structure and evolution of a plastome cpn60 gene from a cryptomonad

Introns within introns (twintrons) are known only from the Euglena chloroplast genome. Twintrons are group II or III introns, into which another group II or III intron has been transposed. In this paper we describe a non-Euglena twintron structure within a plastid-encoded chaperone gene (cpn60) of the cryptomonad alga Pyrenomonas salina. In addition, the evolutionary relationships between members of the Cpn60 protein family are determined. Our findings permit the inclusion of cryptomonad plastomes in phylogenetic studies of intron evolution and present further evidence for the origin of modern plastids from a cyanobacterial ancestor.This paper is dedicated to Prof. Dr. Peter Sitte on the occasion of his 65th birthday     

Gene expression in autumn leaves

Two cDNA libraries were prepared, one from leaves of a field-grown aspen (Populus tremula) tree, harvested just before any visible sign of leaf senescence in the autumn, and one from young but fully expanded leaves of greenhouse-grown aspen (Populus tremula x tremuloides). Expressed sequence tags (ESTs; 5,128 and 4,841, respectively) were obtained from the two libraries. A semiautomatic method of annotation and functional classification of the ESTs, according to a modified Munich Institute of Protein Sequences classification scheme, was developed, utilizing information from three different databases. The patterns of gene expression in the two libraries were strikingly different. In the autumn leaf library, ESTs encoding metallothionein, early light-inducible proteins, and cysteine proteases were most abundant. Clones encoding other proteases and proteins involved in respiration and breakdown of lipids and pigments, as well as stress-related genes, were also well represented. We identified homologs to many known senescence-associated genes, as well as seven different genes encoding cysteine proteases, two encoding aspartic proteases, five encoding metallothioneins, and 35 additional genes that were up-regulated in autumn leaves. We also indirectly estimated the rate of plastid protein synthesis in the autumn leaves to be less that 10% of that in young leaves.     

Highly biased type 1 immune responses in mice deficient in LFA-1 in Listeria monocytogenes infection are caused by elevated IL-12 production by granulocytes

LFA-1 (CD11a/CD18) plays a key role in various inflammatory responses. Here we show that the acquired immune response to Listeria monocytogenes is highly biased toward type 1 in the absence of LFA-1. At the early stage of listeriosis, numbers of IFN-gamma producers in the liver and spleen of LFA-1(-/-) mice were markedly increased compared with heterozygous littermates and Valpha14(+)NKT cell-deficient mice, and NK cells were major IFN-gamma producers. Numbers of IL-12 producers were also markedly elevated in LFA-1(-/-) mice compared with heterozygous littermates, and endogenous IL-12 neutralization impaired IFN-gamma production by NK cells. Granulocyte depletion diminished numbers of IL-12 producers and IFN-gamma-secreting NK cells in the liver of LFA-1(-/-) mice. Granulocytes from the liver of L. monocytogenes-infected LFA-1(-/-) mice were potent IL-12 producers. Thus, in the absence of LFA-1, granulocytes are a major source of IL-12 at the early stage of listeriosis. We assume that highly biased type 1 immune responses in LFA-1(-/-) mice are caused by increased levels of IL-12 from granulocytes and that granulocytes play a major role in IFN-gamma secretion by NK cells. In conclusion, LFA-1 regulates type 1 immune responses by controlling prompt infiltration of IL-12-producing granulocytes into sites of inflammation.     

Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis

Protective immunity against Mycobacterium tuberculosis involves major histocompatibility complex class I (MHC-I)- and CD1-restricted CD8 T cells, but the mechanisms underlying antigen delivery to antigen-presenting molecules remain enigmatic. Macrophages, the primary host cells for mycobacteria, are CD1-negative. Here we show that M. tuberculosis phagosomes are secluded from the cytosolic MHC-I processing pathway and that mycobacteria-infected cells lose their antigen-presenting capacity. We also show that mycobacteria induce apoptosis in macrophages, causing the release of apoptotic vesicles that carry mycobacterial antigens to uninfected antigen-presenting cells (APCs). Inhibition of apoptosis reduced transfer of antigens to bystander cells and activation of CD8 T cells. Uninfected dendritic cells, which engulfed extracellular vesicles, were indispensable for subsequent cross-presentation of antigens, through MHC-I and CD1b, to T cells from mycobacteria-sensitized donors. This new 'detour' pathway for presentation of antigens from a phagosome-contained pathogen shows the functional significance of infection-induced apoptosis in the activation of CD8 T cells specific for both protein and glycolipid antigens in tuberculosis.