Cytosolic persistence of mouse brain CYP1A1 in chronic heme deficiency

Previous work has demonstrated that the function of extrahepatic cytochrome P450 CYP1A1 is dependent on the availability of heme. CYP1A1 is involved in the activation of polyaromatic hydrocarbons. In the present study we used a transgenic mouse model with chronic impairment of heme synthesis - female porphobilinogen deaminase-deficient (PBGD-/-) mice - to investigate the effects of limited heme in untreated and β-naphthoflavone (β-NF)-treated animals on the function of CYP1A1 in brain. The heme content of PBGD-/- mice was diminished in the liver and brain compared to wild types. In the liver, partial heme deficiency led to less potent induction of CYP1A1 mRNA after β-NF treatment. In the brain, CYP1A1 protein was detected not only at the endoplasmic reticulum (ER), but also in the cytosol of PBGD-/- mice. Furthermore, 7-deethylation of ethoxyresorufin, an indicator of CYP1A1 metabolic activity, could be restored by heme in cytosol of PBGD-/- mouse brain. Independent of the genotype, we found only one cyp1a1 gene product, indicating that the cytosolic appearance of CYP1A1 most likely did not originate from mutant alleles. We conclude that heme deficiency in the brain leads to incomplete heme saturation of CYP1A1, which causes its improper incorporation into the ER membrane and persistence in the cytosol. It is suggested that diseases caused by relative heme deficiency, such as hepatic porphyrias, may lead to impaired hemoprotein function in brai

Reservoir Competence of Native North American Birds for the Lyme Disease Spirochete, Borrelia burgdorferi

Reservoir competence for the Lyme disease spirochete, Borrelia burgdorferi, was tested for six species of native North American birds: American robin, gray catbird, brown thrasher, eastern towhee, song sparrow, and northern cardinal. Wild birds collected by mist netting on Fire Island, NY, were held in a field laboratory in cages over water and locally collected larval ticks were placed on the birds, harvested from the water after engorgement, and tested for infection by direct fluorescent-antibody staining after molting to the nymphal stage. American robins were competent reservoirs, infecting 16.1% of larvae applied to wild-caught birds, compared with 0% of control ticks placed on uninfected laboratory mice. Robins that were previously infected in the laboratory by nymphal feeding infected 81.8% of applied larvae. Wild-caught song sparrows infected 4.8% of applied larvae and 21.1% when infected by nymphal feeding. Results suggest moderate levels of reservoir competence for northern cardinals, lower levels for gray catbirds, and little evidence of reservoir competence for eastern towhees or brown thrashers. Lower infection rates in larvae applied to wild-caught birds compared with birds infected in the laboratory suggest that infected birds display temporal variability in infectiousness to larval ticks. Engorged larvae drop from birds abundantly during daylight, so the abundance of these bird species in the peridomestic environment suggests that they might contribute infected ticks to lawns and gardens

The Nature of the Halo Population of NGC 5128 Resolved with NICMOS on the Hubble Space Telescope

We present the first infrared color-magnitude diagram (CMD) for the halo of a giant elliptical galaxy. The CMD for the stars in the halo of NGC 5128 (Centaurus A) was constructed from HST NICMOS observations of the WFPC2 CHIP-3 field of Soria et al. (1996) to a 50% completeness magnitude limit of [F160W]=23.8. This field is located at a distance of 08'50" (~9 kpc) south of the center of the galaxy. The luminosity function (LF) shows a marked discontinuity at [F160W]=20.0. This is 1-2 mag above the tip of the red giant branch (TRGB) expected for an old population (~12 Gyr) at the distance modulus of NGC 5128. We propose that the majority of stars above the TRGB have intermediate ages (~2 Gyr), in agreement with the WFPC2 observations of Soria et al. (1996). Five stars with magnitudes brighter than the LF discontinuity are most probably due to Galactic contamination. The weighted average of the mean giant branch color above our 50% completeness limit is [F110W]-[F160W]=1.22+-0.08 with a dispersion of 0.19 mag. From our artificial-star experiments we determine that the observed spread in color is real, suggesting a real spread in metallicity. We estimate the lower and upper bounds of the stellar metallicity range by comparisons with observations of Galactic star clusters and theoretical isochrones. Assuming an old population, we find that, in the halo field of NGC 5128 we surveyed, stars have metallicities ranging from roughly 1% of solar at the blue end of the color spread to roughly solar at the red end, with a mean of [Fe/H]=-0.76 and a dispersion of 0.44 dex.Comment: Accepted for publication in AJ, 23 pages of text, 13 figures, uses aastex v5.

Effects of Caregiver Burden and Satisfaction on Affect of Older End-Stage Renal Disease Patients and Their Spouses

We examined the extent to which a 2-factor model of affect explains how the burdens and satisfactions experienced by caregivers influence their own well-being and that of the spouses for whom they provide care. Using data from 315 older patients with end-stage renal disease and their spouses, we extended tests of Lawton et al.\u27s (1991) 2-factor model both longitudinally and dyadically. Multilevel modeling analyses partially support the 2-factor model. Consistent with the model, mean caregiver burden has a stronger effect on both caregiver and patient negative affect than does mean caregiver satisfaction. Contrary to the model, mean caregiver satisfaction has an effect on caregiver positive affect that is similar to that of mean caregiver burden, and it has no effect on patient positive affect. Time-varying effects of caregiver burden are consistent with the 2-factor model for caregiver but not patient negative affect. Time-varying effects of caregiver satisfaction are not consistent with the 2-factor model for either patients or caregivers. Results highlight the powerful role of caregiver burden for both caregivers and patients and suggest important new directions for conducting health-related research with late-life marital dyads

Vertical integration and firm boundaries : the evidence

Since Ronald H. Coase's (1937) seminal paper, a rich set of theories has been developed that deal with firm boundaries in vertical or input–output structures. In the last twenty-five years, empirical evidence that can shed light on those theories also has been accumulating. We review the findings of empirical studies that have addressed two main interrelated questions: First, what types of transactions are best brought within the firm and, second, what are the consequences of vertical integration decisions for economic outcomes such as prices, quantities, investment, and profits. Throughout, we highlight areas of potential cross-fertilization and promising areas for future work

Genome Sequence Of Bacillus Safensis Cfa06, Isolated From Biodegraded Petroleum In Brazil.

Bacillus safensis is a microorganism recognized for its biotechnological and industrial potential due to its interesting enzymatic portfolio. Here, as a means of gathering information about the importance of this species in oil biodegradation, we report a draft genome sequence of a strain isolated from petroleum.

Woodland Type and Spatial Distribution of Nymphal Ixodes scapularis (Acari: Ixodidae)

Spatial distribution patterns of black-legged ticks, Ixodes scapularis, in deciduous and coniferous woodlands were studied by sampling ticks in different woodland types and at sites from which deer had been excluded and by quantifying movement patterns of tick host animals (mammals and birds) at the Lighthouse Tract, Fire Island, NY, from 1994 to 2000. Densities of nymphal ticks were greater in deciduous than coniferous woods in 3 of 7 yr. Only engorged ticks survived the winter, and overwintering survival of engorged larvae in experimental enclosures did not differ between deciduous and coniferous woods. Nymphs were not always most abundant in the same forest type as they had been as larvae, and the habitat shift between life stages differed in direction in different years. Therefore, forest type by itself did not account for tick distribution patterns. Nymphal densities were lower where deer had been excluded compared with areas with deer present for 3 yr after exclusion, suggesting that movement patterns of vertebrate hosts influenced tick distribution, but nymphal densities increased dramatically in one of the enclosures in the fourth year. Therefore, movements of ticks on animal hosts apparently contribute substantially to tick spatial distribution among woodland types, but the factor(s) that determine spatial distribution of nymphal I. scapularis shift from year to year

Africanizing scientific knowledge: the Multilateral Initiative on Malaria as a model?

In November 2009, the fifth Pan African Malaria conference was held in Nairobi. Thirteen years after the founding initiative in Dakar, the first African Secretariat based in Africa (TANZANIA) organized this major event for the malaria community. Looking back, it has been a long way: changes in the research landscape, new funding opportunities came out and establishment of new partnerships between Europe, America and Africa. Goals identified in 1997 have not all been achieved because the critical mass of scientists has not been reached yet. However a new generation of African scientists have emerged through MIM/TDR funding and advocacy for more support remains on the agenda. Could it be rightly stated today that the MIM concept reflects the africanization of malaria research

Interferon α/β and Interleukin 12 Responses to Viral Infections: Pathways Regulating Dendritic Cell Cytokine Expression In Vivo

Interferon (IFN)-α/β and interleukin (IL)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. The studies presented here identified a novel subset of dendritic cells (DCs) as major producers of the cytokines during murine cytomegalovirus (MCMV) but not lymphocytic choriomeningitis virus (LCMV) infections. These DCs differed from those activated by Toxoplasma antigen but were related to plasmacytoid cells, as assessed by their CD8α+Ly6G/C+CD11b− phenotype. Another DC subset (CD8α2Ly6G/C−CD11b+) also contributed to IL-12 production in MCMV-infected immunocompetent mice, modestly. However, it dramatically increased IL-12 expression in the absence of IFN-α/β functions. Conversely, IFN-α/β production was greatly reduced under these conditions. Thus, a cross-regulation of DC subset cytokine responses was defined, whereby secretion of type I IFNs by CD8α+ DCs resulted in responses limiting IL-12 expression by CD11b+ DCs but enhancing overall IFN-α/β production. Taken together, these data indicate that CD8α+Ly6G/C+CD11b− DCs play important roles in limiting viral replication and regulating immune responses, through cytokine production, in some but not all viral infections. They also illustrate the plasticity of cellular sources for innate cytokines in vivo and provide new insights into the roles of IFNs in shaping immune responses to viruses