Novel multiparameter correlates of Coxiella burnetii infection and vaccination identified by longitudinal deep immune profiling.

Q-fever is a flu-like illness caused by Coxiella burnetii (Cb), a highly infectious intracellular bacterium. There is an unmet need for a safe and effective vaccine for Q-fever. Correlates of immune protection to Cb infection are limited. We proposed that analysis by longitudinal high dimensional immune (HDI) profiling using mass cytometry combined with other measures of vaccination and protection could be used to identify novel correlates of effective vaccination and control of Cb infection. Using a vaccine-challenge model in HLA-DR transgenic mice, we demonstrated significant alterations in circulating T-cell and innate immune populations that distinguished vaccinated from naïve mice within 10 days, and persisted until at least 35 days post-vaccination. Following challenge, vaccinated mice exhibited reduced bacterial burden and splenomegaly, along with distinct effector T-cell and monocyte profiles. Correlation of HDI data to serological and pathological measurements was performed. Our data indicate a Th1-biased response to Cb, consistent with previous reports, and identify Ly6C, CD73, and T-bet expression in T-cell, NK-cell, and monocytic populations as distinguishing features between vaccinated and naïve mice. This study refines the understanding of the integrated immune response to Cb vaccine and challenge, which can inform the assessment of candidate vaccines for Cb.

How individuals coping with HIV/AIDS use the Internet.

Although identified 20 years ago, HIV/AIDS remains among the most serious disease epidemics of modern times. Because of the stigmatization associated with infection, no health crisis has rivaled HIV/AIDS in underscoring the need for emotional, informational and instrumental support. The critical role that support plays in coping with HIV/AIDS is well documented. Adults with HIV/AIDS have utilized traditional means of support--family, friends and community-based service organizations--in coping with their illness. Recently, however, the Internet has been recognized as a potential avenue for support. Although the Internet may prove promising, little is known about how the wide array of resources available via the Internet is used. The purpose of this study was to investigate how individuals with HIV/AIDS use the Internet in coping with their illness. This research study employed a descriptive qualitative design that used in-depth, semi-structured, face-to-face interviews for data collection. The sample of 10 purposefully selected individuals living with HIV/AIDS reflected diversity in gender, age, race, education, employment, number of years living with HIV/AIDS and Internet use. Data analysis guided by the constant comparative method revealed four themes. Individuals with HIV/AIDS use the Internet for finding information, making social connections, advocating and escaping.

Coping in cyberspace: the impact of Internet use on the ability of HIV-positive individuals to deal with their illness.

The human immunodeficiency virus (HIV) poses one of the greatest health threats of modern times. The Internet provides unparalleled access to resources that can assist individuals coping with HIV infection. Despite the promise of online resources to help individuals manage and cope with their illness, few studies have investigated the impact of their use. Those that have looked primarily at Internet use from a group perspective. These studies were usually "bounded" as well, focusing on electronic support groups or highly structured computer-based support systems that offer select users prescribed resource options. Little is known about how individuals who are "on their own"--without access to these services--use the vast, unstructured array of resources available through the Internet. The purpose of this study was to investigate the impact of Internet use on the coping ability of HIV-positive individuals. This research study employed a descriptive qualitative design that used indepth, semi structured, face-to-face interviews for data collection. The sample of 10 purposefully selected HIV-positive individuals reflected diversity in gender, age, race, education, employment, number of years living with HIV, and Internet use. Data analysis guided by the constant comparative method revealed that the impact of Internet use on coping ability involved three themes: The Internet promotes empowerment, augments social support, and facilitates helping others.

Interactions of Escherichia coli SO-187 tRNA(IVal) with Bacillus stearothermophilus valine-tRNA synthetase studied by 13C-NMR.

Uracil isotopically labelled with 13C at C4 and C5 has been incorporated into nucleic acids of the Escherichia coli uracil auxotroph, SO-187. [4,5-13C]uracil-labeled tRNA(IVal) was isolated and purified. 13C longitudinal relaxation times measured at 67.8 MHz demonstrated that the C5 dipole caused a 20-50% increase in the C4 relaxation. Interactions of this tRNA with valine-tRNA synthetase (VTS) purified from Bacillus stearothermophilus were established by 13C-NMR. Specific spectral changes were seen at 4-thiouridine, ribothymidine and pseudouridine of the 'bend' in the three-dimensional structure, and particularly at the uridine-5-oxyacetic acid in the wobble position of the anticodon. Thus, the protein seems to be in contact along the entire tRNA molecule, including the anticodon loop.

In vivo [31P]NMR studies on the influence of age on rat brain hypoxia.

In this paper the response of cerebral phosphate metabolism to mild hypoxia in young, medium and old rats has been studied via in-vivo [31P]nuclear magnetic resonance (NMR). It was found that the young adults (5-6 months) were more sensitive to this mild stress than either the mature adult (11-12 months) or senescent (23-24 months) rats even though the depth of hypoxia (paO2 = 45-55 mm Hg) was equal for all age groups. They displayed an earlier onset of acidosis, a greater fall in PCr and larger rise in Pi. This response is presumably an attempt to maintain adequate adenosine triphosphate (ATP) levels via anaerobic glycolysis. In contrast, mature adults and senescent adults appear to be able to maintain ATP levels by increasing mitochondrial rates. Acidosis is less severe as are drops in PCr and rises in Pi. Recovery is less complete for the young rats: Pi levels remain high while PCr and pHi levels stay low after normoxia has been reinstigated. All metabolite levels in the mature and senescent adults return to within 10% of control levels. All the data were analyzed and differences were found to be statistically significant. This study reveals that, contrary to popular belief, mature and old rats respond more favorably to reduced O2 than younger individuals. This is due to a more severe anaerobic acidosis in the latter age group. Speculations to explain this disparity are based on the fact that previous in-vitro studies involve systems that are totally or partially disconnected from the organism will not account for important feedback control present in an in-vivo system as studied here.

Aging, diazepam exposure and benzodiazepine receptors in rat cortex.

Densities of two benzodiazepine receptor subtypes (BDZ1 and BDZ2) in the frontal cortex of 10- and 27-month-old male Fischer-344 rats were nearly identical. Acute diazepam pretreatment produced a 73% increase in receptor density in the aged rats, mainly in the BDZ2 sites, whereas with the normal adult rat the density increased 42%, primarily due to stimulation of BDZ1 sites. Chronic exposure elicited similar increases of 28-29% in both normal and aged rats but there were subtle differences in the distribution of specific receptors. This study demonstrates a definite effect of age on the response of benzodiazepine receptors to diazepam pretreatment.