Pre-ART Levels of Inflammation and Coagulation Markers Are Strong Predictors of Death in a South African Cohort with Advanced HIV Disease

BACKGROUND: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. METHODS: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. RESULTS: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). CONCLUSIONS: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted. TRIAL REGISTRATION: Parent study: ClinicalTrials.gov NCT00342355

The Host Galaxies of AGN

We examine the properties of the host galaxies of 22,623 narrow-line AGN with 0.02<z<0.3 selected from a complete sample of 122,808 galaxies from the Sloan Digital Sky Survey. We focus on the luminosity of the [OIII]$\lambda$5007 emission line as a tracer of the strength of activity in the nucleus. We study how AGN host properties compare to those of normal galaxies and how they depend on L[OIII]. We find that AGN of all luminosities reside almost exclusively in massive galaxies and have distributions of sizes, stellar surface mass densities and concentrations that are similar to those of ordinary early-type galaxies in our sample. The host galaxies of low-luminosity AGN have stellar populations similar to normal early-types. The hosts of high- luminosity AGN have much younger mean stellar ages. The young stars are not preferentially located near the nucleus of the galaxy, but are spread out over scales of at least several kiloparsecs. A significant fraction of high- luminosity AGN have strong H$\delta$ absorption-line equivalent widths, indicating that they experienced a burst of star formation in the recent past. We have also examined the stellar populations of the host galaxies of a sample of broad-line AGN. We conclude that there is no significant difference in stellar content between type 2 Seyfert hosts and QSOs with the same [OIII] luminosity and redshift. This establishes that a young stellar population is a general property of AGN with high [OIII] luminosities.Comment: submitted to MNRAS, 44 pages, version with full resolution figures available at http://www.mpa-garching.mpg.de/~gamk/agnpaper/agnpaper.p

Optical Trapping with High Forces Reveals Unexpected Behaviors of Prion Fibrils

Amyloid fibrils are important in diverse cellular functions, feature in many human diseases and have potential applications in nanotechnology. Here we describe methods that combine optical trapping and fluorescent imaging to characterize the forces that govern the integrity of amyloid fibrils formed by a yeast prion protein. A crucial advance was to use the self-templating properties of amyloidogenic proteins to tether prion fibrils, enabling their manipulation in the optical trap. At normal pulling forces the fibrils were impervious to disruption. At much higher forces (up to 250 pN), discontinuities occurred in force-extension traces before fibril rupture. Experiments with selective amyloid-disrupting agents and mutations demonstrated that such discontinuities were caused by the unfolding of individual subdomains. Thus, our results reveal unusually strong noncovalent intermolecular contacts that maintain fibril integrity even when individual monomers partially unfold and extend fibril length.National Institutes of Health (U.S.) (Grant GM025874)National Science Foundation (U.S.). CAREER (Award 0643745

Composition of foods : baby foods : raw, processed, prepared /

Loose-leaf for updating.Chiefly tables.Includes bibliography.Mode of access: Internet

Composition of foods : fruits and fruit juices : raw, processed, prepared /

Mode of access: Internet

Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses

Although tissue-resident memory T cells (TRM cells) are critical in fighting infection, their fate after local pathogen re-encounter is unknown. Here we found that skin TRM cells engaged virus-infected cells, proliferated in situ in response to local antigen encounter and did not migrate out of the epidermis, where they exclusively reside. As a consequence, secondary TRM cells formed from pre-existing TRM cells, as well as from precursors recruited from the circulation. Newly recruited antigen-specific or bystander TRM cells were generated in the skin without displacement of the pre-existing TRM cell pool. Thus, pre-existing skin TRM cell populations are not displaced after subsequent infections, which enables multiple TRM cell specificities to be stably maintained within the tissue.S.L.P. was supported by the University of Melbourne (Elizabeth and Vernon Puzey Postgraduate Scholarship). T.G. was supported by a fellowship from the Sylvia and Charles Viertel Charitable Foundation. This work was supported by the National Health and Medical Research Council of Australia (to S.N.M. and L.K.M.) and the Australian Research Council (to S.N.M.)