Escape from the Phagosome: The Explanation for MHC-I Processing of Mycobacterial Antigens?

Mycobacterium tuberculosis (Mtb) is thought to live in an altered phagosomal environment. In this setting, the mechanisms by which mycobacterial antigens access the major histocompatibility class I (MHC-I) processing machinery remain incompletely understood. There is evidence that Mtb antigens can be processed in both endocytic and cytosolic environments, with different mechanisms being proposed for how Mtb antigens can access the cytosol. Recently, electron microscopy was used to demonstrate that Mtb has the potential to escape the phagosome and reside in the cytosol. This was postulated as the primary mechanism by which Mtb antigens enter the MHC-I processing and presentation pathway. In this commentary, we will review data on the escape of Mtb from the cytosol and whether this escape is required for antigen presentation to CD8+ T cells

Quantifying Cerebellum Grey Matter and White Matter Perfusion Using Pulsed Arterial Spin Labeling

To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values

Heterogeneous seismic velocity structure of the upper lithosphere at Kane oceanic core complex, Mid-Atlantic Ridge

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 10 (2009): Q10001, doi:10.1029/2009GC002586.The Kane oceanic core complex (OCC) is a large, corrugated megamullion that was formed by a long-lived detachment fault at the axis of the Mid-Atlantic Ridge adjacent to Kane Fracture Zone between 2.1 and 3.3 Ma. We use refracted arrivals recorded along a 6-km-long hydrophone streamer during a multichannel seismic survey to constrain the shallow seismic velocity structure of the OCC. Results are presented in high-resolution traveltime seismic tomographic models along six lines that cover all of the main morphological features of the megamullion. The models show large lateral variability in P wave velocity within the upper ∼0.5–2.0 km of the lithosphere, and these variations correlate to first order with observed variations in lithology, documented by in situ basement samples and seafloor morphology. Lithological interpretation of the velocity models indicates that there is marked lateral variability in distribution of gabbroic intrusions, serpentinized peridotites, and basalts at scales of a few kilometers to ∼10 km. Serpentinized peridotites appear to dominate the central and older parts of the OCC. High-velocity gabbros are consistently (but not exclusively) present closer to the termination of the Kane detachment fault and toward the ends of the OCC. The structure of the lithosphere exhumed by the Kane detachment fault is far from the standard ophiolite-based Penrose model, and it does not show segment-centered magmatism that is commonly interpreted at slow spreading ridges. If the gabbros exhumed toward the termination of the OCC were emplaced deep (∼10 km) beneath the spreading axis, they may have constituted a weak zone that focused initiation of the Kane detachment fault. Alternately, as the OCC footwall was being exhumed the gabbros may have been emplaced because of dynamic changes in melt supply, changes in mantle fertility, or decompression melting. Late stage volcanism is clearly associated with a major high-angle normal fault that cuts the detachment surface; this volcanism may have been stimulated or enhanced by bending stresses in the bending footwall. The shape of the large-scale corrugated morphology of the OCC is nearly invariant in the dip direction across major changes in basement lithology, indicating that once established, the form of the Kane detachment fault was highly resistant to modification.This research was supported by NSF grants OCE-9987004 and OCE-0621660

Epidemic History and Evolutionary Dynamics of Hepatitis B Virus Infection in Two Remote Communities in Rural Nigeria

BACKGROUND: In Nigeria, hepatitis B virus (HBV) infection has reached hyperendemic levels and its nature and origin have been described as a puzzle. In this study, we investigated the molecular epidemiology and epidemic history of HBV infection in two semi-isolated rural communities in North/Central Nigeria. It was expected that only a few, if any, HBV strains could have been introduced and effectively transmitted among these residents, reflecting limited contacts of these communities with the general population in the country. METHODS AND FINDINGS: Despite remoteness and isolation, approximately 11% of the entire population in these communities was HBV-DNA seropositive. Analyses of the S-gene sequences obtained from 55 HBV-seropositive individuals showed the circulation of 37 distinct HBV variants. These HBV isolates belong predominantly to genotype E (HBV/E) (n=53, 96.4%), with only 2 classified as sub-genotype A3 (HBV/A3). Phylogenetic analysis showed extensive intermixing between HBV/E variants identified in these communities and different countries in Africa. Quasispecies analysis of 22 HBV/E strains using end-point limiting-dilution real-time PCR, sequencing and median joining networks showed extensive intra-host heterogeneity and inter-host variant sharing. To investigate events that resulted in such remarkable HBV/E diversity, HBV full-size genome sequences were obtained from 47 HBV/E infected persons and P gene was subjected to Bayesian coalescent analysis. The time to the most recent common ancestor (tMRCA) for these HBV/E variants was estimated to be year 1952 (95% highest posterior density (95% HPD): 1927-1970). Using additional HBV/E sequences from other African countries, the tMRCA was estimated to be year 1948 (95% HPD: 1924-1966), indicating that HBV/E in these remote communities has a similar time of origin with multiple HBV/E variants broadly circulating in West/Central Africa. Phylogenetic analysis and statistical neutrality tests suggested rapid HBV/E population expansion. Additionally, skyline plot analysis showed an increase in the size of the HBV/E-infected population over the last approximately 30-40 years. CONCLUSIONS: Our data suggest a massive introduction and relatively recent HBV/E expansion in the human population in Africa. Collectively, these data show a significant shift in the HBV/E epidemic dynamics in Africa over the last century