Novel Biomarkers Distinguishing Active Tuberculosis from Latent Infection Identified by Gene Expression Profile of Peripheral Blood Mononuclear Cells

BACKGROUND: Humans infected with Mycobacterium tuberculosis (MTB) can delete the pathogen or otherwise become latent infection or active disease. However, the factors influencing the pathogen clearance and disease progression from latent infection are poorly understood. This study attempted to use a genome-wide transcriptome approach to identify immune factors associated with MTB infection and novel biomarkers that can distinguish active disease from latent infection. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray analysis, we comprehensively determined the transcriptional difference in purified protein derivative (PPD) stimulated peripheral blood mononuclear cells (PBMCs) in 12 individuals divided into three groups: TB patients (TB), latent TB infection individuals (LTBI) and healthy controls (HC) (n = 4 per group). A transcriptional profiling of 506 differentially expressed genes could correctly group study individuals into three clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection (TB&LTBI) and active disease (TB) were identified, respectively. The validation study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed the expression patterns of 81% of the microarray identified genes. Decision tree analysis indicated that three genes of CXCL10, ATP10A and TLR6 could differentiate TB from LTBI subjects. Additional validation was performed to assess the diagnostic ability of the three biomarkers within 36 subjects, which yielded a sensitivity of 71% and specificity of 89%. CONCLUSIONS/SIGNIFICANCE: The transcription profiles of PBMCs induced by PPD identified distinctive gene expression patterns associated with different infectious status and provided new insights into human immune responses to MTB. Furthermore, this study indicated that a combination of CXCL10, ATP10A and TLR6 could be used as novel biomarkers for the discrimination of TB from LTBI

Spatial Vision in a Flat World: Optical and Neural Adaptations in Arthropods

We review evidence to show that in several arthropod families eyes and supporting neural control systems are shaped according to the spatial layout of their environment Amphibious crabs that live at sandy beaches and mudflats and insects that live above or below the water surface have horizontally aligned acute zones for vertical resolution in those eye regions that look at the horizon. In amphibious crabs acute zones are aligned with the horizon by visual, leg — proprioceptive and statocyst reflexes whereby optokinetic sensitivity to movement around roll and pitch axes reaches a sharp maximum at the eye equator. There is clear evidence of a position dependent mechanism of eye alignment to the horizon in at least two species of flat world crabs. Optokinetic sensitivity to movement around the yaw axis is restricted to the dorsal visual field in flat world crabs and in waterstriders with a maximum just above the eye equator. We discuss the relevance of these specialisations for spatial vision in a flat world