Analysis of Influenza and RSV dynamics in the community using a 'Local Transmission Zone' approach.

Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored. Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons. We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy.

Conditional protein stabilization via the small molecules Shld-1 and rapamycin increases the signal-to-noise ratio with tet-inducible gene expression.

Cellular mechanisms control one or more of the three basic levels of regulation (transcription, translation, and protein activity/locality), allowing for finely tuned spatial and temporal regulation of protein expression patterns. Gene regulation constructs in wide use today often employ a constitutively expressed transcription factor whose activity is determined by the presence or absence of a small molecule. A case in point is the tet transcription system, wherein transcription is regulated by doxycycline (Dox), allowing the researcher to turn protein expression on or off depending on the presence/absence of Dox. However in many applications of that system, there is basal transcription from the promoter element that is independent of Dox. Moreover, in vivo, heterogeneous distribution of Dox leads to concurrent differences in gene expression. We addressed these limitations by introducing conditional destabilizing elements to the system. First, we created a transactivator protein fusion regulated at the additional level of protein stability. This modification enabled a system that demonstrated an off state that is less sensitive to variations in Dox concentrations. We also regulated the stability of the protein expressed from the tet operator cassette, observing greatly improved signal-to-noise ratios. The results underscore how investigator-defined regulation at multiple levels of protein expression can attain afiner degree of control over the final expression of introduced genes.

Immune response and virus population composition: HIV as a case study.

Based on the current understanding of the immune response, we present what we believe to be a new model of intrahost virus dynamics. The model takes into account the relationship between virus replication rate and the level of antigen displayed by infected cells, and shows how the cell-directed immune response controls both virus load and virus replication rate. In contrast to conventional wisdom, it shows that the predominant virus variant does not necessarily have the highest replication rate. A strong immune response produces a selective advantage for latent viruses, whereas a deteriorating immune response invites in viruses of higher replication rates. The model is analysed in light of the well-studied HIV/AIDS disease progression, and shows how a wide range of major, seemingly unrelated issues in the study of HIV may be accounted for in a simple and unified manner.