Peter H. Hagedorn | Searcharxiv

arXiv2006

Brownian Motion after Einstein: Some new applications and new experiments

The first half of this chapter describes the development in mathematical models of Brownian motion after Einstein's seminal papers and current applications to optical tweezers. This instrument of choice among single-molecule biophysicists is also an instrument of precision that requires an understanding of Brownian motion beyond Einstein's. This is illustrated with some applications, current and potential, and it is shown how addition of a controlled forced motion on the nano-scale of the tweezed object's thermal motion can improve the calibration of the instrument in general, and make it possible also in complex surroundings. The second half of the present chapter, starting with Sect. 9, describes the co-evolution of biological motility models with models of Brownian motion, including very recent results for how to derive cell-type-specific motility models from experimental cell trajectories.

physics.bio-ph↗

arXiv2004

Functional immunomics: Microarray analysis of IgG autoantibody repertoires predicts the future response of NOD mice to an inducer of accelerated diabetes

One's present repertoire of antibodies encodes the history of one's past immunological experience. Can the present autoantibody repertoire be consulted to predict resistance or susceptibility to the future development of an autoimmune disease? Here we developed an antigen microarray chip and used bioinformatic analysis to study a model of type 1 diabetes developing in non-obese diabetic (NOD) male mice in which the disease was accelerated and synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We obtained sera from 19 individual mice, treated the mice to induce cyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9 mice became severely diabetic while 10 mice permanently resisted diabetes. We again obtained serum from each mouse afterCAD induction. We then analyzed the patterns of antibodies in the individualmice to 266 different antigens spotted on the antigen chip. We identified a select panel of 27 different antigens (10% of the array) that revealed a pattern of IgG antibody reactivity in the pre-CAD serathat discriminated between the mice resistant or susceptible to CAD with 100% sensitivity and 82% specificity (p=0.017). Surprisingly, the set of IgG antibodies that was informative before CAD induction did not separate the resistant and susceptible groups after the onset of CAD; new antigens became criticalfor post-CAD repertoire discrimination. Thus, at least for a model disease, present antibody repertoires can predict future disease; predictive and diagnostic repertoires can differ; and decisive information about immune system behavior can be mined by bioinformatic technology. Repertoires matter.

q-bio.TO↗