Biology subjects

Camargo, M. M. d.

Publications and source records attributed to Camargo, M. M. d..

3 recordsLinked to original sources

bioRxiv2018

Hysteresis in the thermal relaxation dynamics of an immune complex as basis for molecular memory

Proteins search their vast conformational space in order to attain the native fold and bind productively to relevant biological partners. In particular, most proteins must be able to alternate between at least one active conformational state and back to an inactive conformer, especially for the macromolecules that perform work and need to optimize energy usage. This property may be invoked by a physical stimulus (temperature, radiation) or by a chemical ligand, and may occur through mapping of the protein external environment onto a subset of protein conformers. We have stimulated with temperature cycles two partners of an immune complex before and after assembly, and revealed that properties of the external stimulus (period, phase) are also found in the characteristics of the immune complex (i.e. periodic variations in the binding affinity). These results are important for delineating the bases of molecular memory ex vivo and could serve in the optimization of protein based sensors.

biophysics↗

bioRxiv2018

Febrile temperatures increase in vitro antibody affinity for malaria and dengue antigens

Fever is a regulated elevation in the body setpoint temperature and may arise as a result of infectious and noninfectious causes. While beneficial in modulating immune responses to infection, the potential of febrile temperatures in regulating antigen binding affinity to antibodies has not been explored. We have investigated this process under in vitro conditions using selected malaria or dengue antigens and specific monoclonal antibodies, and observed a marked increase in the affinity of these antibody-antigen complexes at 40{degrees}C, compared to physiological (37{degrees}C) or pathophysiological temperatures (42{degrees}C). Induced thermal equilibration of the protein partners at these temperatures, prior to measurements, further increased their binding affinity. These results may indicate an unexpected beneficial and adaptive role for fever in vivo, and highlight the positive role of thermal priming in enhancing protein-protein affinity for samples of scarce availability.

biochemistry↗

bioRxiv2017

Negative Correlation Between The Expression Of tlr4 And grp78 Is Characteristic Of Sepsis Onset And Progression

In sepsis caused by Gram-negative bacteria, modulation of Toll-like receptor 4 (TLR4) activity by modulators such as glucose-regulated protein 78 kDa (GRP78), is believed to shift the equilibrium between pro- and anti-inflammatory downstream signaling cascade. We measured daily mRNA tlr4 and grp78 expression levels in peripheral blood of a cohort of septic patients, upon intensive care admission, and modeled these mRNA values based on a sine damping function. We obtained negative correlations between tlr4 and grp78 mRNA in the survivor group. In contrast, such relation is lost in the deceased patients. Loss of homeostasis predicted by our model within the initial 5 days of hospitalization was confirmed by death of those patients up to 28 days later. Measuring the correlation patterns of the expression of these two genes serves as a robust means to gauge sepsis progression, requiring only three points of measurement on the first day of hospitalization.

molecular biology↗