Biology subjects

Stan, R.

Publications and source records attributed to Stan, R..

3 recordsLinked to original sources

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

A mathematical model relates intracellular TLR4 oscillations to sepsis progression

Oscillations drive many biological processes and their modulation is determinant for various pathologies. In sepsis syndrome, Toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its expression and activity, along with its intracellular trafficking rates shift the equilibrium between the pro- and anti-inflammatory downstream signaling cascades, leading to either the physiological resolution of the bacterial stimulation or to sepsis. We hypothesize that the initial tlr4 expression in patients diagnosed with sepsis and TLR4 dynamic concentration changes on the cell membrane or intracellularly, dictates how the sepsis syndrome is initiated. Using a set of three differential equations, we defined the TLR4 flux between relevant cell organelles. We obtained three different regions in the phase space: 1. a limit-cycle describing unstimulated physiological oscillations, 2. a fixed-point attractor resulting from moderate LPS stimulation that is resolved and 3. a double-attractor resulting from sustained LPS stimulation that leads to sepsis. We tested the models against hospital data of sepsis patients and we correctly evaluate the clinical outcome of these patients.

immunology↗

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↗