Inferring causation from time series in Earth system sciences

The heart of the scientific enterprise is a rational effort to understand the causes behind the phenomena we observe. In large-scale complex dynamical systems such as the Earth system, real experiments are rarely feasible. However, a rapidly increasing amount of observational and simulated data opens up the use of novel data-driven causal methods beyond the commonly adopted correlation techniques. Here, we give an overview of causal inference frameworks and identify promising generic application cases common in Earth system sciences and beyond. We discuss challenges and initiate the benchmark platform causeme.net to close the gap between method users and developers

Retinol and retinol-binding protein stabilize transthyretin via formation of retinol transport complex.

Transthyretin (TTR) is a plasma hormone carrier protein associated with hereditary and senile forms of systemic amyloid disease, wherein slow tetramer disassembly is thought to be an obligatory step. Plasma transport of retinol is carried out exclusively by the retinol-binding protein (RBP), through complexation with transthyretin. Using mass spectrometry to examine the subunit exchange dynamics, we find that retinol stabilizes the quaternary structure of transthyretin, through its interactions with RBP, reducing the rate of transthyretin disassembly ∼17-fold compared to apoTTR. In the absence of retinol but in the presence of RBP, transthyretin is only marginally stabilized with the rate of disassembly reduced ∼two-fold with respect to apoTTR. Surprisingly, we found two retinoids that stabilize transthyretin directly, in the absence of RBP, whereas retinol itself requires RBP in order to stabilize transthyretin. Our results demonstrate new roles for RBP and retinoids as stabilizers of transthyretin