Human serum albumin (HSA) is the most abundant protein in the circulatory system. Its principal function is to transport fatty acids, but it is also capable of binding a great variety of metabolites and drugs. Despite intensive efforts, the detailed structural basis of fatty acid binding to HSA has remained elusive. We have now determined the crystal structure of HSA complexed with five molecules of myristate at 2.5 A resolution. The fatty acid molecules bind in long, hydrophobic pockets capped by polar side chains, many of which are basic. These pockets are distributed asymmetrically throughout the HSA molecule, despite its symmetrical repeating domain structure.

Changes in brain activity accompanying shifts in vigilance and arousal can interfere with the study of other intrinsic and task-evoked characteristics of brain function. However, the difficulty of tracking and modeling the arousal state during functional MRI (fMRI) typically precludes the assessment of arousal-dependent influences on fMRI signals. Here we combine fMRI, electrophysiology, and the monitoring of eyelid behavior to demonstrate an approach for tracking continuous variations in arousal level from fMRI data. We first characterize the spatial distribution of fMRI signal fluctuations that track a measure of behavioral arousal; taking this pattern as a template, and using the local field potential as a simultaneous and independent measure of cortical activity, we observe that the timevarying expression level of this template in fMRI data provides a close approximation of electrophysiological arousal. We discuss the potential benefit of these findings for increasing the sensitivity of fMRI as a cognitive and clinical biomarker.resting-state fMRI | spontaneous fluctuations | arousal | electrophysiology D uring both active task engagement and rest, the human brain exhibits fluctuations in neural activity that can be readily measured using functional MRI (fMRI). In recent years, examining the spatiotemporal organization of these fluctuations has generated novel insight into the functional architecture of the human brain and its changes with development and disease (1). A prominent approach for mapping this architecture is to study interregional correlations in the fMRI signal fluctuations, which, even during rest, appear to be indicative of networks supporting specific functions. However, despite the promise and rapidly increasing application of this technique in the endeavor of brain connectomics (2-4), its sensitivity and specificity are compromised by unexplained variability arising from multiple neural and nonneural sources (e.g., refs. 5-11). As a result, the interpretation of resting-state fMRI data and the efficacy of these data as a biomarker rely critically on understanding and accounting for such sources of variability (11-13).Changes in arousal, mediated by an interaction between the ascending arousal system and the neocortex, may strongly modulate neuronal activity in much of the brain (14-18). Indeed, changes in vigilance and arousal (hereafter described jointly as "arousal"), which can be especially prevalent during the passive and uncontrolled resting state, result in fMRI signal variability that may confound the extraction of functional networks (5, 19). For example, the amplitude and extent of correlations in restingstate fMRI data vary with EEG-and behaviorally defined indicators of drowsiness and light sleep (20)(21)(22)(23)(24)(25) and are altered by sleep deprivation (26-28) and caffeine-induced changes in arousal state (29). Distinct patterns of functional connectivity across multiple networks have been associated with distinct EEG-defined sleep stages (30, 31) with sufficient reliabilit...

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