The study of metabolomics can provide valuable information about biochemical pathways and processes at the molecular level. There have been many reports that have examined the structure, identity and concentrations of metabolites in biological systems. However, the binding of metabolites with proteins is also of growing interest. This review examines past reports that have looked at the binding of various types of metabolites with proteins. An overview of the techniques that have been used to characterize and study metabolite-protein binding is first provided. This is followed by examples of studies that have investigated the binding of hormones, fatty acids, drugs or other xenobiotics, and their metabolites with transport proteins and receptors. These examples include reports that have considered the structure of the resulting solute-protein complexes, the nature of the binding sites, the strength of these interactions, the variations in these interactions with solute structure, and the kinetics of these reactions. The possible effects of metabolic diseases on these processes, including the impact of alterations in the structure and function of proteins, are also considered.

Background: Mortality after congenital heart defect surgery has dropped dramatically in the last few decades. Current research on long-term outcomes has focused on preventing secondary neurological sequelae, for which embolic burden is suspected. In children, little is known of the correlation between specific surgical maneuvers and embolic burden. Transcranial Doppler ultrasound is highly useful for detecting emboli but has not been widely used with infants and children. Methods: Bilateral middle cerebral artery blood flow was continuously monitored from sternal incision to chest closure in 20 infants undergoing congenital heart defect repair or palliative surgery. Embolus counts for specific maneuvers were recorded using widely accepted criteria for identifying emboli via high-intensity transient signals (HITS). Results: An average of only 13% of all HITS detected during an operation were correlated with any of the surgical maneuvers of interest. The highest mean number of HITS associated with a specific maneuver occurred during cross-clamp removal. Cross-clamp placement also had elevated HITS counts that significantly differed from other maneuvers. Conclusions: In this study of infants undergoing cardiac surgery with cardiopulmonary bypass, the great majority of HITS detected are not definitively associated with a specific subset of surgical maneuvers. Among the measured maneuvers, removal of the aortic cross-clamp was associated with the greatest occurrence of HITS. Future recommended research efforts include identifying and confirming other sources for emboli and longitudinal outcome studies to determine if limiting embolic burden affects long-term neurological outcomes.

Pneumotactile somatosensory stimulation is a potent stimulus that can evoke large, rapid hemodynamic changes, with adaptation between successive stimulus applications. Due to its high temporal resolution, fTCD is useful for identifying quickly evolving hemodynamic responses, and for correlating changes in hemodynamic parameters such as pulsatility index (PI) and CBFV.

Functional transcranial Doppler ultrasound (fTCD) is a noninvasive sensing modality that measures cerebral blood flow velocity (CBFV) with high temporal resolution. CBFV change is correlated to changes in cerebral oxygen uptake, enabling fTCD to measure brain activity and lateralization with high accuracy. However, few studies have examined the relationship of CBFV change during visual search and visual memory tasks. Here a protocol to compare lateralization between these two similar cognitive tasks using fTCD is demonstrated. Ten healthy volunteers (age 21±2 years) were shown visual scenes on a computer and performed visual search and visual memory tasks while CBFV in the bilateral middle cerebral arteries was monitored with fTCD. Each subject completed 40 trials, consisting of baseline (25 s), calibration (variable), instruction (2.5 s), and task (20 s) epochs. Lateralization was computed for each task by calculating the bilateral CBFV envelope percent change from baseline and subtracting the right side from the left side. The results showed significant lateralization (p < 0.001) of the visual memory and visual search tasks, with memory reaching lateralization of 1.6% and search reaching lateralization of 0.5%, suggesting that search is more right lateralized (and therefore may be related to “holistic” or global perception) and memory is more left lateralized (and therefore may be related to local perception). This method could be used to compare cerebral activity for any related cognitive tasks as long as the same stimulus is used in all tasks. The protocol is straightforward and the equipment is inexpensive, introducing a low-cost high temporal resolution technique to further study lateralization of the brain.

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Systematic patterns of eye movements during scene perception suggest a functional distinction between two viewing modes: an ambient mode (characterized by short fixations and large saccades) thought to reflect dorsal activity involved with spatial analysis, and a focal mode (characterized by long fixations and small saccades) thought to reflect ventral activity involved with object analysis. Little neuroscientific evidence exists supporting this claim. Here, functional transcranial Doppler ultrasound was used to investigate whether these modes show hemispheric specialization. Participants viewed scenes for 20 seconds under instructions to search or memorize. Overall, early viewing was right lateralized, whereas later viewing was left lateralized. This right-to-left shift interacted with viewing task (more pronounced in the memory task). Importantly, changes in lateralization correlated with changes in eye movements. This is the first demonstration of right hemisphere bias for eye movements servicing spatial analysis and left hemisphere bias for eye movements servicing object analysis.

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