The l‐type amino acid transporter 1 (LAT1, SLC7A5) imports dietary amino acids and amino acid drugs (e. g., l‐DOPA) into the brain, and plays a role in cancer metabolism. Though there have been numerous reports of LAT1‐targeted amino acid‐drug conjugates (prodrugs), identifying the structural determinants to enhance substrate activity has been challenging. In this work, we investigated the position and orientation of a carbonyl group in linking hydrophobic moieties including the anti‐inflammatory drug ketoprofen to l‐tyrosine and l‐phenylalanine. We found that esters of meta‐carboxyl l‐phenylalanine had better LAT1 transport rates than the corresponding acylated l‐tyrosine analogues. However, as the size of the hydrophobic moiety increased, we observed a decrease in LAT1 transport rate with a concomitant increase in potency of inhibition. Our results have important implications for designing amino acid prodrugs that target LAT1 at the blood‐brain barrier or on cancer cells.
Although the domestic pigeon is commonly used in learning experiments, it is a notoriously difficult subject in auditory psychophysical experiments, even those in which it need only respond when it detects a sound. This is because pigeons tend to respond in the absence of sound -that is, they have a high false-positive rate-which makes it difficult to determine a pigeon's audiogram. However, false positives are easily controlled in the method of conditioned suppression/avoidance, in which a pigeon is trained to peck a key to obtain food and to stop pecking whenever it detects a sound that signals impending electric shock. Here, we describe how to determine psychophysical thresholds in pigeons using a method of conditioned suppression in which avoidable shock is delivered through a bead chain wrapped around the base of a pigeon's wings. The resulting audiogram spans the range from 2 to 8000 Hz; it falls approximately in the middle of the distribution of previous pigeon audiograms and supports the finding of Kreithen and Quine (Journal of Comparative Physiology 129:1-4, 1979) that pigeons hear infrasound.
The pure-tone thresholds of three mallard ducks were determined from 16 Hz to 9 kHz. The purpose was to determine whether the mallard duck hears infrasound, which then may potentially be used for navigation, similar to how it is proposed that pigeons use it for homing. At a level of 60 dB sound pressure level (re 20 μN/m), their hearing range extends 6.85 octaves from 66 Hz to 7.6 kHz, with a best sensitivity of 12.5 dB at 2 kHz. However, at no frequency, including the lowest tested, were the ducks' thresholds lower than those of humans. Therefore, unlike pigeons and chickens, but like budgerigars, mallard ducks do not hear infrasound. Thus, the fact that a bird may fly long distances does not necessarily indicate that it hears infrasound.
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