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Amino acids are necessary for life, and many must be consumed because they cannot be endogenously synthesized. Typically, we eat them as proteins and peptides, which have little taste. However, we also directly ingest free amino acids, several of which are aversive because they elicit bitterness. This bitterness often prevents many patient populations from taking formulas and supplements containing free amino acids. Here, we characterize which amino acids are the most bitter, their concentration-intensity functions, and individual differences in bitterness perception, and we explore how sodium salts suppress the bitterness of amino acids. We found that the essential amino acids comprise the most bitter stimuli, with six of them conveying the most bitterness. Clustering and correlating amino acids by individual differences in bitterness perception show that there are approximately four groupings of amino acids and suggest that within these clusters, amino acids may be activating the same or overlapping TAS2Rs. We also show that bitterness can be largely suppressed by sodium salts for 5 of the 6 most bitter amino acids. These results hold promise for managing the bitter taste of nutritional supplements that contain amino acids and improving compliance.

The savory or umami taste of the amino acid glutamate is synergistically enhanced by the addition of the purines inosine 5'-monophosphate (IMP) and guanosine 5'-monophosphate (GMP) disodium salt. We hypothesized that the addition of purinergic ribonucleotides, along with the pyrimidine ribonucleotides, would decrease the absolute detection threshold of (increase sensitivity to) l-glutamic acid potassium salt (MPG). To test this, we measured both the absolute detection threshold of MPG alone and with a background level (3 mM) of 5 different 5'-ribonucleotides. The addition of the 3 purines IMP, GMP, and adenosine 5'-monophosphate (AMP) lowered the MPG threshold in all participants (P < 0.001), indicating they are positive modulators or enhancers of glutamate taste. The average detection threshold of MPG was 2.08 mM, and with the addition of IMP, the threshold was decreased by approximately 1.5 orders of magnitude to 0.046 mM. In contrast to the purines, the pyrimidines uridine 5'-monophosphate (UMP) and cytidine 5'-monophosphate (CMP) yielded different results. CMP reliably raised glutamate thresholds in 10 of 17 subjects, suggesting it is a negative modulator or diminisher of glutamate taste for them. The rank order of effects on increasing sensitivity to glutamate was IMP > GMP> AMP >> UMP// CMP. These data confirm that ribonucleotides are modulators of glutamate taste, with purines enhancing sensitivity and pyrimidines displaying variable and even negative modulatory effects. Our ability to detect the co-occurrence of glutamate and purines is meaningful as both are relatively high in evolutionarily important sources of nutrition, such as insects and fermented foods., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In addition to being responsible for bitter taste, type 2 taste receptors (T2Rs) regulate endocrine, behavioral, and immunological responses. T2R agonists include indicators of incoming threats to metabolic homeostasis, pathogens, and irritants. This review will provide an overview of T2R-regulated processes throughout the body that function defensively. We propose a broader definition of T2Rs as chemosensory sentinels that monitor toxic, metabolic, and infectious threats and initiate defensive responses., Competing Interests: Conflict of Interest Statement Nothing declared.

Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the "antenatal investment hypothesis". We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.

Successful implementation in a redesigning organization does not happen without a sound design, good implementation planning and effective leadership. The focus of the implementation preparation must change prior to and after the "go live" implementation date. Implementation preparation requires intentional steps to build systems, communicate effectively and develop operational understanding among clinicians, physicians and management. Early effort should focus on planning for efficient day-to-day operations, development of measurement systems and contingency planning. Immediately prior to and after implementation the focus should be on communication, goal setting, issues prioritization and fact-based issues resolution. After the first couple of months of implementation, the focus should move toward mentoring teams/individuals, building outcome measurement systems, identifying sources of future improvement and transferring more authority as appropriate to teams. Commit to comprehensive implementation preparation. Time spent on implementation preparation will pay large dividends during the challenging times of transitioning your organization to a redesigned world.