Every day, humans make countless decisions that require the integration of information about potential benefits (i.e. rewards) with other decision features (i.e. effort required, probability of an outcome or time delays). Here, we examine the overlap and dissociation of behavioral preferences and neural representations of subjective value in the context of three different decision features (physical effort, probability and time delays) in a healthy adult life span sample. While undergoing functional neuroimaging, participants (N = 75) made incentive compatible choices between a smaller monetary reward with lower physical effort, higher probability, or a shorter time delay versus a larger monetary reward with higher physical effort, lower probability, or a longer time delay. Behavioral preferences were estimated from observed choices, and subjective values were computed using individual hyperbolic discount functions. We found that discount rates were uncorrelated across tasks. Despite this apparent behavioral dissociation between preferences, we found overlapping subjective value-related activity in the medial prefrontal cortex across all three tasks. We found no consistent evidence for age differences in either preferences or the neural representations of subjective value across adulthood. These results suggest that while the tolerance of decision features is behaviorally dissociable, subjective value signals share a common representation across adulthood.

In diabetes, toxic oxidative pathways are triggered by persistent hyperglycemia and contribute to diabetes complications. A major proposed pathogenic mechanism is the accumulation of protein modifications that are called advanced glycation end products. However, other nonenzymatic post-translational modifications may also contribute to pathogenic protein damage in diabetes. We demonstrate that hypohalous acid–derived modifications of renal tissues and extracellular matrix (ECM) proteins are significantly elevated in experimental diabetic nephropathy. Moreover, diabetic renal ECM shows diminished binding of α1β1 integrin consistent with the modification of collagen IV by hypochlorous (HOCl) and hypobromous acids. Noncollagenous (NC1) hexamers, key connection modules of collagen IV networks, are modified via oxidation and chlorination of tryptophan and bromination of tyrosine residues. Chlorotryptophan, a relatively minor modification, has not been previously found in proteins. In the NC1 hexamers isolated from diabetic kidneys, levels of HOCl-derived oxidized and chlorinated tryptophan residues W28 and W192 are significantly elevated compared with nondiabetic controls. Molecular dynamics simulations predicted a more relaxed NC1 hexamer tertiary structure and diminished assembly competence in diabetes; this was confirmed using limited proteolysis and denaturation/refolding. Our results suggest that hypohalous acid–derived modifications of renal ECM, and specifically collagen IV networks, contribute to functional protein damage in diabetes.

1.Creatinine clearance and urine excretion have been measured in fifty-five patients admitted with suspected myocardial infarction. Patients were grouped on the basis of their radiological report on the first day, irrespective of their diagnosis. The first group consisted of twenty-six patients with normal chest X-rays, the second group of twenty-two patients with radiological evidence of upper zone vessel dilatation and the third group of seven patients with radiological evidence of pulmonary oedema, who were significantly older.2. The mean creatinine clearance on the first day in patients with upper zone vessel dilatation was significantly higher than the creatinine clearance in patients with normal radiographs. By the third and fourth days the clearances were similar in both groups. The patients with pulmonary oedema had low creatinine clearances on all 4 days.3. Glomerular filtration rate was measured with 51Cr-labelled EDTA on twenty occasions, and the results correlated well with the creatinine clearance values obtained on the same day.4. The mean urine volumes on day 1 (2245 f 286 m1/24 h) and day 2 (2219 f232 d/24 h) in patients with upper zone vessel dilatation who had not received diuretics, were significantly higher (P< 0.01) than the urine volumes on day 1 (1652f 145 d/24 h) and day2(1713 f 118 d/ 24 h) in patients with normal radiographs. All the patients with pulmonary oedema had 43 received diuretics during the study and were therefore excluded from this analysis.5. It is concluded that patients with radiological evidence of upper zone vessel dilatation show an elevation of glomerular filtration rate and an increase in urinary output. It is suggested that these responses are mediated via the stimulation of receptors in the left side of the heart and fulfil a homeostaticfunction, to unload an overdistended heart.

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