John B Pierce Laboratory

New Haven, CT, United States

John B Pierce Laboratory

New Haven, CT, United States
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City University of New York and John B Pierce Laboratory | Date: 2016-11-10

Fluorescent proteins (Chlopsid FP I from Kaupichthys hyoproroides and Chlopsid FP II from Kaupichthys n. sp.) are used in a method for detecting bilirubin. The proteins are based on transcriptome analysis of the false moray eels, Kaupichthys hyoproroides and Kaupichthys n. sp., the later representing a heretofore undescribed species.


Burke M.V.,Yale Medical School | Burke M.V.,John B Pierce Laboratory | Small D.M.,Yale Medical School | Small D.M.,John B Pierce Laboratory | And 2 more authors.
Physiology and Behavior | Year: 2015

Evidence linking sugar-sweetened beverage (SSB) consumption to weight gain and other negative health outcomes has prompted many individuals to resort to artificial, non-nutritive sweetener (NNS) substitutes as a means of reducing SSB intake. However, there is a great deal of controversy regarding the biological consequences of NNS use, with accumulating evidence suggesting that NNS consumption may influence feeding and metabolism via a variety of peripheral and central mechanisms. Here we argue that NNSs are not physiologically inert compounds and consider the potential biological mechanisms by which NNS consumption may impact energy balance and metabolic function, including actions on oral and extra-oral sweet taste receptors, and effects on metabolic hormone secretion, cognitive processes (e.g. reward learning, memory, and taste perception), and gut microbiota. © 2015 Elsevier Inc.


Tellez L.A.,John B Pierce Laboratory | Tellez L.A.,Yale University | Han W.,John B Pierce Laboratory | Han W.,Yale University | And 9 more authors.
Nature Neuroscience | Year: 2016

Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is, however, unknown whether sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We found in mice that separate basal ganglia circuitries mediated the hedonic and nutritional actions of sugar. During sugar intake, suppressing hedonic value inhibited dopamine release in ventral, but not dorsal, striatum, whereas suppressing nutritional value inhibited dopamine release in dorsal, but not ventral, striatum. Consistently, cell-specific ablation of dopamine-excitable cells in dorsal, but not ventral, striatum inhibited sugar's ability to drive the ingestion of unpalatable solutions. Conversely, optogenetic stimulation of dopamine-excitable cells in dorsal, but not ventral, striatum substituted for sugar in its ability to drive the ingestion of unpalatable solutions. Our data indicate that sugar recruits a distributed dopamine-excitable striatal circuitry that acts to prioritize energy-seeking over taste quality. © 2016 Nature America, Inc. All rights reserved.


Cao G.,Yale University | Cao G.,University of Texas at Austin | Platisa J.,John B Pierce Laboratory | Platisa J.,University of Belgrade | And 5 more authors.
Cell | Year: 2013

Nervous systems process information by integrating the electrical activity of neurons in complex networks. This motivates the long-standing interest in using optical methods to simultaneously monitor the membrane potential of multiple genetically targeted neurons via expression of genetically encoded fluorescent voltage indicators (GEVIs) in intact neural circuits. No currently available GEVIs have demonstrated robust signals in intact brain tissue that enable reliable recording of individual electrical events simultaneously in multiple neurons. Here, we show that the recently developed "ArcLight" GEVI robustly reports both subthreshold events and action potentials in genetically targeted neurons in the intact Drosophila fruit fly brain and reveals electrical signals in neurite branches. In the same way that genetically encoded fluorescent sensors have revolutionized the study of intracellular Ca2+ signals, ArcLight now enables optical measurement in intact neural circuits of membrane potential, the key cellular parameter that underlies neuronal information processing. © 2013 Elsevier Inc.


Stice E.,Oregon Research Institute | Yokum S.,Oregon Research Institute | Burger K.S.,Oregon Research Institute | Epstein L.H.,State University of New York at Buffalo | And 2 more authors.
Journal of Neuroscience | Year: 2011

Obese humans, compared with normal-weight humans, have less striatalD2receptors and striatal response to food intake; weaker striatal response to food predicts weight gain for individuals at genetic risk for reduced dopamine (DA) signaling, consistent with the rewarddeficit theory of obesity. Yet these may not be initial vulnerability factors, as overeating reduces D2 receptor density, D2 sensitivity, reward sensitivity, and striatal response to food. Obese humans also show greater striatal, amygdalar, orbitofrontal cortex, and somatosensory region response to food images than normal-weight humans do, which predicts weight gain for those not at genetic risk for compromised dopamine signaling, consonant with the reward-surfeit theory of obesity. However, after pairings of palatable food intake and predictive cues, DA signaling increases in response to the cues, implying that eating palatable food contributes to increased responsivity. Using fMRI, we tested whether normal-weight adolescents at high- versus low-risk for obesity showed aberrant activation of reward circuitry in response to receipt and anticipated receipt of palatable food and monetary reward. High-risk youth showed greater activation in the caudate, parietal operculum, and frontal operculum in response to food intake and in the caudate, putamen, insula, thalamus, and orbitofrontal cortex in response to monetary reward. No differences emerged in response to anticipated food or monetary reward. Data indicate that youth at risk for obesity show elevated reward circuitry responsivity in general, coupled with elevated somatosensory region responsivity to food, which may lead to overeating that produces blunted dopamine signaling and elevated responsivity to food cues. Copyright © 2011 the authors.


De Araujo I.E.,John B Pierce Laboratory | De Araujo I.E.,Yale University | Lin T.,John B Pierce Laboratory | Veldhuizen M.G.,John B Pierce Laboratory | And 3 more authors.
Current Biology | Year: 2013

Identification of energy sources depends upon the ability to form associations between food cues and nutritional value. As such, cues previously paired with calories elicit neuronal activation in the nucleus accumbens (NAcc), which reflects the reinforcing value of food [1-4]. The identity of the physiological signals regulating this response remains elusive. Using fMRI, we examined brain response to noncaloric versions of flavors that had been consumed in previous days with either 0 or 112.5 calories from undetected maltodextrin. We report a small but perceptually meaningful increase in liking for the flavor that had been paired with calories and find that change in liking was associated with changes in insular responses to this beverage. In contrast, NAcc and hypothalamic response to the calorie-paired flavor was unrelated to liking but was strongly associated with the changes in plasma glucose levels produced by ingestion of the beverage when consumed previously with calories. Importantly, because each participant ingested the same caloric dose, the change in plasma glucose depended upon individual differences in glucose metabolism. We conclude that glucose metabolism is a critical signal regulating NAcc and hypothalamic response to food cues, and that this process operates independently from the ability of calories to condition liking. © 2013 Elsevier Ltd.


Felsted J.A.,John B Pierce Laboratory | Ren X.,John B Pierce Laboratory | Ren X.,Yale University | Chouinard-Decorte F.,John B Pierce Laboratory | And 2 more authors.
Journal of Neuroscience | Year: 2010

Combining genetic and neuroimaging techniques may elucidate the biological underpinnings of individual differences in neurophysiology and potential vulnerabilities to disease. The TaqIA A1 variant is associated with diminished dopamine D2 receptor density, higher body mass, and food reinforcement. It also moderates the relationship between brain response to food and future weight gain. This suggests that the polymorphism is associated with a fundamental difference in the neurophysiology of food that may predispose toward overeating. An alternative possibility is that factors, such as impulsivity, eating style, reward drive, and perception, which may covary with the polymorphism, influence reward coding and eating behavior. To distinguish between these alternatives, we used functional magnetic resonance imaging to measure neural response to the ingestion of palatable and caloric milkshakes in healthy subjects with (A1+; n=13) and without (A1-; n=13) the TaqIA A1 allele. The groups were selected from a larger group to be matched for linked individual factors such as age, gender, education, body mass index, impulsivity, eating style, and perceptual responses to the milkshake. We demonstrate an interaction between genotype (A1+ vs A1-) and stimulus (milkshake vs a tasteless/odorless baseline) in the midbrain, thalamus, and orbital frontal cortex; whereas A1-shows increased responses to milkshake, A1+shows decreased responses to milkshake relative to baseline. This interaction occurs despite similar ratings of milkshake pleasantness, intensity, and familiarity. We therefore conclude that there is a specific association between the TaqIA A1 polymorphism and brain response during ingestion of a palatable food. Copyright © 2010 the authors.


Rudenga K.J.,Yale University | Rudenga K.J.,John B Pierce Laboratory | Sinha R.,Yale University | Small D.M.,John B Pierce Laboratory | Small D.M.,Yale University
International Journal of Obesity | Year: 2013

Objective: Stress is associated with an increased intake of palatable foods and with weight gain, particularly in overweight women. Stress, food and body mass index (BMI) have been separately shown to affect amygdala activity. However, it is not known whether stress influences amygdala responses to palatable foods, and whether this response is associated with chronic stress or BMI. Design: A total of 14 overweight and obese women participated in a functional magnetic resonance imaging (fMRI) scan as they consumed a palatable milkshake during script-driven, autobiographical, guided imagery of stressful and neutral-relaxing scenarios. Results: We report that a network including insula, somatomotor mouth area, ventral striatum and thalamus responds to milkshake receipt, but none of these areas are affected by stress. In contrast, whereas the left amygdala responds to milkshake irrespective of condition, the right amygdala responds to milkshake only under stressful conditions. Moreover, this right amygdala response is positively associated with basal cortisol levels, an objective measure of chronic stress. We also found a positive relationship between BMI and stress-related increased response to milkshake in the orbitofrontal cortex (OFC). Conclusion: These results demonstrate that acute stress potentiates response to food in the right amygdala and OFC as a function of chronic stress and body weight, respectively. This suggests that the influence of acute stress in potentiating amygdala and OFC responses to food is dependent upon individual factors like BMI and chronic stress. We conclude that BMI and chronic stress play a significant role in brain response to food and in stress-related eating. © 2013 Macmillan Publishers Limited All rights reserved.


Jastreboff A.M.,Yale University | Sinha R.,Yale University | Lacadie C.,Yale University | Small D.M.,Yale University | And 3 more authors.
Diabetes Care | Year: 2013

OBJECTIVE-Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. RESEARCH DESIGN AND METHODS-Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. RESULTS-Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. CONCLUSIONS-These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.© 2013 by the American Diabetes Association.


Stachenfeld N.S.,John B Pierce Laboratory | Stachenfeld N.S.,Yale University
Reproductive Sciences | Year: 2014

Reproductive surgeries leave women more susceptible to postoperative hypervolemic hyponatremia because during this period women can retain water at an accelerated pace and much faster than they do sodium. This review proposes that estrogen and progestogen exposure play an important role in the increased risk of hyponatremia in menopausal women. Estrogen and progesterone exposure have important effects on both body fluid regulation and cardiovascular function and both of these reproductive hormones impact blood pressure responses to sodium loads. This article provides information on the effects of female reproductive hormones and hormone therapy (HT) on fluid regulation and cardiovascular function during menopause. Thirst- and fluid-regulating hormones respond to both osmotic and volume stimuli. Aging women maintain thirst sensitivity to osmotic stimuli but lose some thirst sensitivity to changes in central body fluid volume. Thus, older adults are more at risk of dehydration because they may replenish fluids at a slower rate. Estrogen therapy increases osmotic sensitivity for mechanisms to retain body water so may help menopausal women control body fluids and avoid dehydration. Some progestogens can mitigate estradiol effects on water and sodium retention through competition with aldosterone for the mineralocorticoid receptor and attenuating aldosterone-mediated sodium retention in the distal tubule. However, some progestogens can increase cardiovascular risks. Appropriate balance of these hormones within HT is important to avoid the negative consequences of body fluid and sodium retention, including edema and hypertension. © The Author(s) 2013.

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