Children's inhibitory control abilities in the presence of rewards are related to weight status and eating in the absence of hunger.

The Reflective-Impulsive Dual Processes Model suggests that overeating occurs when the temptation to consume food overrides inhibitory control processes. However, how rewards interact with inhibitory control and their relation to children's weight status and food intake is not understood. Here, 7-to-11-year-old children (n = 66; 32 overweight/obese) completed two versions (baseline [i.e., non-reward incentivized/control] and reward incentivized [food, money, no reward]) of a Go/Nogo task. Intake of palatable foods in the absence of hunger (i.e., eating in the absence of hunger-EAH) was measured following a standardized meal. A drift diffusion model was used to characterize children's performance parameters on the Go/Nogo. On the baseline Go/Nogo, children with higher weight status responded more cautiously, but on reward trials for food/money children were more cautions and made more false alarms relative to the no reward condition. Energy intake during EAH positively correlated with FA errors for food and money vs. no reward, but sex moderated this effect such that FA positively associated with EAH in girls but not boys. Independent of sex, FA for money vs. no reward and food vs. money were both positively associated with energy consumed during EAH. These results suggest that the presence of food and money rewards impair inhibitory control processing, especially in children with higher weight status. Further, increased inhibitory control impairment in response to food rewards, specifically, may be a risk factor for disinhibited eating in girls. Though preliminary, results may be useful in the development of targeted treatments to help moderate excess consumption in children.

Food or money? Children's brains respond differently to rewards regardless of weight status.

BACKGROUND: Brain responses to both food and monetary rewards have been linked to weight gain and obesity in adults, suggesting that general sensitivity to reward contributes to overeating. However, the relationship between brain reward response and body weight in children is unclear. OBJECTIVE: The objective of this study was to assess the brain's response to multiple rewards and the relationship to body weight in children. METHODS: We tested this by performing functional magnetic resonance imaging while children (7- to 11-years-old; healthy weight [n = 31], overweight/obese [n = 30]) played a modified card-guessing task to assess blood-oxygen-level-dependent (BOLD) response to anticipating and winning food and money rewards. Functional magnetic resonance imaging data were analysed using a region of interest and exploratory whole-brain approach. RESULTS: Region of interest results demonstrated increased BOLD response in the striatum to anticipating food vs. neutral (control) and winning money vs. neutral. Whole-brain data showed that winning money vs. food was associated with increased activation in the striatum, as well as regions associated with cognitive control and emotion. Notably, for both approaches, these effects were independent of child weight status. Additionally, children's reported food responsiveness and emotional overeating were negatively correlated with the BOLD response in the left cingulate gyrus for winning food vs. money. CONCLUSION: Overall, findings from this study show that regions associated with reward, cognitive control and emotion may play a role in the brain's response to food and money rewards, independently of how much the child weighs. These findings provide insight into reward sensitivity in children, which may have implications for understanding overeating and the development of obesity.

Differential influence of safe versus threatening facial expressions on decision-making during an inhibitory control task in adolescence and adulthood.

Social cognition matures dramatically during adolescence and into early adulthood, supported by continued improvements in inhibitory control. During this time, developmental changes in interpreting and responding to social signals such as facial expressions also occur. In the present study, subjects performed a Go No-Go task that required them to respond or inhibit responding based on threat or safety cues present in facial expressions. Subjects (N = 112) were divided into three age groups: adolescent (12-15 years), emerging adult (18-25 years) and adult (26-44 years). Analyses revealed a significant improvement in accuracy on No-Go trials, but not Go trials, during both safe and threat face conditions, with changes evident through early adulthood. In order to better identify the decision-making processes responsible for these changes in inhibitory control, a drift diffusion model (DDM) was fit to the accuracy and reaction time data, generating measures of caution, response bias, nondecision time (encoding + motor response), and drift rate (face processing efficiency). Caution and nondecision time both increased significantly with age while bias towards the Go response decreased. Drift rate analyses revealed significant age-related improvements in the ability to map threat faces to a No-Go response while drift rates on all other trial types were equivalent across age groups. These results suggest that both stimulus-independent and stimulus-dependent processes contribute to improvements in inhibitory control in adolescence with processing of negative social cues being specifically impaired by self-regulatory demands. Findings from this novel investigation of emotional responsiveness integrated with inhibitory control may provide useful insights about healthy development that can be applied to better understand adolescent risk-taking behavior and the elevated incidence of related forms of psychopathology during this period of life.

Opposing effects of coupled and uncoupled NOS activity on the Na+-K+ pump in cardiac myocytes.

Pharmacological delivery of nitric oxide (NO) stimulates the cardiac Na(+)-K(+) pump. However, effects of NO synthesized by NO synthase (NOS) often differ from the effects of NO delivered pharmacologically. In addition, NOS can become "uncoupled" and preferentially synthesize O(2)(.-), which often has opposing effects to NO. We tested the hypothesis that NOS-synthesized NO stimulates Na(+)-K(+) pump activity, and uncoupling of NOS inhibits it. To image NO, we loaded isolated rabbit cardiac myocytes with 4,5-diaminofluorescein-2 diacetate (DAF-2 DA) and measured fluorescence with confocal microscopy. L-arginine (L-arg; 500 micromol/l) increased DAF-2 DA fluorescence by 51% compared with control (n = 8; P < 0.05). We used the whole cell patch-clamp technique to measure electrogenic Na(+)-K(+) pump current (I(p)). Mean I(p) of 0.35 +/- 0.03 pA/pF (n = 44) was increased to 0.48 +/- 0.03 pA/pF (n = 7, P < 0.05) by 10 micromol/l L-Arg in pipette solutions. This increase was abolished by NOS inhibition with radicicol or by NO-activated guanylyl cyclase inhibition with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. We next examined the effect of uncoupling NOS using paraquat. Paraquat (1 mmol/l) induced a 51% increase in the fluorescence intensity of O(2)(.-)-sensitive dye dihydroethidium compared with control (n = 9; P < 0.05). To examine the functional effects of uncoupling, we measured I(p) with 100 micromol/l paraquat included in patch pipette solutions. This decreased I(p) to 0.28 +/- 0.03 pA/pF (n = 12; P < 0.001). The paraquat-induced pump inhibition was abolished by superoxide dismutase (in pipette solutions). We conclude that NOS-mediated NO synthesis stimulates the Na(+)-K(+) pump, whereas uncoupling of NOS causes O(2)(.-)-mediated pump inhibition.

Comparative validity of seven scoring systems for the instrumental activities of daily living scale in rural elders.

Lawton and Brody's eight-item Instrumental Activities of Daily Living (IADL) scale is used often with elderly patients but scored in several different ways. We scored the IADL with seven popular procedures ranging from relatively simple to complex (Guttman scores, summed and Rasch scores from dichotomous, trichotomous, and polytomous items) in a sample of rural elders (N = 231). We compared the IADL scales' prediction of concurrent cognitive functioning, depressive symptoms, psychosocial functioning, and health care use (medications, outpatient visits, inpatient days). Validity coefficients ranged from small to large among outcome variables but were highly consistent across IADL scoring procedures. Consequently, researchers and clinicians may prefer to use simpler IADL scoring procedures with this population.

Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "next-step" practices.

BACKGROUND: Many patients treated for major depression require more than one antidepressant trial to achieve or sustain response. However, the literature provides few treatment algorithms or effectiveness studies that empirically support "next-step" options available to clinicians. We conducted a survey of psychiatrists and other medical specialists who treat depression to ascertain what clinicians actually do when faced with patients who suboptimally respond to an adequate course of selective serotonin reuptake inhibitor (SSRI) therapy. METHOD: Attendees at a psychopharmacology course (N = 801) were queried about their top choices for antidepressant-treatment nonresponders: a minimal responder after 4 weeks of adequate SSRI treatment, a partial responder after 8 weeks of adequate SSRI therapy, a nonresponder after 8 weeks of adequate SSRI therapy, and a relapser on long-term SSRI maintenance therapy. Choices included raising the dose, augmenting or combining with another agent, switching to a second SSRI. or switching to a non-SSRI agent. RESULTS: 432 (54%) of the surveys were returned. Raising the dose was the most frequently reported next-step strategy for a patient with minimal response after 4 weeks of adequate SSRI therapy, partial response after 8 weeks of adequate SSRI therapy, and relapse on long-term SSRI therapy. Switching to a non-SSRI agent was the most frequently chosen option for nonresponders to an adequate trial of SSRI therapy. CONCLUSION: Our findings suggest that clinicians select different next-step strategies when patients are nonresponders versus when patients are partial responders or relapsers.

Gibberellins and seed development in maize. I. Evidence that gibberellin/abscisic acid balance governs germination versus maturation pathways.

Abscisic acid (ABA) is required for the regulation of seed maturation in maize (Zea mays L.). Mutants blocked in ABA synthesis (such as viviparous-5) do not mature to quiescent, desiccation-tolerant seeds, but germinate on the ear midway through kernel development. Because gibberellins (GA) and ABA act antagonistically in many aspects of plant development, we hypothesized that ABA antagonizes a positive GA signal for precocious germination in maize. In these experiments, we show that a GA deficiency early in seed development, induced genetically or via biosynthesis inhibitors, suppresses vivipary in ABA-deficient developing kernels. The resulting seeds have both desiccation tolerance and storage longevity. Temporal analysis of GA accumulation in wild-type kernels revealed the accumulation of bioactive GA(1) and GA(3) prior to the peak in ABA content. We speculate that these GAs stimulate a developmental program leading to vivipary in the absence of normal amounts of ABA, and that a reduction of GA content re-establishes an ABA/GA ratio appropriate for suppression of germination and induction of maturation. In contrast, the induction of a GA deficiency did not suppress vivipary in viviparous-1 mutant kernels, suggesting that VP1 acts downstream of both GA and ABA in programming seed development.

Gibberellins and seed development in maize. II. Gibberellin synthesis inhibition enhances abscisic acid signaling in cultured embryos.

Abscisic acid (ABA) is required for seed maturation in maize (Zea mays L.) and other plants. Gibberellins (GAs) are also present in developing maize embryos, and mutual antagonism of GAs and ABA appears to govern the choice between precocious germination or quiescence and maturation. Exogenous ABA can also induce quiescence and maturation in immature maize embryos in culture. To examine the role of GAs versus ABA in regulating maize embryo maturation, the effects of modulating GA levels were compared with those of ABA in embryos cultured at successive stages of development. The effects of GA synthesis inhibition or exogenous GA application differed markedly in embryos at different stages of development, indicating changes in both endogenous GA levels and in the capacity for GA synthesis as embryogenesis and maturation progress. In immature embryos, the inhibition of GA synthesis mimicked the effects of exogenous ABA, as shown by the suppression of germination, the acquisition of anthocyanin pigments, and the accumulation of a variety of maturation-phase mRNAs. We suggest that GA antagonizes ABA signaling in developing maize embryos, and that the changing hormone balance provides temporal control over the maturation phase.

Silk gland-specific tRNA(Ala) genes interact more weakly than constitutive tRNA(Ala) genes with silkworm TFIIIB and polymerase III fractions.

Constitutive and silk gland-specific tRNA(Ala) genes from silkworms have very different transcriptional properties in vitro. Typically, the constitutive type, which encodes tRNA(AlaC), directs transcription much more efficiently than does the silk gland-specific type, which encodes tRNA(AlaSG). We think that the inefficiency of the tRNA(AlaCG) gene underlies its capacity to be turned off in non-silk gland cells. An economical model is that the tRNA(AlaSG) promoter interacts poorly, relative to the tRNA(AlaC) promoter, with one or more components of the basal transcription machinery. As a consequence, the tRNA(AlaSG) gene directs the formation of fewer transcription complexes or of complexes with reduced cycling ability. Here we show that the difference in the number of active transcription complexes accounts for the difference in tRNA(AlaC) and tRNA(AlaSG) transcription rates. To determine whether a particular component of the silkworm transcription machinery is responsible for reduced complex formation on the tRNA(AlaSG) gene, we measured competition by templates for defined fractions of this machinery. We find that the tRNA(AlaSG) gene is greatly impaired, in comparison with the tRNA(AlaC) gene, in competition for either TFIIIB or RNA polymerase III. Competition for each of these fractions is also strongly influenced by the nature of the 5' flanking sequence, the promoter element responsible for the distinctive transcriptional properties of tRNA(AlaSG) and tRNA(AlaC) genes. These results suggest that differential interaction with TFIIIB or RNA polymerase III is a critical functional distinction between these genes.

Variation in heat-shock proteins among species of desert fishes (Poeciliidae, Poeciliopsis).

Analysis of the heat-shock proteins (hsps) of six closely related species of Poeciliopsis demonstrated the existence of biochemical diversity in the hsp100, hsp70, hsp60, and hsp30 protein families among species. Each species expressed five to seven hsp70-related isoforms. Constitutive 70-kD isoforms were identical among species, but four different patterns of heat-inducible isoforms were seen in these six species. Members of the hsp70 family of molecular chaperones are included among the most highly conserved proteins known, and the possibility of variation in hsp70 among closely related species has rarely been addressed. The hsp30 family is known to be less conserved than the hsp70 family, and, as expected, the Poeciliopsis hsp30 patterns showed more variation. Most of the hsp30 isoforms characteristic of a particular species were unique to that species. Hsp100 and hsp60 were identical in five of the species, but alternate isoforms were found in P. monacha. The small size and limited geographical distribution of the P. monacha population have probably contributed to the uniqueness of the monacha pattern. Two of the species were shown to acquire thermotolerance, the ability to withstand normally lethal temperatures when subjected to a gradual temperature increase. Rapid-heating protocols commonly used to establish critical thermal maxima of organisms do not include this inducible component of thermoresistance and therefore do not adequately assess an organism's capacity to withstand thermal stress.

Stress mRNA metabolism in canavanine-treated chicken embryo cells.

Four major chicken stress mRNAs with apparent molecular weights of 1.2 X 10(6), 0.88 X 10(6), 0.59 X 10(6), and 0.25 X 10(6) to 0.28 X 10(6) were separated on acidic agarose-urea gels. Using cell-free translation, the coding assignments of these mRNAs were determined to be stress proteins with apparent molecular weights of 88,000, 71,000, 35,000, and 23,000. Despite high levels of translational activity in vivo and in vitro, no newly synthesized mRNA for the 23-kilodalton stress protein was detected on gels under conditions which readily allowed detection of other stress mRNAs, suggesting activation of a stored or incompletely processed mRNA. Cloned Drosophila heat shock genes were used to identify and measure changes in cellular levels of the two largest stress mRNAs. Synthesis of these mRNAs increased rapidly during the first hour of canavanine treatment and continued at a high rate for at least 7 h, with the mRNAs attaining new steady-state levels by ca. 3 h. Both of these inducible stress mRNAs had very short half-lives compared with other animal cell mRNAs. Using an approach-to-steady-state analysis, the half-lives were calculated to be 89 min for the mRNA encoding the 88-kilodalton stress protein and 46 min for the mRNA encoding the 71-kilodalton stress protein. Chicken 18S and 28S rRNA synthesis was inhibited, and actin mRNA levels measured with cloned cDNA encoding chicken beta-actin slowly declined in canavanine-treated cells.

Synthesis and breakdown of pppA2'p5'A2'p5'A and transient inhibiton of protein synthesis in extracts from interferon-treated and control cells.

Incubation of the mouse L-cell-free system with a concentration of pppA2'p5'A2'p5'A [(2'-5')An] just sufficient to inhibit protein synthesis results in formation of a high-molecular-weight, heatlabile inhibitor and enhanced ribonuclease activity and in the rapid breakdown of (2'-5')An to ATP. The (2'-5')An-enhanced ribonuclease activity is also unstable and in the absence of a (2'-5')-An-regenerating system inhibiton of protein synthesis is transient. Although interferon treatment enhances the synthesis of (2'-5')An, the rates of degradation of (2'-5')An and levels of activatible nuclease are similar in extracts prepared from control or interferon-treated cells. Interestingly, the sensitivity of different cell-free systems to (2'-5')An, varies with the source of the cell-free systems and with the methods used in their preparation. There is, however, no obvious correlation between the sensitivities of the system and the rate of breakdown of (2'-5')An. The significance of these results is discussed in relation to a possible control function for the (2'-5')An system in both interferon-treated and control cells.

Oligonucleotide inhibitor of protein synthesis made in extracts of interferon-treated chick embryo cells: comparison with the mouse low molecular weight inhibitor.

Cytoplasmic extracts of interferon-treated primary chick embryo cells contain an enzyme activity that synthesized an inhibitor of chick cell-free protein synthesis. The same activity was detected in extracts of cells treated with mock preparations of interferon, but at <0.3% of the level found in interferon-treated cell extracts. The enzyme was activated by double-stranded RNA and could be isolated by binding to columns of poly(I)-poly(C)-agarose. In the column-bound state, the enzyme reacted with ATP to synthesize the inhibitor, which could then be continuously eluted from the column. The inhibitor was purified and its structure and function were compared with those of the low molecular weight inhibitor of protein synthesis made by an enzyme from interferon-treated mouse L cells. The avian and mammalian inhibitors comigrated on thin layers of polyethyleneimine-cellulose during chromatography in three different solvent systems, and they coeluted as a series of peaks from columns of DEAE-cellulose during sodium chloride gradient elution. Digestion with bacterial alkaline phosphatase or snake venom phosphodiesterase yielded products that similarly comigrated. Functionally, the two inhibitors were interchangeable: both inhibited protein synthesis in extracts of mammalian and avian cells, producing 50% inhibition at a concentration of about 0.3 nM (AMP equivalents). We conclude that the chick cell-derived oligonucleotide inhibitor has a structure that is closely related or identical to that of the inhibitor made in the mouse system, and that both preparations inhibit cell-free protein synthesis in a non-species-specific manner.

Order of transcription of genes of vesicular stomatitis virus.

The effect of ultraviolet radiation on the expression of the genes of vesicular stomatitis virus (VSV) was studied in a cell-free system which executed coupled transcription and translation of the viral genes. In this system, which contained detergent-activated virus and a cytoplasmic extract of mouse L-cells, three of the five viral proteins (N, NS, and M) were synthesized accurately and efficiently; a putative precursor to the viral glycoprotein (G) was also made, but synthesis of the L protein was not detected. In response to irradiation of VSV, the synthesis of each protein in the coupled system displayed a characteristic single-hit inhibition. This permitted calculation of the apparent target-sizes for expression of the different viral genes relative to the entire genome (3.6 to 4.0 X 10(6) daltons) as measured by loss of infectivity. These are: N, 0.55 X 10(6); NS, 0.83 X 10(6); M, 1.12 X 10(6); G, 1.76 X 10(6) daltons of RNA. Only the N protein gene has a target-size which corresponds to that predicted from the molecular weight of its messenger RNA (molecular weight: 0.55 X 10(6)). The target-sizes for the other three genes are two to four times larger than expected, and are not proportional to the molecular weights of their corresponding messenger RNAs (molecular weights: NS, 0.28 X 10(6); M, 0.28 X 10(6); G, 0.7 X 10(6)). The polar effect of UV irradiation is inconsistent with independent transcription of each of the genes of VSV. Rather, the target-sizes appear to be cumulative, suggesting that trnascription initiates at a single point on VSV RNA and proceeds in the order 3'-N-NS-M-G-(L)-5'.