Genetic variation of the dopamine D2 receptor gene: association with the reinforcing value of food and eating in the absence of hunger in Chilean children

BACKGROUND: food is a powerful reinforcer that motivates people to eat. The TaqI A1 polymorphism (rs1800497; T>C) downstream of the dopamine D2 receptor (DRD2) gene has been associated with diminished DRD2 receptor density, higher food reinforcement, and impaired eating behavior in adults. OBJECTIVE: to evaluate the association between the rs1800497 polymorphism and the reinforcing value of food and eating in the absence of hunger in Chilean children. MATERIAL AND METHOD: nineteen Chilean children (aged 8-12 years) who were carriers of the A1-allele and 19 age- and gender-matched non-carriers (A2-allele) were evaluated on the reinforcing value of food and eating in the absence of hunger. Anthropometric measures were performed by standard procedures. Briefly, children received a standard pre-load lunch followed by an ad-libitum exposure to palatable foods. RESULTS: no differences were found between A1-allele carriers and non-carriers, whether obese or non-obese, in ad libitum energy intake, macronutrient consumption, or the relative reinforcing value of food (p > 0.05). In obese children, A1 carriers reported significantly lower satiety and fullness before lunch (p < 0.05). However, in children with normal weight A1 carriers were found to exhibit trends for greater satiety and fullness before lunch when compared to non-carriers, but this trend reversed after lunch such that carriers exhibited lower satiety and fullness (p = 0.06). CONCLUSIONS: although TaqI A1 may play an important role in some eating behavior-related traits such as satiety and fullness, especially in obese children, our findings indicate that this polymorphism does not appear to affect eating in the absence of hunger or food reinforcement in children

Glycotope structures and intramolecular affinity factors of plant lectins for Tn/T antigens

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Building up spacetime with quantum entanglement

In this essay, we argue that the emergence of classically connected spacetimes is intimately related to the quantum entanglement of degrees of freedom in a non-perturbative description of quantum gravity. Disentangling the degrees of freedom associated with two regions of spacetime results in these regions pulling apart and pinching off from each other in a way that can be quantified by standard measures of entanglement.Comment: Gravity Research Foundation essay, 7 pages, LaTeX, 5 figure

Snail1 controls bone mass by regulating Runx2 and VDR expression during osteoblast differentiation

Bone undergoes continuous remodelling throughout adult life, and the equilibrium between bone formation by osteoblasts and bone resorption by osteoclasts defines the final bone mass. Here we show that Snail1 regulates this balance by controlling osteoblast differentiation. Snail1 is necessary for the early steps of osteoblast development, and it must be downregulated for their final differentiation. At the molecular level, Snail1 controls bone mass by repressing the transcription of both the osteoblast differentiation factor Runx2 and the vitamin D receptor (VDR) genes in osteoblasts. Sustained activation of Snail1 in transgenic mice provokes deficient osteoblast differentiation, which, together with the loss of vitamin D signalling in the bone, also impairs osteoclastogenesis. Indeed, the mineralisation of the bone matrix is severely affected, leading to hypocalcemia-independent osteomalacia. Our data show that the impact of Snail1 activity on the osteoblast population regulates the course of bone cells differentiation and ensures normal bone remodelling

Association Between Clinical Pathways Leading to Medical Management and Prognosis in Patients With NSTEACS.

: A large proportion of patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) are initially selected for medical management (MM) and do not undergo coronary revascularization during or immediately after the index event. The aim of this study was to explore the clinical pathways leading to MM in NSTEACS patients and their influence on prognosis. : Patient characteristics, pathways leading to MM, and 2-year outcomes were recorded in a prospective cohort of 5591 NSTEACS patients enrolled in 555 hospitals in 20 countries across Europe and Latin America. Cox models were used to assess the impact of hospital management on postdischarge mortality. : Medical management was the selected strategy in 2306 (41.2%) patients, of whom 669 (29%) had significant coronary artery disease (CAD), 451 (19.6%) had nonsignificant disease, and 1186 (51.4%) did not undergo coronary angiography. Medically managed patients were older and had higher risk features than revascularized patients. Two-year mortality was higher in medically managed patients than in revascularized patients (11.0% vs 4.4%; P &lt; .001), with higher mortality rates in patients who did not undergo angiography (14.6%) and in those with significant CAD (9.3%). Risk-adjusted mortality was highest for patients who did not undergo angiography (HR = 1.81; 95%CI, 1.23-2.65), or were not revascularized in the presence of significant CAD (HR = 1.90; 95%CI, 1.23-2.95) compared with revascularized patients. : Medically managed NSTEACS patients represent a heterogeneous population with distinct risk profiles and outcomes. These differences should be considered when designing future studies in this population.<br/

On the perturbative S-matrix of generalized sine-Gordon models

Motivated by its relation to the Pohlmeyer reduction of AdS_5 x S^5 superstring theory we continue the investigation of the generalized sine-Gordon model defined by SO(N+1)/SO(N) gauged WZW theory with an integrable potential. Extending our previous work (arXiv:0912.2958) we compute the one-loop two-particle S-matrix for the elementary massive excitations. In the N = 2 case corresponding to the complex sine-Gordon theory it agrees with the charge-one sector of the quantum soliton S-matrix proposed in hep-th/9410140. In the case of N > 2 when the gauge group SO(N) is non-abelian we find a curious anomaly in the Yang-Baxter equation which we interpret as a gauge artifact related to the fact that the scattered particles are not singlets under the residual global subgroup of the gauge group

Integrable models: from dynamical solutions to string theory

We review the status of integrable models from the point of view of their dynamics and integrability conditions. Some integrable models are discussed in detail. We comment on the use it is made of them in string theory. We also discuss the Bethe Ansatz solution of the SO(6) symmetric Hamiltonian with SO(6) boundary. This work is especially prepared for the seventieth anniversaries of Andr\'{e} Swieca (in memoriam) and Roland K\"{o}berle.Comment: 24 pages, to appear in Brazilian Journal of Physic

Preliminary definitions for the sonographic features of synovitis in children

Objectives Musculoskeletal ultrasonography (US) has the potential to be an important tool in the assessment of disease activity in childhood arthritides. To assess pathology, clear definitions for synovitis need to be developed first. The aim of this study was to develop and validate these definitions through an international consensus process. Methods The decision on which US techniques to use, the components to be included in the definitions as well as the final wording were developed by 31 ultrasound experts in a consensus process. A Likert scale of 1-5 with 1 indicating complete disagreement and 5 complete agreement was used. A minimum of 80% of the experts scoring 4 or 5 was required for final approval. The definitions were then validated on 120 standardized US images of the wrist, MCP and tibiotalar joints displaying various degrees of synovitis at various ages. Results B-Mode and Doppler should be used for assessing synovitis in children. A US definition of the various components (i.e. synovial hypertrophy, effusion and Doppler signal within the synovium) was developed. The definition was validated on still images with a median of 89% (range 80-100) of participants scoring it as 4 or 5 on a Likert scale. Conclusions US definitions of synovitis and its elementary components covering the entire pediatric age range were successfully developed through a Delphi process and validated in a web-based still images exercise. These results provide the basis for the standardized US assessment of synovitis in clinical practice and research

On semiclassical approximation for correlators of closed string vertex operators in AdS/CFT

We consider the 2-point function of string vertex operators representing string state with large spin in AdS_5. We compute this correlator in the semiclassical approximation and show that it has the expected (on the basis of state-operator correspondence) form of the strong-coupling limit of the 2-point function of single trace minimal twist operators in gauge theory. The semiclassical solution representing the stationary point of the path integral with two vertex operator insertions is found to be related to the large spin limit of the folded spinning string solution by a euclidean continuation, transformation to Poincare coordinates and conformal map from cylinder to complex plane. The role of the source terms coming from the vertex operator insertions is to specify the parameters of the solution in terms of quantum numbers (dimension and spin) of the corresponding string state. Understanding further how similar semiclassical methods may work for 3-point functions may shed light on strong-coupling limit of the corresponding correlators in gauge theory as was recently suggested by Janik et al in arXiv:1002.4613.Comment: 19 pages, 1 figure; minor corrections, references added, footnote below eq. (4.5) adde

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate