Heritability of daytime cortisol levels in children

INTRODUCTION Cortisol is a steroid hormone secreted by the outer cortex of the adrenal gland. Its secretion is stimulated by ACTH (adrenocorticotrophic hormone), produced in the pituitary in response to corticotropin-releasing hormone (CRH), a product from neurons in the paraventricular nucleus of the hypothalamus.After its release, the major part of cortisol binds to the plasma proteins corticosteroid binding globulin (CBG, or transcortin) and albumin, which prevents the hormone from penetrating the membranes of their target cells. About 3--5% of the total cortisol is the unbound, biologically active fraction. This active fraction has permissive, suppressive, stimulatory, and preparative action effects in the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology (Sapolsky, Romero, and Munck, 2000). Although cortisol is mainly known for its pivotal role in generating an adequate response to phy

Studies on Wild House Mice. VII. Prenatal Maternal Environment and Aggression

The effect of the maternal environment on intermale aggression was studied by means of embryo transfer of genetically selected aggressive (SAL) and nonaggressive wild house mice (LAL), and their reciprocal F1's, to standard (NMRI) females. No effect was found on the attack latency scores (ALS), i.e., aggression: all genotypes born and raised under natural conditions showed an ALS similar that of genotypes born and raised by NMRI females. Since previous studies on wild house mice failed to demonstrate postnatal effects on aggression, and the present results indicate the absence of prenatal maternal environmental effects on aggression, the primacy of genetic over maternal variance in the development of adult intermale aggression in wild house mice is indicated

Sizing the association between lifestyle behaviours and fatness in a large, heterogeneous sample of youth of multiple ethnicities from 4 countries

Background:&nbsp;The magnitude of the relationship between lifestyle risk factors for obesity and adiposity is not clear.&nbsp;The aim of this study was to clarify this in order to determine the level of importance of lifestyle factors in obesity&nbsp;aetiology.Methods: A cross-sectional analysis was carried out on data on youth who were not trying to change weight&nbsp;(n = 5714), aged 12 to 22 years and from 8 ethnic groups living in New Zealand, Australia, Fiji and Tonga.&nbsp;Demographic and lifestyle data were measured by questionnaires. Fatness was measured by body mass index (BMI),&nbsp;BMI z-score and bioimpedance analysis, which was used to estimate percent body fat and total fat mass (TFM).&nbsp;Associations between lifestyle and body composition variables were examined using linear regression and forest plots.Results: TV watching was positively related to fatness in a dose-dependent manner. Strong, dose-dependent&nbsp;associations were observed between fatness and soft drink consumption (positive relationship), breakfast consumption&nbsp;(inverse relationship) and after-school physical activity (inverse relationship). Breakfast consumption-fatness associations&nbsp;varied in size across ethnic groups. Lifestyle risk factors for obesity were associated with percentage differences in body&nbsp;composition variables that were greatest for TFM and smallest for BMI.Conclusions: Lifestyle factors were most strongly related to TFM, which suggests that studies that use BMI alone to&nbsp;quantify fatness underestimate the full effect of lifestyle on adiposity. This study clarifies the size of lifestyle-fatness&nbsp;relationships observed in previous studies.</div

Genetics of testosterone and the aggression-hostility-anger (AHA) syndrome: a study of middle-aged male twins.

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Probenecid Blocks Human P2X7 Receptor-Induced Dye Uptake via a Pannexin-1 Independent Mechanism

P2X7 is a ligand-gated ion channel which is activated by ATP and displays secondary permeability characteristics. The mechanism of development of the secondary permeability pathway is currently unclear, although a role for the hemichannel protein pannexin-1 has been suggested. In this study we investigated the role of pannexin-1 in P2X7-induced dye uptake and ATP-induced IL-1β secretion from human monocytes. We found no pharmacological evidence for involvement of pannexin-1 in P2X7-mediated dye uptake in transfected HEK-293 cells with no inhibition seen for carbenoxolone and the pannexin-1 mimetic inhibitory peptide, 10Panx1. However, we found that probenecid inhibited P2X7-induced cationic and anionic dye uptake in stably transfected human P2X7 HEK-293 cells. An IC50 value of 203 μM was calculated for blockade of ATP-induced responses at human P2X7. Probenecid also reduced dye uptake and IL-1β secretion from human CD14+ monocytes whereas carbenoxolone and 10Panx1 showed no inhibitory effect. Patch clamp and calcium indicator experiments revealed that probenecid directly blocks the human P2X7 receptor

The recent intellectual structure of geography

An active learning project in an introductory graduate course used multidimensional scaling of the name index in Geography in America at the Dawn of the 21st Century, by Gary Gaile and Cort Willmott, to reveal some features of the discipline\u27s recent intellectual structure relevant to the relationship between human and physical geography. Previous analyses, dating to the 1980s, used citation indices or Association of American Geographers spe- cialty-group rosters to conclude that either the regional or the methods and environmental subdisciplines bridge human and physical geography. The name index has advantages over those databases, and its analysis reveals that the minimal connectivity that occurs between human and physical geography has recently operated more through environmental than through either methods or regional subdisciplines

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Model for amorphous aggregation processes

The amorphous aggregation of proteins is associated with many phenomena, ranging from the formation of protein wine haze to the development of cataract in the eye lens and the precipitation of recombinant proteins during their expression and purification. While much literature exists describing models for linear protein aggregation, such as amyloid fibril formation, there are few reports of models which address amorphous aggregation. Here, we propose a model to describe the amorphous aggregation of proteins which is also more widely applicable to other situations where a similar process occurs, such as in the formation of colloids and nanoclusters. As first applications of the model, we have tested it against experimental turbidimetry data of three proteins relevant to the wine industry and biochemistry, namely, thaumatin, a thaumatinlike protein, and α-lactalbumin. The model is very robust and describes amorphous experimental data to a high degree of accuracy. Details about the aggregation process, such as shape parameters of the aggregates and rate constants, can also be extracted.Samuel D. Stranks, Heath Ecroyd, Steven Van Sluyter, Elizabeth J. Waters, John A. Carver, and Lorenz von Smeka

P2 purinergic receptor modulation of cytokine production

Cytokines serve important functions in controlling host immunity. Cells involved in the synthesis of these polypeptide mediators have evolved highly regulated processes to ensure that production is carefully balanced. In inflammatory and immune disorders, however, mis-regulation of the production and/or activity of cytokines is recognized as a major contributor to the disease process, and therapeutics that target individual cytokines are providing very effective treatment options in the clinic. Leukocytes are the principle producers of a number of key cytokines, and these cells also express numerous members of the purinergic P2 receptor family. Studies in several cellular systems have provided evidence that P2 receptor modulation can affect cytokine production, and mechanistic features of this regulation have emerged. This review highlights three separate examples corresponding to (1) P2Y6 receptor mediated impact on interleukin (IL)-8 production, (2) P2Y11 receptor-mediated affects on IL-12/23 output, and (3) P2X7 receptor mediated IL-1β posttranslational processing. These examples demonstrate important roles of purinergic receptors in the modulation of cytokine production. Extension of these cellular observations to in vivo situations may lead to new therapeutic strategies for treating cytokine-mediated diseases