The taq IA and Ser311Cys polymorphisms in the dopamine D2 receptor gene and obesity

Dopamine D2 receptors (DRD2) in the central nervous system are involved in the regulation of feeding. It remains to be elucidated if mutations in the DRD2 gene contribute to the development of obesity. The aim of the present study was to investigate whether the Taq IA and Ser311Cys polymorphisms in the DRD2 gene are associated with obesity in Nauruan and Australian subjects. Subjects were selected based on extremes of the body mass index (BMI) distribution. Two groups of Australian women were selected. The leanest group had a mean BMI of 22.5 kg/m2 (range: 20.3-24.3) and the heaviest group had a mean of 36.1 kg/m2 (32.5-44.1). Four groups of Nauruan subjects were selected. Leanest men had a mean BMI of 33.0 kg/m2 (28.4-36.9), heaviest men had a mean of 52.8 kg/m2 (46.5-69.2), leanest women had a mean of 34.8 kg/m2 (28.2-41.8) and heaviest women had a mean of 55.1 kg/m2 (49.3-73.8). Subjects were genotyped for the Taq IA and Ser311Cys polymorphisms using polymerase chain reaction (PCR) restriction fragment length polymorphism analysis and allelic discrimination TaqmanTM PCR respectively. Leanest and heaviest groups were examined for differences in genotype frequency. Taq IA and Ser311Cys genotype frequencies did not differ significantly between leanest and heaviest Nauruan groups, or between leanest and heaviest Australians. Haplotype frequencies of these polymorphisms did not differ between leanest and heaviest groups. The Taq IA and Ser311Cys polymorphisms in the DRD2 gene are unlikely to be common causes of obesity in these populations.

Reactions of Nb2 and Nb3 with CO, D2, N2, and O2 : reconciling experimental kinetics with density functional theory-calculated reaction profiles

 Calculated energy profiles for the reactions of neutral Nb₂ and Nb₃ metal clusters with CO, D₂, N₂, and O₂ are presented. In each reaction path, both a physisorption energy minimum, where the reactant remains intact, and a chemisorption energy minimum, where the reactant has dissociated, are calculated and linked by saddle points. We calculate branching ratios for the forward (dissociative) and reverse reactions which we compare with the experimental kinetic data. It is found that a combination of average thermal energies and barrier heights leads to wide variation in branching ratios which compares favourably to previously determined experimental reaction rates.

The prolactin response to sulpiride in major depression: the role of the D2 receptor in depression.

Multiple lines of investigations have implicated the role of the dopaminergic system in depression. The aim of the study was to characterise the Dopamine D2 receptor sensitivity status in depressed patients versus controls by means of a novel neuro-endocrine challenge test, the prolactin response to sulpiride. In this intervention, ten patients and ten age matched male volunteers were studied. The patients were diagnosed according to DSM-IV criteria, and Montgomery Asberg and Zung scales were done. There was no significant difference in baseline levels of prolactin between the depressed and control groups. Significantly higher prolactin levels after sulpiride challenge were however found in depressed patients than controls at all time points after sulpiride administration. This neuroendocrine challenge paradigm suggests that the prolactin response to sulpiride, a D2 receptor antagonist, is enhanced in depression, which suggests that this receptor might be supersensitive in depression compared to controls. This adds to the data implicating the dopaminergic system in the pathophysiology of depression, and suggests that dopaminergic mechanisms might be a target of therapeutic interest.

Effect of single and double austenitization treatments on the microstructure and hardness of AISI D2 tool steel

This investigation is concerned with the study of effect of Double Austenitization (DA) and Single Austenitization (SA) heat treatment processes on microstructure and mechanical property of AISI D2type cold worked tool steel. To maximize hardness, tool steels are used in a quenched and tempered condition. This involves heating the material to the austenitizing temperature (~850-1100. °C), quenching at an appropriate rate to form martensite, and tempering to reduce the retained austenite content and induce toughness. The merits of DA treatment isto promote dissolution of carbides at the same time proscribe grain coarsening significantly was attempted in D2 tool steel. The study has found that DA treatment has induced high hardness with insignificant growth in grains. The increase in hardness is attributed to increase in carbon content in matrix due to dissolution of carbides; whereas finer grains due to role of inclusions.

Ferritic nitrocarburising of tool steels

Four different tool steel materials, P20, H13, M2 and D2, were nitrocarburised at 570°C in a fluidised bed furnace. The reactive diffusion of nitrogen and carbon into the various substrate microstructures is compared and related to the different alloy carbide distributions. The effect of carbon bearing gas (carbon dioxide, natural gas) on carbon absorption is reported, as well as its influence on compound layer growth and porosity. Partial reduction of Fe3O4 at the surface resulted in the formation of a complex, epsi-nitride containing oxide layer. In H13, carbon was deeply absorbed throughout the entire diffusion zone, affecting the growth of grain boundary cementite, nitrogen diffusivity and the sharpness of the compound layer: diffusion zone interface. When natural gas was used, carbon became highly concentrated in the compound layer, while surface decarburisation occurred with carbon dioxide. These microstructural effects are discussed in relation to hardness profiles, and compound layer hardness and ductility. The surfaces were characterised using glow discharge optical emission spectroscopy, optical and scanning electron microscopy and X-ray diffraction.

Natural and environmentally responsive building envelopes

In a context of global warming and our needs to reduce CO\d2 emissions, building envelopes will play an important role. A new imperative has been put forth to architects and engineers to develop innovative materials, components and systems, in order to make building envelopes adaptive and responsive to variable and extreme climate conditions. Envelopes serve multiple functions, from shielding the interior environment to collecting, storing and generating energy. Perhaps a more recent concern of terrestrial habitats is permeability and leakages within the building envelope. Such airtight and concealed envelopes with zero particle exchange are a necessity and already exist in regard to space capsules and habitats.

This paper attempts to acknowledge existing and visionary envelope concepts and their functioning in conjunction with maintaining a favorable interior environment. It introduces several criteria and requirements of advanced fa\acades along with interior pressurization control. Furthermore, the paper also takes a closer look at the principles of "biomimicry" of natural systems combined with the most up-to-date building materials and construction technologies, trying to integrate the notions of adaptation - where the capacity to survive depends on the ability to adjust to the environment - within the concept of technological evolution and innovation. An "adaptive" attitude in the way in which we conceive our built structures provides a conceptual basis for the advanced building design of our future, as well as one concerned about the efficient management of the available resources. Built environments of the future (in extreme climates or not) will need to respond to Renewable, Adaptive, Recyclable and Environmental (R.A.R.E.) concepts in order to coexist in a sustainable way with their surroundings.

Sexual selection and individual genetic diversity in a songbird

Here, we report for the first time, to our knowledge, a strong correlation between a measure of individual genetic diversity and song complexity, a sexually selected male trait in sedge warblers, Acrocephalus schoenobaenus. We also find that females prefer to mate with males who will maximize this diversity in individual progeny. The genetic diversity of each offspring is further increased by means of nonrandom fertilization, as we also show that the fertilizing sperm contains a haplotype more genetically distant to that of the egg than expected by chance. These findings suggest that species' mating preferences may be subject to fine tuning aimed at increasing offspring viability through increased genetic diversity. This includes external and internal mechanisms of selection, even within the ejaculate of a single male.

Dynamic advertising under vertical product differentiation

We investigate a dynamic advertising model where product quality is endogenous. In the differential game between single-product firms, there exists a parameter range where the low-quality firm uses a more efficient advertising technology and earns higher profits than the rival. Moreover, we show that equilibrium qualities are the same under duopoly, multiproduct monopoly, and social planning, the only distortion being concerned with the output levels.

Identification and possible disease mechanisms of an under-recognized fungus, Aureobasidium pullulans

Background: Investigations into the occurrence and health effects of yeast-like fungi in the outdoor air in the US have been limited. We sought to identify a respirable-sized fungus common in the Pasadena air, locate a major source for the emissions and investigate its relevance to allergic disease. Methods: Yeast-like fungi sampled from the environment were isolated, microscopically examined and sequenced. Pasadena allergy patients were skin tested with commercially available fungal extracts. Patient serum was immunoanalyzed for specific IgE reactivity. Nearby vegetation was analyzed in a controlled emission chamber to find a major source for the aerosols. Results: Hyaline unicellular conidia comprised up to 90% (41,250 m^-3 of air) of total fungal counts and generally peaked at night and during periods of rainfall and ensuing winds throughout the fall and winter. Flowers were determined to be a major source of the emissions. The cellular and colonial morphology of isolates were consistent with Aureobasidium species. The sequence of the D1/D2 region of the 26S ribosomal subunit of isolates from flowers showed identity to two strains of Aureohasidium pullulans (black yeast). Seventeen percent (16/94) of atopic individuals had positive skin testing with A. pullulans extract. Patient sera gE identified several high molecular weight allergens in Aureobasidium extracts. Conclusions: Respirable-sized conidia of A. pullulans are emitted from flowers and form high concentrations in the air. They are associated with immediate reactivity on skin tests, bind to patient sera IgE, and might be relevant in allergic upper and lower airway diseases.

Effects of temperature in relation to sheet metal stamping

The demand to reduce the use of lubricants and increase tool life in sheet metal stamping has resulted in increased research on the sliding contact between the tool and the sheet materials. Unlubricated sliding wear tests for soft carbon steel sliding on D2 tool steel were performed using a pin-on-disk tribometer. The results revealed that temperature has an influencing role in the wear of tool steel and that material transfer between tool and sheet can be minimized at a certain temperature range in sheet metal stamping.

Differential involvement of rat medial prefrontal cortex dopamine receptors in modulation of hypothalamic- pituitary-adrenal axis responses to different stressors

Recent investigations have implicated the medial prefrontal cortex (mPFC) in modulation of subcortical pathways that contribute to the generation of behavioural, autonomic and endocrine responses to stress. However, little is known of the mechanisms involved. One of the key neurotransmitters involved in mPFC function is dopamine, and we therefore aimed, in this investigation, to examine the role of mPFC dopamine in response to stress in Wistar rats. In this regard, we infused dopamine antagonists SCH23390 or sulpiride into the mPFC via retrodialysis. We then examined changes in numbers of cells expressing the c-fos immediate-early gene protein product, Fos, in subcortical neuronal populations associated with regulation of hypothalamic-pituitary-adrenal (HPA) axis stress responses in response to either of two stressors; systemic injection of interleukin-1β, or air puff. The D1 antagonist, SCH23390, and the D2 antagonist, sulpiride, both attenuated expression of Fos in the medial parvocellular hypothalamic paraventricular nucleus (mpPVN) corticotropin-releasing factor cells at the apex of the HPA axis, as well as in most extra-hypothalamic brain regions examined in response to interleukin-1β. By contrast, SCH23390 failed to affect Fos expression in response to air puff in any brain region examined, while sulpiride resulted in an attenuation of the air puff-induced response in only the mpPVN and the bed nucleus of the stria terminalis. These results indicate that the mPFC differentially processes the response to different stressors and that the two types of dopamine receptor may have different roles.

PPARγ ligands, 15-deoxy-Δ12,14-prostaglandin J2 and rosiglitazone regulate human cultured airway smooth muscle proliferation through different mechanisms

1. The influence of two peroxisome proliferator-activated receptor γ (PPARγ) ligands, a thiazolidinedione, rosiglitazone (RG) and the prostaglandin D2 metabolite 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) on the proliferation of human cultured airway smooth muscle (HASM) was examined.

2. The increases in HASM cell number in response to basic fibroblast growth factor (bFGF, 300 pm) or thrombin (0.3 U ml−1) were significantly inhibited by either RG (1–10 μm) or 15d-PGJ2 (1–10 μm). The effects of RG, but not 15d-PGJ2, were reversed by the selective PPARγ antagonist GW9662 (1 μm).

3. Neither RG nor 15d-PGJ2 (10 μm) decreased cell viability, or induced apoptosis, suggesting that the regulation of cell number was due to inhibition of proliferation, rather than increased cell death.

4. Flow-cytometric analysis of HASM cell cycle distribution 24 h after bFGF addition showed that RG prevented the progression of cells from G1 to S phase. In contrast, 15d-PGJ2 caused an increase in the proportion of cells in S phase, and a decrease in G2/M, compared to bFGF alone.

5. Neither RG nor 15d-PGJ2 inhibited ERK phosphorylation measured 6 h post mitogen addition. The bFGF-mediated increase in cyclin D1 protein levels after 8 h was reduced in the presence of 15d-PGJ2, but not RG.

6. Although both RG and 15d-PGJ2 can inhibit proliferation of HASM irrespective of the mitogen used, only the antiproliferative effects of RG appear to be PPARγ-dependent. The different antimitogenic mechanisms of 15d-PGJ2 and synthetic ligands for PPARγ may be exploited to optimise the potential for these compounds to inhibit airway remodelling in asthma.

The value of impulsivity to define subgroups of addicted individuals differing in personality dysfunction, craving, psychosocial adjustment, and wellbeing: A latent class analysis

High impulsivity is common to substance and gambling addictions. Despite these commonalities, there is still substantial heterogeneity on impulsivity levels within these diagnostic groups, and variations in impulsive levels predict higher severity of symptoms and poorer outcomes. We addressed the question of whether impulsivity scores can yield empirically driven subgroups of addicted individuals that will exhibit different clinical presentations and outcomes. We applied latent class analysis (LCA) to trait (UPPS-P impulsive behavior scale) and cognitive impulsivity (Stroop and d2 tests) scores in three predominantly male addiction diagnostic groups: Cocaine with Personality Disorders, Cocaine Non-comorbid, and Gambling and analyzed the usefulness of the resulting subgroups to differentiate personality beliefs and relevant outcomes: Craving, psychosocial adjustment, and quality of life. In accordance with impulsivity scores, the three addiction diagnostic groups are best represented as two separate classes: Class 1 characterized by greater trait impulsivity and poorer cognitive impulsivity performance and Class 2 characterized by lower trait impulsivity and better cognitive impulsivity performance. The two empirically derived classes showed significant differences on personality features and outcome variables (Class 1 exhibited greater personality dysfunction and worse clinical outcomes), whereas conventional diagnostic groups showed non-significant differences on most of these measures. Trait and cognitive impulsivity scores differentiate subgroups of addicted individuals with more versus less severe personality features and clinical outcomes.

Secure outsourced attribute-based signatures

Attribute-based signature (ABS) enables users to sign messages over attributes without revealing any information other than the fact that they have attested to the messages. However, heavy computational cost is required during signing in existing work of ABS, which grows linearly with the size of the predicate formula. As a result, this presents a significant challenge for resource-constrained devices (such as mobile devices or RFID tags) to perform such heavy computations independently. Aiming at tackling the challenge above, we first propose and formalize a new paradigm called Outsourced ABS, i.e., OABS, in which the computational overhead at user side is greatly reduced through outsourcing intensive computations to an untrusted signing-cloud service provider (S-CSP). Furthermore, we apply this novel paradigm to existing ABS schemes to reduce the complexity. As a result, we present two concrete OABS schemes: i) in the first OABS scheme, the number of exponentiations involving in signing is reduced from O(d) to O(1) (nearly three), where d is the upper bound of threshold value defined in the predicate; ii) our second scheme is built on Herranz et al.'s construction with constant-size signatures. The number of exponentiations in signing is reduced from O(d2) to O(d) and the communication overhead is O(1). Security analysis demonstrates that both OABS schemes are secure in terms of the unforgeability and attribute-signer privacy definitions specified in the proposed security model. Finally, to allow for high efficiency and flexibility, we discuss extensions of OABS and show how to achieve accountability as well.

Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: association with N-methyl-d-aspartic acid receptor up-regulation

Abnormalities in glutamatergic signalling are proposed in schizophrenia in light of the schizophreniform psychosis elicited by NMDA antagonists. The metabotropic glutamate receptor 5 (mGluR5) interacts closely with the NMDA receptor and is implicated in several behavioural endophenotypes of schizophrenia. We have demonstrated that mice lacking mGluR5 have increased sensitivity to the hyperlocomotive effects of the NMDA antagonist MK-801. Mice lacking mGluR5 also show abnormal locomotor patterns, reduced prepulse inhibition (PPI), and deficits on performance of a short-term spatial memory task on the Y-maze. Chronic administration of the antipsychotic drug clozapine ameliorated the locomotor disruption and reversed the PPI deficit, but did not improve Y-maze performance. Chronic clozapine increased NMDA receptor binding ([3H]MK-801) but did not alter dopamine D2 ([3H]YM-09151), 5-HT2A ([3H]ketanserin), or muscarinic M1/M4 receptor ([3H]pirenzepine), binding in these mice. These results demonstrate behavioural abnormalities that are relevant to schizophrenia in the mGluR5 knockout mouse and a reversal of behaviours with clozapine treatment. These results highlight both the interactions between mGluR5 and NMDA receptors in the determination of schizophreniform behaviours and the potential for the effects of clozapine to be mediated by NMDA receptor regulation.
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