Materials with the pyrochlore/fluorite structure have diverse technological applications, from magnetism to nuclear waste disposal. Here we report the observation of structural instability present in ...the pyrochlores A
Zr
O
O' (A = Pr, La) and Yb
Ti
O
O', that exists despite ideal stoichiometry, ideal cation-ordering, the absence of lone pair effects, and a lack of magnetic order. Though these materials appear to have good long-range order, local structure probes find displacements, of the order of 0.01 nm, within the pyrochlore framework. The pattern of displacements of the A
O' sublattice mimics the entropically-driven fluxional motions characteristic of and well-known in the silica mineral β-cristobalite. The universality of such displacements within the pyrochlore structure adds to the known structural diversity and explains the extreme sensitivity to composition found in quantum spin ices and the lack of ferroelectric behavior in pyrochlores.
The role of histamine H
1
, H
2
, H
3
and H
4
receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into ...the back of the neck and ‘itch’ assessed by quantifying the scratching evoked.
Histamine (0.03–80
μ
mol), histamine‐trifluoromethyl‐toluidine (HTMT, H
1
agonist, 0.002–2
μ
mol), clobenpropit (H
4
agonist, H
3
antagonist, 0.002–0.6
μ
mol) and to a lesser extent imetit (H
3
/H
4
agonist, 0.03–3
μ
mol) all induced dose‐dependent scratching. Dimaprit (H
2
agonist, 0.04–40
μ
mol) did not cause scratching.
Mepyramine (H
1
antagonist, 20 mg kg
−1
, i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H
3
or H
4
agonists. Thioperamide (H
3
/H
4
antagonist, 20 mg kg
−1
, i.p.) reduced scratching induced by histamine, H
3
and H
4
agonists, but not that caused by HTMT. The non‐sedating H
1
antagonist, terfenadine, also significantly reduced the scratching induced by the H
1
agonist, HTMT. Cimetidine (H
2
antagonist, 20 mg kg
−1
, i.p.) did not affect histamine‐induced scratching.
These results indicate that activation of histamine H
4
receptors causes itch in mice, in addition to the previously recognised role for H
1
receptors in evoking itch. Histamine H
4
receptor antagonists therefore merit investigation as antipruritic agents.
British Journal of Pharmacology
(2004)
142
, 374–380. doi:
10.1038/sj.bjp.0705754
Nicotine binds to nicotinic acetylcholine receptors and studies in animal models have shown that α4β2 receptors mediate many behavioral effects of nicotine. Human genetics studies have provided ...support that variation in the gene that codes for the α4 subunit influences nicotine dependence (ND), but the evidence for the involvement of the β2 subunit gene is less convincing. In this study, we examined the genetic association between variation in the genes that code for the α4 (CHRNA4) and β2 (CHRNB2) subunits of the nicotinic acetylcholine receptor and a quantitative measure of lifetime DSM‐IV ND symptom counts. We performed this analysis in two longitudinal family‐based studies focused on adolescent antisocial drug abuse: the Center on Antisocial Drug Dependence (CADD, N = 313 families) and Genetics of Antisocial Drug Dependence (GADD, N = 111 families). Family‐based association tests were used to examine associations between 14 single nucleotide polymorphisms (SNPs) in CHRNA4 and CHRNB2 and ND symptoms. Symptom counts were corrected for age, sex and clinical status prior to the association analysis. Results, when the samples were combined, provided modest evidence that SNPs in CHRNA4 are associated with ND. The minor allele at both rs1044394 (A; Z = 1.988, P = 0.047, unadjusted P‐value) and rs1044396 (G; Z = 2.398, P = 0.017, unadjusted P‐value) was associated with increased risk of ND symptoms. These data provide suggestive evidence that variation in the α4 subunit of the nicotinic acetylcholine receptor may influence ND liability.
Genetic variation in the α4 subunit of the nicotinic acetylcholine receptor is nominally associated with nicotine dependence liability.
The goal of this study was to assess whether diabetes prevalence varies by countries at different economic levels and whether this can be explained by known risk factors.
The prevalence of diabetes, ...defined as self-reported or fasting glycemia ≥7 mmol/L, was documented in 119,666 adults from three high-income (HIC), seven upper-middle-income (UMIC), four lower-middle-income (LMIC), and four low-income (LIC) countries. Relationships between diabetes and its risk factors within these country groupings were assessed using multivariable analyses.
Age- and sex-adjusted diabetes prevalences were highest in the poorer countries and lowest in the wealthiest countries (LIC 12.3%, UMIC 11.1%, LMIC 8.7%, and HIC 6.6%; P < 0.0001). In the overall population, diabetes risk was higher with a 5-year increase in age (odds ratio 1.29 95% CI 1.28-1.31), male sex (1.19 1.13-1.25), urban residency (1.24 1.11-1.38), low versus high education level (1.10 1.02-1.19), low versus high physical activity (1.28 1.20-1.38), family history of diabetes (3.15 3.00-3.31), higher waist-to-hip ratio (highest vs. lowest quartile; 3.63 3.33-3.96), and BMI (≥35 vs. <25 kg/m(2); 2.76 2.52-3.03). The relationship between diabetes prevalence and both BMI and family history of diabetes differed in higher- versus lower-income country groups (P for interaction < 0.0001). After adjustment for all risk factors and ethnicity, diabetes prevalences continued to show a gradient (LIC 14.0%, LMIC 10.1%, UMIC 10.9%, and HIC 5.6%).
Conventional risk factors do not fully account for the higher prevalence of diabetes in LIC countries. These findings suggest that other factors are responsible for the higher prevalence of diabetes in LIC countries.
This review comprises the most extensive literature search and evidence evaluation to date on the most important international BLS interventions, diagnostics, and prognostic factors for cardiac ...arrest victims. It reemphasizes that the critical lifesaving steps of BLS are (1) prevention, (2) immediate recognition and activation of the emergency response system, (3) early high-quality CPR, and (4) rapid defibrillation for shockable rhythms. Highlights in prevention indicate the rational and judicious deployment of search-and-rescue operations in drowning victims and the importance of education on opioid-associated emergencies. Other 2015 highlights in recognition and activation include the critical role of dispatcher recognition and dispatch-assisted chest compressions, which has been demonstrated in multiple international jurisdictions with consistent improvements in cardiac arrest survival. Similar to the 2010 ILCOR BLS treatment recommendations, the importance of high quality was reemphasized across all measures of CPR quality: rate, depth, recoil, and minimal chest compression pauses, with a universal understanding that we all should be providing chest compressions to all victims of cardiac arrest. This review continued to focus on the interface of BLS sequencing and ensuring high-quality CPR with other important BLS interventions, such as ventilation and defibrillation. In addition, this consensus statement highlights the importance of EMS systems, which employ bundles of care focusing on providing high-quality chest compressions while extricating the patient from the scene to the next level of care. Highlights in defibrillation indicate the global importance of increasing the number of sites with public-access defibrillation programs. Whereas the 2010 ILCOR Consensus on Science provided important direction for the “what” in resuscitation (ie, what to do), the 2015 consensus has begun with the GRADE methodology to provide direction for the quality of resuscitation. We hope that resuscitation councils and other stakeholders will be able to translate this body of knowledge of international consensus statements to build their own effective resuscitation guidelines.
SEX STEROID CONTROL OF MOOD, MENTAL STATE AND MEMORY Fink, George; Sumner, Barbara EH; McQueen, Judith K. ...
Clinical and experimental pharmacology & physiology,
October 1998, Letnik:
25, Številka:
10
Journal Article
Recenzirano
SUMMARY
1. Sex steroid hormones exert profound effects on mood and mental state. Thus, in women, oestrogen is thought to protect against depression and delay the onset of schizophrenia and ...Alzheimer's disease.
2. Our studies in the female rat show that oestradiol, in its positive feedback mode for gonadotrophin release, increases the expression of genes for the 5‐hydroxytryptamine 5‐HT2A receptor and the serotonin transporter (SERT) in the dorsal raphe nucleus and the density of 5‐HT2A receptor and SERT sites in regions of the forebrain that, in the human, are concerned with cognition, mental state, emotion and memory.
3. In the male rat, castration decreases while oestrogen and testosterone, but not 5α‐dihydrotestosterone (5α‐DHT), increase the density of 5‐HT2A receptors in forebrain. The fact that 5α‐DHT has no effect suggests that the action of testosterone depends on its conversion to oestradiol by aromatase.
4. In intact rats, the density of 5‐HT2A receptors in cerebral cortex is significantly higher in prooestrous female than in male and dioestrous female rats, showing that the spontaneous, preovulatory surge of oestradiol that reaches a peak at 12.00 h of pro‐oestrus also increases the density of 5‐HTZA receptors in cortex.
5. Oestrogen and testosterone (by way of its conversion to oestrogen) also stimulate the expression of the arginine vasopressin gene in the bed nucleus of the stria terminalis of the rodent, a mechanism that plays a key role in olfactory memory.
6. These actions of sex steroid hormones are discussed in the context of genomic versus non‐genomic mechanisms, the recent discovery that there are two oestradiol receptors with different distributions in brain, the significance of our findings for our understanding of the control of mood, mental state and memory and the mechanism by which oestrogen stimulation of the 5‐HT2A receptor could delay the onset of Alzheimer's disease.
Neuronal nicotinic acetylcholine receptors have been implicated in various measures of nicotine dependence. In this paper, we present findings from an exploratory study of single nucleotide ...polymorphisms (SNPs) in the CHRNB3 and CHRNA6 genes with tobacco and alcohol phenotypes, including frequency of use and three subjective response factors occurring shortly after initiation of use. Subjects were 1056 ethnically diverse adolescents ascertained from clinical and community settings. The most significant associations were found between two CHRNB3 SNPs (rs4950 and rs13280604) and the three subjective response factors to initial tobacco use. These findings were replicated in a separate community sample of 1524 families participating in the National Longitudinal Study of Adolescent Health. Both CHRNB3 SNPs were found to be associated with similar measures of subjective response to tobacco. These results indicate that early subjective response to nicotine may be a valuable endophenotype for genetic studies aimed at uncovering genes contributing to nicotine use and addiction.
The aim of this work was to study the role of the cell wall protein expansin in elongation growth. Expansins increase cell wall extensibility in vitro and are thought to be involved in cell ...elongation. Here, we studied the regulation of two tomato (Lycopersicon esculentum cv Moneymaker) expansin genes, LeExp2 and LeExp18, in rapidly expanding tissues. LeExp2 was strongly expressed in the elongation zone of hypocotyls and in the faster growing stem part during gravitropic stimulation. LeExp18 expression did not correlate with elongation growth. Exogenous application of hormones showed a substantial auxin-stimulation of LeExp2 mRNA in etiolated hypocotyls and a weaker auxin-stimulation of LeExp18 mRNA in stem tissue. Analysis of transcript accumulation revealed higher levels of LeExp2 and LeExp18 in light-treated, slow-growing tissue than in dark-treated, rapidly elongating tissue. Expansin protein levels and cell wall extension activities were similar in light- and dark-grown hypocotyl extracts. The results show a strong correlation between expansin gene expression and growth rate, but this correlation is not absolute. We conclude that elongation growth is likely to be controlled by expansin acting in concert with other factors that may limit growth under some physiological conditions.
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