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

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

The association between failed quit attempts and increased levels of psychological distress in smokers in a large New Zealand cohort

<p>Abstract</p> <p>Background</p> <p>Although the association between smoking status and poorer mental health has been well documented, the association between quit status and psychological distress is less clear. The aim of the present study is to investigate the association of smoking status and quit status with psychological distress.</p> <p>Methods</p> <p>Data for this study is from a single year of the Survey of Families, Income and Employment (SoFIE) conducted in New Zealand (2004/05) (n = 18,525 respondents). Smoking status and quit status were treated as exposure variables, and psychological distress (Kessler-10) was treated as the outcome variable. Logistic regression analyses were performed to determine the association of smoking with psychological distress in the whole adult population and quit status with psychological distress in the ex- and current-smoking population.</p> <p>Results</p> <p>Current smokers had higher rates of high and very high psychological distress compared to never smokers (adjusted odds ratio (aOR) = 1.45; 95% CI: 1.24-1.69). Unsuccessful quitters had much higher levels of high to very high levels of psychological distress (16%) than any other group. Moreover, compared to long-term ex-smokers, unsuccessful quitters had a much higher odds of high to very high levels of psychological distress (aOR = 1.73; 95% CI: 1.36-2.21).</p> <p>Conclusion</p> <p>These findings suggest that the significant association between smoking and psychological distress might be partly explained by increased levels of psychological distress among current smokers who made a quit attempt in the last year. This issue needs further study as it has implications for optimising the design of quitting support.</p

Engendering harm: a critique of sex selection for 'family balancing'

The most benign rationale for sex-selection is deemed to be “family balancing.” On this view, provided the sex-distribution of an existing offspring group is “unbalanced,” one may legitimately use reproductive technologies to select the sex of the next child. I present four novel concerns with granting “family balancing” as a justification for sex-selection: (a) families or family subsets should not be subject to medicalization; (b) sex selection for “family balancing” entrenches heteronormativity, inflicting harm in at least three specific ways; (c) the logic of affirmative action is appropriated; (d) the moral mandate of reproductive autonomy is misused. I conclude that the harms caused by “family balancing” are sufficiently substantive to over-ride any claim arising from a supposed right to sex selection as an instantiation of procreative autonomy

Relation between body mass index and depression: a structural equation modeling approach

<p>Abstract</p> <p>Background</p> <p>Obesity and depression are two major diseases which are associated with many other health problems such as hypertension, dyslipidemia, diabetes mellitus, coronary heart disease, stroke, myocardial infarction, heart failure in patients with systolic hypertension, low bone mineral density and increased mortality. Both diseases share common health complications but there are inconsistent findings concerning the relationship between obesity and depression. In this work we used the <it>structural equation modeling </it>(SEM) technique to examine the relation between body mass index (BMI), as a proxy for obesity, and depression using the Canadian Community Health Survey, Cycle 1.2.</p> <p>Methods</p> <p>In this SEM model we postulate that 1) BMI and depression are directly related, 2) BMI is directly affected by the physical activity and, 3)depression is directly influenced by stress. SEM was also used to assess the relation between BMI and depression separately for males and females.</p> <p>Results</p> <p>The results indicate that higher BMI is associated with more severe form of depression. On the other hand, the more severe form of depression may result in less weight gain. However, the association between depression and BMI is gender dependent. In males, the higher BMI may result in a more severe form of depression while in females the relation may not be the same. Also, there was a negative relationship between physical activity and BMI.</p> <p>Conclusion</p> <p>In general, use of SEM method showed that the two major diseases, obesity and depression, are associated but the form of the relation is different among males and females. More research is necessary to further understand the complexity of the relationship between obesity and depression. It also demonstrated that SEM is a feasible technique for modeling the relation between obesity and depression.</p

Domestic Water Demand During Droughts in Temperate Climates: Synthesising Evidence for an Integrated Framework

In the upcoming years, as the population is growing and ageing, as lifestyle changes create the need for more water and as fewer people live in each household, the UK water sector will have to deal with challenges in the provision of adequate water services. Unless critical action is taken, every area in the UK may face a supply-demand gap by the 2080s. Extreme weather events and variations that alter drought and flood frequency add to these pressures. However, little evidence is available about householders’ response to drought and there are few if any studies incorporating this evidence into models of demand forecasting. The present work lays the groundwork for modelling domestic water demand response under drought conditions in temperate climates. After discussing the current literature on estimating and forecasting domestic water consumption under both ‘normal’ and drought conditions, this paper identifies the limited ability of current domestic demand forecasting techniques to include the many different and evolving factors affecting domestic consumption and it stresses the need for the inclusion of inter and intra household factors as well as water use practices in future demand forecasting models

Studies on the Restriction of Murine Leukemia Viruses by Mouse APOBEC3

APOBEC3 proteins function to restrict the replication of retroviruses. One mechanism of this restriction is deamination of cytidines to uridines in (−) strand DNA, resulting in hypermutation of guanosines to adenosines in viral (+) strands. However, Moloney murine leukemia virus (MoMLV) is partially resistant to restriction by mouse APOBEC3 (mA3) and virtually completely resistant to mA3-induced hypermutation. In contrast, the sequences of MLV genomes that are in mouse DNA suggest that they were susceptible to mA3-induced deamination when they infected the mouse germline. We tested the possibility that sensitivity to mA3 restriction and to deamination resides in the viral gag gene. We generated a chimeric MLV in which the gag gene was from an endogenous MLV in the mouse germline, while the remainder of the viral genome was from MoMLV. This chimera was fully infectious but its response to mA3 was indistinguishable from that of MoMLV. Thus, the Gag protein does not seem to control the sensitivity of MLVs to mA3. We also found that MLVs inactivated by mA3 do not synthesize viral DNA upon infection; thus mA3 restriction of MLV occurs before or at reverse transcription. In contrast, HIV-1 restricted by mA3 and MLVs restricted by human APOBEC3G do synthesize DNA; these DNAs exhibit APOBEC3-induced hypermutation

Short-Term Analysis of Human Dental Pulps After Direct Capping with Portland Cement

This study evaluated the short-term response of human pulp tissue when directly capped with Portland cement. In this series of cases, twenty human third molars that were scheduled for extraction were used. After cavity preparation, pulp exposure was achieved and Portland cement pulp capping was performed. Teeth were extracted after 1, 7, 14 and 21 days following treatment and prepared for histological examination and bacterial detection. Each group had 5 teeth. The results were descriptively analysed. Dentin bridge formation was seen in two teeth with some distance from the material interface (14 and 21 days). Soft inflammatory responses were observed in most of the cases. Bacteria were not disclosed in any specimen. PC exhibited some features of biocompatibility and capability of inducing mineral pulp response in short-term evaluation. The results suggested that PC has a potential to be used as a less expensive pulp capping material in comparison to other pulp capping materials