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

Variability of disk emission in pre-main sequence and related stars. II. Variability in the gas and dust emission of the Herbig Fe star SAO 206462

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.We present 13 epochs of near-infrared (0.8-5 μm) spectroscopic observations of the pre-transitional, "gapped" disk system in SAO 206462 (=HD 135344B). In all, six gas emission lines (Brα, Brγ, Paβ, Paγ, Paδ, Paepsilon, and the 0.8446 μm line of O I) along with continuum measurements made near the standard J, H, K, and L photometric bands were measured. A mass accretion rate of approximately 2 × 10–8 M ☉ yr–1 was derived from the Brγ and Paβ lines. However, the fluxes of these lines varied by a factor of over two during the course of a few months. The continuum also varied, but by only ~30%, and even decreased at a time when the gas emission was increasing. The H I line at 1.083 μm was also found to vary in a manner inconsistent with that of either the hydrogen lines or the dust. Both the gas and dust variabilities indicate significant changes in the region of the inner gas and the inner dust belt that may be common to many young disk systems. If planets are responsible for defining the inner edge of the gap, they could interact with the material on timescales commensurate with what is observed for the variations in the dust, while other disk instabilities (thermal, magnetorotational) would operate there on longer timescales than we observe for the inner dust belt. For SAO 206462, the orbital period would likely be 1-3 years. If the changes are being induced in the disk material closer to the star than the gap, a variety of mechanisms (disk instabilities, interactions via planets) might be responsible for the changes seen. The He I feature is most likely due to a wind whose orientation changes with respect to the observer on timescales of a day or less. To further constrain the origin of the gas and dust emission will require multiple spectroscopic and interferometric observations on both shorter and longer timescales that have been sampled so far.This work was supported by NASA ADP grants NNH06CC28C and NNX09AC73G, Hubble Space Telescope grants HST-GO-10764 and HST-GO-10864, Chilean National TAC grants CNTAC-010A-064

Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition

Eliminating Malaria Vectors.

Malaria vectors which predominantly feed indoors upon humans have been locally eliminated from several settings with insecticide treated nets (ITNs), indoor residual spraying or larval source management. Recent dramatic declines of An. gambiae in east Africa with imperfect ITN coverage suggest mosquito populations can rapidly collapse when forced below realistically achievable, non-zero thresholds of density and supporting resource availability. Here we explain why insecticide-based mosquito elimination strategies are feasible, desirable and can be extended to a wider variety of species by expanding the vector control arsenal to cover a broader spectrum of the resources they need to survive. The greatest advantage of eliminating mosquitoes, rather than merely controlling them, is that this precludes local selection for behavioural or physiological resistance traits. The greatest challenges are therefore to achieve high biological coverage of targeted resources rapidly enough to prevent local emergence of resistance and to then continually exclude, monitor for and respond to re-invasion from external populations

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

Probing the structure, dynamics, and bonding of coinage metal complexes of white phosphorus

A series of cationic white phosphorus complexes of the coinage metals Au and Cu have been synthesised and characterised both in the solid state and in solution. All complexes feature a P4 unit coordinated through an edge P-P vector (η(2)-like), although the degree of activation (as measured by the coordinated P-P bond length) is greater in the gold species. All of the cations are fluxional on the NMR timescale at room temperature, but in the case of the gold systems fluxionality is frozen out at -90 °C. Electronic structure calculations suggest that this fluxionality proceeds via an η(1)-coordinated M-P4 intermediate

Lying Behavior, Family Functioning and Adjustment in Early Adolescence

Item does not contain fulltextCommunication between children and parents has been the subject of several studies, examining the effects of, for example, disclosure and secrecy on adolescents' social relationships and adjustment. Less attention has paid to adolescent deception. We developed and tested a new instrument on lying behavior in a sample of 671 parent-adolescent couples. Analyses on the psychometric properties showed that this instrument had one principal component, and high internal consistency, item-total correlations and inter-item correlations. Lying was moderately associated with other indicators of parent-child communication, the quality of the parent-child relationship, and with parenting practices. In addition, frequent lying was moderately related to behavioral problems and emotional problems.10 p

Understanding 'monitoring' data-the association between measured stressors and athlete responses within a holistic basketball performance framework.

This study examined associations between cumulative training load, travel demands and recovery days with athlete-reported outcome measures (AROMs) and countermovement jump (CMJ) performance in professional basketball. Retrospective analysis was performed on data collected from 23 players (mean±SD: age = 24.7±2.5 years, height = 198.3±7.6 cm, body mass = 98.1±9.0 kg, wingspan = 206.8±8.4 cm) from 2018-2020 in the National Basketball Association G-League. Linear mixed models were used to describe variation in AROMs and CMJ data in relation to cumulative training load (previous 3- and 10-days), hours travelled (previous 3- and 10-day), days away from the team's home city, recovery days (i.e., no travel/minimal on-court activity) and individual factors (e.g., age, fatigue, soreness). Cumulative 3-day training load had negative associations with fatigue, soreness, and sleep, while increased recovery days were associated with improved soreness scores. Increases in hours travelled and days spent away from home over 10 days were associated with increased sleep quality and duration. Cumulative training load over 3 and 10 days, hours travelled and days away from home city were all associated with changes in CMJ performance during the eccentric phase. The interaction of on-court and travel related stressors combined with individual factors is complex, meaning that multiple athletes response measures are needed to understand fatigue and recovery cycles. Our findings support the utility of the response measures presented (i.e., CMJ and AROMs), but this is not an exhaustive battery and practitioners should consider what measures may best inform training periodization within the context of their environment/sport

Facial Cosmetics and Attractiveness: Comparing the Effect Sizes of Professionally-Applied Cosmetics and Identity

Forms of body decoration exist in all human cultures. However, in Western societies, women are more likely to engage in appearance modification, especially through the use of facial cosmetics. How effective are cosmetics at altering attractiveness? Previous research has hinted that the effect is not large, especially when compared to the variation in attractiveness observed between individuals due to differences in identity. In order to build a fuller understanding of how cosmetics and identity affect attractiveness, here we examine how professionally-applied cosmetics alter attractiveness and compare this effect with the variation in attractiveness observed between individuals. In Study 1, 33 YouTube models were rated for attractiveness before and after the application of professionally-applied cosmetics. Cosmetics explained a larger proportion of the variation in attractiveness compared with previous studies, but this effect remained smaller than variation caused by differences in attractiveness between individuals. Study 2 replicated the results of the first study with a sample of 45 supermodels, with the aim of examining the effect of cosmetics in a sample of faces with low variation in attractiveness between individuals. While the effect size of cosmetics was generally large, between-person variability due to identity remained larger. Both studies also found interactions between cosmetics and identity-more attractive models received smaller increases when cosmetics were worn. Overall, we show that professionally- applied cosmetics produce a larger effect than self-applied cosmetics, an important theoretical consideration for the field. However, the effect of individual differences in facial appearance is ultimately more important in perceptions of attractiveness

Effect of Mouth Rinsing and Ingestion of Carbohydrate Solutions on Mood and Perceptual Responses During Exercise

Background: The aim of this study was to investigate whether mouth rinsing or ingesting carbohydrate (CHO) solutions impact on perceptual responses during exercise. Methods: Nine moderately trained male cyclists underwent a 90-min glycogen-reducing exercise, and consumed a low CHO meal, prior to completing an overnight fast. A 1-h cycle time trial was performed the following morning. Four trials, each separated by 7days, were conducted in a randomized, counterbalanced study design: 15% CHO mouth rinse (CHOR), 7.5% CHO ingestion (CHOI), placebo mouth rinse (PLAR) and placebo ingestion (PLAI). Solution volumes (1.5ml·g-1 ingestion trials and 0.33ml·kg-1 rinsing trials) were provided after every 12.5% of completed exercise. Perceptual scales were used to assess affective valence (feeling scale, FS), arousal (felt arousal scale, FAS), exertion (ratings of perceived exertion, RPE) and mood (profile of mood states, POMS) before, during and immediately after exercise. Results: There was no difference in RPE (CHOI, 14.0±9; CHOR, 14.2±.7; PLAI, 14.6±1.8; PLAR, 14.6±2.0; P=0.35), FS (CHOI, 0.0±1.7; CHOR, -0.2±1.5; PLAI, -0.8±1.4; PLAR, -0.8±1.6; P0.15), or FAS (CHOI, 3.6±1.1; CHOR, 3.5±1.0; PLAI, 3.4±1.4; PLAR, 3.3±1.3; P=725) scores between trials. While overall POMS score did not appear to differ between trials, the 'vigour' subscale indicated that CHOI may facilitate the maintenance of 'vigour' scores over time, in comparison to the steady decline witnessed in other trials (P=0.04). There was no difference in time trial performance between trials (CHOI, 65.3±4.8min; CHOR, 68.4±3.9min; PLAI, 68.7±5.3min; PLAR, 68.3±5.2min; P=0.21) but power output was higher in CHOI (231.0±33.2 W) relative to other trials (221-223.6 W; Plt0.01). Conclusions: In a CHO-reduced state, mouth rinsing with a CHO solution did not impact on perceptual responses during high-intensity exercise in trained cyclists and triathletes. On the other hand CHO ingestion improved perceived ratings of vigour and increased power output during exercise