Mutational analysis of Sse1 (Hsp110) suggests an integral role for this chaperone in yeast prion propagation in vivo.

The yeast Hsp110 chaperone Sse1 is a conserved protein that is a noncanonical member of the Hsp70 protein superfamily. Sse1 influences the cellular response to heat stress and has also been implicated in playing a role in the propagation of prions in yeast. Sse1 can seemingly exert its effects in vivo through direct or indirect actions by influencing the nucleotide exchange activity of canonical cytosolic Hsp70s. Using a genetic screen based on the inability to propagate the yeast [PSI(+)] prion, we have identified 13 new Sse1 mutants that are predicted to alter chaperone function through a variety of different mechanisms. Not only are these new Sse1 mutants altered in the ability to propagate and cure yeast prions but also to varying degrees in the ability to grow at elevated temperatures. The expression levels of chaperone proteins known to influence yeast prion propagation are unaltered in the Sse1 mutants, suggesting that the observed phenotypic effects are caused by direct functional alterations in these mutants. Mapping the location of the mutants onto the Sse1 crystal structure suggests that more than one functional alteration in Sse1 may result in changes in prion propagation and ability to function at elevated temperatures. All Sse1 mutants isolated provide essential functions in the cell under normal growth conditions, further demonstrating that essential chaperone functions in vivo can to some degree at least be detached from those related to propagation of prions. Our results suggest that Sse1 can influence prion propagation through a variety of different mechanisms

EP-1711: Effect of Noise Floor Suppression on Diffusion Kurtosis for Prostate Brachytherapy

WOS: 000467786304224

Capillary electrophoresis of human follicular fluid

Some of the major serum proteins that are also found in follicular fluid, including transferrin, α-macroglobulin and albumin, are thought to play a role in oocyte maturation. This study set out to identify proteins in human follicular fluid by capillary zone electrophoresis and to investigate their relationship to follicular/oocyte maturity and fertility outcome. 176 individual follicular fluid samples, from 30 women undertaking in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI), were run using an optimized capillary zone electrophoresis method that gave a good separation of sixteen peaks in most samples. Nine of the peaks were identified and quantified but seven remain unknown and require further proteomic identification. Of the identified protein peaks, levels of each were corrected for follicular volume and total content calculated. No significant difference in protein levels was found with regard to oocyte recovery and fertilization. Protein concentrations tended to decrease as the follicular sphere increased whilst total content in follicular fluid increased in proportion to size. This is consistent with simple transudation across a sphere surface area which does not increase in proportion to the follicular fluid. This is not true of the concentration and content pattern of other proteins/biomolecules which are produced by follicular cells locally. In conclusion, neither concentration nor absolute levels of nine major proteins identified in follicular fluids correlated with oocyte presence and fertility outcome. Future work to remove more concentrated proteins (e.g. albumin) would enhance separation of smaller peaks and identification of the unknown molecules

Hearing speech against spatially separate competing speech versus competing noise

Listeners had the task of following a target speech signal heard against two competitors either located at the same spatial position as the target or displaced symmetrically to locations flanking it. When speech was the competitor, there was a significantly higher separation effect (maintained intelligibility with reduced target sound level), as compared with either steady-state or fluctuating noises. Increasing the extent of spatial separation slightly increased the effect, and a substantial contribution of interaural time differences was observed. When same- and opposite-sex voices were used, a hypothesis that the similarity between target and competing speech would explain the role for spatial separation was partly supported. High- and low-pass filtering showed that both parts of an acoustically similar competing signal contribute to the phenomenon. We conclude that, in parsing the auditory array, attention to spatial cues is heightened when the components of the array are confusable on other acoustic grounds

Photometry and the Metallicity Distribution of the Outer Halo of M31

We have conducted a wide-field CCD-mosaic study of the resolved red-giant branch (RGB) stars of M31, in a field located 20 kpc from the nucleus along the SE minor axis. In our (I, V-I) color-magnitude diagram, RGB stars in the top three magnitudes of the M31 halo are strongly present. Photometry of a more distant control field to subtract field contamination is used to derive the `cleaned' luminosity function and metallicity distribution function (MDF) of the M31 halo field. From the color distribution of the foreground Milky Way halo stars, we find a reddening E(V-I)= 0.10 +/- 0.02 for this field, and from the luminosity of the RGB tip, we determine a distance modulus (m-M)_o = 24.47 +/- 0.12 (= 783 +/- 43 kpc). The MDF is derived from interpolation within an extensive new grid of RGB models (Vandenberg et al. 2000). The MDF is dominated by a moderately high-metallicity population ([m/H]~ -0.5) found previously in more interior M31 halo/bulge fields, and is much more metal-rich than the [m/H]~ -1.5 level in the Milky Way halo. A significant (~30% - 40%, depending on AGB star contribution) metal-poor population is also present. To first order, the shape of the MDF resembles that predicted by a simple, single-component model of chemical evolution starting from primordial gas with an effective yield y=0.0055. It strongly resembles the MDF recently found for the outer halo of the giant elliptical NGC 5128 (Harris et al. 2000), though NGC 5128 has an even lower fraction of low-metallicity stars. Intriguingly, in both NGC 5128 and M31, the metallicity distribution of the globular clusters in M31 does not match the halo stars; the clusters are far more heavily weighted to metal-poor objects. We suggest similarities in the formation and early evolution of massive, spheroidal stellar systems.Comment: to appear in the Astronomical Journal; 43 pages, including 15 figure

A stepped wedge cluster randomized control trial of dried blood spot testing to improve the uptake of hepatitis C antibody testing within UK prisons

Background: The prevalence of hepatitis C (HCV) is elevated within prison populations, yet diagnosis in prisons remains low. Dried blood spot testing (DBST) is a simple procedure for the detection of HCV antibodies; its impact on testing in the prison context is unknown. Methods: We carried out a stepped-wedge cluster-randomized control trial of DBST for HCV among prisoners within five male prisons and one female prison. Each prison was a separate cluster. The order in which the intervention (training in use of DBST for HCV testing and logistic support) was introduced was randomized across clusters. The outcome measure was the HCV testing rate by prison. Imputation analysis was carried out to account for missing data. Planned and actual intervention times differed in some prisons; data were thus analysed by intention to treat (ITT) and by observed step times. Results: There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time (OR: 0.84; 95% CI: 0.68�1.03; P = 0.088) or using the actual intervention time (OR: 0.86; 95% CI: 0.71�1.06; P = 0.153). This was confirmed by the pooled results of five imputed data sets. Conclusions: DBST as a stand-alone intervention was insufficient to increase HCV diagnosis within the UK prison setting. Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery. We demonstrate that prisons can conduct rigorous studies of new interventions, but data collection can be problematic. Trial registration: International Standard Randomized Controlled Trial Number Register (ISRCTN number ISRCTN05628482)

Adolescents’ preferences for sexual dimorphism are influenced by relative exposure to male and female faces

Exposure to a particular population of faces can increase ratings of the normality and attractiveness of similar-looking faces. Such exposure can also refine the perceived boundaries of that face population, such that other faces are more readily perceived as dissimilar. We predicted that relatively less exposure to opposite-sex faces, as experienced by children at single-sex compared with mixed-sex schools, would decrease ratings of the attractiveness of sexual dimorphism in opposite-sex faces (that is, boys at single-sex schools would show a decreased preference for feminised faces, and girls at single-sex schools would show a decreased preference for masculinised faces). Consistent with this prediction, girls at single-sex compared with mixed-sex schools demonstrated significantly stronger preferences for facial femininity in both male and female faces. Boys at single-sex compared with mixed-sex schools demonstrated marginally stronger preferences for facial masculinity in male faces, but did not differ in their ratings of female faces. These effects were attenuated among some single-sex school pupils by the presence of adolescent opposite-sex siblings. These data add to the evidence that long-term exposure to a particular face population can influence judgements of other faces, and contribute to our understanding of the factors leading to individual differences in face preferences

Cross-cultural effects of color, but not morphological masculinity, on perceived attractiveness of men's faces

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 ElsevierMuch attractiveness research has focused on face shape. The role of masculinity (which for adults is thought to be a relatively stable shape cue to developmental testosterone levels) in male facial attractiveness has been examined, with mixed results. Recent work on the perception of skin color (a more variable cue to current health status) indicates that increased skin redness, yellowness, and lightness enhance apparent health. It has been suggested that stable cues such as masculinity may be less important to attractiveness judgments than short-term, more variable health cues. We examined associations between male facial attractiveness, masculinity, and skin color in African and Caucasian populations. Masculinity was not found to be associated with attractiveness in either ethnic group. However, skin color was found to be an important predictor of attractiveness judgments, particularly for own-ethnicity faces. Our results suggest that more plastic health cues, such as skin color, are more important than developmental cues such as masculinity. Further, unfamiliarity with natural skin color variation in other ethnic groups may limit observers' ability to utilize these color cues

The β6/β7 region of the Hsp70 substrate-binding domain mediates heat-shock response and prion propagation.

Hsp70 is a highly conserved chaperone that in addition to providing essential cellular functions and aiding in cell survival following exposure to a variety of stresses is also a key modulator of prion propagation. Hsp70 is composed of a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). The key functions of Hsp70 are tightly regulated through an allosteric communication network that coordinates ATPase activity with substrate-binding activity. How Hsp70 conformational changes relate to functional change that results in heat shock and prion-related phenotypes is poorly understood. Here, we utilised the yeast [PSI +] system, coupled with SBD-targeted mutagenesis, to investigate how allosteric changes within key structural regions of the Hsp70 SBD result in functional changes in the protein that translate to phenotypic defects in prion propagation and ability to grow at elevated temperatures. We find that variants mutated within the β6 and β7 region of the SBD are defective in prion propagation and heat-shock phenotypes, due to conformational changes within the SBD. Structural analysis of the mutants identifies a potential NBD:SBD interface and key residues that may play important roles in signal transduction between domains. As a consequence of disrupting the β6/β7 region and the SBD overall, Hsp70 exhibits a variety of functional changes including dysregulation of ATPase activity, reduction in ability to refold proteins and changes to interaction affinity with specific co-chaperones and protein substrates. Our findings relate specific structural changes in Hsp70 to specific changes in functional properties that underpin important phenotypic changes in vivo. A thorough understanding of the molecular mechanisms of Hsp70 regulation and how specific modifications result in phenotypic change is essential for the development of new drugs targeting Hsp70 for therapeutic purposes