High affinity single-chain variable fragments are specific and versatile targeting motifs for extracellular vesicles

Exosomes are extracellular vesicles that mediate cell-to-cell communication by transferring biological cargo, such as DNA, RNA and proteins. Through genetic engineering of exosome-producing cells or manipulation of purified exosomes, it is possible to load exosomes with therapeutic molecules and target them to specific cells via the display of targeting moieties on their surface. This provides an opportunity to exploit a naturally-occurring biological process for therapeutic purposes. In this study, we explored the potential of single chain variable fragments (scFv) as targeting domains to achieve delivery of exosomes to cells expressing a cognate antigen. We generated exosomes targeting the Her2 receptor and, by varying the affinity of the scFvs and the Her2 expression level on recipient cells, we determined that both a high-affinity anti-Her2-scFv (KD ≤ 1 nM) and cells expressing a high level (≥106 copies per cell) of Her2 were optimally required to enable selective uptake. We also demonstrate that targeting exosomes to cells via a specific cell surface receptor can alter their intracellular trafficking route, providing opportunities to influence the efficiency of delivery and fate of intracellular cargo. These experiments provide solid data to support the wider application of exosomes displaying antibody fragments as vehicles for the targeted delivery of therapeutic molecules

Do red deer stags (Cervus elaphus) use roar fundamental frequency (F0) to assess rivals?

It is well established that in humans, male voices are disproportionately lower pitched than female voices, and recent studies suggest that this dimorphism in fundamental frequency (F0) results from both intrasexual (male competition) and intersexual (female mate choice) selection for lower pitched voices in men. However, comparative investigations indicate that sexual dimorphism in F0 is not universal in terrestrial mammals. In the highly polygynous and sexually dimorphic Scottish red deer Cervus elaphus scoticus, more successful males give sexually-selected calls (roars) with higher minimum F0s, suggesting that high, rather than low F0s advertise quality in this subspecies. While playback experiments demonstrated that oestrous females prefer higher pitched roars, the potential role of roar F0 in male competition remains untested. Here we examined the response of rutting red deer stags to playbacks of re-synthesized male roars with different median F0s. Our results show that stags’ responses (latencies and durations of attention, vocal and approach responses) were not affected by the F0 of the roar. This suggests that intrasexual selection is unlikely to strongly influence the evolution of roar F0 in Scottish red deer stags, and illustrates how the F0 of terrestrial mammal vocal sexual signals may be subject to different selection pressures across species. Further investigations on species characterized by different F0 profiles are needed to provide a comparative background for evolutionary interpretations of sex differences in mammalian vocalizations

How do you say ‘hello’? Personality impressions from brief novel voices

On hearing a novel voice, listeners readily form personality impressions of that speaker. Accurate or not, these impressions are known to affect subsequent interactions; yet the underlying psychological and acoustical bases remain poorly understood. Furthermore, hitherto studies have focussed on extended speech as opposed to analysing the instantaneous impressions we obtain from first experience. In this paper, through a mass online rating experiment, 320 participants rated 64 sub-second vocal utterances of the word ‘hello’ on one of 10 personality traits. We show that: (1) personality judgements of brief utterances from unfamiliar speakers are consistent across listeners; (2) a two-dimensional ‘social voice space’ with axes mapping Valence (Trust, Likeability) and Dominance, each driven by differing combinations of vocal acoustics, adequately summarises ratings in both male and female voices; and (3) a positive combination of Valence and Dominance results in increased perceived male vocal Attractiveness, whereas perceived female vocal Attractiveness is largely controlled by increasing Valence. Results are discussed in relation to the rapid evaluation of personality and, in turn, the intent of others, as being driven by survival mechanisms via approach or avoidance behaviours. These findings provide empirical bases for predicting personality impressions from acoustical analyses of short utterances and for generating desired personality impressions in artificial voices

Voice-based assessments of trustworthiness, competence, and warmth in blind and sighted adults

The study of voice perception in congenitally blind individuals allows researchers rare insight into how a lifetime of visual deprivation affects the development of voice perception. Previous studies have suggested that blind adults outperform their sighted counterparts in low-level auditory tasks testing spatial localization and pitch discrimination, as well as in verbal speech processing; however, blind persons generally show no advantage in nonverbal voice recognition or discrimination tasks. The present study is the first to examine whether visual experience influences the development of social stereotypes that are formed on the basis of nonverbal vocal characteristics (i.e., voice pitch). Groups of 27 congenitally or early-blind adults and 23 sighted controls assessed the trustworthiness, competence, and warmth of men and women speaking a series of vowels, whose voice pitches had been experimentally raised or lowered. Blind and sighted listeners judged both men’s and women’s voices with lowered pitch as being more competent and trustworthy than voices with raised pitch. In contrast, raised-pitch voices were judged as being warmer than were lowered-pitch voices, but only for women’s voices. Crucially, blind and sighted persons did not differ in their voice-based assessments of competence or warmth, or in their certainty of these assessments, whereas the association between low pitch and trustworthiness in women’s voices was weaker among blind than sighted participants. This latter result suggests that blind persons may rely less heavily on nonverbal cues to trustworthiness compared to sighted persons. Ultimately, our findings suggest that robust perceptual associations that systematically link voice pitch to the social and personal dimensions of a speaker can develop without visual input

Step Frequency And Perceived Self-Motion

There is a discrepancy between the ability to correctly match the gains of visual and motor speed in virtual reality (VR) when walking on solid ground and the failure of this ability when walking on a treadmill. Moreover, this discrepancy has been found to interact with effects of the structure of the visual environment. The authors used a high-fidelity treadmill VR system to reproduce the high interactivity of normal walking in wide-area VR. Under these conditions, it was found that gain matches in a richly structured near environment differ by only about 10% in treadmill VR from matches in wide-area VR and that trial-to-trial variations in step frequency predicted changes in perceived locomotor speed. Gait differences resulting from treadmill walking (which are shown not to be a product of wearing a head-mounted display), apparently lead to an overestimation of motor speed on treadmills. When the near visual environment represented an empty hallway, additional errors were present that could be accounted for by known illusions in the perception of visual speed during self-motion. A study of normal gait at different speeds measured by head-tracker is reported as evidence of other possible sources of perceptual estimates of locomotor speed in normal walkin

Sociosexual attitudes and dyadic sexual desire independently predict women’s preferences for male vocal masculinity

Research suggests that the desire to behave sexually with a partner (dyadic sexual desire) may reflect desire for intimacy whereas solitary sexual desire may reflect pleasure seeking motivations more generally. Because direct reproductive success can only be increased with a sexual partner, we tested whether dyadic sexual desire was a better predictor of women’s preferences for lower pitched men’s voices (a marker of relatively high reproductive success) than was solitary sexual desire. In Study 1, women (N = 95) with higher dyadic sexual desire scores on the Sexual Desire Inventory-2 preferred masculinized male voices more than did women with lower dyadic sexual desire scores. We did not find a significant relationship between women’s vocal masculinity preferences and their solitary sexual desire scores. In Study 2, we tested whether the relationship between voice preferences and dyadic sexual desire scores was related to differences in sociosexual orientation. Women (N = 80) with more positive attitudes towards uncommitted sex had stronger vocal masculinity preferences regardless of whether men’s attractiveness was judged for short-term or long-term relationships. Independent of the effect of sociosexual attitudes, dyadic sexual desire positively predicted women’s masculinity preferences when assessing men’s attractiveness for short-term but not long-term relationships. These effects were independent of women’s own relationship status and hormonal contraceptive use. Our results provide further evidence that women’s mate preferences may independently reflect individual differences in both sexual desire and openness to short-term relationships, potentially with the ultimate function of maximizing the fitness benefits of women’s mate choices

Holistic needs assessment and care plans for women with gynaecological cancer: do they improve cancer-specific health-related quality of life? A randomised controlled trial using mixed methods

Holistic needs assessment (HNA) and care planning is proposed to address unmet needs of people treated for cancer. We tested whether HNA and care planning by an allied health professional improved cancer-specific quality of life for women following curative treatment for stage I-III gynaecological cancer. Methods Consecutive women were invited to participate in a randomised controlled study (HNA and care planning vs. usual care) at a UK cancer centre. Data were collected by questionnaire at baseline, three and six months. The outcomes were six month change in EORTC-QLQ-C30 global score (primary), and in EORTC sub-scales, generic quality of life, self-efficacy (secondary). The study was blinded for data management and analysis. Differences in outcomes were compared between groups. Health service utilisation and Quality Adjusted Life Years (from SF-6) were gathered for a cost-effectiveness analysis. Thematic analysis was used to interpret data from an exit interview. Results 150 women consented (75 per group), ten undertook interviews. For 124 participants (61 intervention, 63 controls) with complete data, no statistically significant differences were seen between groups in the primary end-point. The majority of those interviewed reported important personal gains they attributed to the intervention which reflected trends to improvement seen in EORTC functional and symptom scales. Economic analysis suggests a 62% probability of cost-effectiveness at a £30,000/QALY threshold. Conclusion: Care plan development with an allied health professional is cost-effective, acceptable and useful for some women treated for stage 1-111 gynaecological cancer. We recommend its introduction early in the pathway to support person-centred care

Integrating fundamental and formant frequencies in women's preferences for men's voices

Prior work has emphasized independent effects of voice pitch and apparent vocal tract length on women's preferences for men's voices. An interaction between the effects of pitch and apparent vocal tract length on male vocal attractiveness might be expected, however, given interactions between the effects of voice pitch and apparent vocal tract length on perceptions of body size, age, and sex. Here, we present empirical evidence for such an interaction. Women preferred low pitch in men's voices more when associated with large vocal tracts than when associated with small vocal tracts and preferred large vocal tracts in men's voices more when associated with low pitch than when associated with high pitch. Collectively, these findings demonstrate integration of different vocal cues in women's mate preferences, potentially allowing women to better assess the quality of potential mates. Copyright 2011, Oxford University Press.

Apparent height and body mass index influence perceived leadership ability in three-dimensional faces

Facial appearance has a well-documented effect on perceived leadership ability. Face judgments of leadership ability predict political election outcomes across the world, and similar judgments of business CEOs predict company profits. Body height is also associated with leadership ability, with taller people attaining positions of leadership more than their shorter counterparts in both politics and in the corporate world. Previous studies have found some face characteristics that are associated with leadership judgments, however there have been no studies with three-dimensional faces. We assessed which facial characteristics drive leadership judgments in three-dimensional faces. We found a perceptual relationship between height and leadership ability. We also found that facial maturity correlated with leadership judgments, and that faces of people with an unhealthily high body mass index received lower leadership ratings. We conclude that face attributes associated with body size and maturity alter leadership perception, and may influence real-world democratic leadership selection