Human preferences for sexually dimorphic faces may be evolutionarily novel

This article has been made available through the Brunel Open Access Publishing Fund.A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from largescale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples

Chronic Myeloid Leukemia Stem Cell Biology

Leukemia progression and relapse is fueled by leukemia stem cells (LSC) that are resistant to current treatments. In the progression of chronic myeloid leukemia (CML), blast crisis progenitors are capable of adopting more primitive but deregulated stem cell features with acquired resistance to targeted therapies. This in turn promotes LSC behavior characterized by aberrant self-renewal, differentiation, and survival capacity. Multiple reports suggest that cell cycle alterations, activation of critical signaling pathways, aberrant microenvironmental cues from the hematopoietic niche, and aberrant epigenetic events and deregulation of RNA processing may facilitate the enhanced survival and malignant transformation of CML progenitors. Here we review the molecular evolution of CML LSC that promotes CML progression and relapse. Recent advances in these areas have identified novel targets that represent important avenues for future therapeutic approaches aimed at selectively eradicating the LSC population while sparing normal hematopoietic progenitors in patients suffering from chronic myeloid malignancies

Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community

Background The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention. Methods/design The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally. Discussion There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world. The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1

Alzheimer's disease (AD) afflicts around 20 million people worldwide and so there is an urgent need for effective treatment. Our research showing that herpes simplex virus type 1 (HSV1) is a risk factor for AD for the brains of people who possess a specific genetic factor and that the virus causes accumulation of key AD proteins (β-amyloid (Aβ) and abnormally phosphorylated tau (P-tau)), suggests that anti-HSV1 antiviral agents might slow AD progression. However, currently available antiviral agents target HSV1 DNA replication and so might be successful in AD only if Aβ and P-tau accumulation depend on viral DNA replication. Therefore, we investigated firstly the stage(s) of the virus replication cycle required for Aβ and P-tau accumulation, and secondly whether antiviral agents prevent these changes using recombinant strains of HSV1 that progress only partly through the replication cycle and antiviral agents that inhibit HSV1 DNA replication. By quantitative immunocytochemistry we demonstrated that entry, fusion and uncoating of HSV1, are insufficient to induce Aβ and P-tau production. We showed also that none of the “immediate early” viral proteins is directly responsible, and that Aβ and P-tau are produced at a subsequent stage of the HSV1 replication cycle. Importantly, the anti-HSV1 antiviral agents acyclovir, penciclovir and foscarnet reduced Aβ and P-tau accumulation, as well as HSV1, with foscarnet being less effective in each case. P-tau accumulation was found to depend on HSV1 DNA replication, whereas Aβ accumulation was not. The antiviral-induced decrease in Aβ is attributable to the reduced number of new viruses, and hence the reduction in viral spread. Since antiviral agents reduce greatly Aβ and P-tau accumulation in HSV1-infected cells, they would be suitable for treating AD with great advantage unlike current AD therapies, only the virus, not the host cell, would be targeted

Prior and Present Evidence: How Prior Experience Interacts with Present Information in a Perceptual Decision Making Task

Vibrotactile discrimination tasks have been used to examine decision making processes in the presence of perceptual uncertainty, induced by barely discernible frequency differences between paired stimuli or by the presence of embedded noise. One lesser known property of such tasks is that decisions made on a single trial may be biased by information from prior trials. An example is the time-order effect whereby the presentation order of paired stimuli may introduce differences in accuracy. Subjects perform better when the first stimulus lies between the second stimulus and the global mean of all stimuli on the judged dimension ("preferred" time-orders) compared to the alternative presentation order ("nonpreferred" time-orders). This has been conceptualised as a "drift" of the first stimulus representation towards the global mean of the stimulus-set (an internal standard). We describe the influence of prior information in relation to the more traditionally studied factors of interest in a classic discrimination task.Sixty subjects performed a vibrotactile discrimination task with different levels of uncertainty parametrically induced by increasing task difficulty, aperiodic stimulus noise, and changing the task instructions whilst maintaining identical stimulus properties (the "context").The time-order effect had a greater influence on task performance than two of the explicit factors-task difficulty and noise-but not context. The influence of prior information increased with the distance of the first stimulus from the global mean, suggesting that the "drift" velocity of the first stimulus towards the global mean representation was greater for these trials.Awareness of the time-order effect and prior information in general is essential when studying perceptual decision making tasks. Implicit mechanisms may have a greater influence than the explicit factors under study. It also affords valuable insights into basic mechanisms of information accumulation, storage, sensory weighting, and processing in neural circuits

Toward Improved Lifetimes of Organic Solar Cells under Thermal Stress: Substrate-Dependent Morphological Stability of PCDTBT:PCBM Films and Devices

Morphological stability is a key requirement for outdoor operation of organic solar cells. We demonstrate that morphological stability and lifetime of polymer/fullerene based solar cells under thermal stress depend strongly on the substrate interface on which the active layer is deposited. In particular, we find that the stability of benchmark PCDTBT/PCBM solar cells under modest thermal stress is substantially increased in inverted solar cells employing a ZnO substrate compared to conventional devices employing a PEDOT:PSS substrate. This improved stability is observed to correlate with PCBM nucleation at the 50 nm scale, which is shown to be strongly influenced by different substrate interfaces. Employing this approach, we demonstrate remarkable thermal stability for inverted PCDTBT:PC70BM devices on ZnO substrates, with negligible (<2%) loss of power conversion efficiency over 160 h under 85 °C thermal stress and minimal thermally induced “burn-in” effect. We thus conclude that inverted organic solar cells, in addition to showing improved environmental stability against ambient humidity exposure as widely reported previously, can also demonstrate enhanced morphological stability. As such we show that the choice of suitable substrate interfaces may be a key factor in achieving prolonged lifetimes for organic solar cells under thermal stress conditions

The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs

BACKGROUND: Recent reports have raised concerns that postnatal steroids may cause neuro-developmental impairment in preterm infants. This systematic review was performed with the objective of determining whether glucocorticoid therapy, to prevent or treat bronchopulmonary dysplasia, impairs neuro-developmental outcomes in preterm infants. METHOD: A systematic review of the literature was performed. Medline was searched and articles retrieved using predefined criteria. Data from randomized controlled trials with adequate neuro-developmental follow up (to at least one year) were entered into a meta-analysis to determine the effects of postnatal treatment of preterm infants with glucocorticoids. Cerebral palsy rates, and neuro-developmental impairment (developmental score more than 2SD below the mean, or cerebral palsy or blindness) were analyzed. The studies were divided into 2 groups according to the extent of contamination of the results by treatment of controls with steroids after the initial study period, those with less than 30% contamination, and those with more than 30% contamination or size of contamination not reported. RESULTS: Postnatal steroid therapy is associated with an increase in cerebral palsy and neuro-developmental impairment. The studies with less contamination show a greater effect of the steroids, consistent with a real direct toxic effect of steroids on the developing central nervous system. The typical relative risk for the development of cerebral palsy derived from studies with less than 30% contamination is 2.86 (95% CI 1.95, 4.19). The typical relative risk for the development of neuro-developmental disability among followed up infants from studies with less than 30% contamination is 1.66 (95% CI 1.26, 2.19). From this subgroup of studies, the number of premature infants who need to be treated to have one more infant with cerebral palsy (number needed to harm, NNH) is 7; to have one more infant with neuro-developmental impairment the NNH is 11. CONCLUSIONS: Postnatal pharmacologic steroid treatment for prevention or treatment of bronchopulmonary dysplasia is associated with dramatic increases in neuro-developmental impairment. As there is no clear evidence in the literature of long term benefit, their use for this indication should be abandoned

Interactions Between Laminin Receptor and the Cytoskeleton During Translation and Cell Motility

Human laminin receptor acts as both a component of the 40S ribosomal subunit to mediate cellular translation and as a cell surface receptor that interacts with components of the extracellular matrix. Due to its role as the cell surface receptor for several viruses and its overexpression in several types of cancer, laminin receptor is a pathologically significant protein. Previous studies have determined that ribosomes are associated with components of the cytoskeleton, however the specific ribosomal component(s) responsible has not been determined. Our studies show that laminin receptor binds directly to tubulin. Through the use of siRNA and cytoskeletal inhibitors we demonstrate that laminin receptor acts as a tethering protein, holding the ribosome to tubulin, which is integral to cellular translation. Our studies also show that laminin receptor is capable of binding directly to actin. Through the use of siRNA and cytoskeletal inhibitors we have shown that this laminin receptor-actin interaction is critical for cell migration. These data indicate that interactions between laminin receptor and the cytoskeleton are vital in mediating two processes that are intimately linked to cancer, cellular translation and migration