Human preferences for sexually dimorphic faces may be evolutionarily novel.

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 large-scale, 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 and, 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.

Facial width-to-height ratio predicts self-reported dominance and aggression in males and females, but a measure of masculinity does not.

Recently, associations between facial structure and aggressive behaviour have been reported. Specifically, the facial width-to-height ratio (fWHR) is thought to link to aggression, although it is unclear whether this association is related to a specific dimension of aggression, or to a more generalized concept of dominance behaviour. Similarly, an association has been proposed between facial masculinity and dominant and aggressive behaviour, but, to date, this has not been formally tested. Because masculinity and fWHR are negatively correlated, it is unlikely that both signal similar behaviours. Here, we thus tested these associations and show that: (i) fWHR is related to both self-reported dominance and aggression; (ii) physical aggression, verbal aggression and anger, but not hostility are associated with fWHR; (iii) there is no evidence for a sex difference in associations between fWHR and aggression; and (iv) the facial masculinity index does not predict dominance or aggression. Taken together, these results indicate that fWHR, but not a measure of facial masculinity, cues dominance and specific types of aggression in both sexes.

Increased CNV-region deletions in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects in the ADNI sample.

We investigated the genome-wide distribution of CNVs in the Alzheimer's disease (AD) Neuroimaging Initiative (ADNI) sample (146 with AD, 313 with Mild Cognitive Impairment (MCI), and 181 controls). Comparison of single CNVs between cases (MCI and AD) and controls shows overrepresentation of large heterozygous deletions in cases (p-value<0.0001). The analysis of CNV-Regions identifies 44 copy number variable loci of heterozygous deletions, with more CNV-Regions among affected than controls (p=0.005). Seven of the 44 CNV-Regions are nominally significant for association with cognitive impairment. We validated and confirmed our main findings with genome re-sequencing of selected patients and controls. The functional pathway analysis of the genes putatively affected by deletions of CNV-Regions reveals enrichment of genes implicated in axonal guidance, cell-cell adhesion, neuronal morphogenesis and differentiation. Our findings support the role of CNVs in AD, and suggest an association between large deletions and the development of cognitive impairment.

MMB4 DMS nanoparticle suspension formulation with enhanced stability for the treatment of nerve agent intoxication.

Various oximes are currently fielded or under investigation in the United States and other countries as a component of autoinjector emergency treatment systems for organophosphate nerve agent chemical weapons. Bis-pyridinium oximes in general have greater efficacy against a broad spectrum of nerve agents, but they have poor stability due to hydrolytic degradation at elevated temperatures. 1,1'-Methylenebis-4-[(hydroxyimino)methyl]pyridinium dimethanesulfonate (MMB4 DMS) is a leading candidate for next-generation nerve agent treatment systems, because it is more stable than other bis-pyridinium oximes, but it still degrades quickly at temperatures often encountered during storage and field use. The primary goal is to increase the stability and shelf life of MMB4 while maintaining the desirable pharmacokinetic (PK) properties of the aqueous formulation. We have developed a formulation to be used in a phase 1 clinical trial consisting of MMB4 micro/nanoparticles suspended in cottonseed oil, a biocompatible vegetable oil. Through various milling techniques, the average particle size can be controlled from approximately 200 to 6000 nm to produce non-Newtonian formulations that are viscous enough to resist rapid particle sedimentation while remaining injectable at a range of concentrations from 5 to 400 mg/mL. The preliminary accelerated stability test shows that MMB4 in these formulations is stable for at least 2 years at temperatures up to 80°C. Preliminary preclinical in vivo studies have demonstrated that all concentrations and particle sizes have desirable PK properties, including high bioavailability and rapid absorption, which is critical to combat potent and fast-acting nerve agents.

Good manufacturing practice: manufacturing of a nerve agent antidote nanoparticle suspension.

We have established a current good manufacturing practice (GMP) manufacturing process to produce a nanoparticle suspension of 1,1'-methylenebis-4-[(hydroxyimino)methyl]pyridinium dimethanesulfonate (MMB4 DMS) in cottonseed oil (CSO) as a nerve agent antidote for a Phase 1 clinical trial. Bis-pyridinium oximes such as MMB4 were previously developed for emergency treatment of organophosphate nerve agent intoxication. Many of these compounds offer efficacy superior to monopyridinium oximes, but they have poor thermal stability due to hydrolytic cleavage in aqueous solution. We previously developed a nonaqueous nanoparticle suspension to improve the hydrothermal stability, termed Enhanced Formulation (EF). An example of this formulation technology is a suspension of MMB4 DMS nanoparticles in CSO. Due to the profound effect of particle size distribution on product quality and performance, particle size must be controlled during the manufacturing process. Therefore, a particle size analysis method for MMB4 DMS in CSO was developed and validated to use in support of good laboratory practice/GMP development and production activities. Manufacturing of EF was accomplished by milling MMB4 DMS with CSO and zirconia beads in an agitator bead mill. The resulting bulk material was filled into 5-mL glass vials at a sterile fill facility and terminally sterilized by gamma irradiation. The clinical lot was tested and released, a Certificate of Analysis was issued, and a 3-year International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) stability study started. The drug product was placed in storage for Phase 1 clinical trial distribution. A dose delivery uniformity study was undertaken to ensure that the correct doses were delivered to the patients in the clinic.

Applications of the pipeline environment for visual informatics and genomics computations.

BACKGROUND: Contemporary informatics and genomics research require efficient, flexible and robust management of large heterogeneous data, advanced computational tools, powerful visualization, reliable hardware infrastructure, interoperability of computational resources, and detailed data and analysis-protocol provenance. The Pipeline is a client-server distributed computational environment that facilitates the visual graphical construction, execution, monitoring, validation and dissemination of advanced data analysis protocols. RESULTS: This paper reports on the applications of the LONI Pipeline environment to address two informatics challenges - graphical management of diverse genomics tools, and the interoperability of informatics software. Specifically, this manuscript presents the concrete details of deploying general informatics suites and individual software tools to new hardware infrastructures, the design, validation and execution of new visual analysis protocols via the Pipeline graphical interface, and integration of diverse informatics tools via the Pipeline eXtensible Markup Language syntax. We demonstrate each of these processes using several established informatics packages (e.g., miBLAST, EMBOSS, mrFAST, GWASS, MAQ, SAMtools, Bowtie) for basic local sequence alignment and search, molecular biology data analysis, and genome-wide association studies. These examples demonstrate the power of the Pipeline graphical workflow environment to enable integration of bioinformatics resources which provide a well-defined syntax for dynamic specification of the input/output parameters and the run-time execution controls. CONCLUSIONS: The LONI Pipeline environment http://pipeline.loni.ucla.edu provides a flexible graphical infrastructure for efficient biomedical computing and distributed informatics research. The interactive Pipeline resource manager enables the utilization and interoperability of diverse types of informatics resources. The Pipeline client-server model provides computational power to a broad spectrum of informatics investigators--experienced developers and novice users, user with or without access to advanced computational-resources (e.g., Grid, data), as well as basic and translational scientists. The open development, validation and dissemination of computational networks (pipeline workflows) facilitates the sharing of knowledge, tools, protocols and best practices, and enables the unbiased validation and replication of scientific findings by the entire community.

Women's probability of conception is associated with their preference for flirtatious but not masculine facial movement.

Women's preferences for facial structure vary over the menstrual cycle. Little is known, however, as to how preferences for behavior may be influenced by hormonal factors. Here, we demonstrate that social properties of facial motion influence attractiveness judgments in the absence of other cues, and that women's preferences for these displays vary over the menstrual cycle, as has been demonstrated for structural traits of men's faces in static stimuli. We produced shape-standardized facial models that were animated with male movement and assessed for flirtatiousness by 16 women and attractiveness by 47 women. In fertile phases of the menstrual cycle, women showed stronger preferences for flirtatious movement, but not for absolute movement. These data show that women (1) recognize specific mating-relevant social cues in male facial movement and (2) are differentially influenced by these cues at different phases of the menstrual cycle. This preference for flirtatiousness may promote the adaptive allocation of mating effort towards men who are, in turn, likely to respond positively.

Why rate when you could compare? Using the "EloChoice" package to assess pairwise comparisons of perceived physical strength.

We introduce "EloChoice", a package for R which uses Elo rating to assess pairwise comparisons between stimuli in order to measure perceived stimulus characteristics. To demonstrate the package and compare results from forced choice pairwise comparisons to those from more standard single stimulus rating tasks using Likert (or Likert-type) items, we investigated perceptions of physical strength from images of male bodies. The stimulus set comprised images of 82 men standing on a raised platform with minimal clothing. Strength-related anthropometrics and grip strength measurements were available for each man in the set. UK laboratory participants (Study 1) and US online participants (Study 2) viewed all images in both a Likert rating task, to collect mean Likert scores, and a pairwise comparison task, to calculate Elo, mean Elo (mElo), and Bradley-Terry scores. Within both studies, Likert, Elo and Bradley-Terry scores were closely correlated to mElo scores (all rs > 0.95), and all measures were correlated with stimulus grip strength (all rs > 0.38) and body size (all rs > 0.59). However, mElo scores were less variable than Elo scores and were hundreds of times quicker to compute than Bradley-Terry scores. Responses in pairwise comparison trials were 2/3 quicker than in Likert tasks, indicating that participants found pairwise comparisons to be easier. In addition, mElo scores generated from a data set with half the participants randomly excluded produced very comparable results to those produced with Likert scores from the full participant set, indicating that researchers require fewer participants when using pairwise comparisons.

Turning the other cheek: the viewpoint dependence of facial expression after-effects.

How do we visually encode facial expressions? Is this done by viewpoint-dependent mechanisms representing facial expressions as two-dimensional templates or do we build more complex viewpoint independent three-dimensional representations? Recent facial adaptation techniques offer a powerful way to address these questions. Prolonged viewing of a stimulus (adaptation) changes the perception of subsequently viewed stimuli (an after-effect). Adaptation to a particular attribute is believed to target those neural mechanisms encoding that attribute. We gathered images of facial expressions taken simultaneously from five different viewpoints evenly spread from the three-quarter leftward to the three-quarter rightward facing view. We measured the strength of expression after-effects as a function of the difference between adaptation and test viewpoints. Our data show that, although there is a decrease in after-effect over test viewpoint, there remains a substantial after-effect when adapt and test are at differing three-quarter views. We take these results to indicate that neural systems encoding facial expressions contain a mixture of viewpoint-dependent and viewpoint-independent elements. This accords with evidence from single cell recording studies in macaque and is consonant with a view in which viewpoint-independent expression encoding arises from a combination of view-dependent expression-sensitive responses.

Synthesis and self-assembly of an amphiphilic poly(phenylene ethynylene) ionomer.

We have synthesized a conjugated amphiphilic polyelectrolyte, a poly(phenylene ethynylene) (PPE), and the structurally analogous neutral polymer. The solution-phase aggregation of the uncharged PPE can be reversibly controlled by varying the solvent polarity and concentration, while the charged polymer appears to self-assemble at any concentration in compatible solvents. These conclusions are based on a combination of absorption and photoluminescence spectroscopy and dynamic light scattering. Photoinduced absorption spectroscopy was also employed to investigate interchain electronic communication and the photoinduced production of free charge carriers. The uncharged PPE had a relatively high polaron yield, indicating pi-stacking of adjacent PPE chains and efficient exciton splitting, while the charged polymer did not produce polarons, indicating that the polymers are not pi-stacked despite their tendency to form aggregates. This is most likely due to the presence of the cationic trimethylammonium side chains which force neighboring polymer chains too far apart to achieve effective pi-orbital overlap. Polarons were observed in both polymers after chemical doping with iodine. The ability to control aggregation and interchain electronic communication could be a useful tool in designing nanostructured electronic materials.

Photostimulation induces rapid growth of song-control brain regions in male and female chickadees (Poecile atricapilla).

To examine the effect of photoperiodic condition on song-control nuclei we examined three groups of male and female black-capped chickadees (Poecile atricapilla). Photorefractory birds were held on long days for several months and had fully regressed gonads. Photosensitive birds were held on short days for several months and had small gonads. Photostimulated birds were transferred to long days for 16 days following several months of short days. Following these photoperiod treatments we determined the volume of the song-control nuclei HVc, Area X, and (RA). There were significant sex differences in HVc and Area X, but not in RA. There were also significant photoperiod effects in HVc and Area X. Thus, sex and photoperiod differences in the song system exist in a species in which both sexes produce learned calls year-round.

Do men's faces really signal heritable immunocompetence?

In the literature on human mate choice, masculine facial morphology is often proposed to be an intersexual signal of heritable immunocompetence, and hence an important component of men's attractiveness. This hypothesis has received considerable research attention, and is increasingly treated as plausible and well supported. In this article, we propose that the strength of the evidence for the immunocompetence hypothesis is somewhat overstated, and that a number of difficulties have been under-acknowledged. Such difficulties include (1) the tentative nature of the evidence regarding masculinity and disease in humans, (2) the complex and uncertain picture emerging from the animal literature on sexual ornaments and immunity, (3) the absence of consistent, cross-cultural support for the predictions of the immunocompetence hypothesis regarding preferences for masculinized stimuli, and (4) evidence that facial masculinity contributes very little, if anything, to overall attractiveness in real men. Furthermore, alternative explanations for patterns of preferences, in particular the proposal that masculinity is primarily an intrasexual signal, have been neglected. We suggest that immunocompetence perspectives on masculinity, whilst appealing in many ways, should still be regarded as speculative, and that other perspectives-and other traits-should be the subject of greater attention for researchers studying human mate preferences.

Self-assembling semiconducting polymers--rods and gels from electronic materials.

In an effort to favor the formation of straight polymer chains without crystalline grain boundaries, we have synthesized an amphiphilic conjugated polyelectrolyte, poly(fluorene-alt-thiophene) (PFT), which self-assembles in aqueous solutions to form cylindrical micelles. In contrast to many diblock copolymer assemblies, the semiconducting backbone runs parallel, not perpendicular, to the long axis of the cylindrical micelle. Solution-phase micelle formation is observed by X-ray and visible light scattering. The micelles can be cast as thin films, and the cylindrical morphology is preserved in the solid state. The effects of self-assembly are also observed through spectral shifts in optical absorption and photoluminescence. Solutions of higher-molecular-weight PFT micelles form gel networks at sufficiently high aqueous concentrations. Rheological characterization of the PFT gels reveals solid-like behavior and strain hardening below the yield point, properties similar to those found in entangled gels formed from surfactant-based micelles. Finally, electrical measurements on diode test structures indicate that, despite a complete lack of crystallinity in these self-assembled polymers, they effectively conduct electricity.

Next generation sequence analysis and computational genomics using graphical pipeline workflows.

Whole-genome and exome sequencing have already proven to be essential and powerful methods to identify genes responsible for simple Mendelian inherited disorders. These methods can be applied to complex disorders as well, and have been adopted as one of the current mainstream approaches in population genetics. These achievements have been made possible by next generation sequencing (NGS) technologies, which require substantial bioinformatics resources to analyze the dense and complex sequence data. The huge analytical burden of data from genome sequencing might be seen as a bottleneck slowing the publication of NGS papers at this time, especially in psychiatric genetics. We review the existing methods for processing NGS data, to place into context the rationale for the design of a computational resource. We describe our method, the Graphical Pipeline for Computational Genomics (GPCG), to perform the computational steps required to analyze NGS data. The GPCG implements flexible workflows for basic sequence alignment, sequence data quality control, single nucleotide polymorphism analysis, copy number variant identification, annotation, and visualization of results. These workflows cover all the analytical steps required for NGS data, from processing the raw reads to variant calling and annotation. The current version of the pipeline is freely available at http://pipeline.loni.ucla.edu. These applications of NGS analysis may gain clinical utility in the near future (e.g., identifying miRNA signatures in diseases) when the bioinformatics approach is made feasible. Taken together, the annotation tools and strategies that have been developed to retrieve information and test hypotheses about the functional role of variants present in the human genome will help to pinpoint the genetic risk factors for psychiatric disorders.

Does masculinity matter? The contribution of masculine face shape to male attractiveness in humans.

BACKGROUND: In many animals, exaggerated sex-typical male traits are preferred by females, and may be a signal of both past and current disease resistance. The proposal that the same is true in humans--i.e., that masculine men are immunocompetent and attractive--underpins a large literature on facial masculinity preferences. Recently, theoretical models have suggested that current condition may be a better index of mate value than past immunocompetence. This is particularly likely in populations where pathogenic fluctuation is fast relative to host life history. As life history is slow in humans, there is reason to expect that, among humans, condition-dependent traits might contribute more to attractiveness than relatively stable traits such as masculinity. To date, however, there has been little rigorous assessment of whether, in the presence of variation in other cues, masculinity predicts attractiveness or not. METHODOLOGY/PRINCIPAL FINDINGS: The relationship between masculinity and attractiveness was assessed in two samples of male faces. Most previous research has assessed masculinity either with subjective ratings or with simple anatomical measures. Here, we used geometric morphometric techniques to assess facial masculinity, generating a morphological masculinity measure based on a discriminant function that correctly classified >96% faces as male or female. When assessed using this measure, there was no relationship between morphological masculinity and rated attractiveness. In contrast, skin colour--a fluctuating, condition-dependent cue--was a significant predictor of attractiveness. CONCLUSIONS/SIGNIFICANCE: These findings suggest that facial morphological masculinity may contribute less to men's attractiveness than previously assumed. Our results are consistent with the hypothesis that current condition is more relevant to male mate value than past disease resistance, and hence that temporally fluctuating traits (such as colour) contribute more to male attractiveness than stable cues of sexual dimorphism.

Critical structural and functional roles for the N-terminal insertion sequence in surfactant protein B analogs.

BACKGROUND: Surfactant protein B (SP-B; 79 residues) belongs to the saposin protein superfamily, and plays functional roles in lung surfactant. The disulfide cross-linked, N- and C-terminal domains of SP-B have been theoretically predicted to fold as charged, amphipathic helices, suggesting their participation in surfactant activities. Earlier structural studies with Mini-B, a disulfide-linked construct based on the N- and C-terminal regions of SP-B (i.e., approximately residues 8-25 and 63-78), confirmed that these neighboring domains are helical; moreover, Mini-B retains critical in vitro and in vivo surfactant functions of the native protein. Here, we perform similar analyses on a Super Mini-B construct that has native SP-B residues (1-7) attached to the N-terminus of Mini-B, to test whether the N-terminal sequence is also involved in surfactant activity. METHODOLOGY/RESULTS: FTIR spectra of Mini-B and Super Mini-B in either lipids or lipid-mimics indicated that these peptides share similar conformations, with primary alpha-helix and secondary beta-sheet and loop-turns. Gel electrophoresis demonstrated that Super Mini-B was dimeric in SDS detergent-polyacrylamide, while Mini-B was monomeric. Surface plasmon resonance (SPR), predictive aggregation algorithms, and molecular dynamics (MD) and docking simulations further suggested a preliminary model for dimeric Super Mini-B, in which monomers self-associate to form a dimer peptide with a "saposin-like" fold. Similar to native SP-B, both Mini-B and Super Mini-B exhibit in vitro activity with spread films showing near-zero minimum surface tension during cycling using captive bubble surfactometry. In vivo, Super Mini-B demonstrates oxygenation and dynamic compliance that are greater than Mini-B and compare favorably to full-length SP-B. CONCLUSION: Super Mini-B shows enhanced surfactant activity, probably due to the self-assembly of monomer peptide into dimer Super Mini-B that mimics the functions and putative structure of native SP-B.

An amphiphilic poly(phenylene ethynylene) as the structure-directing agent for periodic nanoscale silica composite materials.

We have synthesized optically active nanostructured composite materials by using an amphiphilic semiconducting polymer, a poly(phenylene ethynylene) (PPE), and a conventional ammonium surfactant as the structure-directing agents. The PPE consists of phenylene units para-substituted with an octyloxy chain and a charged trimethylammoniumethoxy group, resulting in a surfactant-like structure that can assemble into cylindrical micelles. The resulting silica/organic composite material has a hexagonal honeycomb structure with a repeat distance of 45.3 A, as confirmed by low-angle X-ray diffraction and transmission electron microscopy. Scanning electron microscopy indicates that the larger scale particle size is on the order of micrometers. The incorporation of the polymer into the composite was confirmed by elemental analysis, photoluminescence spectroscopy, and fluorescence microscopy. The polymer retains its photophysical properties in the composite, showing luminescence similar to polymers in the solution phase. The polymer displays a high degree of luminescence polarization anisotropy, indicating that the polymer chains are straight and isolated from each other in the composite.