Beyond Synchrony: Joint Action in a Complex Production Task Reveals Beneficial Effects of Decreased Interpersonal Synchrony.

A variety of joint action studies show that people tend to fall into synchronous behavior with others participating in the same task, and that such synchronization is beneficial, leading to greater rapport, satisfaction, and performance. It has been noted that many of these task environments require simple interactions that involve little planning of action coordination toward a shared goal. The present study utilized a complex joint construction task in which dyads were instructed to build model cars while their hand movements and heart rates were measured. Participants built these models under varying conditions, delimiting how freely they could divide labor during a build session. While hand movement synchrony was sensitive to the different tasks and outcomes, the heart rate measure did not show any effects of interpersonal synchrony. Results for hand movements show that the more participants were constrained by a particular building strategy, the greater their behavioral synchrony. Within the different conditions, the degree of synchrony was predictive of subjective satisfaction and objective product outcomes. However, in contrast to many previous findings, synchrony was negatively associated with superior products, and, depending on the constraints on the interaction, positively or negatively correlated with higher subjective satisfaction. These results show that the task context critically shapes the role of synchronization during joint action, and that in more complex tasks, not synchronization of behavior, but rather complementary types of behavior may be associated with superior task outcomes.

The green ash transcriptome and identification of genes responding to abiotic and biotic stresses.

BACKGROUND: To develop a set of transcriptome sequences to support research on environmental stress responses in green ash (Fraxinus pennsylvanica), we undertook deep RNA sequencing of green ash tissues under various stress treatments. The treatments, including emerald ash borer (EAB) feeding, heat, drought, cold and ozone, were selected to mimic the increasing threats of climate change and invasive pests faced by green ash across its native habitat. RESULTS: We report the generation and assembly of RNA sequences from 55 green ash samples into 107,611 putative unique transcripts (PUTs). 52,899 open reading frames were identified. Functional annotation of the PUTs by comparison to the Uniprot protein database identified matches for 63 % of transcripts and for 98 % of transcripts with ORFs. Further functional annotation identified conserved protein domains and assigned gene ontology terms to the PUTs. Examination of transcript expression across different RNA libraries revealed that expression patterns clustered based on tissues regardless of stress treatment. The transcripts from stress treatments were further examined to identify differential expression. Tens to hundreds of differentially expressed PUTs were identified for each stress treatment. A set of 109 PUTs were found to be consistently up or down regulated across three or more different stress treatments, representing basal stress response candidate genes in green ash. In addition, 1956 simple sequence repeats were identified in the PUTs, of which we identified 465 high quality DNA markers and designed flanking PCR primers. CONCLUSIONS: North American native ash trees have suffered extensive mortality due to EAB infestation, creating a need to breed or select for resistant green ash genotypes. Stress from climate change is an additional concern for longevity of native ash populations. The use of genomics could accelerate management efforts. The green ash transcriptome we have developed provides important sequence information, genetic markers and stress-response candidate genes.

Mitogenomes reveal diversity of the European Lyme borreliosis vector Ixodes ricinus in Italy.

In Europe, the Ixodes ricinus tick is the most important vector of the etiological agents of Lyme borreliosis and several other emerging tick-borne diseases. Because tick-borne pathogens are dependent on their vectors for transmission, understanding the vector population structure is crucial to inform public health research of pathogen dynamics and spread. However, the population structure and dynamics of this important vector species are not well understood as most genetic studies utilize short mitochondrial and nuclear sequences with little diversity. Herein we obtained and analyzed complete mitochondrial genome (hereafter "mitogenome") sequences to better understand the genetic diversity and the population structure of I. ricinus from two long-standing tick-borne disease foci in northern Italy. Complete mitogenomes of 23 I. ricinus ticks were sequenced at high coverage. Out of 23 mitogenome sequences we identified 17 unique haplotypes composed of 244 segregating sites. Phylogenetic reconstruction using 18 complete mitogenome sequences revealed the coexistence of four highly divergent I. ricinus maternal lineages despite the narrow spatial scale over which these samples were obtained (100km). Notably, the estimated coalescence time of the 18 mitogenome haplotypes is ∼427 thousand years ago (95% HPD 330, 540). This divergence between I. ricinus lineages is consistent with the mitochondrial diversity of other arthropod vector species and indicates that long-term I. ricinus populations may have been less structured and larger than previously thought. Thus, this study suggests that a rapid and accurate retrieval of full mitochondrial genomes from this disease vector enables fine-resolution studies of tick intraspecies genetic relationships, population differentiation, and demographic history.

It Depends Who Is Watching You: 3-D Agent Cues Increase Fairness.

Laboratory and field studies have demonstrated that exposure to cues of intentional agents in the form of eyes can increase prosocial behavior. However, previous research mostly used 2-dimensional depictions as experimental stimuli. Thus far no study has examined the influence of the spatial properties of agency cues on this prosocial effect. To investigate the role of dimensionality of agency cues on fairness, 345 participants engaged in a decision-making task in a naturalistic setting. The experimental treatment included a 3-dimensional pseudo-realistic model of a human head and a 2-dimensional picture of the same object. The control stimuli consisted of a real plant and its 2-D image. Our results partly support the findings of previous studies that cues of intentional agents increase prosocial behavior. However, this effect was only found for the 3-D cues, suggesting that dimensionality is a critical variable in triggering these effects in a real-world settings. Our research sheds light on a hitherto unexplored aspect of the effects of environmental cues and their morphological properties on decision-making.

Genome-wide analysis of signatures of selection in populations of African honey bees (Apis mellifera) using new web-based tools.

BACKGROUND: With the development of inexpensive, high-throughput sequencing technologies, it has become feasible to examine questions related to population genetics and molecular evolution of non-model species in their ecological contexts on a genome-wide scale. Here, we employed a newly developed suite of integrated, web-based programs to examine population dynamics and signatures of selection across the genome using several well-established tests, including F ST, pN/pS, and McDonald-Kreitman. We applied these techniques to study populations of honey bees (Apis mellifera) in East Africa. In Kenya, there are several described A. mellifera subspecies, which are thought to be localized to distinct ecological regions. RESULTS: We performed whole genome sequencing of 11 worker honey bees from apiaries distributed throughout Kenya and identified 3.6 million putative single-nucleotide polymorphisms. The dense coverage allowed us to apply several computational procedures to study population structure and the evolutionary relationships among the populations, and to detect signs of adaptive evolution across the genome. While there is considerable gene flow among the sampled populations, there are clear distinctions between populations from the northern desert region and those from the temperate, savannah region. We identified several genes showing population genetic patterns consistent with positive selection within African bee populations, and between these populations and European A. mellifera or Asian Apis florea. CONCLUSIONS: These results lay the groundwork for future studies of adaptive ecological evolution in honey bees, and demonstrate the use of new, freely available web-based tools and workflows ( http://usegalaxy.org/r/kenyanbee ) that can be applied to any model system with genomic information.

Building trust: Heart rate synchrony and arousal during joint action increased by public goods game.

The physiological processes underlying trust are subject of intense interest in the behavioral sciences. However, very little is known about how trust modulates the affective link between individuals. We show here that trust has an effect on heart rate arousal and synchrony, a result consistent with research on joint action and experimental economics. We engaged participants in a series of joint action tasks which, for one group of participants, was interleaved with a PGG, and measured their heart synchrony and arousal. We found that the introduction of the economic game shifted participants' attention to the dynamics of the interaction. This was followed by increased arousal and synchrony of heart rate profiles. Also, the degree of heart rate synchrony was predictive of participants' expectations regarding their partners in the economic game. We conclude that the above changes in physiology and behavior are shaped by the valuation of other people's social behavior, and ultimately indicate trust building process.

Comparative and population mitogenomic analyses of Madagascar's extinct, giant 'subfossil' lemurs.

Humans first arrived on Madagascar only a few thousand years ago. Subsequent habitat destruction and hunting activities have had significant impacts on the island's biodiversity, including the extinction of megafauna. For example, we know of 17 recently extinct 'subfossil' lemur species, all of which were substantially larger (body mass ∼11-160 kg) than any living population of the ∼100 extant lemur species (largest body mass ∼6.8 kg). We used ancient DNA and genomic methods to study subfossil lemur extinction biology and update our understanding of extant lemur conservation risk factors by i) reconstructing a comprehensive phylogeny of extinct and extant lemurs, and ii) testing whether low genetic diversity is associated with body size and extinction risk. We recovered complete or near-complete mitochondrial genomes from five subfossil lemur taxa, and generated sequence data from population samples of two extinct and eight extant lemur species. Phylogenetic comparisons resolved prior taxonomic uncertainties and confirmed that the extinct subfossil species did not comprise a single clade. Genetic diversity estimates for the two sampled extinct species were relatively low, suggesting small historical population sizes. Low genetic diversity and small population sizes are both risk factors that would have rendered giant lemurs especially susceptible to extinction. Surprisingly, among the extant lemurs, we did not observe a relationship between body size and genetic diversity. The decoupling of these variables suggests that risk factors other than body size may have as much or more meaning for establishing future lemur conservation priorities.

Culture's building blocks: investigating cultural evolution in a LEGO construction task.

ONE OF THE MOST ESSENTIAL BUT THEORETICALLY VEXING ISSUES REGARDING THE NOTION OF CULTURE IS THAT OF CULTURAL EVOLUTION AND TRANSMISSION: how a group's accumulated solutions to invariant challenges develop and persevere over time. But at the moment, the notion of applying evolutionary theory to culture remains little more than a suggestive trope. Whereas the modern synthesis of evolutionary theory has provided an encompassing scientific framework for the selection and transmission of biological adaptations, a convincing theory of cultural evolution has yet to emerge. One of the greatest challenges for theorists is identifying the appropriate time scales and units of analysis in order to reduce the intractably large and complex phenomenon of "culture" into its component "building blocks." In this paper, we present a model for scientifically investigating cultural processes by analyzing the ways people develop conventions in a series of LEGO construction tasks. The data revealed a surprising pattern in the selection of building bricks as well as features of car design across consecutive building sessions. Our findings support a novel methodology for studying the development and transmission of culture through the microcosm of interactive LEGO design and assembly.

A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques.

The evolution rate and genetic changes that occur during chronic infection with Helicobacter pylori have been analysed, but little is known about the genomic changes during the initial, acute bacterial infection phase. Here we analyse the rate and pattern of genome evolution in H. pylori from the genomes of two input strains isolated from human volunteers with asymptomatic infection, and the genomes of two output strains collected 20 and 44 days after re-infection. Similarly, we analyse genome evolution in bacteria from the genome sequences of input and output strains sequentially taken after experimental infection of a rhesus macaque. The estimated mutation rate reveals a mutation burst during the acute infection phase that is over 10 times faster than the mutation rate during chronic infection, and orders of magnitude faster than mutation rates in any other bacteria. The elevated frequency of mutations in outer membrane protein genes suggests that the mutation burst facilitates rapid host adaptation of the bacteria.

A genome-wide RNAi screen identifies novel targets of neratinib sensitivity leading to neratinib and paclitaxel combination drug treatments.

ErbB2 is frequently activated in tumors, and influences a wide array of cellular functions, including proliferation, apoptosis, cell motility and adhesion. HKI-272 (neratinib) is a small molecule pan-kinase inhibitor of the ErbB family of receptor tyrosine kinases, and shows strong antiproliferative activity in ErbB2-overexpressing breast cancer cells. We undertook a genome-wide pooled lentiviral RNAi screen to identify synthetic lethal or enhancer (synthetic modulator screen) genes that interact with neratinib in a human breast cancer cell line (SKBR-3). These genes upon knockdown would modulate cell viability in the presence of subeffective concentrations of neratinib. We discovered a diverse set of genes whose depletion selectively impaired or enhanced the viability of SKBR-3 cells in the presence of neratinib. We observed diverse pathways including EGFR, hypoxia, cAMP, and protein ubiquitination that, when co-treated with RNAi and neratinib, resulted in arrest of cell proliferation. Examining the changes of these genes and their protein products also led to a rationale for clinically relevant drug combination treatments. Treatment of cells with either paclitaxel or cytarabine in combination with neratinib resulted in a strong antiproliferative effect. The identification of novel mediators of cellular response to neratinib and the development of potential drug combination treatments have expanded our understanding of neratinib's mode-of-action for the development of more effective therapeutic regimens. Notably, our findings support a paclitaxel and neratinib phase III clinical trial in breast cancer patients.

Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance.

OBJECTIVE: Using a patient targeted survey, we sought to assess patient representations of how physicians responded when patients presented with possible adverse drug reactions (ADRs). As a demonstration case, we took one widely prescribed drug class, the HMG-CoA reductase inhibitors ('statins'). This information was used to assess whether a patient-targeted ADR surveillance approach may complement provider reporting, potentially fostering identification of additional patients with possible or probable ADRs. METHODS: A total of 650 adult patients taking statins with self-reported ADRs completed a survey. Depending on the problems reported, some patients completed additional surveys specific to the most commonly cited statin ADRs: muscle, cognitive or neuropathy related. Patients were asked to report drug, dose, ADR character, time course of onset with drug, recovery with discontinuation, recurrence with rechallenge, quality-of-life impact, and interactions with their physician in relation to the perceived ADR. This paper focuses on patients' representation of the doctor-patient interaction and physicians' attribution, when patients report perceived ADRs. RESULTS: Eighty-seven percent of patients reportedly spoke to their physician about the possible connection between statin use and their symptom. Patients reported that they and not the doctor most commonly initiated the discussion regarding the possible connection of drug to symptom (98% vs 2% cognition survey, 96% vs 4% neuropathy survey, 86% vs 14% muscle survey; p < 10(-8) for each). Physicians were reportedly more likely to deny than affirm the possibility of a connection. Rejection of a possible connection was reported to occur even for symptoms with strong literature support for a drug connection, and even in patients for whom the symptom met presumptive literature-based criteria for probable or definite drug-adverse effect causality. Assuming that physicians would not likely report ADRs in these instances, these patient-submitted ADR reports suggest that targeting patients may boost the yield of ADR reporting systems. CONCLUSIONS: Since low reporting rates are considered to contribute to delays in identification of ADRs, findings from this study suggest that additional putative cases may be identified by targeting patients as reporters, potentially speeding recognition of ADRs.

Genomic and bioinformatics analyses of HAdV-4vac and HAdV-7vac, two human adenovirus (HAdV) strains that constituted original prophylaxis against HAdV-related acute respiratory disease, a reemerging epidemic disease.

Vaccine strains of human adenovirus serotypes 4 and 7 (HAdV-4vac and HAdV-7vac) have been used successfully to prevent adenovirus-related acute respiratory disease outbreaks. The genomes of these two vaccine strains have been sequenced, annotated, and compared with their prototype equivalents with the goals of understanding their genomes for molecular diagnostics applications, vaccine redevelopment, and HAdV pathoepidemiology. These reference genomes are archived in GenBank as HAdV-4vac (35,994 bp; AY594254) and HAdV-7vac (35,240 bp; AY594256). Bioinformatics and comparative whole-genome analyses with their recently reported and archived prototype genomes reveal six mismatches and four insertions-deletions (indels) between the HAdV-4 prototype and vaccine strains, in contrast to the 611 mismatches and 130 indels between the HAdV-7 prototype and vaccine strains. Annotation reveals that the HAdV-4vac and HAdV-7vac genomes contain 51 and 50 coding units, respectively. Neither vaccine strain appears to be attenuated for virulence based on bioinformatics analyses. There is evidence of genome recombination, as the inverted terminal repeat of HAdV-4vac is initially identical to that of species C whereas the prototype is identical to species B1. These vaccine reference sequences yield unique genome signatures for molecular diagnostics. As a molecular forensics application, these references identify the circulating and problematic 1950s era field strains as the original HAdV-4 prototype and the Greider prototype, from which the vaccines are derived. Thus, they are useful for genomic comparisons to current epidemic and reemerging field strains, as well as leading to an understanding of pathoepidemiology among the human adenoviruses.

Genomic and bioinformatics analysis of HAdV-4, a human adenovirus causing acute respiratory disease: implications for gene therapy and vaccine vector development.

Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD.

Axotomy abolishes NeuN expression in facial but not rubrospinal neurons.

The neuronal nuclei (NeuN) antibody, which binds to a poorly characterized antigen/antigens, is increasingly being used in several areas of study as a specific marker to identify neuronal populations. Despite the increasing reliance on NeuN as a panneuronal marker, changes of NeuN expression following axonal injury have not yet been examined. In the present study, NeuN immunoreactivity was analyzed in adult rodent facial motoneurons [peripheral nervous system (PNS) model] following nerve resection or crush and in rubrospinal neurons [central nervous system (CNS) model] after lesion of the dorsal lateral funiculus at the cervical level of the spinal cord. Peripheral nerve resection in the rat and mouse resulted in an almost complete loss of NeuN immunoreactivity in facial motoneurons by 3 days postinjury and remained absent at 28 days post-resection despite the survival of the neurons as evidenced by neuronal tracing. These results were confirmed with Western blot. In the peripheral nerve crush model of injury, there was an initial decline in NeuN immunoreactivity in facial motoneurons, but unlike the resection model, NeuN immunoreactivity began to return within 7 days postinjury and returned to the uninjured level of expression by 28 days. In contrast, axotomy in the CNS model resulted in little decline in NeuN immunoreactivity in the rubrospinal neurons, even after 28 days postaxotomy. These results indicate that NeuN expression in response to axonal injury is different in separate neuronal populations (PNS and CNS), and that care must be taken when addressing cell survival based on NeuN staining alone.

Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury.

Scientific interest to find a treatment for spinal cord injuries has led to the development of numerous experimental strategies to promote axonal regeneration across the spinal cord injury site. Although these strategies have been developed in acute injury paradigms and hold promise for individuals with spinal cord injuries in the future, little is known about their applicability for the vast majority of paralyzed individuals whose injury occurred long ago and who are considered to have a chronic injury. Some studies have shown that the effectiveness of these approaches diminishes dramatically within weeks after injury. Here we investigated the regenerative capacity of rat rubrospinal neurons whose axons were cut in the cervical spinal cord 1 year before. Contrary to earlier reports, we found that rubrospinal neurons do not die after axotomy but, rather, they undergo massive atrophy that can be reversed by applying brain-derived neurotrophic factor to the cell bodies in the midbrain. This administration of neurotrophic factor to the cell body resulted in increased expression of growth-associated protein-43 and Talpha1 tubulin, genes thought to be related to axonal regeneration. This treatment promoted the regeneration of these chronically injured rubrospinal axons into peripheral nerve transplants engrafted at the spinal cord injury site. This outcome is a demonstration of the regenerative capacity of spinal cord projection neurons a full year after axotomy.