Social cognitive processes explain bias in juror decisions.

Jury decisions are among the most consequential social decisions in which bias plays a notable role. While courts take measures to reduce the influence of non-evidentiary factors, jurors may still incorporate biases into their decisions. One common bias, crime-type bias, is the extent to which the perceived strength of a prosecutor's case depends on the severity of the crime. Moral judgment, affect and social cognition have been proposed as core processes underlying this and other biases. Behavioral evidence alone has been insufficient to distinguish these explanations. To identify the mechanism underlying crime-type bias, we collected functional magnetic resonance imaging patterns of brain activation from mock jurors reading criminal scenarios. Brain patterns from crime-type bias were most similar to those associated with social cognition (mentalizing and racial bias) but not affect or moral judgment. Our results support a central role for social cognition in juror decisions and suggest that crime-type bias and cultural bias may arise from similar mechanisms.

Social connections predict brain structure in a multidimensional free-ranging primate society.

Reproduction and survival in most primate species reflects management of both competitive and cooperative relationships. Here, we investigated the links between neuroanatomy and sociality in free-ranging rhesus macaques. In adults, the number of social partners predicted the volume of the mid-superior temporal sulcus and ventral-dysgranular insula, implicated in social decision-making and empathy, respectively. We found no link between brain structure and other key social variables such as social status or indirect connectedness in adults, nor between maternal social networks or status and dependent infant brain structure. Our findings demonstrate that the size of specific brain structures varies with the number of direct affiliative social connections and suggest that this relationship may arise during development. These results reinforce proposed links between social network size, biological success, and the expansion of specific brain circuits.

Neural Support for Contributions of Utility and Narrative Processing of Evidence in Juror Decision Making.

Efforts to explain complex human decisions have focused on competing theories emphasizing utility and narrative mechanisms. These are difficult to distinguish using behavior alone. Both narrative and utility theories have been proposed to explain juror decisions, which are among the most consequential complex decisions made in a modern society. Here, we asked jury-eligible male and female subjects to rate the strength of a series of criminal cases while recording the resulting patterns of brain activation. We compared patterns of brain activation associated with evidence accumulation to patterns of brain activation derived from a large neuroimaging database to look for signatures of the cognitive processes associated with different models of juror decision-making. Evidence accumulation correlated with multiple narrative processes, including reading and recall. Of the cognitive processes traditionally viewed as components of utility, activation patterns associated with uncertainty, but not value, were more active with stronger evidence. Independent of utility and narrative, activations linked to reasoning and relational logic also correlated with increasing evidence. Hierarchical modeling of cognitive processes associated with evidence accumulation supported a more prominent role for narrative in weighing evidence in complex decisions. However, utility processes were also associated with evidence accumulation. These complementary findings support an emerging view that integrates utility and narrative processes in complex decisions.SIGNIFICANCE STATEMENT The last decade has seen a sharply increased interest in narrative as a central cognitive process in human decision-making and as an important factor in the evolution of human societies. However, the roles of narrative versus utility models of decision-making remain hotly debated. While available models frequently produce similar behavioral predictions, they rely on different cognitive processes and so their roles can be separated using the right neural tests. Here, we use brain imaging during mock juror decisions to show that cognitive processes associated with narrative, and to a lesser extent utility, were engaged while subjects evaluated evidence. These results are consistent with interactions between narrative and utility processes during complex decision-making.

Modelling the effects of crime type and evidence on judgments about guilt.

Concerns over wrongful convictions have spurred an increased focus on understanding criminal justice decision-making. This study describes an experimental approach that complements conventional mock-juror experiments and case studies by providing a rapid, high-throughput screen for identifying preconceptions and biases that can influence how jurors and lawyers evaluate evidence in criminal cases. The approach combines an experimental decision task derived from marketing research with statistical modeling to explore how subjects evaluate the strength of the case against a defendant. The results show that, in the absence of explicit information about potential error rates or objective reliability, subjects tend to overweight widely used types of forensic evidence, but give much less weight than expected to a defendant's criminal history. Notably, for mock jurors, the type of crime also biases their confidence in guilt independent of the evidence. This bias is positively correlated with the seriousness of the crime. For practicing prosecutors and other lawyers, the crime-type bias is much smaller, yet still correlates with the seriousness of the crime.

Nociceptor-Enriched Genes Required for Normal Thermal Nociception.

Here, we describe a targeted reverse genetic screen for thermal nociception genes in Drosophila larvae. Using laser capture microdissection and microarray analyses of nociceptive and non-nociceptive neurons, we identified 275 nociceptor-enriched genes. We then tested the function of the enriched genes with nociceptor-specific RNAi and thermal nociception assays. Tissue-specific RNAi targeted against 14 genes caused insensitive thermal nociception while targeting of 22 genes caused hypersensitive thermal nociception. Previously uncategorized genes were named for heat resistance (i.e., boilerman, fire dancer, oven mitt, trivet, thawb, and bunker gear) or heat sensitivity (firelighter, black match, eucalyptus, primacord, jet fuel, detonator, gasoline, smoke alarm, and jetboil). Insensitive nociception phenotypes were often associated with severely reduced branching of nociceptor neurites and hyperbranched dendrites were seen in two of the hypersensitive cases. Many genes that we identified are conserved in mammals.

Differential gene expression in dentate granule cells in mesial temporal lobe epilepsy with and without hippocampal sclerosis.

OBJECTIVE: Hippocampal sclerosis is the most common neuropathologic finding in cases of medically intractable mesial temporal lobe epilepsy. In this study, we analyzed the gene expression profiles of dentate granule cells of patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations, and to shed light on the transcriptional changes associated with hippocampal sclerosis. METHODS: RNA was extracted, and complementary DNA (cDNA) was prepared and amplified from dentate granule cells that had been harvested by laser capture microdissection from surgically resected hippocampi from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis. Sequencing libraries were sequenced, and the resulting sequencing reads were aligned to the reference genome. Differential expression analysis was used to ascertain expression differences between patients with and without hippocampal sclerosis. RESULTS: Greater than 90% of the RNA-Seq reads aligned to the reference. There was high concordance between transcriptional profiles obtained for duplicate samples. Principal component analysis revealed that the presence or absence of hippocampal sclerosis was the main determinant of the variance within the data. Among the genes up-regulated in the hippocampal sclerosis samples, there was significant enrichment for genes involved in oxidative phosphorylation. SIGNIFICANCE: By analyzing the gene expression profiles of dentate granule cells from surgically resected hippocampal specimens from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis, we have demonstrated the utility of next-generation sequencing methods for producing biologically relevant results from small populations of homogeneous cells, and have provided insight on the transcriptional changes associated with this pathology.

Diversity and evolution of the primate skin microbiome.

Skin microbes play a role in human body odour, health and disease. Compared with gut microbes, we know little about the changes in the composition of skin microbes in response to evolutionary changes in hosts, or more recent behavioural and cultural changes in humans. No studies have used sequence-based approaches to consider the skin microbe communities of gorillas and chimpanzees, for example. Comparison of the microbial associates of non-human primates with those of humans offers unique insights into both the ancient and modern features of our skin-associated microbes. Here we describe the microbes found on the skin of humans, chimpanzees, gorillas, rhesus macaques and baboons. We focus on the bacterial and archaeal residents in the axilla using high-throughput sequencing of the 16S rRNA gene. We find that human skin microbial communities are unique relative to those of other primates, in terms of both their diversity and their composition. These differences appear to reflect both ancient shifts during millions of years of primate evolution and more recent changes due to modern hygiene.

Correction to 'Diversity and evolution of the primate skin microbiome'.

[This corrects the article DOI: 10.1098/rspb.2015.2586.].

Balboa binds to pickpocket in vivo and is required for mechanical nociception in Drosophila larvae.

The Drosophila gene pickpocket (ppk) encodes an ion channel subunit of the degenerin/epithelial sodium channel (DEG/ENaC) family. PPK is specifically expressed in nociceptive, class IV multidendritic (md) neurons and is functionally required for mechanical nociception responses. In this study, in a genome-wide genetic screen for other ion channel subunits required for mechanical nociception, we identify a gene that we name balboa (also known as CG8546, ppk26). Interestingly, the balboa locus encodes a DEG/ENaC ion channel subunit highly similar in amino acid sequence to PPK. Moreover, laser-capture isolation of RNA from larval neurons and microarray analyses reveal that balboa is also highly enriched in nociceptive neurons. The requirement for Balboa and PPK in mechanical nociception behaviors and their specific expression in larval nociceptors led us to hypothesize that these DEG/ENaC subunits form an ion channel complex in vivo. In nociceptive neurons, Balboa::GFP proteins distribute uniformly throughout dendrites but remarkably localize to discrete foci when ectopically expressed in other neuron subtypes (where PPK is not expressed). Indeed, ectopically coexpressing ppk transforms this punctate Balboa::GFP expression pattern to the uniform distribution observed in its native cell type. Furthermore, ppk-RNAi in class IV neurons alters the broad Balboa::GFP pattern to a punctate distribution. Interestingly, this interaction is mutually codependent as balboa-RNAi eliminates Venus::PPK from the sensory dendrites of nociceptors. Finally, using a GFP-reconstitution approach in transgenic larvae, we directly detect in vivo physical interactions among PPK and Balboa subunits. Combined, our results indicate a critical mechanical nociception function for heteromeric PPK and Balboa channels in vivo.

Genetic origins of social networks in rhesus macaques.

Sociality is believed to have evolved as a strategy for animals to cope with their environments. Yet the genetic basis of sociality remains unclear. Here we provide evidence that social network tendencies are heritable in a gregarious primate. The tendency for rhesus macaques, Macaca mulatta, to be tied affiliatively to others via connections mediated by their social partners - analogous to friends of friends in people - demonstrated additive genetic variance. Affiliative tendencies were predicted by genetic variation at two loci involved in serotonergic signalling, although this result did not withstand correction for multiple tests. Aggressive tendencies were also heritable and were related to reproductive output, a fitness proxy. Our findings suggest that, like humans, the skills and temperaments that shape the formation of multi-agent relationships have a genetic basis in nonhuman primates, and, as such, begin to fill the gaps in our understanding of the genetic basis of sociality.

Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation.

The folate pathway plays a crucial role in the regeneration and repair of the adult CNS after injury. Here, we have shown in rodents that such repair occurs at least in part through DNA methylation. In animals with combined spinal cord and sciatic nerve injury, folate-mediated CNS axon regeneration was found to depend on injury-related induction of the high-affinity folate receptor 1 (Folr1). The activity of folate was dependent on its activation by the enzyme dihydrofolate reductase (Dhfr) and a functional methylation cycle. The effect of folate on the regeneration of afferent spinal neurons was biphasic and dose dependent and correlated closely over its dose range with global and gene-specific DNA methylation and with expression of both the folate receptor Folr1 and the de novo DNA methyltransferases. These data implicate an epigenetic mechanism in CNS repair. Folic acid and possibly other nontoxic dietary methyl donors may therefore be useful in clinical interventions to promote brain and spinal cord healing. If indeed the benefit of folate is mediated by epigenetic mechanisms that promote endogenous axonal regeneration, this provides possible avenues for new pharmacologic approaches to treating CNS injuries.

Role of GAP-43 in sequestering phosphatidylinositol 4,5-bisphosphate to Raft bilayers.

The lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) is critical for a number of physiological functions, and its presence in membrane microdomains (rafts) appears to be important for several of these spatially localized events. However, lipids like PIP(2) that contain polyunsaturated hydrocarbon chains are usually excluded from rafts, which are enriched in phospholipids (such as sphingomyelin) containing saturated or monounsaturated chains. Here we tested a mechanism by which multivalent PIP(2) molecules could be transferred into rafts through electrostatic interactions with polybasic cytoplasmic proteins, such as GAP-43, which bind to rafts via their acylated N-termini. We analyzed the interactions between lipid membranes containing raft microdomains and a peptide (GAP-43P) containing the linked N-terminus and the basic effector domain of GAP-43. In the absence or presence of nonacylated GAP-43P, PIP(2) was found primarily in detergent-soluble membranes thought to correspond to nonraft microdomains. However, when GAP-43P was acylated by palmitoyl coenzyme A, both the peptide and PIP(2) were greatly enriched in detergent-resistant membranes that correspond to rafts; acylation of GAP-43P changed the free energy of transfer of PIP(2) from detergent-soluble membranes to detergent-resistant membranes by -1.3 kcal/mol. Confocal microscopy of intact giant unilamellar vesicles verified that in the absence of GAP-43P PIP(2) was in nonraft microdomains, whereas acylated GAP-43P laterally sequestered PIP(2) into rafts. These data indicate that sequestration of PIP(2) to raft microdomains could involve interactions with acylated basic proteins such as GAP-43.

OntologyWidget - a reusable, embeddable widget for easily locating ontology terms.

BACKGROUND: Biomedical ontologies are being widely used to annotate biological data in a computer-accessible, consistent and well-defined manner. However, due to their size and complexity, annotating data with appropriate terms from an ontology is often challenging for experts and non-experts alike, because there exist few tools that allow one to quickly find relevant ontology terms to easily populate a web form. RESULTS: We have produced a tool, OntologyWidget, which allows users to rapidly search for and browse ontology terms. OntologyWidget can easily be embedded in other web-based applications. OntologyWidget is written using AJAX (Asynchronous JavaScript and XML) and has two related elements. The first is a dynamic auto-complete ontology search feature. As a user enters characters into the search box, the appropriate ontology is queried remotely for terms that match the typed-in text, and the query results populate a drop-down list with all potential matches. Upon selection of a term from the list, the user can locate this term within a generic and dynamic ontology browser, which comprises the second element of the tool. The ontology browser shows the paths from a selected term to the root as well as parent/child tree hierarchies. We have implemented web services at the Stanford Microarray Database (SMD), which provide the OntologyWidget with access to over 40 ontologies from the Open Biological Ontology (OBO) website 1. Each ontology is updated weekly. Adopters of the OntologyWidget can either use SMD's web services, or elect to rely on their own. Deploying the OntologyWidget can be accomplished in three simple steps: (1) install Apache Tomcat 2 on one's web server, (2) download and install the OntologyWidget servlet stub that provides access to the SMD ontology web services, and (3) create an html (HyperText Markup Language) file that refers to the OntologyWidget using a simple, well-defined format. CONCLUSION: We have developed OntologyWidget, an easy-to-use ontology search and display tool that can be used on any web page by creating a simple html description. OntologyWidget provides a rapid auto-complete search function paired with an interactive tree display. We have developed a web service layer that communicates between the web page interface and a database of ontology terms. We currently store 40 of the ontologies from the OBO website 1, as well as a several others. These ontologies are automatically updated on a weekly basis. OntologyWidget can be used in any web-based application to take advantage of the ontologies we provide via web services or any other ontology that is provided elsewhere in the correct format. The full source code for the JavaScript and description of the OntologyWidget is available from http://smd.stanford.edu/ontologyWidget/.

Antibodies against the NG2 proteoglycan promote the regeneration of sensory axons within the dorsal columns of the spinal cord.

The NG2 chondroitin sulfate proteoglycan inhibits axon growth in vitro. Levels of NG2 increase rapidly in the glial scars that form at sites of CNS injury, suggesting that NG2 may inhibit axon regeneration. To determine the functions of NG2, we infused mixtures of neutralizing or non-neutralizing anti-NG2 monoclonal antibodies into the dorsally transected adult rat spinal cord and analyzed the regeneration of ascending mechanosensory axons anatomically. At 1 week after injury, ascending sensory axons in control animals terminated caudal to the lesion within an area containing dense deposits of NG2 immunoreactivity. In animals treated with the neutralizing anti-NG2 antibodies, labeled axons penetrated the caudal border of the lesion and grew into and beyond the lesion center. The low intrinsic growth capacity of adult neurons may also limit the ability of damaged axons to regenerate. To enhance growth, we combined antibody treatment with a peripheral nerve conditioning lesion. After a conditioning lesion and treatment with control, non-neutralizing antibodies, many sensory axons grew into the lesion core. These axons did not grow past the rostral border of the lesion; rather, they grew along the dorsal surface of the spinal cord and within any remaining pieces of the dorsal roots. In contrast, combining a peripheral nerve conditioning lesion with neutralizing anti-NG2 antibodies resulted in sensory axon regeneration past the glial scar and into the white matter rostral to the injury site. The combinatorial approach used here that neutralizes extrinsic inhibition and increases intrinsic growth results in anatomically correct axon regeneration, a prerequisite for functional recovery.

Folic acid supplementation enhances repair of the adult central nervous system.

Folic acid supplementation has proved to be extremely effective in reducing the occurrence of neural tube defects (NTDs) and other congenital abnormalities in humans, suggesting that folic acid can modulate key mechanisms for growth and differentiation in the central nervous system (CNS). To prevent NTDs, however, supplemental folate must be provided early in gestation. This suggests that the ability of folic acid to activate growth and differentiation mechanisms may be confined to the early embryonic period. Here, we show that folic acid can enhance growth and repair mechanisms even in the adult CNS. Using lesion models of CNS injury, we found that intraperitoneal treatment of adult rats with folic acid significantly improves the regrowth of sensory spinal axons into a grafted segment of peripheral nerve in vivo. Regrowth of retinal ganglion cell (RGC) axons into a similar graft also was enhanced, although to a smaller extent than spinal axons. Furthermore, folic acid supplementation enhances neurological recovery from a spinal cord contusion injury, showing its potential clinical impact. The results show that the effects of folic acid supplementation on CNS growth processes are not restricted to the embryonic period, but can also be effective for enhancing growth, repair, and recovery in the injured adult CNS.

A new millenium for spinal cord regeneration: growth-associated genes.

INTRODUCTION: Neurons surviving spinal cord injury undergo extensive reorganization that may result in the formation of functional synaptic contacts. Many neurons, however, fail to activate the necessary mechanisms for successful regeneration. In this review, we discuss the implications of growth cone genes that we have correlated with successful spinal cord axonal regeneration. METHOD: Factors that inhibit regeneration, and activation of genes that promote it are discussed. RESULTS/DISCUSSION: The early progress n understanding mechanisms that seem to promote or inhibit regeneration in the central nervous system may have significant clinical utility in the future.