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Publications (84)
The decision-making process of jurors is complex, and jurors likely retrieve personal information and knowledge to make sense of the case. We test the hypothesis that perceived realism underpins case strength decisions, where realism reflects a good match between the case and retrieved information. To assess how realism affects juror decisions, jur...
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 o...
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. Her...
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,...
Jury decisions are among the most consequential social decisions in which bias plays a notable role. While courts take a number of measures to reduce the influence of bias on decisions about case strength or deserved punishment based on evidence introduced during a trial, jurors may still incorporate personal biases based on knowledge, experience,...
A high-quality rhesus macaque genome
Genome technology has improved substantially since the first full organismal genomes were generated. Applying new technology, Warren et al. refined the genome of the rhesus macaque, a model nonhuman primate. Long-read technology and other recent advances in sequencing technology were applied to generate a genome...
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. Her...
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...
As empirical testing in forensics moves forward, courts will continue to face challenges to forensic evidence with varying degrees of empirical validation, which may include substantial empirical evidence of validity that nonetheless falls short of the most rigorous criteria for scientific validation, either foundation-ally or as applied. While cou...
Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional...
[This corrects the article DOI: 10.1098/rspb.2015.2586.].
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 nocic...
Here, we describe a targeted reverse genetic screen for thermal nociception genes of 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 nocice...
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 m...
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 commu...
An ethological approach to attention predicts that organisms orient preferentially to valuable sources of information in the environment. For many gregarious species, orienting to other individuals provides valuable social information but competes with food acquisition, water consumption and predator avoidance. Individual variation in vigilance beh...
The Drosophila gene pickpocket (ppk) encodes an ion channel subunit of the degenerin/epithelial sodium channel (DEG/ENaC) family [1]. PPK is specifically expressed in nociceptive, class IV multidendritic (md) neurons and is functionally required for mechanical nociception responses [2, 3]. In this study, in a genome-wide genetic screen for other io...
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 media...
Supplementary Files
Using a test-replication split-sample design we examined how genetic variability in the dopaminergic and serotonergic systems may account for individual variability in economic preferences (total sample N~1400). Our independent phenotypes – risk preference, loss aversion, and strategic use – were derived from incentive-compatible economic tasks. Ou...
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...
Reversible modifications of cellular proteins often serve as key steps in signal transduction and effector pathways, and the investigation of these modifications has been a principal route of access to signaling mechanisms. Ten years ago, for example, tyrosine phosphorylation was an intriguing oddity—a posttranslational modification known to occur...
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 ar...
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...
Songbirds have one of the most accessible neural systems for the study of brain mechanisms of behavior. However, neuroethological studies in songbirds have been limited by the lack of high-throughput molecular resources and gene-manipulation tools. To overcome these limitations, we constructed 21 regular, normalized, and subtracted full-length cDNA...
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 tra...
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 provid...
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 axo...
Introduction. Neurons surviving spinal cord 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 c...
Selective death of motor neurons beginning in mid life is the hallmark of the most abundant motor-neuron disease of adults, amyotrophic lateral sclerosis (ALS). An unexpected insight into potential causes of the disorder is now provided by mice lacking the hypoxia response element of the promoter of the gene encoding the vascular endothelial cell g...
A pivotal event in neural development is the point at which differentiating neurons become competent to extend long axons. Initiation of axon growth is equally critical for regeneration. Yet we have a limited understanding of the signaling pathways that regulate the capacity for axon growth during either development or regeneration. Expression of a...
In contrast to peripheral nerves, damaged axons in the mammalian brain and spinal cord rarely regenerate. Peripheral nerve injury stimulates neuronal expression of many genes that are not generally induced by CNS lesions, but it is not known which of these genes are required for regeneration. Here we show that co-expressing two major growth cone pr...
In the mammalian cortex, the initial formation of synaptic connections is followed by a prolonged period during which synaptic circuits are functional, but retain an elevated capacity for activity-dependent remodeling and functional plasticity. During this period, synaptic terminals appear fully mature, morphologically and physiologically. We show...
Members of the ADP-ribosylation factor (ARF) family of small guanosine triphosphate-binding proteins play an essential role in membrane trafficking which subserves constitutive protein transport along exocytic and endocytic pathways within eukaryotic cell bodies. In growing neurons, membrane trafficking within motile growth cones distant from the c...
Tissue-specific gene transcription can be determined by the use of either positive-acting or negative-acting DNA regulatory elements. We have analyzed a promoter from the growth-associated protein 43 (GAP-43) gene and found that it uses both of these mechanisms to achieve its high degree of neuron-specific activity. Two novel transcription factor b...
Multiple signaling pathways are thought to control the selective expression of genes over the course of neuronal differentiation. One approach to elucidating these pathways is to identify specific cis-acting elements that serve as the final targets for these signaling pathways in neural-specific genes. We now identify a novel repressive element fro...
Axon interruption elicits a complex neuronal response that leaves neurons poised precariously between death and regeneration. The signals underlying this dichotomy are not fully understood. The transcription factor c-Jun is one of the earliest and most consistent markers for neurons that respond to nerve-fiber transection, and its expression can be...
Although maturing neurons undergo a precipitous decline in the expression of genes associated with developmental axon growth, structural changes in axon arbors occur in the adult nervous system under both normal and pathological conditions. Furthermore, some neurons support extensive regrowth of long axons after nerve injury. Analysis of adult dors...
Biological roles of protein palmitoylation have been investigated principally through mutational analysis of individual protein substrates.1-4 An important limitation of this approach is its inability to examine dynamic aspects of palmitoylation. This approach also is confined to analysis of individual, cloned protein substrates and by the availabi...
Neurons throughout the vertebrate nervous system selectively activate the gene for a growth cone component, GAP-43, during embryonic development, and then decrease its expression abruptly as they form synapses. Distal interruption of mature axons in the central nervous system (CNS) of fish and amphibians, but not in the mammalian CNS reverses the d...
In neuronal growth cones, the advancing tips of elongating axons and dendrites, specific protein substrates appear to undergo cycles of posttranslational modification by covalent attachment and removal of long-chain fatty acids. We show here that ongoing fatty acylation can be inhibited selectively by long-chain homologues of the antibiotic tunicam...
Nitric oxide, a free-radical gas produced endogenously by several mammalian cell types, has been implicated as a diffusible intercellular messenger subserving use-dependent modification of synaptic efficacy in the mature central nervous system. It has been suggested on theoretical grounds that nitric oxide might play an analogous role during the es...
Peripheral nerve injury results in the increased synthesis and axonal transport of the growth-associated protein GAP-43 in dorsal root ganglion (DRG) neurons, coincident with regenerative growth of the injured peripheral axon branches. To determine whether the injury-associated signalling mechanism which leads to GAP-43 induction also operates thro...
A conspicuous correlate of the developmental transformation of axonal growth cones to synaptic terminals is a marked increase in synthesis and axonal transport of a methionine-rich, acidic polypeptide of approximately 25 kDa. This polypeptide, designated "super protein" (SuP), is the most prominent species among methionine-labeled proteins conveyed...
In an effort to identify cis-acting elements that respond to signals controlling different stages of neural differentiation, we have analyzed the promoter and surrounding regulatory sequences of the rat GAP-43 gene. Expression of this gene is both neural specific and, within neurons, strongly modulated by signals related to axon integrity. Expressi...
Recent evidence suggests that GAP-43 expression is not restricted to the nervous system, but may also occur outside the neural cell lineage. Two distinct patterns of GAP-43 regulation can therefore be distinguished. The first is the regulation of GAP-43 expression in multiple cell-types, and the second is the gene's temporal modulation within one s...
Proteins characteristic of growing axons often fail to be induced or transported along axons that have been interrupted far from their cell bodies in the adult mammalian CNS. Here, we inquire whether long axons in the mammalian CNS can support efficient axonal transport and deposition of one such protein, GAP-43, when the protein is induced in neur...
GAP-43, a neuron specific growth-associated protein, is selectively distributed to the axonal domain in developing neurons; it is absent from dendrites and their growth cones. Using immunofluorescence microscopy, we have further examined the distribution of GAP-43 during the development of hippocampal neurons in culture, in order to determine when...
In most neurons, the maturation of axonal growth cones to become stable synaptic terminals is accompanied by a dramatic decline in the abundance of a major growth cone component, GAP-43. Accumulation of GAP-43 persists, however, in a minority of mature synaptic terminals. What properties of axons and their terminals are affected by these changes in...
GAP-43 (a.k.a. B-50, F1, pp46, or neuromodulin) is a major growth cone membrane protein whose expression is widely correlated with successful axon elongation, but whose function remains unknown. To distinguish the structural features of GAP-43 most relevant to its cellular functions, we have determined features of the protein that are most highly c...
Growth cones, the motile apparatus at the ends of elongating axons, are sites of extensive and dynamic membrane-cytoskeletal interaction and insertion of new membrane into the growing axon. One of the most abundant proteins in growth cone membranes is a protein designated GAP-43, whose synthesis increases dramatically in most neurons during periods...
Elongation ofaxons and active remodeling of their terminal arbors under lies the assembly of neural circuits during development, determines the success or fai lure of nerve regeneration, and may contribute to some forms of synaptic plast icity in adult brains. For most neurons, elongation of a principal axon is confined to a few days or weeks duri...
Outgrowth of distinct axonal and dendritic processes is essential for the development of the functional polarity of nerve cells. In cultures of neurons from the hippocampus, where the differential outgrowth of axons and dendrites is readily discernible, we have sought molecules that might underlie the distinct modes of elongation of these two types...
Following traumatic injury to the adult rat sciatic nerve the synthesis and accumulation of soluble, extra-cellular, 37 kDa protein is increased. This protein, which accumulates in the extracellular space of the injured nerve, accounts for nearly 5% of the total soluble pool of protein in an injured nerve 3 weeks after injury. 8 weeks after injury,...
Nerve regeneration and developmental outgrowth of axons are both correlated with increased synthesis of an axonal membrane protein designated GAP-43. Phosphorylation of an apparently identical protein, present at lower abundance in adult brains, has been correlated with long-term potentiation, a form of synaptic plasticity. We have now isolated a c...
Axons of the adult mammalian CNS typically fail to regenerate after injury. Among the hypotheses to account for this failure is the proposition that certain axonal proteins necessary for axon growth are expressed in much greater abundance in developing than in mature neurons, and that these proteins are not reinduced after injury to mature axons (S...
Growth cones are specialized structures that form the distal tips of growing axons. During both normal development of the nervous system and regeneration of injured nerves, growth cones are essential for elongation and guidance of growing axons. Developmental and regenerative axon growth is frequently accompanied by elevated synthesis of a protein...
Development or regeneration of axons in several systems is accompanied by 20-100-fold increases in the synthesis of an acidic, axonally transported membrane protein with an apparent molecular weight of 43-50,000 (Benowitz and Lewis, 1983; Skene and Willard, 1981a, b), which we designate GAP-43. We have proposed that some step(s) in axon growth requ...
A 37-kDa glycoprotein has been described recently, whose synthesis is dramatically increased after injury of the rat sciatic and optic nerves. Cells in the nerve sheath, distal to the site of injury, produce and secrete large amounts of this protein, so that by 3 weeks after injury, it represents 2-5% of the total soluble extracellular protein in t...
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The mature, steady-state axon is a temporally ephemeral collection of matter whose apparent constancy reflects a delicate balance between the continuous introduction of materials from the cell body by the process of axonal transport and their exit. At a given instant, the major morphological manifestations of this steady state are the arrays of neu...
With the realization that viral genes responsible for oncogenic transformation are derived from normal vertebrate genes, molecular biologists have begun to assume that these normal cellular ‘oncogenes’ are important regulators of cell growth and differentiation2,3. Two recent reports1,6 now show that the product of one such cellular oncogene is exp...
When rat sciatic nerves are crushed, Schwann cells or other supporting cells distal to the injury site begin to synthesize and secrete an acidic 37-kilodalton (kDa) protein. This crush-induced protein accumulates within the nerve sheath and accounts for 2-5% of the total extracellular protein in the distal nerve stump. Synthesis of the 37-kDa prote...
Excerpt
The static beauty of the structure of an axon belies its dynamic nature. An axon typically comprises a scaffolding of linear elements, the microtubules and neurofilaments, that are connected to each other and to the plasma membrane by a lattice of cross-linkers (Fig. 1). Embedded in this lattice, and communicating with the linear elements b...
We consider whether a neuron must alter its program of gene expression in order to regenerate an injured axon. We conclude that certain information required for axon growth is encoded in the normal constituents of a quiescent axon, and certain aspects of axon growth may be regulated by environmental information impinging directly on the normal cons...
The GAPs (growth associated proteins, axonally transported at elevated levels during periods of axon elongation) and fodrin (polypeptides associated with the outer cytoplasm of neurons and other cells) are novel, rapidly axonally transported proteins. The behavior of the GAPS suggests that the modulation of neuronal gene expression is a critical fe...
As a preliminary step to studying changes in axonal transport in regenerating neurons, we have analyzed the composition and organization of polypeptides normally axonally transported in a neuronal system capable of regeneration, i.e., the retinal ganglion cells of the toad, Bufo marinus. We labeled proteins synthesized in the retina with 35S-methio...
We report here certain properties of three polypeptides that are rapidly transported in greatly increased amounts during the regeneration of toad optic nerves. All three of these growth-associated polypeptides (GAPs) are associated with a membrane(s) with a buoyant density similar to the plasma membrane. Since none of these GAPs are solubilized sub...
In an effort to understand the regulation of the transition of a mature neuron to the growth, or regenerating, state we have analyzed the composition of the axonally transported proteins in the retinal ganglion cells of the toad Bufo marinus after inducing axon regeneration by crushing the optic nerve. At increasing intervals after axotomy, we labe...
In an effort to determine whether the "growth state" and the "mature state" of a neuron are differentiated by different programs of gene expression, we have compared the rapidly transported (group I) proteins in growing and nongrowing axons in rabbits. We observed two polypeptides (GAP-23 and GAP-43) which were of particular interest because of the...
Polypeptide H (mol wt 195,000) is axonally transported in rabbit retinal ganglion cells at a velocity of 0.7--1.1 mm/d, i.e., in the most slowly moving of the five transport groups described in these neurons. To identify the organelle with which H is associated, we purified H, prepared antibodies directed against it, and adsorbed the antibodies ont...
We labeled proteins in the cell bodies of rabbit retinal ganglion cells with [35S]methionine and subsequently observed the appearance of radioactive actin in tissues containing the axons and synaptic terminals of these neurons, i.e., the optic nerve (ON), optic tract (OT), lateral geniculate nucleus (LGN) and the superior colliculus (SC). The tempo...
Chromatography on controlled pore glass in combination with chaotropic buffers makes possible, in a single step, protein purifications
of several hundredfold. The new emphasis is on highly selective controllable adsorption. The method is useful for the purification
and concentration of proteins from large volumes of complex media and for the purifi...
The GAPs (growth associated proteins, axonally transported at elevated levels during periods of axon elongation) and fodrin (polypeptides associated with the outer cytoplasm of neurons and other cells) are novel, rapidly axonally transported proteins. The behavior of the GAPS suggests that the modulation of neuronal gene expression is a critical fe...