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Search Results: 1 - 10 of 229326 matches for " Luke R. Johnson "
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Pavlovian Fear Conditioning Activates a Common Pattern of Neurons in the Lateral Amygdala of Individual Brains
Hadley C. Bergstrom,Craig G. McDonald,Luke R. Johnson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015698
Abstract: Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram.
Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress?
Kwang Choi,Luke R. Johnson,Robert J. Ursano
Frontiers in Behavioral Neuroscience , 2011, DOI: 10.3389/fnbeh.2011.00046
Abstract: Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear, and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database1 and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK), the cyclin-dependent kinase, the mitogen-activated protein kinase (MAPK), and the protein kinase C (PKC) in the prefrontal cortex (PFC) of mood disorder patients died with suicide (N = 45) and without suicide (N = 38). We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (N = 46). The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (false discovery rate, FDR-adjusted p < 0.05, fold change >1.1). Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05). These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress associated neural plasticity, and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.
The Importance of Reporting Housing and Husbandry in Rat Research
Eric M. Prager,Hadley C. Bergstrom,Luke R. Johnson
Frontiers in Behavioral Neuroscience , 2011, DOI: 10.3389/fnbeh.2011.00038
Localization of Mineralocorticoid Receptors at Mammalian Synapses
Eric M. Prager,Jennifer Brielmaier,Hadley C. Bergstrom,Jennifer McGuire,Luke R. Johnson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014344
Abstract: In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.
Regulation of the Fear Network by Mediators of Stress: Norepinephrine Alters the Balance between Cortical and Subcortical Afferent Excitation of the Lateral Amygdala
Luke R. Johnson,Mian Hou,Eric M. Prager,Joseph E. LeDoux
Frontiers in Behavioral Neuroscience , 2011, DOI: 10.3389/fnbeh.2011.00023
Abstract: Pavlovian auditory fear conditioning involves the integration of information about an acoustic conditioned stimulus (CS) and an aversive unconditioned stimulus in the lateral nucleus of the amygdala (LA). The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE), regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased toward the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance toward the faster but more primitive subcortical input.
Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear
Kwang H. Choi, Thien Le, Jennifer McGuire, Jennifer Coyner, Brandon W. Higgs, Suad Diglisic, Luke R. Johnson, David M. Benedek, Robert J. Ursano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049183
Abstract: A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.
Choreography of the Transcriptome, Photophysiology, and Cell Cycle of a Minimal Photoautotroph, Prochlorococcus
Erik R. Zinser, Debbie Lindell, Zackary I. Johnson, Matthias E. Futschik, Claudia Steglich, Maureen L. Coleman, Matthew A. Wright, Trent Rector, Robert Steen, Nathan McNulty, Luke R. Thompson, Sallie W. Chisholm
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005135
Abstract: The marine cyanobacterium Prochlorococcus MED4 has the smallest genome and cell size of all known photosynthetic organisms. Like all phototrophs at temperate latitudes, it experiences predictable daily variation in available light energy which leads to temporal regulation and partitioning of key cellular processes. To better understand the tempo and choreography of this minimal phototroph, we studied the entire transcriptome of the cell over a simulated daily light-dark cycle, and placed it in the context of diagnostic physiological and cell cycle parameters. All cells in the culture progressed through their cell cycles in synchrony, thus ensuring that our measurements reflected the behavior of individual cells. Ninety percent of the annotated genes were expressed, and 80% had cyclic expression over the diel cycle. For most genes, expression peaked near sunrise or sunset, although more subtle phasing of gene expression was also evident. Periodicities of the transcripts of genes involved in physiological processes such as in cell cycle progression, photosynthesis, and phosphorus metabolism tracked the timing of these activities relative to the light-dark cycle. Furthermore, the transitions between photosynthesis during the day and catabolic consumption of energy reserves at night— metabolic processes that share some of the same enzymes — appear to be tightly choreographed at the level of RNA expression. In-depth investigation of these patterns identified potential regulatory proteins involved in balancing these opposing pathways. Finally, while this analysis has not helped resolve how a cell with so little regulatory capacity, and a ‘deficient’ circadian mechanism, aligns its cell cycle and metabolism so tightly to a light-dark cycle, it does provide us with a valuable framework upon which to build when the Prochlorococcus proteome and metabolome become available.
An Integrated Approach to Address Endemic Fluorosis in Jharkhand, India  [PDF]
Luke H. MacDonald, Gopal Pathak, Burton Singer, Peter R. Jaffé
Journal of Water Resource and Protection (JWARP) , 2011, DOI: 10.4236/jwarp.2011.37056
Abstract: This paper presents the grounds for an integrated approach to address endemic fluorosis in Jharkhand, India, an approach that encompasses health monitoring, community-based water systems management, and locally synthesized hydroxyapatite, a sustainable water treatment technology. The results of this study, focusing on kinetics and sorption isotherms, demonstrate that an inexpensive, locally synthesized hydroxyapatite effectively removes fluoride from water and that the Dean Index, a measure of dental fluorosis, of school children provides a sensitive, rapid biometric to track the success of a fluoride water treatment intervention. Previous efforts to manage the fluoride problem in Jharkhand were unsuccessful, largely due to lack of accountability and inadequate community involvement. This paper explores how integrating the production of a locally synthesized hydroxyapatite with community health monitoring via the Dean Index fits into a management strategy with robust accountability mechanisms and community participation that, as historical examples suggest, is likely to succeed in Jharkhand.
Quantum Monte Carlo applied to solids
Luke Shulenburger,Thomas R. Mattsson
Physics , 2013, DOI: 10.1103/PhysRevB.88.245117
Abstract: We apply diffusion quantum Monte Carlo (DMC) to a broad set of solids, benchmarking the method by comparing bulk structural properties (equilibrium volume and bulk modulus) to experiment and DFT based theories. The test set includes materials with many different types of binding including ionic, metallic, covalent and van der Waals. We show that, on average, the accuracy is comparable to or better than that of density functional theory (DFT) when using the new generation of functionals, including one hybrid functional and two dispersion corrected functionals. The excellent performance of quantum Monte Carlo (QMC) on solids is promising for its application to heterogeneous systems and high-pressure/high density conditions. Important to the results here is the application of a consistent procedure with regards to the several approximations that are made, such as finite-size corrections and pseudo-potential approximations. This test set allows for any improvements in these methods to be judged in a systematic way.
Optimal Multilevel Matching in Clustered Observational Studies: A Case Study of the School Voucher System in Chile
Luke Keele,Jose R. Zubizarreta
Statistics , 2014,
Abstract: A distinctive feature of a clustered observational study is its multilevel or nested data structure arising from the assignment of treatment, in a non-random manner, to groups or clusters of individuals. Examples are ubiquitous in the health and social sciences including patients in hospitals, employees in firms, and students in schools. What is the optimal matching strategy in a clustered observational study? At first thought, one might start by matching clusters of individuals and then, within matched clusters, continue by matching individuals. But, as we discuss in this paper, the optimal strategy is the opposite: first match individuals and, once all possible combinations of matched individuals are known, then match clusters. In this paper we use dynamic and integer programming to implement this strategy and extend optimal matching methods to hierarchical and multilevel settings. In particular, our method attempts to replicate a paired clustered randomized study by finding the largest sample of matched pairs of treated and control individuals within matched pairs of treated and control clusters that is balanced according to specifications given by the user. We illustrate our method on a case study of the comparative effectiveness of public versus private voucher schools in Chile, a question of intense policy debate in the country at the present.
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