Information Processing in the Orbitofrontal Cortex and the Ventral Striatum in Rats Performing an Economic Decision-Making Task

University of Minnesota Ph.D. dissertation. August 2015. Major: Neuroscience. Advisor: David Redish. 1 computer file (PDF); vi, 144 pages.The orbitofrontal cortex (OFC) and ventral striatum (vStr) are key brain structures that represent information about value during decision-making tasks. Despite their very different anatomical properties, numerous studies have found similar patterns of value-related signaling in these structures. In particular, both structures are intimately involved in delay-discounting tasks, which involve a tradeoff between reward magnitude and delay to reward. However, the overlapping activity profiles of these brain regions makes it difficult to tease apart their specific contributions to delay-discounting behavior, and to economic decision-making more generally. In order to better understand the contributions of these two regions to value-based choice, we made simultaneous recordings in the OFC and vStr in rats performing a spatial variant of a traditional delay-discounting task. This allowed us to compare OFC and vStr activity directly in the same subjects while they engaged in a prototypical economic decision-making task, and additionally it allowed us to leverage the tools of spatial decoding analysis to measure non-local reward signaling. Chapter 1 provides an introduction to current theories of OFC and vStr function within the decision-making literature, in particular contrasting the concepts of neuroeconomics with the multiple decision-making systems framework. Chapter 2 describes the methods used in this thesis, including the design of the spatial delay-discounting task and the analysis of the neural data. Chapter 3 presents the results of single-unit and Bayesian decoding analyses from this dataset. We found that activity in the OFC and vStr was quite similar at the single-unit level, and inconsistent with the neuroeconomic account of value signaling in a common currency. Instead, when we looked specifically at moments of deliberative decision-making (as emphasized by the multiple systems account), we found important differences between the OFC and vStr. Both the OFC and the vStr showed covert reward signaling during deliberative, vicarious trial-and-error (VTE) behaviors. But vStr signals emerged earlier, before the moment of choice, while covert reward coding in the OFC appeared after the rats had committed to their decision. These analyses were extended to the level of local field potentials (LFPs), recorded from the same dataset. Local field potentials are a useful tool for studying local processing and interactions between brain regions. Chapter 4 describes the LFP results. Important among these was the finding that the vStr led the OFC at the LFP level (again showing temporal precedence), and furthermore, that the vStr was a stronger driver of OFC activity than vice versa, particularly during VTE. The implications of these results, along with those from the single-unit and Bayesian decoding analyses, are discussed in Chapter 5. Emphasis is placed on our emerging understanding of the role of the vStr in flexible behavior, and how the OFC and the vStr might cooperate to influence value-based choice

Correlation of Tire Intensity Levels and Passby Sound Pressure Levels

The object of the work reported here was to relate the acoustic intensity level measured near the contact patch of a driven tire on a passenger vehicle with the passby noise levels measured at a sideline microphone during coast and cruise conditions. Based on those measurements it was then possible to estimate the tire noise contribution to the passby level measured when the vehicle under test was accelerating. As part of this testing program, data was collected using five vehicles at fourteen passby sites in the United States: in excess of 800 data sets were obtained

Differential Expression of Immune Response Genes in Steller Sea Lions (\u3ci\u3eEumetopias jubatus\u3c/i\u3e): An Indicator of Ecosystem Health?

Characterization of the polygenic and polymorphic features of the Steller sea lion major histocompatibility complex (MHC) provides an ideal window for evaluating immunologic vigor of the population and identifying emergence of new genotypes that reflect ecosystem pressures. MHC genotyping can be used to measure the potential immunologic vigor of a population. However, since ecosystem-induced changes to MHC genotype can be slow to emerge, measurement of differential expression of these genes can potentially provide real-time evidence of immunologic perturbations. MHC DRB genes were cloned and sequenced using peripheral blood mononuclear leukocytes derived from 10 Steller sea lions from southeast Alaska, Prince William Sound, and the Aleutian Islands. Nine unique DRB gene sequences were represented in each of ten animals. MHC DRB gene expression was measured in a subset of six sea lions. Although DRB in genomic DNA was identical in all individuals, relative levels of expressed DRB mRNA was highly variable. Selective suppression of MHC DRB genes could be indicative of geographically disparate environmental pressures, thereby serving as an immediate and sensitive indicator of population and ecosystem health

Anticancer Activity and Biophysical Reactivity of Copper Complexes of 2-(benzo[d][1,3]dioxol-5-ylmethylene)-N-Alkylhydrazinecarbothioamides

A series of copper complexes were synthesized from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) thiosemicarbazones (RHpTSC where R = H, CH3, C2H5 or C6H5 (Ph)). The complexes show interesting variations in geometry depending on the thiosemicarbazone; a dinuclear complex [Cu(HpTSC)Cl]2, a mononuclear complex [Cu(RHpTSC)2Cl2] (R = CH3 or C2H5) and another mononuclear complex [Cu(PhHpTSC)(PhpTSC)Cl] was generated. The complexes bind in a moderately strong fashion to DNA with binding constants on the order of 104 M− 1. They are also strong binders of human serum albumin with binding constants near 104 M− 1. The complexes show good in vitro cytotoxic profiles against two human colon cancer cell lines (HCT-116 and HT29) and two human breast cancer cell lines (MCF-7 and MDA-MB-231) with IC50 values in the low millimolar concentration range

Loss of FBXO7 results in a Parkinson’s-like dopaminergic degeneration via an RPL23-MDM2-TP53 pathway

The field of Parkinson’s disease research has been impeded by the absence of animal models that clearly phenocopy the features of this neurodegenerative condition. Mutations in FBXO7/PARK15 are associated with both sporadic Parkinson’s disease and a severe form of autosomal recessive early-onset Parkinsonism. Here we report that conditional deletion of Fbxo7 in the midbrain dopamine neurons results in an early reduction in striatal dopamine levels, together with a slow, progressive loss of midbrain dopamine neurons and onset of locomotor defects. Unexpectedly, a later compensatory response led to a near-full restoration of dopaminergic fibre innervation in the striatum, but nigral cell loss was irreversible. Mechanistically, there was increased expression in the dopamine neurons of FBXO7-interacting protein, RPL23, which is a sensor of ribosomal stress that inhibits MDM2, the negative regulator of p53. A corresponding activated p53 transcriptional signature biased towards pro-apoptotic genes was also observed. These data suggest the neuroprotective role of FBXO7 involves its suppression of the RPL23-MDM2-p53 axis that promotes cell death in dopaminergic midbrain neurons.Biotechnology and Biological Sciences Research Council (BB/J007846/1), DDPDgenes, Parkinson's UK and the CurePD Trust, and Wellcome Trust-MRC funded Cambridge Stem Cell Institute and an NIHR award of a Biomedical Research Centre for Addenbrooke’s Hospital/University of Cambridge

Anthropogenic sound exposure-induced stress in captive dolphins and implications for cetacean health

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Yang, W.-C., Chen, C.-F., Chuah, Y.-C., Zhuang, C.-R., Chen, I.-H., Mooney, T. A., Stott, J., Blanchard, M., Jen, I.-F., & Chou, L.-S. Anthropogenic sound exposure-induced stress in captive dolphins and implications for cetacean health. Frontiers in Marine Science, 8,(2021): 606736, https://doi.org/10.3389/fmars.2021.606736.Many cetaceans are exposed to increasing pressure caused by anthropogenic activities in their marine environment. Anthropogenic sound has been recognized as a possible stressor for cetaceans that may have impacts on health. However, the relationship between stress, hormones, and cytokines secretion in cetaceans is complex and not fully understood. Moreover, the effects of stress are often inconsistent because the character, intensity, and duration of the stressors are variable. For a better understanding of how anthropogenic sounds affect the psychophysiology of cetaceans, the present study compared the changes of cortisol concentration and cytokine gene transcriptions in blood samples and behaviors of captive bottlenose dolphins (Tursiops truncatus) after sound exposures. The sound stimuli were 800 Hz pure-tone multiple impulsive sound for 30 min at three different sound levels (estimated mean received SPL: 0, 120, and 140 dB re 1 μPa) that likely cause no permanent and temporary hearing threshold shift in dolphins. Six cytokine genes (IL-2Rα, IL-4, IL-10, IL-12, TNF-α, and IFN-γ) were selected for analysis. Cortisol levels and IL-10 gene transcription increased and IFNγ/IL-10 ratio was lower after a 30-min high-level sound exposure, indicating the sound stimuli used in this study could be a stressor for cetaceans, although only minor behavior changes were observed. This study may shed light on the potential impact of pile driving-like sounds on the endocrine and immune systems in cetaceans and provide imperative information regarding sound exposure for free-ranging cetaceans.This work was supported by the Ministry of Science and Technology in Taiwan (MOST 108-2313-B-002-021 and MOST 109-2628-B-002-028)

Understanding and Enhancing Soil Biological Health: The Solution for Reversing Soil Degradation

Our objective is to provide an optimistic strategy for reversing soil degradation by increasing public and private research efforts to understand the role of soil biology, particularly microbiology, on the health of our world’s soils. We begin by defining soil quality/soil health (which we consider to be interchangeable terms), characterizing healthy soil resources, and relating the significance of soil health to agroecosystems and their functions. We examine how soil biology influences soil health and how biological properties and processes contribute to sustainability of agriculture and ecosystem services. We continue by examining what can be done to manipulate soil biology to: (i) increase nutrient availability for production of high yielding, high quality crops; (ii) protect crops from pests, pathogens, weeds; and (iii) manage other factors limiting production, provision of ecosystem services, and resilience to stresses like droughts. Next we look to the future by asking what needs to be known about soil biology that is not currently recognized or fully understood and how these needs could be addressed using emerging research tools. We conclude, based on our perceptions of how new knowledge regarding soil biology will help make agriculture more sustainable and productive, by recommending research emphases that should receive first priority through enhanced public and private research in order to reverse the trajectory toward global soil degradation

Cell sorting by deterministic cell rolling

Authors Manuscript 2013 April 21.This communication presents the concept of “deterministic cell rolling”, which leverages transient cell-surface molecular interactions that mediate cell rolling to sort cells with high purity and efficiency in a single step.National Institutes of Health (U.S.) (Grant HL-095722)National Institutes of Health (U.S.) (Grant HL-097172)National Science Foundation (U.S.) (CAREER Award 0952493)Deshpande Center for Technological InnovationNational Science Foundation (U.S.). Chemical and Biological Separation

The KMOS Cluster Survey (KCS). I. The Fundamental Plane and the Formation Ages of Cluster Galaxies at Redshift 1.4 < Z < 1.6

We present the analysis of the fundamental plane (FP) for a sample of 19 massive red-sequence galaxies (${M}_{\star }\gt 4\times {10}^{10}$ ${M}_{\odot }$) in three known overdensities at $1.39\lt z\lt 1.61$ from the K-band Multi-object Spectrograph (KMOS) Cluster Survey, a guaranteed-time program with spectroscopy from the KMOS at the VLT and imaging from the Hubble Space Telescope. As expected, we find that the FP zero-point in B band evolves with redshift, from the value 0.443 of Coma to −0.10 ± 0.09, −0.19 ± 0.05, and −0.29 ± 0.12 for our clusters at z = 1.39, z = 1.46, and z = 1.61, respectively. For the most massive galaxies ($\mathrm{log}{M}_{\star }/{M}_{\odot }\gt 11$) in our sample, we translate the FP zero-point evolution into a mass-to-light-ratio M/L evolution, finding ${\rm{\Delta }}\mathrm{log}M/{L}_{B}=(-0.46\pm 0.10)z$, ${\rm{\Delta }}\mathrm{log}M/{L}_{B}=(-0.52\pm 0.07)z$, to ${\rm{\Delta }}\mathrm{log}M/{L}_{B}=(-0.55\pm 0.10)z$, respectively. We assess the potential contribution of the galaxy structural and stellar velocity dispersion evolution to the evolution of the FP zero-point and find it to be ~6%–35% of the FP zero-point evolution. The rate of M/L evolution is consistent with galaxies evolving passively. Using single stellar population models, we find an average age of ${2.33}_{-0.51}^{+0.86}$ Gyr for the $\mathrm{log}{M}_{\star }/{M}_{\odot }\gt 11$ galaxies in our massive and virialized cluster at z = 1.39, ${1.59}_{-0.62}^{+1.40}$ Gyr in a massive but not virialized cluster at z = 1.46, and ${1.20}_{-0.47}^{+1.03}$ Gyr in a protocluster at z = 1.61. After accounting for the difference in the age of the universe between redshifts, the ages of the galaxies in the three overdensities are consistent within the errors, with possibly a weak suggestion that galaxies in the most evolved structure are older

Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

&lt;p&gt;Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.&lt;/p&gt; &lt;p&gt;Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.&lt;/p&gt; &lt;p&gt;Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.&lt;/p&gt; &lt;p&gt;Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.&lt;/p&gt