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Open Access Publications from the University of California

Scholarly Works (12 results)

  • Article
  • Peer Reviewed
Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 37 (2015)
The current study sought to investigate the relationship between attention, perception and memory in the perception and recall of attended and unattended properties of objects. Two experiments tested whether the intention to perceive maximum overhead reaching height with the use of handheld rods with different mass and rotational inertia yielded information for participants to remember the rods’ heaviness after they were removed from view. Participants remembered the difference in heaviness of rods but only when haptic information was solely available during the earlier perception of overhead reaching height and vision was occluded. The results support an ecological approach to perception, attention and memory, and suggest that information detected for perception can be later used to remember other object properties that have a correlated informational basis.
    Cover page: The perception and memory of object properties: The role of attention, intention, and information detection
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2017)

    A major challenge in understanding complex rheumatologic and inflammatory diseases has been to understand the relative contributions and influences of multiple cytokines and cell types to disease pathogenesis. Progress has been limited by our inadequate knowledge of the underlying mechanisms responsible for regulating inflammatory responses, both in circumstances of human disease, but also at a fundamental level of how transcription factors (TFs), chromatin, and diverse stimuli regulate inducible transcription in immune cells. We have utilized in-vitro models of mouse macrophage activation combined with hi-throughput sequencing in order to provide a high-resolution view of the inflammatory response. The long- term goal is to identify modes of regulation governing inducible gene expression with the expectation that the knowledge gained will provide insight into how the immune response can be manipulated in the setting of human disease. Here, we provide evidence for both broad trends governing inducible transcription as well as examples of highly specific forms of regulation occurring at individual genes. We further provide support for utilizing mouse models in relation to questions regarding human physiology, as well as address the role of Interluekin-10 in the inhibition of inducible chromatin at sites upstream of inhibited genes.

      Cover page: Highly Selective Changes in Chromatin Accessibility in Response to Pro-Inflammatory and Anti-Inflammatory Stimuli
      • Article
      Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 40 (2018)
      Joint actions require successful coordination between two or more individuals toward shared goals. Successful motorperformance can be influenced by agency and anxiety; however, these factors could also serve as regulation mechanismsthat enhance coordination in joint action tasks. The current experiment assessed the influence of anxiety and sense ofagency on the dynamics of action coordination between two people during a car-braking task. Both individuals wererequired to contribute toward the braking task to avoid crashing into a stop sign. Using an actor partner interdependencemodel (APIM), results suggested that individuals seated to the right decreased their contribution to braking after individualsseated on the left increased their braking, but the reciprocal relation was not present. Visual feedback appears to influenceaction coordination, however no differences in reported anxiety or agency were found. This leader-follower effect suggeststhat a driver-passenger dynamic might have emerged.
        Cover page: Leader-follower Dynamics, Agency, and Anxiety in Joint Action Braking: AFirst-Order Dynamical Systems Model
        • Thesis
        • Peer Reviewed
        UCLA Electronic Theses and Dissertations (2020)

        Galaxy Clusters (GCls) are the largest known virialized objects in the Universe. About one-third of GCls exhibit an extended radio halo associated with a population of nonthermal electrons emitting synchrotron radiation in a microgauss level magnetic field. The cooling time for the nonthermal electrons is about two orders of magnitude below the diffusion time needed to explain the radio halo, indicating that the electrons are created locally. The electrons may either be accelerated directly in the turbulent cluster medium or created as secondary products from nonthermal protons colliding with the intracluster medium. Observed gamma-ray emission can therefore resolve the contribution from these two mechanisms. Despite the empirical and theoretical motivation for the existence of gamma-ray emission from GCls, so far it remains undetected. In this talk VERITAS observations are used to analyze a 6x8 degree field of the Coma galaxy cluster and evaluate the existence of possible extended gamma-ray emission. To achieve this, a method is developed which utilizes cosmic rays as a calibration source to determine a background measurement across the full field of view. The resulting excess demonstrates a small significance of 2.7 sigma in the central 1.5 degree radius of the cluster. This observed central excess, while alone is not significant, has an angular extent in agreement with simulations and corresponds to a similar significance level seen by Fermi-LAT in the same region, and hence it is worth further investigation by VERITAS and future instruments such as CTA.

          Cover page: Probing for Extended Gamma-ray Emission Within and Beyond the Virial Radius from the Coma Galaxy Cluster
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2015)
          A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.
            Cover page: Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older AdultsCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2016)
            Much has been learned about transcriptional cascades and networks from large-scale systems analyses of high-throughput datasets. However, analysis methods that optimize statistical power through simultaneous evaluation of thousands of ChIP-seq peaks or differentially expressed genes possess substantial limitations in their ability to uncover mechanistic principles of transcriptional control. By examining nascent transcript RNA-seq, ChIP-seq, and binding motif datasets from lipid A-stimulated macrophages with increased attention to the quantitative distribution of signals, we identified unexpected relationships between the in vivo binding properties of inducible transcription factors, motif strength, and transcription. Furthermore, rather than emphasizing common features of large clusters of co-regulated genes, our results highlight the extent to which unique mechanisms regulate individual genes with key biological functions. Our findings demonstrate the mechanistic value of stringent interrogation of well-defined sets of genes as a complement to broader systems analyses of transcriptional cascades and networks.
              Cover page: A Stringent Systems Approach Uncovers Gene-Specific Mechanisms Regulating Inflammation
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2024)
              Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq and single-cell ATAC-seq that enriched for genomic regions most likely to undergo remodeling revealed that the transcription factor nuclear factor κB (NF-κB) bound to all high-confidence peaks marking remodeling during the primary response to the TLR4 ligand, lipid A. Deletion of NF-κB subunits RelA and c-Rel resulted in the loss of remodeling at high-confidence ATAC-seq peaks, and CRISPR-Cas9 mutagenesis of NF-κB-binding motifs impaired remodeling. Remodeling selectivity at defined regions was conferred by collaboration with other inducible factors, including IRF3- and MAP-kinase-induced factors. Thus, NF-κB is unique among TLR4-activated transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its ability to activate poised enhancers and promoters assembled into open chromatin.
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2017)
                Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs) to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways contributing to the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, two PRR pathways-the Toll-like receptor (TLR) and Stimulator of Interferon Gene (STING) pathways-were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated a pro-inflammatory program while STING signaling activated an antiviral/type I interferon response with live but not killed S. aureus. This STING response was largely dependent on the cytosolic DNA sensor cyclic guanosine-adenosine synthase (cGAS). Using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus. TLR signaling was required for host defense, with its absence reducing interleukin (IL)-1β production and neutrophil recruitment, resulting in increased bacterial growth. In contrast, absence of STING signaling had the opposite effect, enhancing the ability to restrict the infection. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered by S. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus.
                  Cover page: Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2019)
                  Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.
                    Cover page: Single cell analysis reveals immune cell–adipocyte crosstalk regulating the transcription of thermogenic adipocytesCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2018)
                    Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging. Assay for transposase-accessible chromatin sequencing (ATAC-seq), ChIP-seq, and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and C/EBPβ recruitment to key enhancer regions. These findings expand our understanding of the relationship between inflammatory signaling pathways and adipose tissue function and provide insight into the physiological control of thermogenesis that could inform future therapy.
                      Cover page: IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure
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