Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast.

Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.

Crafting analytical tools to study institutional change

Most powerful analytical tools used in the social sciences are well suited for studying static situations. Static and mechanistic analysis, however, is not adequate to understand the changing world in which we live. In order to adequately address the most pressing social and environmental challenges looming ahead, we need to develop analytical tools for analyzing dynamic situations -particularly institutional change. In this paper, we develop an analytical tool to study institutional change, more specifically, the evolution of rules and norms. We believe that in order for such an analytical tool to be useful to develop a general theory of institutional change, it needs to enable the analyst to concisely record the processes of change in multiple specific settings so that lessons from such settings can eventually be integrated into a more general predictive theory of change. Copyright © The JOIE Foundation 2010.

A neural biomarker of psychological vulnerability to future life stress.

We all experience a host of common life stressors such as the death of a family member, medical illness, and financial uncertainty. While most of us are resilient to such stressors, continuing to function normally, for a subset of individuals, experiencing these stressors increases the likelihood of developing treatment-resistant, chronic psychological problems, including depression and anxiety. It is thus paramount to identify predictive markers of risk, particularly those reflecting fundamental biological processes that can be targets for intervention and prevention. Using data from a longitudinal study of 340 healthy young adults, we demonstrate that individual differences in threat-related amygdala reactivity predict psychological vulnerability to life stress occurring as much as 1 to 4 years later. These results highlight a readily assayed biomarker, threat-related amygdala reactivity, which predicts psychological vulnerability to commonly experienced stressors and represents a discrete target for intervention and prevention.

Narrative centrality and negative affectivity: independent and interactive contributors to stress reactions.

Reactions to stressful negative events have long been studied using approaches based on either the narrative interpretation of the event or the traits of the individual. Here, we integrate these 2 approaches by using individual-differences measures of both the narrative interpretation of the stressful event as central to one's life and the personality characteristic of negative affectivity. We show that they each have independent contributions to stress reactions and that high levels on both produce greater than additive effects. The effects on posttraumatic stress symptoms are substantial for both undergraduates (Study 1, n = 2,296; Study 3, n = 488) and veterans (Study 2, n = 104), with mean levels for participants low on both measures near floor on posttraumatic stress symptoms and those high on both measures scoring at or above diagnostic thresholds. Study 3 included 3 measures of narrative centrality and 3 of negative affectivity to demonstrate that the effects were not limited to a single measure. In Study 4 (n = 987), measures associated with symptoms of posttraumatic stress correlated substantially with either measures of narrative centrality or measures of negative affectivity. The concepts of narrative centrality and negative affectivity and the results are consistent with findings from clinical populations using similar measures and with current approaches to therapy. In broad nonclinical populations, such as those used here, the results suggest that we might be able to substantially increase our ability to account for the severity of stress response by including both concepts.

Peace and war: trajectories of posttraumatic stress disorder symptoms before, during, and after military deployment in Afghanistan.

In the study reported here, we examined posttraumatic stress disorder (PTSD) symptoms in 746 Danish soldiers measured on five occasions before, during, and after deployment to Afghanistan. Using latent class growth analysis, we identified six trajectories of change in PTSD symptoms. Two resilient trajectories had low levels across all five times, and a new-onset trajectory started low and showed a marked increase of PTSD symptoms. Three temporary-benefit trajectories, not previously described in the literature, showed decreases in PTSD symptoms during (or immediately after) deployment, followed by increases after return from deployment. Predeployment emotional problems and predeployment traumas, especially childhood adversities, were predictors for inclusion in the nonresilient trajectories, whereas deployment-related stress was not. These findings challenge standard views of PTSD in two ways. First, they show that factors other than immediately preceding stressors are critical for PTSD development, with childhood adversities being central. Second, they demonstrate that the development of PTSD symptoms shows heterogeneity, which indicates the need for multiple measurements to understand PTSD and identify people in need of treatment.

Autobiographical memory for stressful events: the role of autobiographical memory in posttraumatic stress disorder.

To provide the three-way comparisons needed to test existing theories, we compared (1) most-stressful memories to other memories and (2) involuntary to voluntary memories (3) in 75 community dwelling adults with and 42 without a current diagnosis of posttraumatic stress disorder (PTSD). Each rated their three most-stressful, three most-positive, seven most-important and 15 word-cued autobiographical memories, and completed tests of personality and mood. Involuntary memories were then recorded and rated as they occurred for 2 weeks. Standard mechanisms of cognition and affect applied to extreme events accounted for the properties of stressful memories. Involuntary memories had greater emotional intensity than voluntary memories, but were not more frequently related to traumatic events. The emotional intensity, rehearsal, and centrality to the life story of both voluntary and involuntary memories, rather than incoherence of voluntary traumatic memories and enhanced availability of involuntary traumatic memories, were the properties of autobiographical memories associated with PTSD.

The coherence of memories for trauma: evidence from posttraumatic stress disorder.

Participants with posttraumatic stress disorder (PTSD) and participants with a trauma but without PTSD wrote narratives of their trauma and, for comparison, of the most-important and the happiest events that occurred within a year of their trauma. They then rated these three events on coherence. Based on participants' self-ratings and on naïve-observer scorings of the participants' narratives, memories of traumas were not more incoherent than the comparison memories in participants in general or in participants with PTSD. This study comprehensively assesses narrative coherence using a full two (PTSD or not) by two (traumatic event or not) design. The results are counter to most prevalent theoretical views of memory for trauma.

A memory-based model of posttraumatic stress disorder: evaluating basic assumptions underlying the PTSD diagnosis.

In the mnemonic model of posttraumatic stress disorder (PTSD), the current memory of a negative event, not the event itself, determines symptoms. The model is an alternative to the current event-based etiology of PTSD represented in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000). The model accounts for important and reliable findings that are often inconsistent with the current diagnostic view and that have been neglected by theoretical accounts of the disorder, including the following observations. The diagnosis needs objective information about the trauma and peritraumatic emotions but uses retrospective memory reports that can have substantial biases. Negative events and emotions that do not satisfy the current diagnostic criteria for a trauma can be followed by symptoms that would otherwise qualify for PTSD. Predisposing factors that affect the current memory have large effects on symptoms. The inability-to-recall-an-important-aspect-of-the-trauma symptom does not correlate with other symptoms. Loss or enhancement of the trauma memory affects PTSD symptoms in predictable ways. Special mechanisms that apply only to traumatic memories are not needed, increasing parsimony and the knowledge that can be applied to understanding PTSD.

Memory and coping with stress: the relationship between cognitive-emotional distinctiveness, memory valence, and distress.

Cognitive-emotional distinctiveness (CED), the extent to which an individual separates emotions from an event in the cognitive representation of the event, was explored in four studies. CED was measured using a modified multidimensional scaling procedure. The first study found that lower levels of CED in memories of the September 11 terrorist attacks predicted greater frequency of intrusive thoughts about the attacks. The second study revealed that CED levels are higher in negative events, in comparison to positive events and that low CED levels in emotionally intense negative events are associated with a pattern of greater event-related distress. The third study replicated the findings from the previous study when examining CED levels in participants' memories of the 2004 Presidential election. The fourth study revealed that low CED in emotionally intense negative events is associated with worse mental health. We argue that CED is an adaptive and healthy coping feature of stressful memories.

Memory in posttraumatic stress disorder: properties of voluntary and involuntary, traumatic and nontraumatic autobiographical memories in people with and without posttraumatic stress disorder symptoms.

One hundred fifteen undergraduates rated 15 word-cued memories and their 3 most negatively stressful, 3 most positive, and 7 most important events and completed tests of personality and depression. Eighty-nine also recorded involuntary memories online for 1 week. In the first 3-way comparisons needed to test existing theories, comparisons were made of memories of stressful events versus control events and involuntary versus voluntary memories in people high versus low in posttraumatic stress disorder (PTSD) symptom severity. For all participants, stressful memories had more emotional intensity, more frequent voluntary and involuntary retrieval, but not more fragmentation. For all memories, participants with greater PTSD symptom severity showed the same differences. Involuntary memories had more emotional intensity and less centrality to the life story than voluntary memories. Meeting the diagnostic criteria for traumatic events had no effect, but the emotional responses to events did. In 533 undergraduates, correlations among measures were replicated and the Negative Intensity factor of the Affect Intensity Measure correlated with PTSD symptom severity. No special trauma mechanisms were needed to account for the results, which are summarized by the autobiographical memory theory of PTSD.

Flashbulb memories and posttraumatic stress reactions across the life span: age-related effects of the German occupation of Denmark during World War II.

A representative sample of older Danes were interviewed about experiences from the German occupation of Denmark in World War II. The number of participants with flashbulb memories for the German invasion (1940) and capitulation (1945) increased with participants' age at the time of the events up to age 8. Among participants under 8 years at the time of their most traumatic event, age at the time correlated positively with the current level of posttraumatic stress reactions and the vividness of stressful memories and their centrality to life story and identity. These findings were replicated in Study 2 for self-nominated stressful events sampled from the entire life span using a representative sample of Danes born after 1945. The results are discussed in relation to posttraumatic stress disorder and childhood amnesia.

The centrality of event scale: a measure of integrating a trauma into one's identity and its relation to post-traumatic stress disorder symptoms.

We introduce a new scale that measures how central an event is to a person's identity and life story. For the most stressful or traumatic event in a person's life, the full 20-item Centrality of Event Scale (CES) and the short 7-item scale are reliable (alpha's of .94 and .88, respectively) in a sample of 707 undergraduates. The scale correlates .38 with PTSD symptom severity and .23 with depression. The present findings are discussed in relation to previous work on individual differences related to PTSD symptoms. Possible connections between the CES and measures of maladaptive attributions and rumination are considered along with suggestions for future research.

Thermodynamic and dynamic contributions to future changes in regional precipitation variance: focus on the Southeastern United States

© 2014, Springer-Verlag Berlin Heidelberg.The frequency and severity of extreme events are tightly associated with the variance of precipitation. As climate warms, the acceleration in hydrological cycle is likely to enhance the variance of precipitation across the globe. However, due to the lack of an effective analysis method, the mechanisms responsible for the changes of precipitation variance are poorly understood, especially on regional scales. Our study fills this gap by formulating a variance partition algorithm, which explicitly quantifies the contributions of atmospheric thermodynamics (specific humidity) and dynamics (wind) to the changes in regional-scale precipitation variance. Taking Southeastern (SE) United States (US) summer precipitation as an example, the algorithm is applied to the simulations of current and future climate by phase 5 of Coupled Model Intercomparison Project (CMIP5) models. The analysis suggests that compared to observations, most CMIP5 models (~60 %) tend to underestimate the summer precipitation variance over the SE US during the 1950–1999, primarily due to the errors in the modeled dynamic processes (i.e. large-scale circulation). Among the 18 CMIP5 models analyzed in this study, six of them reasonably simulate SE US summer precipitation variance in the twentieth century and the underlying physical processes; these models are thus applied for mechanistic study of future changes in SE US summer precipitation variance. In the future, the six models collectively project an intensification of SE US summer precipitation variance, resulting from the combined effects of atmospheric thermodynamics and dynamics. Between them, the latter plays a more important role. Specifically, thermodynamics results in more frequent and intensified wet summers, but does not contribute to the projected increase in the frequency and intensity of dry summers. In contrast, atmospheric dynamics explains the projected enhancement in both wet and dry summers, indicating its importance in understanding future climate change over the SE US. The results suggest that the intensified SE US summer precipitation variance is not a purely thermodynamic response to greenhouse gases forcing, and cannot be explained without the contribution of atmospheric dynamics. Our analysis provides important insights to understand the mechanisms of SE US summer precipitation variance change. The algorithm formulated in this study can be easily applied to other regions and seasons to systematically explore the mechanisms responsible for the changes in precipitation extremes in a warming climate.

Exploring Mechanisms of Bacterial Adaptation to Seasonal Temperature Change

This research examines three potential mechanisms by which bacteria can adapt to different temperatures: changes in strain-level population structure, gene regulation and particle colonization. For the first two mechanisms, I utilize bacterial strains from the Vibrionaceae family due to their ease of culturability, ubiquity in coastal environments and status as a model system for marine bacteria. I first examine vibrio seasonal dynamics in temperate, coastal water and compare the thermal performance of strains that occupy different thermal environments. Our results suggest that there are tradeoffs in adaptation to specific temperatures and that thermal specialization can occur at a very fine phylogenetic scale. The observed thermal specialization over relatively short evolutionary time-scales indicates that few genes or cellular processes may limit expansion to a different thermal niche. I then compare the genomic and transcriptional changes associated with thermal adaptation in closely-related vibrio strains under heat and cold stress. The two vibrio strains have very similar genomes and overall exhibit similar transcriptional profiles in response to temperature stress but their temperature preferences are determined by differential transcriptional responses in shared genes as well as temperature-dependent regulation of unique genes. Finally, I investigate the temporal dynamics of particle-attached and free-living bacterial community in coastal seawater and find that microhabitats exert a stronger forcing on microbial communities than environmental variability, suggesting that particle-attachment could buffer the impacts of environmental changes and particle-associated communities likely respond to the presence of distinct eukaryotes rather than commonly-measured environmental parameters. Integrating these results will offer new perspectives on the mechanisms by which bacteria respond to seasonal temperature changes as well as potential adaptations to climate change-driven warming of the surface oceans.

Essays on the Dynamic Decisions of Homeowners and Retailers

Urban problems have several features that make them inherently dynamic. Large transaction costs all but guarantee that homeowners will do their best to consider how a neighborhood might change before buying a house. Similarly, stores face large sunk costs when opening, and want to be sure that their investment will pay off in the long run. In line with those concerns, different areas of Economics have made recent advances in modeling those questions within a dynamic framework. This dissertation contributes to those efforts.

Chapter 2 discusses how to model an agent’s location decision when the agent must learn about an exogenous amenity that may be changing over time. The model is applied to estimating the marginal willingness to pay to avoid crime, in which agents are learning about the crime rate in a neighborhood, and the crime rate can change in predictable (Markovian) ways.

Chapters 3 and 4 concentrate on location decision problems when there are externalities between decision makers. Chapter 3 focuses on the decision of business owners to open a store, when its demand is a function of other nearby stores, either through competition, or through spillovers on foot traffic. It uses a dynamic model in continuous time to model agents’ decisions. A particular challenge is isolating the contribution of spillovers from the contribution of other unobserved neighborhood attributes that could also lead to agglomeration. A key contribution of this chapter is showing how we can use information on storefront ownership to help separately identify spillovers.

Finally, chapter 4 focuses on a class of models in which families prefer to live

close to similar neighbors. This chapter provides the first simulation of such a model in which agents are forward looking, and shows that this leads to more segregation than it would have been observed with myopic agents, which is the standard in this literature. The chapter also discusses several extensions of the model that can be used to investigate relevant questions such as the arrival of a large contingent high skilled tech workers in San Francisco, the immigration of hispanic families to several southern American cities, large changes in local amenities, such as the construction of magnet schools or metro stations, and the flight of wealthy residents from cities in the Rust belt, such as Detroit.