The Role of mRNA Translation in the Regulation of Ribosome Trafficking to the Endoplasmic Reticulum

The goal of this research is to identify the trafficking patterns that direct ribosomes to the endoplasmic reticulum (ER). It is widely believed that the SRP pathway is the only mechanism that cells use to localize mRNA and ribosomes to the ER, but this has been found not to be a sufficient explanation for the patterns of RNA localization in cells, namely that non-signal sequence-containing mRNA are translated on the ER and that ribosomes retain their membrane association after translation termination. First, a summary of the history of the field is presented to provide context for the key, unanswered questions in the field. Then, experiments employing [32Pi] pulse-chase labeling of HeLa cells over a time course to follow nascent ribosome trafficking are presented. The purpose of the cell labeling was to track rRNA processing and assembly into nascent ribosomes, followed by their export into the cytoplasm and recruitment into active polysomes. A detergent-based cell fractionation procedure was also utilized to separate the cytosol and ER compartments in order to observe ribosomes on their path as they exit the nucleus and either localize to the ER or cytosolic cellular compartment. Through this method, it was seen that ribosomes appear in both compartments at the same time, suggesting a mechanism may be occurring in addition to SRP-dependent ribosome trafficking. This research provides an understanding toward a mechanism that is not currently known, but will one day more fully explain the patterns of ribosomal localization.

Involuntary Memories and Dissociative Amnesia: Assessing Key Assumptions in PTSD Research.

Autobiographical memories of trauma victims are often described as disturbed in two ways. First, the trauma is frequently re-experienced in the form of involuntary, intrusive recollections. Second, the trauma is difficult to recall voluntarily (strategically); important parts may be totally or partially inaccessible-a feature known as dissociative amnesia. These characteristics are often mentioned by PTSD researchers and are included as PTSD symptoms in the DSM-IV-TR (American Psychiatric Association, 2000). In contrast, we show that both involuntary and voluntary recall are enhanced by emotional stress during encoding. We also show that the PTSD symptom in the diagnosis addressing dissociative amnesia, trouble remembering important aspects of the trauma is less well correlated with the remaining PTSD symptoms than the conceptual reversal of having trouble forgetting important aspects of the trauma. Our findings contradict key assumptions that have shaped PTSD research over the last 40 years.

Functional neuroimaging of emotionally intense autobiographical memories in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) affects regions that support autobiographical memory (AM) retrieval, such as the hippocampus, amygdala and ventral medial prefrontal cortex (PFC). However, it is not well understood how PTSD may impact the neural mechanisms of memory retrieval for the personal past. We used a generic cue method combined with parametric modulation analysis and functional MRI (fMRI) to investigate the neural mechanisms affected by PTSD symptoms during the retrieval of a large sample of emotionally intense AMs. There were three main results. First, the PTSD group showed greater recruitment of the amygdala/hippocampus during the construction of negative versus positive emotionally intense AMs, when compared to controls. Second, across both the construction and elaboration phases of retrieval the PTSD group showed greater recruitment of the ventral medial PFC for negatively intense memories, but less recruitment for positively intense memories. Third, the PTSD group showed greater functional coupling between the ventral medial PFC and the amygdala for negatively intense memories, but less coupling for positively intense memories. In sum, the fMRI data suggest that there was greater recruitment and coupling of emotional brain regions during the retrieval of negatively intense AMs in the PTSD group when compared to controls.

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.

Autobiographical Memories for Very Negative Events: The Effects of Thinking about and Rating Memories.

In three related experiments, 250 participants rated properties of their autobiographical memory of a very negative event before and after writing about either their deepest thoughts and emotions of the event or a control topic. Levels of emotional intensity of the event, distress associated with the event, intrusive symptoms, and other phenomenological memory properties decreased over the course of the experiment, but did not differ by writing condition. We argue that the act of answering our extensive questions about a very negative event led to the decrease, thereby masking the effects of expressive writing. To show that the changes could not be explained by the mere passage of time, we replicated our findings in a fourth experiment in which all 208 participants nominated a very negative event, but only half the participants rated properties of their memory in the first session. Implications for reducing the effects of negative autobiographical memories are discussed.

Component Neural Systems for the Creation of Emotional Memories during Free Viewing of a Complex, Real-World Event.

To investigate the neural systems that contribute to the formation of complex, self-relevant emotional memories, dedicated fans of rival college basketball teams watched a competitive game while undergoing functional magnetic resonance imaging (fMRI). During a subsequent recognition memory task, participants were shown video clips depicting plays of the game, stemming either from previously-viewed game segments (targets) or from non-viewed portions of the same game (foils). After an old-new judgment, participants provided emotional valence and intensity ratings of the clips. A data driven approach was first used to decompose the fMRI signal acquired during free viewing of the game into spatially independent components. Correlations were then calculated between the identified components and post-scanning emotion ratings for successfully encoded targets. Two components were correlated with intensity ratings, including temporal lobe regions implicated in memory and emotional functions, such as the hippocampus and amygdala, as well as a midline fronto-cingulo-parietal network implicated in social cognition and self-relevant processing. These data were supported by a general linear model analysis, which revealed additional valence effects in fronto-striatal-insular regions when plays were divided into positive and negative events according to the fan's perspective. Overall, these findings contribute to our understanding of how emotional factors impact distributed neural systems to successfully encode dynamic, personally-relevant event sequences.

Mental hoop diaries: emotional memories of a college basketball game in rival fans.

The rivalry between the men's basketball teams of Duke University and the University of North Carolina-Chapel Hill (UNC) is one of the most storied traditions in college sports. A subculture of students at each university form social bonds with fellow fans, develop expertise in college basketball rules, team statistics, and individual players, and self-identify as a member of a fan group. The present study capitalized on the high personal investment of these fans and the strong affective tenor of a Duke-UNC basketball game to examine the neural correlates of emotional memory retrieval for a complex sporting event. Male fans watched a competitive, archived game in a social setting. During a subsequent functional magnetic resonance imaging session, participants viewed video clips depicting individual plays of the game that ended with the ball being released toward the basket. For each play, participants recalled whether or not the shot went into the basket. Hemodynamic signal changes time locked to correct memory decisions were analyzed as a function of emotional intensity and valence, according to the fan's perspective. Results showed intensity-modulated retrieval activity in midline cortical structures, sensorimotor cortex, the striatum, and the medial temporal lobe, including the amygdala. Positively valent memories specifically recruited processing in dorsal frontoparietal regions, and additional activity in the insula and medial temporal lobe for positively valent shots recalled with high confidence. This novel paradigm reveals how brain regions implicated in emotion, memory retrieval, visuomotor imagery, and social cognition contribute to the recollection of specific plays in the mind of a sports fan.

People who expect to enter psychotherapy are prone to believing that they have forgotten memories of childhood trauma and abuse.

We asked 1004 undergraduates to estimate both the probability that they would enter therapy and the probability that they experienced but could not remember incidents of potentially life-threatening childhood traumas or physical and sexual abuse. We found a linear relation between the expectation of entering therapy and the belief that one had, but cannot now remember, childhood trauma and abuse. Thus individuals who are prone to seek psychotherapy are also prone to accept a suggested memory of childhood trauma or abuse as fitting their expectations. In multiple regressions predicting the probability of forgotten memories of childhood traumas and abuse, the expectation of entering therapy remained as a substantial predictor when self-report measures of mood, anxiety, post-traumatic stress disorder symptom severity, and trauma exposure were included.

A comparison of dimensional models of emotion: evidence from emotions, prototypical events, autobiographical memories, and words.

The intensity and valence of 30 emotion terms, 30 events typical of those emotions, and 30 autobiographical memories cued by those emotions were each rated by different groups of 40 undergraduates. A vector model gave a consistently better account of the data than a circumplex model, both overall and in the absence of high-intensity, neutral valence stimuli. The Positive Activation - Negative Activation (PANA) model could be tested at high levels of activation, where it is identical to the vector model. The results replicated when ratings of arousal were used instead of ratings of intensity for the events and autobiographical memories. A reanalysis of word norms gave further support for the vector and PANA models by demonstrating that neutral valence, high-arousal ratings resulted from the averaging of individual positive and negative valence ratings. Thus, compared to a circumplex model, vector and PANA models provided overall better fits.

The frequency of voluntary and involuntary autobiographical memories across the life span.

In the present study, ratings of the memory of an important event from the previous week on the frequency of voluntary and involuntary retrieval, belief in its accuracy, visual imagery, auditory imagery, setting, emotional intensity, valence, narrative coherence, and centrality to the life story were obtained from 988 adults whose ages ranged from 15 to over 90. Another 992 adults provided the same ratings for a memory from their confirmation day, when they were at about age 14. The frequencies of involuntary and voluntary retrieval were similar. Both frequencies were predicted by emotional intensity and centrality to the life story. The results from the present study-which is the first to measure the frequency of voluntary and involuntary retrieval for the same events-are counter to both cognitive and clinical theories, which consistently claim that involuntary memories are infrequent as compared with voluntary memories. Age and gender differences are noted.

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.

The reappearance hypothesis revisited: recurrent involuntary memories after traumatic events and in everyday life.

Recurrent involuntary memories are autobiographical memories that come to mind with no preceding retrieval attempt and that are subjectively experienced as being repetitive. Clinically, they are classified as a symptom of posttraumatic stress disorder. The present work is the first to systematically examine recurrent involuntary memories outside clinical settings. Study 1 examines recurrent involuntary memories among survivors of the tsunami catastrophe in Southeast Asia in 2004. Study 2 examines recurrent involuntary memories in a large general population. Study 3 examines whether the contents of recurrent involuntary memories recorded in a diary study are duplicates of, or differ from, one another. We show that recurrent involuntary memories are not limited to clinical populations or to emotionally negative experiences; that they typically do not come to mind in a fixed and unchangeable form; and that they show the same pattern regarding accessibility as do autobiographical memories in general. We argue that recurrent involuntary memories after traumas and in everyday life can be explained in terms of general and well-established mechanisms of autobiographical memory.

People believe it is plausible to have forgotten memories of childhood sexual abuse.

Pezdek, Blandon-Gitlin, and Gabbay (2006) found that perceptions of the plausibility of events increase the likelihood that imagination may induce false memories of those events. Using a survey conducted by Gallup, we asked a large sample of the general population how plausible it would be for a person with longstanding emotional problems and a need for psychotherapy to be a victim of childhood sexual abuse, even though the person could not remember the abuse. Only 18% indicated that it was implausible or very implausible, whereas 67% indicated that such an occurrence was either plausible or very plausible. Combined with Pezdek et al.s' findings, and counter to their conclusions, our findings imply that there is a substantial danger of inducing false memories of childhood sexual abuse through imagination in psychotherapy.

When a trauma becomes a key to identity: Enhanced integration of trauma memories predicts posttraumatic stress disorder symptoms

The Centrality of Event Scale (CES) measures the extent to which a traumatic memory forms a central component of personnal identity, a turning point in the life story and a reference point for everyday inferences. In two studies, we show that the CES is positively correlated with severity of PTSD symptoms, even when controlling for measures of anxiety, depression, dissociation and self-consciousness. The findings contradict the widespread view that poor integration of the traumatic memory into one's life story is a main cause of PTSD symptoms. Instead, enhanced integration appears to be a key issue. Copyright © 2006 John Wiley & Sons, Ltd.

Disputes over memory ownership: What memories are disputed?

The ownership of memories is sometimes disputed, particularly by twins. Examination of 77 disputed memories, 71 provided by twins, showed that most of the remembered events are negative and that the disputants appear to be self-serving. They claim for themselves memories for achievements and suffered misfortunes but are more likely to give away memories of personal wrongdoing. The research suggests that some of the memories in which we play a leading role might in fact have been the experiences of others.