Cryptic genetic variation enhances primate L1 retrotransposon survival by enlarging the functional coiled coil sequence space of ORF1p.

Accounting for continual evolution of deleterious L1 retrotransposon families, which can contain hundreds to thousands of members remains a major issue in mammalian biology. L1 activity generated upwards of 40% of some mammalian genomes, including humans where they remain active, causing genetic defects and rearrangements. L1 encodes a coiled coil-containing protein that is essential for retrotransposition, and the emergence of novel primate L1 families has been correlated with episodes of extensive amino acid substitutions in the coiled coil. These results were interpreted as an adaptive response to maintain L1 activity, however its mechanism remained unknown. Although an adventitious mutation can inactivate coiled coil function, its effect could be buffered by epistatic interactions within the coiled coil, made more likely if the family contains a diverse set of coiled coil sequences-collectively referred to as the coiled coil sequence space. Amino acid substitutions that do not affect coiled coil function (i.e., its phenotype) could be "hidden" from (not subject to) purifying selection. The accumulation of such substitutions, often referred to as cryptic genetic variation, has been documented in various proteins. Here we report that this phenomenon was in effect during the latest episode of primate coiled coil evolution, which occurred 30-10 MYA during the emergence of primate L1Pa7-L1Pa3 families. First, we experimentally demonstrated that while coiled coil function (measured by retrotransposition) can be eliminated by single epistatic mutations, it nonetheless can also withstand extensive amino acid substitutions. Second, principal component and cluster analysis showed that the coiled coil sequence space of each of the L1Pa7-3 families was notably increased by the presence of distinct, coexisting coiled coil sequences. Thus, sampling related networks of functional sequences rather than traversing discrete adaptive states characterized the persistence L1 activity during this evolutionary event.

Selective forgetting of self-threatening statements: Mnemic neglect for dementia information in people with mild dementia.

OBJECTIVE: We tested whether people with dementia manifest selective forgetting for self-threatening information, the mnemic neglect effect (MNE). This selective forgetting is observed among healthy adults in the recall, but not the recognition, of self-threatening feedback. METHODS: Sixty-four statements about dementia were rated for their level of negativity by 280 staff and students at University of the West of England. The 12 statements rated as most negative and the 12 statements rated as least negative were then read to 62 people with dementia. Participants were randomized to 1 of 2 conditions with the statements referring either to self or to another person. High-negativity and self-referent statements had strong threat potential. Participants recalled the statements and then completed a recognition task, which consisted of the 24 previously read statements and 24 new statements. RESULTS: Participants manifested the MNE: They recalled fewer high-negativity (compared with low-negativity) statements, but only when these referred to the self rather than another person. This pattern occurred independently of levels of depression or anxiety. Participants also made more self-protective intrusion errors when the statements referred to the self than another person. Participants did not differ in their recognition of statements. CONCLUSION: The MNE occurs among people with dementia. The selective forgetting of highly negative, self-referent statements serves to protect the self against the threat that dementia represents. Given the similarities between the MNE and the clinical phenomenon of repression, the findings may mark psychological processes that are implicated in the acceptance (or lack thereof) of a dementia diagnosis.

Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement.

L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ~ 100 million years (Myr) of activity in primates. L1 replicates in germ line cells and early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2p, a reverse transcriptase that contains an endonuclease domain, and ORF1p, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has periodically undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors and speculate on how coiled coil entanglement could affect coiled coil evolution.

Fabrication of an optical fiber reflective notch coupler.

A method of fabricating a reflective notch coupler in an optical fiber has been developed. The coupler consists of a 45° microprism that penetrates into the core of a multimode optical fiber. One face, at 90° to the fiber axis, is nonreflective, and one face, at 45° to the fiber axis, is reflective. Our method of fabricating a notch and selectively mirroring only the 45° face is low-cost, precise, and easily scalable. The coupler allows near-100% coupling of light into an optical fiber from the side, while allowing coupling of any desired fraction of light out from the core at a 90° angle on the opposite side of the fiber.

The organisation and content of trauma memories in survivors of road traffic accidents.

We investigated the trauma narratives of 131 road traffic accident survivors prospectively, at 1 week, 6 weeks, and 3 months post-trauma. At 1 and 6 weeks, narratives of survivors with acute stress disorder (ASD) or post-traumatic stress disorder (PTSD) were less coherent and included more dissociation content. By 3 months, their narratives also contained more repetition, more non-consecutive chunks, and more sensory words. Traumatic brain injury was associated with a separate characteristic, confusion, at all three time points. Three aspects of narrative organisation at 1 week--repetition, non-consecutive chunks, and coherence--predicted PTSD severity at 3 months after controlling for initial symptoms. The results suggest both a strong concurrent and predictive relationship between narrative disorganisation and ASD/PTSD but that as people recover from ASD, their narratives do not necessarily become less disorganised.

Sleep and posttraumatic stress disorder: a review.

Research seeking to establish the relationship between sleep and posttraumatic stress disorder (PTSD) is in its infancy. An empirically supported theory of the relationship is yet to emerge. The aims of the present paper are threefold: to summarise the literature on the prevalence and treatment of sleep disturbance characteristic of acute stress disorder (ASD) and PTSD, to critically review this literature, and to draw together the disparate theoretical perspectives that have been proposed to account for the empirical findings. After a brief overview of normal human sleep, the literature specifying the relation between sleep disturbance and PTSD is summarized. This includes studies of the prevalence of sleep disturbance and nightmares, content of nightmares, abnormalities in rapid eye movement (REM) sleep, arousal threshold during sleep, body movement during sleep, and breathing-related sleep disorders. In addition, studies of the treatment of sleep disturbance in individuals with PTSD are reviewed. We conclude that the role of sleep in PTSD is complex, but that it is an important area for further elucidating the nature and treatment of PTSD. Areas for future research are specified. In particular, a priority is to improve the methodology of the research conducted.

Traumatic brain injury, dissociation, and posttraumatic stress disorder in road traffic accident survivors.

This study investigated the symptom profiles of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in participants who did and did not sustain traumatic brain injury (TBI), following a road traffic accident. The participants were assessed at three time points: as soon as possible posttrauma as well as at 6 weeks and 3 months posttrauma. At the first assessment, fewer participants from the TBI group recalled feeling fear and helplessness at the time of the trauma, fewer TBI participants reported recurrent intrusive thoughts and images, and more TBI participants reported dissociation since the trauma, relative to the non-TBI group. At the second assessment, fewer participants from the TBI group recalled feeling intense helplessness at the time of the trauma. Fewer TBI participants also reported reliving and physiological reactions on trauma reminders relative to the non-TBI group. At 3 months posttrauma, there was no difference in PTSD symptom profile between non-TBI and TBI groups. Our findings indicate that the presence of TBI is likely to influence the distribution of certain symptoms, but need not be a significant barrier to diagnosing ASD and PTSD.

Coexistence of posttraumatic stress disorder and traumatic brain injury: towards a resolution of the paradox.

The coexistence of posttraumatic stress disorder (PTSD) and traumatic head or brain injury (TBI) in the same individual has been proposed to be paradoxical. It has been argued that individuals who sustain a TBI and have no conscious memory of their trauma will not experience fear, helplessness and horror during the trauma, nor will they develop reexperiencing symptoms or establish the negative associations that underlie avoidance symptoms. However, single case reports and incidence studies suggest that PTSD can be diagnosed following TBI. We highlight critical issues in assessment, definitions, and research methods, and propose two possible resolutions of the paradox. One resolution focuses on ambiguity in the criteria for diagnosing PTSD. The other involves accepting that TBI patients do experience similar symptoms to other PTSD patients, but that there are crucial differences in symptom content.