Neuronal Allocation to a Hippocampal Engram Park, Sungmo; Kramer, Emily E; Mercaldo, Valentina ...
Neuropsychopharmacology (New York, N.Y.),
12/2016, Letnik:
41, Številka:
13
Journal Article
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The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that ...recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation.
Estimates of missense error rates (misreading) during protein synthesis vary from 10(-3) to 10(-4) per codon. The experiments reporting these rates have measured several distinct errors using several ...methods and reporter systems. Variation in reported rates may reflect real differences in rates among the errors tested or in sensitivity of the reporter systems. To develop a more accurate understanding of the range of error rates, we developed a system to quantify the frequency of every possible misreading error at a defined codon in Escherichia coli. This system uses an essential lysine in the active site of firefly luciferase. Mutations in Lys529 result in up to a 1600-fold reduction in activity, but the phenotype varies with amino acid. We hypothesized that residual activity of some of the mutant genes might result from misreading of the mutant codons by tRNA(Lys) (UUUU), the cognate tRNA for the lysine codons, AAA and AAG. Our data validate this hypothesis and reveal details about relative missense error rates of near-cognate codons. The error rates in E. coli do, in fact, vary widely. One source of variation is the effect of competition by cognate tRNAs for the mutant codons; higher error frequencies result from lower competition from low-abundance tRNAs. We also used the system to study the effect of ribosomal protein mutations known to affect error rates and the effect of error-inducing antibiotics, finding that they affect misreading on only a subset of near-cognate codons and that their effect may be less general than previously thought.
Abstract
Background
As COVID-19 continues to spread globally, it is important to understand psychological factors that may influence compliance with social distancing.
Purpose
The present study ...examined whether Theory of Planned Behavior (TPB) constructs were associated with social distancing, with a focus on exploring moderators of the intention–behavior relationship.
Methods
Using a longitudinal design, U.S. adults (N = 507) self-reported TPB constructs and social distancing behavior at baseline and 3 months later. Participants were from 48 U.S. States and the District of Columbia and were on average 50.39 years old (SD = 15.32, range = 18–80). The majority were Non-Hispanic White (71.6%), had a bachelor’s degree or higher (55.3%), and resided in suburban areas (55.8%).
Results
While positive attitudes toward social distancing increased over time (p = .002), subjective norms weakened (p < .001) and perceived behavioral control (PBC) remained stable (p = .22). Interestingly, despite an increase in intentions from baseline to follow-up (p < .001), there was a significant decrease in social distancing behavior over time (p < .001). Consistent with the TPB, baseline attitudes (p < .001), subjective norms (p < .001), and PBC (p < .001) for social distancing were all associated with baseline intentions to social distance. In turn, baseline intentions were significantly associated with social distancing behavior at follow-up (p < .001). Younger adults (p < .001) and non-White participants (p = .002) displayed a greater intention–behavior gap relative to older and White participants. In contrast, participants with more stable intentions over time displayed a stronger intention–behavior relationship (p < .001).
Conclusions
Targeting individuals’ attitudes, norms, and PBC may effectively promote protective behaviors intended to mitigate the spread of COVID-19 and similar viral outbreaks. Future research should examine effective strategies for translating social distancing intentions into actions.
Social distancing attitudes, norms, perceived behavioral control, and intentions were associated with social distancing behavior at 3-month follow-up. Racial minorities and younger adults displayed larger intention-behavior gaps.
Objective
Examine the association between insomnia symptom severity and suicidal ideation (SI), after adjusting for clinical comorbidity in veterans meeting diagnostic criteria for insomnia disorder.
...Methods
Secondary data analyses of psychometrically validated baseline assessments of depression, posttraumatic stress disorder (PTSD), and anxiety symptoms from two online insomnia intervention randomized clinical trials (n = 232; n = 80) were conducted. Multiple linear regression was used to determine the association between insomnia symptom severity and SI, after controlling for clinical comorbidity and demographics.
Results
Insomnia symptom severity was significantly correlated with comorbid depression, PTSD, and anxiety symptoms in both cohorts and significantly correlated with SI in one. After controlling for demographics and clinical comorbidity, insomnia symptom severity was not significantly associated with SI in linear regression models.
Conclusion
Findings extend insomnia‐suicide research by providing evidence that insomnia symptom severity may not confer a unique risk for SI above comorbid mental health symptoms in veterans meeting diagnostic criteria for insomnia disorder.
In eukaryotes, transfer RNAs (tRNAs) are transcribed in the nucleus yet function in the cytoplasm; thus, tRNA movement within the cell was believed to be unidirectional—from the nucleus to the ...cytoplasm. It is now known that mature tRNAs also move in a retrograde direction from the cytoplasm to the nucleus via retrograde tRNA nuclear import, a process that is conserved from yeast to vertebrates. The biological significance of this tRNA nuclear import is not entirely clear. We hypothesized that retrograde tRNA nuclear import might function in proofreading tRNAs to ensure that only proper tRNAs reside in the cytoplasm and interact with the translational machinery. Here we identify two major types of aberrant tRNAs in yeast: a 5′, 3′ end-extended, spliced tRNA and hypomodified tRNAs. We show that both types of aberrant tRNAs accumulate in mutant cells that are defective in tRNA nuclear traffic, suggesting that they are normally imported into the nucleus and are repaired or degraded. The retrograde pathway functions in parallel with the cytoplasmic rapid tRNA decay pathway previously demonstrated to monitor tRNA quality, and cells are not viable if they lack both pathways. Our data support the hypothesis that the retrograde process provides a newly discovered level of tRNA quality control as a pathway that monitors both end processing of pre-tRNAs and the modification state of mature tRNAs.
Background
While the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator use has improved daily life and long‐term prognosis of CF for many with approved CFTR mutations, ...approximately 10% of people with CF (pwCF) have only symptomatic treatments available.
Methods
Between June 10 and July 1, 2021, Emily's Entourage distributed a 38‐question anonymous survey targeted at pwCF not benefitting from approved modulators via social media and email to pwCF and CF advocacy groups in and outside the United States regarding health status, impact of CF, unmet needs, and clinical research interest.
Results
There were 431 survey respondents representing pwCF on five continents. The majority of pwCF had moderate lung disease (50.3%). Ineligibility based on CFTR mutation (64.1%) was the most frequently reported reason pwCF were not on modulators. PwCF reported the most impacted aspects of life were mental (66.7%) and physical (40.7%) health. Financial concerns and feelings of isolation were commonly reported. Witnessing improvements for peers with access to modulators was both uplifting and disheartening. The majority of pwCF would be interested in participating in future clinical research (77.6%), although some living outside of the United States cited lack of opportunity to participate in clinical trials as a barrier.
Conclusions
PwCF who are ineligible, intolerant, or lack access to modulators have a high burden of disease impacting their physical and mental health. Although most are happy for those who are benefiting from modulators, they are eager for the opportunity to experience similar improvements for themselves, and willing to participate in clinical trials of new therapies.
Abstract
Background
Non-Hispanic Black Americans experience the highest, and most rapidly increasing, rates of obesity. Despite evidence that this is at least somewhat related to poor diet quality, ...we have yet to identify effective interventions for improving diet quality long-term. Restrictive diets can be ineffective and often harmful. In contrast, there is a well-established connection between home cooking and lower body mass index, better diet quality, and improved health.
Purpose
The present study applied the Theory of Planned Behavior (TPB) to examine the effect of an intervention delivering cooking instruction, rather than nutrition information, on beliefs, attitudes, and behaviors pertaining to diet quality and cooking among Black adults in the USA.
Methods
An online sample of Black Americans (N = 147), ages 18–76 (M = 30.69, SD = 10.42) were recruited via Prolific and randomized to view either a cooking tutorial video or a “standard of care” control webpage followed by either an implementation intentions (II) writing activity or a “freestyle” control writing activity. Cognitions and behavior related to healthy eating and cooking were measured at baseline, post-intervention, and 1-week follow-up.
Results
Results of mixed-effects modeling indicated that participants randomized to the video condition reported significantly greater post-intervention intentions to cook (p < .001), which positively correlated with cooking behavior over the subsequent week (p < .01). There was no effect of the II intervention on subsequent-week behavior (ps > .413). Importantly, 75% (n = 105) indicated experiencing food insecurity at the time of data collection.
Conclusions
These results highlight a promising pathway for improving nutrition and diet-related health outcomes among Black Americans while highlighting that any intervention must account for food insecurity in this population.
Black American adults randomized to view a brief video cooking tutorial (vs. nutrition information text control) reported greater post-intervention intentions to cook, which further correlated with cooking behavior over the subsequent week. These findings suggest a potential cognitive pathway, and practical application, by which sustainable, culturally informed, non-restrictive dietary changes may be adopted.
Lay Summary
Non-Hispanic Black Americans experience the highest, and most rapidly increasing, rates of obesity and diseases attributed at least in part to poor diet quality. In contrast to restrictive diets, which can be ineffective and often harmful, there is a well-established connection between home cooking and lower body mass index, better diet quality, and improved health. The present study examined the effect of an intervention delivering cooking instruction, rather than nutrition information, on beliefs, attitudes, and behaviors pertaining to diet quality and cooking among Black adults in the USA. An online sample of Black Americans (N = 147) was randomized to view either a cooking tutorial video or a “standard of care” control webpage followed by either an implementation intentions writing activity or a “freestyle” control writing activity. Participants in the video condition reported significantly greater post-intervention intentions to cook, which positively correlated with cooking behavior over the subsequent week. There was no observed effect of the writing activity on behavior. Importantly, 75% (n = 105) indicated experiencing food insecurity at the time of data collection. These results highlight a promising pathway for improving nutrition and diet-related health outcomes among Black Americans while highlighting that any intervention must account for food insecurity in this population.
Abstract Hyperactive comet activity typically becomes evident beyond the frost line (∼3–4 au) where it becomes too cold for water-ice to sublimate. If carbon monoxide (CO) and carbon dioxide (CO 2 ) ...are the species that drive activity at sufficiently large distances, then detailed studies on the production rates of these species are extremely valuable to examine the formation of the solar system because these two species (beyond water) are next culpable for driving cometary activity. The NEOWISE reactivated mission operates at two imaging bandpasses, W 1 and W 2 at 3.4 μ m and 4.6 μ m, respectively, with the W 2 channel being fully capable of detecting CO and CO 2 at 4.67 μ m and 4.23 μ m in the same bandpass. It is extremely difficult to study CO 2 from the ground due to contamination in Earth’s atmosphere. We present our W 1 and W 2 photometry, dust measurements, and findings for comets C/2014 B1 (Schwartz), C/2017 K2 (Pan-STARRS), and C/2010 U3 (Boattini), hereafter, B1, K2, and U3, respectively. Our results assess CO and CO 2 gas production rates observed by NEOWISE. We have determined: (1) comets B1 and K2 have CO 2 and CO gas production rates of ∼10 27 and ∼10 29 molecules s −1 , respectively, if one assumes the excess emission is attributed to either all CO or all CO 2; (2) B1 and K2 are considered hyperactive in that their measured Af ρ dust production values are on the order of ≳10 3 cm; and (3) the CO and CO 2 production rates do not always follow the expected convention of increasing with decreased heliocentric distance, while B1 and K2 exhibit noticeable dust activity on their inbound leg orbits.
Despite strong evidence linking anti-fat bias directed toward others with markers of self-directed anti-fat bias, there is a dearth of theory-based research examining the cognitive pathways ...underlying this relationship, and existing bias-reduction intervention efforts have thus far been conducted with exclusive focus on one domain or the other. Cognitive dissonance (CD)-based interventions have been identified as viable for reducing anti-fat bias directed toward the self and others. However, no study has yet examined whether the effects of these domain-specific interventions (e.g., anti-fat bias towards the self) extend to anti-fat bias in the non-targeted domain (e.g., anti-fat bias towards others). The present study aimed to address these gaps in the literature by comparing effects of brief CD-based interventions targeting anti-fat bias directed toward either the self or others on measures of anti-fat bias. Participants (N = 197, female-identifying undergraduates) were randomized to a writing activity prompting cognitive dissonance about either self-directed or other-directed anti-fat bias, or a bias-consistent control condition. Results indicated that participants in the CD intervention conditions showed significantly greater reductions in both explicit self- and other-directed anti-fat biases than those in the control condition, but results did not significantly differ across CD conditions. This supports the potential utility of interventions simultaneously targeting anti-fat bias in both domains and provides insight into the cognitive pathways underlying these related forms of bias.
•United States military personnel and Veterans are at increased risk for suicide.•Acquired capability for suicide (AC) may be a mechanism that explains this risk.•We systematically reviewed the ...literature to determine factors associated with AC.•Results yielded an empirical base characterized by a high risk of bias.•AC construct assessment and refinement are suggested as future research targets.
Military personnel and Veterans are at increased risk for suicide. Theoretical and conceptual arguments have suggested that elevated levels of acquired capability (AC) could be an explanatory factor accounting for this increased risk. However, empirical research utilizing the Acquired Capability for Suicide Scale (ACSS) in military populations has yielded mixed findings.
To better ascertain what factors are associated with AC, and whether methodological limitations may be contributing to mixed findings, a systematic review was conducted.
A total of 31 articles utilized the ACSS to examine factors associated with AC, including combat history, in United States (U.S.) military personnel and Veterans. Nearly all studies (96.8%) were rated high risk of bias. Use of the ACSS varied, with seven different iterations utilized. Nearly all studies examined correlations between the ACSS and sample characteristics, mental health and clinical factors, Interpersonal Theory of Suicide constructs, and/or suicide-specific variables. Results of higher-level analyses, dominated by cross-sectional designs, often contradicted correlational findings, with inconsistent findings across studies.
Included studies were non-representative of all U.S. military and Veteran populations and may only generalize to these populations.
Due to the high risk of bias, inconsistent use of the ACSS, lack of sample heterogeneity, and variability in factors examined, interpretation of current ACSS empirical data is cautioned. Suggestions for future research, contextualized by these limitations, are discussed.