ABSTRACT
The Penn Electrophysiology of Encoding and Retrieval Study (PEERS) aimed to characterize the behavioral and electrophysiological (EEG) correlates of memory encoding and retrieval in highly practiced individuals. Across five PEERS experiments, 300+ subjects contributed more than 7,000 memory testing sessions with recorded EEG data. Here we tell the story of PEERS: its genesis, evolution, major findings, and the lessons it taught us about taking a big scientific approach in studying memory and the human brain. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
ABSTRACT
While previous work has shown a positive relationship between cognitive performance and lifestyle factors in younger adults, evidence for this relationship among middle-aged and older adults has been mixed. The current study aimed to further test the relationship among physical activity, sleep quality, and memory performance in middle-aged and older adults, and to test whether this relationship holds up during the COVID-19 pandemic. Our results showed that physical activity was associated with better sleep quality and better working memory performance, and better sleep quality was associated with better working memory and self-perceptions of everyday memory abilities. Additionally, we found that the effects of physical activity on working memory were partially mediated by sleep quality. While these effects were small and only correlational in nature, they lend further support to the notion that sleep quality and physical activity are beneficial to memory later in life, even during a global pandemic.
ABSTRACT
Recent work has examined the interaction between space and time in memory search, but there is still limited understanding of this relationship. Here, we test the hypothesis that individuals can exert control over how time and space interact in response to subtle differences in task instructions. To test this hypothesis, we analyzed two experiments where participants completed two immediate free recall tasks, a verbal task involving words presented at a central location and a spatial task involving squares presented at different locations. Some participants were free to recall the words or locations spontaneously in any order they preferred. In contrast, another group was subtly biased toward temporal information by instructions to begin recall from the last presented item before recalling the remaining items in any order they wished. Replicating recent work, all conditions showed clear evidence that recall was organized along both the temporal and the spatial dimensions. Extending this work, we found that the subtle change in recall instructions increased the reliance on temporal information in the spatial recall task. Correlational analyses suggest that spatial and temporal information do not compete when participants search memory spontaneously. However, they do compete when instructions favor temporal information. These findings highlight that individuals can exert some cognitive control over how associative dimensions interact during memory search and emphasize the importance of incorporating such processes into theoretical models.
Subject(s)
Mental Recall , Space Perception , Humans , Mental Recall/physiology , Young Adult , Adult , Space Perception/physiology , Time Perception/physiology , Male , Female , Time Factors , Executive Function/physiology , Memory, Short-Term/physiologyABSTRACT
Recent events are easy to recall, but they also interfere with the recall of more distant, non-recent events. In many computational models, non-recent memories are recalled by using the context associated with those events as a cue. Some models, however, do little to explain how people initially activate non-recent contexts in the service of accurate recall. We addressed this limitation by evaluating two candidate mechanisms within the Context-Maintenance and Retrieval model. The first is a Backward-Walk mechanism that iteratively applies a generate/recognize process to covertly retrieve progressively less recent items. The second is a Post-Encoding Pre-Production Reinstatement (PEPPR) mechanism that formally implements a metacognitive control process that reinstates non-recent contexts prior to retrieval. Models including these mechanisms make divergent predictions about the dynamics of response production and monitoring when recalling non-recent items. Before producing non-recent items, Backward-Walk cues covert retrievals of several recent items, whereas PEPPR cues few, if any, covert retrievals of that sort. We tested these predictions using archival data from a dual-list externalized free recall paradigm that required subjects to report all items that came to mind while recalling from the non-recent list. Simulations showed that only the model including PEPPR accurately predicted covert recall patterns. That same model fit the behavioral data well. These findings suggest that self-initiated context reinstatement plays an important role in recall of non-recent memories and provides a formal model that uses a parsimonious non-hierarchical context representation of how such reinstatement might occur.
Subject(s)
Mental Recall , Metacognition , Humans , Mental Recall/physiology , CuesABSTRACT
Natural variability in menstrual cycle length, coupled with rapid changes in endometrial gene expression, makes it difficult to accurately define and compare different stages of the endometrial cycle. Here we develop and validate a method for precisely determining endometrial cycle stage based on global gene expression. Our 'molecular staging model' reveals significant and remarkably synchronised daily changes in expression for over 3400 endometrial genes throughout the cycle, with the most dramatic changes occurring during the secretory phase. Our study significantly extends existing data on the endometrial transcriptome, and for the first time enables identification of differentially expressed endometrial genes with increasing age and different ethnicities. It also allows reinterpretation of all endometrial RNA-seq and array data that has been published to date. Our molecular staging model will significantly advance understanding of endometrial-related disorders that affect nearly all women at some stage of their lives, such as heavy menstrual bleeding, endometriosis, adenomyosis, and recurrent implantation failure.
Subject(s)
Endometrium , Uterine Diseases , Female , Humans , Endometrium/metabolism , Menstrual Cycle/genetics , Menstrual Cycle/metabolism , Uterine Diseases/metabolism , Transcriptome , BiopsyABSTRACT
A key assumption of some leading memory theories is that information about the relative order of events is automatically encoded whenever memories are formed and automatically retrieved whenever events are remembered. This information is often used to guide memory search: Remembering one event tends to trigger the retrieval of other events previously experienced nearby in time (temporal contiguity effect). The retrieved context framework attributes this temporal contiguity effect to automatic encoding and retrieval processes, predicting temporal contiguity even in incidental encoding and implicit retrieval. There is strong evidence of temporal contiguity following incidental encoding, but does the prediction hold for implicit retrieval? In this experiment, we tested the framework's predictions for recall and repetition priming. Across 30 trials, undergraduates ([Formula: see text]) read a series of words aloud as they appeared onscreen. In each trial, two words were repeated (cue and target), initially separated by |lag[Formula: see text] 1, 2, or 5. On their second presentation, the cue word was presented first, immediately followed by the target word. We found a strong temporal contiguity effect in a surprise free recall test, replicating previous work with explicit retrieval. For implicit retrieval, we compared repetition priming (how quickly subjects began reading a word on its first versus second presentation) for cue and target words. Repeating a cue word enhanced repetition priming for its associated target word, and this effect varied with the initial lag between the cue and target. These results support theories that assume temporal information is encoded and retrieved automatically.
ABSTRACT
The transformation of experiences into meaningful events and memories is intertwined with the notion of time. Temporal perception can influence, and be influenced by, segmenting continuous experience into meaningful events. Episodic memories formed from these events become associated with temporal information as well. However, it is less clear how temporal perception contributes to structuring events and organizing memory: whether it plays a more active or passive role, and whether this temporal information is encoded initially during perception or influenced by retrieval processes. To address these questions, we examined how event segmentation influences temporal representations during initial perception and memory retrieval, without testing temporal information explicitly. Using a neural measure of temporal context extracted from scalp electroencephalography in human participants (N = 170), we found reduced temporal context similarity between studied items separated by an event boundary when compared to items from the same event. Furthermore, while participants freely recalled list items, neural activity reflected reinstatement of temporal context representations from the study phase, including temporal disruption. A computational model of episodic memory, the context maintenance and retrieval (CMR) model, predicted these results, and made novel predictions regarding the influence of temporal disruption on recall order. These findings implicate the impact of event structure on memory organization via temporal representations, underscoring the role of temporal information in event segmentation and episodic memory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Subject(s)
Memory, Episodic , Time Perception , Humans , Mental Recall , Electroencephalography/methodsABSTRACT
Memory tends to be better when items are processed for their meaning (deep processing) rather than their perceptual features (shallow processing). This levels of processing (LOP) effect is well-replicated and has been applied in many settings, but the mechanisms involved are still not well understood. The temporal contiguity effect (TCE), the finding that recalling one event often triggers recall of another event experienced nearby in time, also predicts memory performance. This effect has given rise to several competing theories with specific contiguity-generating mechanisms related to how items are processed. Therefore, studying how LOP and the TCE interact may shed light on the mechanisms underlying both effects. However, it is unknown how LOP and the TCE interact-various theories make differing predictions. In this preregistered study, we tested predictions of three theoretical explanations: accounts which assume temporal information is automatically encoded, accounts based on a trade-off between item and order information, and accounts which emphasize the importance of strategic control processes. Participants completed an immediate free recall task where they either engaged in deep processing, shallow processing, or no additional task while studying each word. Recall and the TCE were highest for no-task lists and greater for deep than shallow processing. Our results support theories which assume temporal associations are automatically encoded and those which emphasize strategic control processes. Both perspectives should be considered in theory development. These findings also suggest temporal information may contribute to better recall under deeper processing with implications for determining which situations benefit from deep processing.
Subject(s)
Memory, Short-Term , Mental Recall , Humans , TimeABSTRACT
The present study is the first to examine individual differences in long-term memory, arousal dysregulation, and intensity of attention within the same experiment. Participants (N = 106) completed 28 lists of an immediate free-recall task while their pupil diameter was recorded via an eye-tracker during the encoding period. Two main pupillary measures were extracted: intraindividual variability in pre-list pupil diameter and evoked pupillary responses during item encoding. Variability in pre-list pupil diameter served as a measure of arousal dysregulation, and evoked pupillary responses served as a measure of intensity of attention. Based on prior work, we hypothesized that there would be a positive association between intensity of attention and recall ability, and that there would be a negative association between arousal dysregulation and recall ability. Collectively these two measures accounted for 19% of interindividual variance in recall, with 5% attributable uniquely to intensity of attention and 12% attributable uniquely to arousal regulation. The findings demonstrate that there are sources of individual differences in long-term memory that can be revealed via pupillometry, notably the amount of effort deployed during item encoding and the degree to which people exhibit dysregulated arousal. Both findings are consistent with recent theorizing regarding the role of the locus coeruleus (LC)-norepinephrine (NE) system's role in goal-directed cognition. Specifically, the LC governs both moment-to-moment arousal and NE release to cortical regions subserving cognitive processing. Among people for whom this system operates most optimally, long-term memory retention is superior.
Subject(s)
Individuality , Pupil , Attention/physiology , Cognition/physiology , Humans , Memory, Long-Term , Norepinephrine/physiology , Pupil/physiologyABSTRACT
People with schizophrenia experience episodic memory impairments that have been theorized to reflect deficits in processing context (e.g., spatio-temporal features tied to a specific event). Although past research has reported episodic memory impairments in young people at-risk for schizophrenia, the extent to which these impairments reflect context processing deficits remains unknown. We addressed this gap in the literature by examining whether children and adolescents at risk for schizophrenia exhibit context processing deficits during free recall, a memory task with high contextual demands. Our sample included three groups (N = 58, 9-16 years old) varying in risk for schizophrenia:16 high-risk, unaffected first-degree relatives of patients with schizophrenia, bipolar disorder, and/or schizoaffective disorder, 22 clinical control participants with a comorbid disorder (ADHD and/or an anxiety disorder), and 20 healthy control participants. Participants first completed a free recall task and then completed a recognition memory task. Based on established theories of episodic memory, we assumed that context processing played a more pivotal role in free recall than recognition memory. Consequently, if schizophrenia risk is associated with context processing deficits, then memory impairment should be present in free recall measures that are most sensitive to context processing (i.e., recall accuracy and temporal contiguity). Consistent with this prediction, free recall accuracy and temporal contiguity were lower for the high-risk group than the healthy controls, whereas recognition memory was comparable across groups. These findings suggest that episodic memory impairments associated with schizophrenia in unaffected, first-degree relatives may reflect context processing deficits.
ABSTRACT
The temporal contiguity effect (TCE) is the tendency for the recall of one event to cue recall of other events originally experienced nearby in time. Retrieved context theory proposes that the TCE results from fundamental properties of episodic memory: binding of events to a drifting context representation during encoding and the reinstatement of those associations during recall. If these processes are automatic, the TCE should not be dependent on any encoding strategy and should, in fact, be present regardless of encoding intentionality. Here, we ask whether this theory is compatible with recent findings that the TCE is dramatically reduced under incidental encoding, even though memory accuracy is only modestly reduced. We begin by attempting to replicate this finding in a new large-scale study with over 5,000 participants in which we manipulated encoding intentionality between participants in both delayed free recall and continual distractor free recall. A small, but reliable, TCE was observed in all conditions, although the effect was dramatically reduced in incidental encoding. In a simulation study, we demonstrated that retrieved context theory can simultaneously account for both overall recall and the strength of the TCE in incidental encoding conditions. Additional analyses revealed that the incidental TCE is not an artifact of theoretically uninteresting factors, such as recency, and is consistent with being generated by the core contextual dynamics of retrieved context theory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Subject(s)
Memory, Episodic , Mental Recall , Humans , TimeABSTRACT
Space and time are both essential aspects of human episodic memory. Yet, behavioral studies into the dynamics of recall have focused more on time than space. For instance, it is now well known that temporally contiguous events are more likely to be subsequently recalled than temporally remote events, as measured by the lag-conditional response probability (lag-CRP), which represents the probability of recalling item i + lag after recalling item i. The present study administered both verbal and spatial delayed free recall (DFR) tasks to a sample of 168 participants in order to measure lag-CRPs along both spatial and temporal associative dimensions. Whereas only the temporal lag-CRP could be measured in the verbal DFR task, both temporal and spatial lag-CRPs could be measured in the spatial DFR task. As expected, the results obtained in the verbal DFR task indicated the typical temporal contiguity effect. More importantly, the results obtained in the spatial DFR task indicated significant contiguity effects along both associative dimensions, and the spatial contiguity effect was found to be significantly larger than the temporal contiguity effect. In addition, the relatively small temporal contiguity effect observed in the spatial DFR task was also found to be significantly smaller than the temporal contiguity effect observed in the verbal DFR task. Altogether, the present findings provided novel evidence that spatial and temporal proximity can both cue sequential dependencies between successive recalls. As such, retrieved context models of episodic memory should be expanded to include spatial context as well as temporal context.
Subject(s)
Memory, Episodic , Humans , Mental Recall , Probability , TimeSubject(s)
Endometriosis , Uterine Diseases , Endometriosis/drug therapy , Endometrium/abnormalities , Female , HumansABSTRACT
The electrophysiological evidence for suppression to date primarily draws upon traditional retrieval-induced forgetting and Think/No-Think paradigms, which involve strategic and intentional restriction of thought. Here event-related potential (ERP) signatures of suppression were examined using a novel task, which unlike traditional paradigms, does not include an initial priming step or intentional thought restraint. Participants were instructed to verbally generate semantically related responses to cue words (e.g., "PIZZA"), and unrelated responses to others. According to an inhibitory account of interference resolution, semantic competition from automatically activated target words must be resolved in order to generate an unrelated response, whereas no resolution is required for generating related responses. In a subsequent phase, accessibility for target words (e.g., "PEPPERONI") that required suppression, words that did not require suppression, as well as new control words was measured using a lexical decision task. We observed a sustained late positivity for unrelated responses in the generation task, and early negative amplitudes of suppressed items in the lexical decision task. These findings are consistent with inhibitory mechanisms operating at retrieval to suppress competitors and show that such processes operate on automatically activated items that are not presented in the context of an experiment, representative of retrieval situations that occur in everyday life.
Subject(s)
Electrophysiological Phenomena/physiology , Inhibition, Psychological , Mental Recall/physiology , Adolescent , Adult , Association Learning/physiology , Cues , Electroencephalography , Evoked Potentials/physiology , Female , Humans , Language , Male , Memory/physiology , Reaction Time/physiology , Semantics , Young AdultABSTRACT
STUDY QUESTION: Do menstrual cycle-dependent changes occur in the histological appearance of superficial peritoneal endometriotic lesions, and are they equivalent to those observed in the eutopic endometrium? SUMMARY ANSWER: Only a small subset of superficial peritoneal endometriotic lesions exhibits some histological features in phase with menstrual cycle-related changes observed in eutopic endometrium. WHAT IS KNOWN ALREADY: Endometriotic lesions are frequently described as implants that follow menstrual cycle-related changes in morphology, as per the eutopic endometrium. This concept has been widely accepted despite the lack of conclusive published evidence. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study of 42 patients, from across the menstrual cycle, with surgically and histologically confirmed endometriosis. Patients were a subset selected from a larger endometriosis study being conducted at the Royal Women's Hospital, Melbourne since 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Histological features of epithelium, stroma and gland morphology were examined in haematoxylin and eosin stained sections of superficial peritoneal endometriotic lesions and matched eutopic endometrium (menstrual: n = 4, proliferative: n = 11, secretory: n = 17, hormone-treated: n = 10). At least two biopsies (average = 4, range = 2-8 biopsies) and a matched endometrial sample were analysed for each patient and results were presented per endometriotic gland profile (n = 1051). Data were analysed using mixed effects logistic regression to account for multiple patients and multiple endometriotic biopsies, each with multiple endometriotic gland profiles. This model also enabled analysis of endometriotic lesions versus eutopic endometrium. MAIN RESULTS AND THE ROLE OF CHANCE: There was considerable inter- and intra-patient variability in the morphology of superficial peritoneal endometriotic lesions. Menstrual cycle-associated changes were only observed for some features in a subset of endometriotic gland profiles. The proportion of endometriotic gland profiles with epithelial mitoses significantly increased in the proliferative phase (18% of gland profiles) relative to the menstrual phase (0% of endometriotic gland profiles) (odds ratios (OR) 9.30; 95% confidence intervals (CI) = 3.71-23.32; P < 0.001). Fewer blood-filled gland lumens were observed in the secretory phase (45% of endometriotic gland profiles) compared to the menstrual phase (67% of endometriotic gland profiles) (OR, 0.30; 95% CI = 0.11-0.79; P = 0.015). The features of the eutopic endometrium analysed in this study did not reflect the results in matched endometriotic lesions (P > 0.05). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: This study focused on features observed in sections of superficial peritoneal lesions and these may differ from features of deep infiltrating endometriosis or ovarian endometriomas. Cycle phases were limited to menstrual, proliferative and secretory phases to allow appropriate statistical modelling. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights heterogeneity in the histological characteristics of superficial peritoneal lesions. It challenges the assumption that lesion morphology consistently reflects menstrual cycle-associated changes. STUDY FUNDING/COMPETING INTEREST(S): Research reported in this publication was supported in part by National Health and Medical Research Council (NHMRC) project grants GNT1012245, GNT1105321 and GNT1026033 (P.A.W.R., J.E.G. and S.J.H.-C.). There are no competing interests.
Subject(s)
Endometriosis , Peritoneal Diseases , Endometrium , Female , Humans , Menstrual Cycle , Retrospective StudiesABSTRACT
Longitudinal designs must deal with the confound between increasing age and increasing task experience (i.e., retest effects). Most existing methods for disentangling these factors rely on large sample sizes and are impractical for smaller scale projects. Here, we show that a measurement burst design combined with a model of retest effects can be used to study age-related change with modest sample sizes. A combined model of age-related change and retest-related effects was developed. In a simulation experiment, we show that with sample sizes as small as n = 8, the model can reliably detect age effects of the size reported in the longitudinal literature while avoiding false positives when there is no age effect. We applied the model to data from a measurement burst study in which eight subjects completed a burst of seven sessions of free recall every year for five years. Six additional subjects completed a burst only in years 1 and 5. They should, therefore, have smaller retest effects but equal age effects. The raw data suggested slight improvement in memory over five years. However, applying the model to the yearly-testing group revealed that a substantial positive retest effect was obscuring stability in memory performance. Supporting this finding, the control group showed a smaller retest effect but an equal age effect. Measurement burst designs combined with models of retest effects allow researchers to employ longitudinal designs in areas where previously only cross-sectional designs were feasible.
ABSTRACT
We examined oscillatory power in electroencephalographic recordings obtained while younger (18-30 years) and older (60+ years) adults studied lists of words for later recall. Power changed in a highly consistent way from word-to-word across the study period. Above 14 Hz, there were virtually no age differences in these neural gradients. But gradients below 14 Hz reliably discriminated between age groups. Older adults with the best memory performance showed the largest departures from the younger adult pattern of neural activity. These results suggest that age differences in the dynamics of neural activity across an encoding period reflect changes in cognitive processing that may compensate for age-related decline.
Subject(s)
Brain/physiology , Cognition/physiology , Electroencephalography , Memory Disorders/physiopathology , Mental Recall/physiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Aging/physiology , Electrophysiological Phenomena , Female , Humans , Male , Middle Aged , Time Factors , Young AdultABSTRACT
STUDY QUESTION: Is male age associated with the clinical outcomes of IVF/ICSI cycles for idiopathic infertility after adjustment for female age? SUMMARY ANSWER: Male ageing is negatively associated with clinical IVF/ICSI outcomes in couples with idiopathic infertility independent of female age. WHAT IS KNOWN ALREADY: The effect of male age on the outcomes of infertility treatments is controversial and poorly explored. In contrast, fertility is known to decline significantly with female age beyond the mid-30s, and reduced oocyte quality plays an important role. The negative effect of male age on sperm quality is largely associated with an increasing susceptibility to sperm DNA damage. Although increasing maternal age has been linked with poorer oocyte quality, studies on the effect of male age have disregarded the need to control for female age making it difficult to define clearly the role of male age in infertile couples. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analysed 2425 cycles of couples with idiopathic infertility selected from a total of 24 411 IVF/ICSI cycles performed at Monash IVF in Australia between 1992 and 2017. The primary outcome was live birth and secondary outcomes were clinical pregnancy and miscarriage. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples with primary/secondary infertility who underwent IVF/ICSI cycles with male partners classified as normozoospermic were selected (inclusion criteria). Couples in which the female partner had endometriosis, tubal factors, polycystic ovarian syndrome, ovarian hyperstimulation syndrome, poor responders (≤3 mature oocytes retrieved) and couples with more than 15 cumulus oocyte complexes retrieved or who used cryopreserved gametes were excluded. Binary logistic multilevel modelling was used to identify the effect of male age and female age on clinical outcomes after controlling for confounding factors. Male age and female age were examined as continuous and categorical (male age: <40, 40-44, 45-49, 50-54, ≥55; female age:<30, 30-34, 35-39, ≥40) predictors. MAIN RESULTS AND THE ROLE OF CHANCE: There was a negative effect of male age and female age on live birth as odds ratios (OR) with 95% CI for each additional year of age (OR-male age: 0.96 [0.94-0.98]; OR-female age: 0.90 [0.88-0.93] P < 0.001). Potential interactions with male age such as type of treatment (IVF/ICSI), embryo transfer day (Day 3/Day 5) and female age did not have significant associations with outcomes (P > 0.05). Secondary outcomes showed a significant reduction in the odds of clinical pregnancy (OR-male age: 0.97 [0.96-0.99]; OR-female age: 0.92 [0.89-0.94] P < 0.001) and an increase in the odds of miscarriage with older age: male age (OR: 1.05 [1.01-1.08]; P = 0.002); female age (OR: 1.11 [1.05-1.18]; P < 0.001). Worse outcomes were associated with more cycles (clinical pregnancy-OR: 0.96 [0.93-0.99] P = 0.03; live birth-OR: 0.96 [0.92-0.99] P = 0.023) while more inseminated oocytes were associated with better outcomes (clinical pregnancy-OR: 1.06 [1.03-1.06] P < 0.001; live birth-OR: 1.07 [1.04-1.11] P < 0.001). Analyses for age categories showed a gradual worsening of clinical outcomes with increasing male age, with a significantly worse live birth and clinical pregnancy outcomes in males aged older than 50 years compared to males younger than 40 years (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: This study is limited to the information on confounding factors included. The study may also be limited in its generalizability to a wider population due the strict selection criteria. Age as a category could potentially result in residual confounding due to categorizing a continuous variable. WIDER IMPLICATIONS OF THE FINDINGS: This study provides information for counselling of couples with idiopathic infertility. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Education Program in Reproduction and Development, Department of Obstetrics and Gynaecology, Monash University. None of the authors has any conflict of interest to report. TRIAL REGISTRATION NUMBER: N/A.
Subject(s)
Birth Rate , Fertilization in Vitro/statistics & numerical data , Paternal Age , Adult , Aged , Aging , Embryo Implantation , Female , Humans , Male , Maternal Age , Middle Aged , Pregnancy , Retrospective Studies , Young AdultABSTRACT
Endometriotic lesions are composed in part of endometrial-like stromal cells, however, there is a shortage of immortalized human endometrial stromal cultures available for research. As genetic factors play a role in endometriosis risk, it is important that genotype is also incorporated into analysis of pathological mechanisms. Human telomerase reverse transcriptase (hTERT) immortalization (using Lenti-hTERT-green fluorescent protein virus) took place following genotype selection; 13 patients homozygous for either the risk or non-risk 'other' allele for one or more important endometriosis risk single nucleotide polymorphism on chromosome 1p36.12 (rs3820282, rs56318008, rs55938609, rs12037376, rs7521902 or rs12061255). Short tandem repeat DNA profiling validated that donor tissue matched that of the immortalized cell lines and confirmed that cultures were genetically novel. Expression of morphological markers (vimentin and cytokeratin) and key genes of interest (telomerase, estrogen and progesterone receptors and LINC00339) were examined and functional assays for cell proliferation, steroid hormone and inflammatory responses were performed for 7/13 cultures. All endometrial stromal cell lines maintained their fibroblast-like morphology (vimentin-positive) and homozygous endometriosis-risk genotype following introduction of hTERT. Furthermore, the new stromal cultures demonstrated positive and diverse responses to hormones (proliferation and decidualisation changes) and inflammation (dose-dependent response), while maintaining hormone receptor expression. In conclusion, we successfully developed a range of human endometrial stromal cell lines that carry important endometriosis-risk alleles. The wider implications of this approach go beyond advancing endometriosis research; these cell lines will be valuable tools for multiple endometrial pathologies offering a level of genetic and phenotypic diversity not previously available.
Subject(s)
Endometriosis/genetics , Founder Effect , Genotype , Stromal Cells/metabolism , Telomerase/genetics , Adult , Biomarkers/metabolism , Cell Line, Transformed , Cell Proliferation , Chromosomes, Human, Pair 1/chemistry , Chromosomes, Human, Pair 1/metabolism , Endometriosis/metabolism , Endometriosis/pathology , Endometrium/metabolism , Endometrium/pathology , Female , Gene Expression , Homozygote , Humans , Keratins/genetics , Keratins/metabolism , Microsatellite Repeats , Polymorphism, Single Nucleotide , RNA, Long Noncoding , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Risk , Stromal Cells/pathology , Telomerase/metabolism , Vimentin/genetics , Vimentin/metabolismABSTRACT
Atkinson and Shiffrin (1968) argued that performance on any memory task reflects the combined influence of both the fixed structure of the memory system and control processes tailored to the specific task. We investigated the role of control processes in governing the temporal contiguity and semantic contiguity effects in free recall-tendencies to organize recall based on proximity in the study list and pre-existing semantic associations. Subjects studied lists that contained four "clusters", each composed of four semantically associated words but presented in random order such that associates were not in adjacent serial positions. Subjects were given either standard free-recall instructions, instructions to focus on order-based associations (i.e., the original order of presentation), or meaning-based associations (i.e., pre-existing semantic relationships). Replicating previous work, lists with strong semantic relationships resulted in a reduced overall temporal contiguity effect when recalled under standard free-recall instructions. However, under meaning-based recall instructions, the temporal contiguity effect was nearly eliminated. Detailed analyses of within-cluster transitions and an order reconstruction task revealed that temporal information was encoded, but control processes prevented it from dominating memory search. These results point to a need for more empirical work exploring how control processes change recall dynamics and for more theoretical work modeling the computational basis of these processes.