Targeting Polycomb systems to regulate gene expression: modifications to a complex story.

Polycomb group proteins are transcriptional repressors that are essential for normal gene regulation during development. Recent studies suggest that Polycomb repressive complexes (PRCs) recognize and are recruited to their genomic target sites through a range of different mechanisms, which involve transcription factors, CpG island elements and non-coding RNAs. Together with the realization that the interplay between PRC1 and PRC2 is more intricate than was previously appreciated, this has increased our understanding of the vertebrate Polycomb system at the molecular level.

Medial prefrontal cortex has a causal role in selectively enhanced consolidation of emotional memories after a 24-hour delay: A TBS study.

Previous research points to an association between retrieval-related activity in the medial prefrontal cortex (mPFC) and preservation of emotional information compared to co-occurring neutral information following sleep. Although the role of the mPFC in emotional memory likely begins at encoding, little research has examined how mPFC activity during encoding interacts with consolidation processes to enhance emotional memory. This issue was addressed in the present study using transcranial magnetic stimulation in conjunction with an emotional memory paradigm. Healthy young adults encoded negative and neutral scenes while undergoing concurrent TMS with a modified short intermittent theta burst stimulation (sTBS) protocol. Participants received stimulation to either the mPFC or an active control site (motor cortex) during the encoding phase. Recognition memory for scene components (objects and backgrounds) was assessed after a short (30-minute) and a long delay (24-hour, including a night of sleep) to obtain measures of specific and gist-based memory processes. The results demonstrated that, relative to control stimulation, sTBS to the mPFC enhanced memory for negative objects on the long delay test (collapsed across specific and gist-based memory measures). mPFC stimulation had no discernable effect on memory for objects on the short delay test nor on the background images at either test. These results suggest that mPFC activity occurring during encoding interacts with consolidation processes to preferentially preserve negatively salient information.SIGNIFICANCE STATEMENT:Understanding how emotional information is remembered over time is critical to understanding memory in the real world. The present study used noninvasive brain stimulation (repetitive transcranial magnetic stimulation, rTMS) to investigate the interplay between mPFC activity that occurs during memory encoding and its subsequent interactions with consolidation processes. rTMS delivered to the mPFC during encoding enhanced memory for negatively valenced pictures on a test following a 24-hr delay, with no such effect on a test occurring shortly after the encoding phase. These results are consistent with the hypothesis that emotional aspects of memories are differentially subjected to consolidation processes, and that the mPFC might contribute to this "tag-and-capture" mechanism during the initial formation of such memories.

Self-limiting fall armyworm: a new approach in development for sustainable crop protection and resistance management.

BACKGROUND: The fall armyworm, Spodoptera frugiperda, is a significant and widespread pest of maize, sorghum, rice, and other economically important crops. Successful management of this caterpillar pest has historically relied upon application of synthetic insecticides and through cultivation of genetically engineered crops expressing insecticidal proteins (Bt crops). Fall armyworm has, however, developed resistance to both synthetic insecticides and Bt crops, which risks undermining the benefits delivered by these important crop protection tools. Previous modelling and empirical studies have demonstrated that releases of insecticide- or Bt-susceptible insects genetically modified to express conditional female mortality can both dilute insecticide resistance and suppress pest populations. RESULTS: Here, we describe the first germline transformation of the fall armyworm and the development of a genetically engineered male-selecting self-limiting strain, OX5382G, which exhibits complete female mortality in the absence of an additive in the larval diet. Laboratory experiments showed that males of this strain are competitive against wild-type males for copulations with wild-type females, and that the OX5382G self-limiting transgene declines rapidly to extinction in closed populations following the cessation of OX5382G male releases. Population models simulating the release of OX5382G males in tandem with Bt crops and non-Bt 'refuge' crops show that OX5382G releases can suppress fall armyworm populations and delay the spread of resistance to insecticidal proteins. CONCLUSIONS: This article describes the development of self-limiting fall armyworm designed to control this pest by suppressing pest populations, and population models that demonstrate its potential as a highly effective method of managing resistance to Bt crops in pest fall armyworm populations. Our results provide early promise for a potentially valuable future addition to integrated pest management strategies for fall armyworm and other pests for which resistance to existing crop protection measures results in damage to crops and impedes sustainable agriculture.

Attention Biases Competition for Visual Representation via Dissociable Influences from Frontal and Parietal Cortex.

What mechanisms underlie the prioritization of neural representations of visually perceived information to guide behavior? We assessed the dynamics whereby attention biases competition for representation of visual stimuli by enhancing representations of relevant information and suppressing the irrelevant. Multivariate pattern analysis (MVPA) classifiers were trained to discriminate patterns of fMRI activity associated with each of three stimuli, within several predefined ROIs. Participants performed a change-detection task wherein two of three presented items flashed at 1 Hz, one to each side of central fixation. Both flashing stimuli would unpredictably change state, but participants covertly counted the number of changes only for the cued item. In the ventral occipito-temporal ROI, MVPA evidence (a proxy for representational fidelity) was dynamically enhanced for attended stimuli and suppressed for unattended stimuli, consistent with a mechanism of biased competition between stimulus representations. Frontal and parietal ROIs displayed a qualitatively distinct, more "source-like" profile, wherein MVPA evidence for only the attended stimulus could be observed above baseline levels. To assess how attentional modulation of ventral occipito-temporal representations might relate to signals originating in the frontal and/or parietal ROIs, we analyzed informational connectivity (IC), which indexes time-varying covariation between regional levels of MVPA evidence. Parietal-posterior IC was elevated during the task, but did not differ for cued versus uncued items. Frontal-posterior IC, in contrast, was sensitive to an item's priority status. Thus, although regions of frontal and parietal cortex act as sources of top-down attentional control, their precise functions likely differ.

The impact of a hospital-based exercise oncology program on cancer treatment-related side effects among rural cancer survivors.

PURPOSE: To assess the impact of the Personal Optimism With Exercise Recovery (POWER) program on cancer treatment-related side effects among rural cancer survivors. METHODS: In this retrospective study of data collected between 2016 and 2019, we assessed change in cardiorespiratory fitness, whole-body muscular endurance, physical function and strength, anthropometrics, fatigue, and quality of life (QoL), after participation in POWER. Descriptive statistics were calculated for demographic and clinical variables. Univariate analysis of variance was carried out with age and BMI at initial assessment as covariates. RESULTS: A total of 239 survivors, 78% rural residents, completed a follow-up assessment. Among rural cancer survivors, the most prevalent cancer sites were breast (42.5%), prostate (12.4%), and lymphoma (5.9%). The majority of survivors were female (70%), non-Hispanic (94.6%), and white (93.5%), with average age and BMI of 62.1 ± 13.2 years and 28.4 ± 6.7 kg/m2, respectively. Rural cancer survivors with cancer stages I-III exhibited significant improvements in fitness (+ 3.07 ml/kg/min, 95% CI 1.93, 4.21; + 0.88 METS, 95% CI 0.55, 1.20), physical function (30-s chair stand: + 2.2 repetitions, 95% CI 1.3, 3.1), muscular endurance (10-repetition maximum: chest press + 4.1 kg, 95% CI 2.0, 6.3; lateral pulldown + 6.6 kg, 95% CI 4.4, 8.9), self-reported fatigue (FACIT-Fatigue score: + 4.9, 95% CI 1.6, 8.1), and QoL (FACT-G7 score + 2.1, 95% CI, 0.9, 3.4). Among stage IV rural and urban cancer survivors, significant improvements were observed in muscular endurance and physical function. CONCLUSION: Participation in POWER was associated with attenuation of cancer treatment-related side effects and may serve as a model exercise oncology program for rural cancer survivors.

Health, economic, and social implications of COVID-19 for China's rural population.

This study examines the effects of local and nationwide COVID-19 disease control measures on the health and economy of China's rural population. We conducted phone surveys with 726 randomly selected village informants across seven rural Chinese provinces in February 2020. Four villages (0.55%) reported infections, and none reported deaths. Disease control measures had been universally implemented in all sample villages. About 74% of informants reported that villagers with wage-earning jobs outside the village had stopped working due to workplace closures. A higher percentage of rural individuals could not work due to transportation, housing, and other constraints. Local governments had taken measures to reduce the impact of COVID-19. Although schools in all surveyed villages were closed, 71% of village informants reported that students were attending classes online. Overall, measures to control COVID-19 appear to have been successful in limiting disease transmission in rural communities outside the main epidemic area. Rural Chinese citizens, however, have experienced significant economic consequences from the disease control measures.

Non-perceptual Regions in the Left Inferior Parietal Lobe Support Phonological Short-term Memory: Evidence for a Buffer Account?

Buffer versus embedded processes accounts of short-term memory (STM) for phonological information were addressed by testing subjects' perception and memory for speech and non-speech auditory stimuli. Univariate and multivariate (MVPA) approaches were used to assess whether brain regions recruited in recognizing speech were involved in maintaining speech representations over a delay. As expected, a left superior temporal region was found to support speech perception. However, contrary to the embedded processes approach, this region failed to show a load effect, or any sustained activation, during a maintenance delay. Moreover, MVPA decoding during the maintenance stage was unsuccessful in this region by a perception classifier or an encoding classifier. In contrast, the left supramarginal gyrus showed both sustained activation and a load effect. Using MVPA, stimulus decoding was successful during the delay period. In addition, a functional connectivity analysis showed that, as memory load increased, the left temporal lobe involved in perception became more strongly connected with the parietal region involved in maintenance. Taken together, the findings provide greater support for a buffer than embedded processes account of phonological STM.

"At three years of age, we can see the future": Cognitive skills and the life cycle of rural Chinese children.

BACKGROUND: While the Chinese education system has seen massive improvements over the past few decades, there still exists large academic achievement gaps between rural and urban areas, which threaten China's long-term development. Additionally, recent literature has underscored the importance of early childhood development (ECD) in later-life human capital development. OBJECTIVES: We analyze the lifecycle of cognitive development and learning outcomes in rural Chinese children by first examining if ECD outcomes affect cognition levels, then seeing if cognitive delays persist as children grow, and finally exploring connections between cognition and education outcomes. METHODS: We combine data from four recent studies examining different age groups (0-3, 4-5, 10-11, 13-14) to track cognitive outcomes. RESULTS: First, we find that ECD outcomes for children in rural China are poor, with almost one-in-two children being cognitively delayed. Second, we find that these cognitive delays seem to persist into middle school, with almost 37% of rural junior high school students being cognitively delayed. Finally, we show that cognition has a close relationship to academic achievement. CONCLUSION: Our results suggest that urban/rural gaps in academic achievement originate at least in part from differences in ECD outcomes. CONTRIBUTIONS: While many papers have analyzed ECD, human capital, and inequality separately, this is the first paper to explicitly connect and combine these topics to analyze the lifecycle of cognitive development in the context of rural China.

Parietal-Occipital Interactions Underlying Control- and Representation-Related Processes in Working Memory for Nonspatial Visual Features.

Although the manipulation of load is popular in visual working memory research, many studies confound general attentional demands with context binding by drawing memoranda from the same stimulus category. In this fMRI study of human observers (both sexes), we created high- versus low-binding conditions, while holding load constant, by comparing trials requiring memory for the direction of motion of one random dot kinematogram (RDK; 1M trials) versus for three RDKs (3M), or versus one RDK and two color patches (1M2C). Memory precision was highest for 1M trials and comparable for 3M and 1M2C trials. And although delay-period activity in occipital cortex did not differ between the three conditions, returning to baseline for all three, multivariate pattern analysis decoding of a remembered RDK from occipital cortex was also highest for 1M trials and comparable for 3M and 1M2C trials. Delay-period activity in intraparietal sulcus (IPS), although elevated for all three conditions, displayed more sensitivity to demands on context binding than to load per se. The 1M-to-3M increase in IPS signal predicted the 1M-to-3M declines in both behavioral and neural estimates of working memory precision. These effects strengthened along a caudal-to-rostral gradient, from IPS0 to IPS5. Context binding-independent load sensitivity was observed when analyses were lateralized and extended into PFC, with trend-level effects evident in left IPS and strong effects in left lateral PFC. These findings illustrate how visual working memory capacity limitations arise from multiple factors that each recruit dissociable brain systems.SIGNIFICANCE STATEMENT Visual working memory capacity predicts performance on a wide array of cognitive and real-world outcomes. At least two theoretically distinct factors are proposed to influence visual working memory capacity limitations: an amodal attentional resource that must be shared across remembered items; and the demands on context binding. We unconfounded these two factors by varying load with items drawn from the same stimulus category ("high demands on context binding") versus items drawn from different stimulus categories ("low demands on context binding"). The results provide evidence for the dissociability, and the neural bases, of these two theorized factors, and they specify that the functions of intraparietal sulcus may relate more strongly to the control of representations than to the general allocation of attention.

Prospective Memory Is a Key Predictor of Functional Independence in Older Adults.

OBJECTIVES: Prospective memory (PM), the ability to execute delayed intentions, has received increasing attention in neuropsychology and gerontology. Most of this research is motivated by the claim that PM is critical for maintaining functional independence; yet, there is a dearth of empirical evidence to back up the claims. Thus, the present study tested whether PM predicts functional independence in older adults using validated behavioral performance measures for both PM and functional independence. METHODS: Fifty-eight healthy older adults performed a computerized PM paradigm, the Virtual Week task, as well as a timed version of an instrumental activities of daily living (TIADL) task. Furthermore, we assessed vocabulary, processing speed, and self-reported prospective remembering. RESULTS: TIADL scores correlated significantly with performance in the Virtual Week task, vocabulary, and processing speed. Hierarchical linear regressions revealed that vocabulary and Virtual Week performance were significant predictors for TIADL. However, self-reported PM scores did not predict everyday functioning. CONCLUSIONS: The findings indicate that PM is an important cognitive ability for successful and independent everyday life beyond vocabulary. Moreover, the results show a substantial incremental contribution of intact PM performance for the prediction of everyday functioning by using objective PM measures. (JINS, 2018, 24, 640-645).

Analysing concurrent transcranial magnetic stimulation and electroencephalographic data: A review and introduction to the open-source TESA software.

The concurrent use of transcranial magnetic stimulation with electroencephalography (TMS-EEG) is growing in popularity as a method for assessing various cortical properties such as excitability, oscillations and connectivity. However, this combination of methods is technically challenging, resulting in artifacts both during recording and following typical EEG analysis methods, which can distort the underlying neural signal. In this article, we review the causes of artifacts in EEG recordings resulting from TMS, as well as artifacts introduced during analysis (e.g. as the result of filtering over high-frequency, large amplitude artifacts). We then discuss methods for removing artifacts, and ways of designing pipelines to minimise analysis-related artifacts. Finally, we introduce the TMS-EEG signal analyser (TESA), an open-source extension for EEGLAB, which includes functions that are specific for TMS-EEG analysis, such as removing and interpolating the TMS pulse artifact, removing and minimising TMS-evoked muscle activity, and analysing TMS-evoked potentials. The aims of TESA are to provide users with easy access to current TMS-EEG analysis methods and to encourage direct comparisons of these methods and pipelines. It is hoped that providing open-source functions will aid in both improving and standardising analysis across the field of TMS-EEG research.

Benefits from retrieval practice are greater for students with lower working memory capacity.

We examined the effects of retrieval practice for students who varied in working memory capacity as a function of the lag between study of material and its initial test, whether or not feedback was given after the test, and the retention interval of the final test. We sought to determine whether a blend of these conditions exists that maximises benefits from retrieval practice for lower and higher working memory capacity students. College students learned general knowledge facts and then restudied the facts or were tested on them (with or without feedback) at lags of 0-9 intervening items. Final cued recall performance was better for tested items than for restudied items after both 10 minutes and 2 days, particularly for longer study-test lags. Furthermore, on the 2-day delayed test the benefits from retrieval practice with feedback were significantly greater for students with lower working memory capacity than for students with higher working memory capacity (r = -.42). Retrieval practice may be an especially effective learning strategy for lower ability students.

Semantic and phonological contributions to short-term repetition and long-term cued sentence recall.

The function of verbal short-term memory is supported not only by the phonological loop, but also by semantic resources that may operate on both short and long time scales. Elucidation of the neural underpinnings of these mechanisms requires effective behavioral manipulations that can selectively engage them. We developed a novel cued sentence recall paradigm to assess the effects of two factors on sentence recall accuracy at short-term and long-term stages. Participants initially repeated auditory sentences immediately following a 14-s retention period. After this task was complete, long-term memory for each sentence was probed by a two-word recall cue. The sentences were either concrete (high imageability) or abstract (low imageability), and the initial 14-s retention period was filled with either an undemanding finger-tapping task or a more engaging articulatory suppression task (Exp. 1, counting backward by threes; Exp. 2, repeating a four-syllable nonword). Recall was always better for the concrete sentences. Articulatory suppression reduced accuracy in short-term recall, especially for abstract sentences, but the sentences initially recalled following articulatory suppression were retained better at the subsequent cued-recall test, suggesting that the engagement of semantic mechanisms for short-term retention promoted encoding of the sentence meaning into long-term memory. These results provide a basis for using sentence imageability and subsequent memory performance as probes of semantic engagement in short-term memory for sentences.

Understanding the relationship between DNA methylation and histone lysine methylation.

DNA methylation acts as an epigenetic modification in vertebrate DNA. Recently it has become clear that the DNA and histone lysine methylation systems are highly interrelated and rely mechanistically on each other for normal chromatin function in vivo. Here we examine some of the functional links between these systems, with a particular focus on several recent discoveries suggesting how lysine methylation may help to target DNA methylation during development, and vice versa. In addition, the emerging role of non-methylated DNA found in CpG islands in defining histone lysine methylation profiles at gene regulatory elements will be discussed in the context of gene regulation.

Levels of processing in working memory: differential involvement of frontotemporal networks.

How does the brain maintain to-be-remembered information in working memory (WM), particularly when the focus of attention is drawn to processing other information? Cognitive models of WM propose that when items are displaced from focal attention recall involves retrieval from long-term memory (LTM). In this fMRI study, we tried to clarify the role of LTM in performance on a WM task and the type of representation that is used to maintain an item in WM during rehearsal-filled versus distractor-filled delays. Participants made a deep or shallow levels-of-processing (LOP) decision about a single word at encoding and tried to recall the word after a delay filled with either rehearsal of the word or a distracting math task. Recalling one word after 10 sec of distraction demonstrated behavioral and neural indices of retrieval from LTM (i.e., LOP effects and medial-temporal lobe activity). In contrast, recall after rehearsal activated cortical areas that reflected reporting the word from focal attention. In addition, areas that showed an LOP effect at encoding (e.g., left ventrolateral VLPFC and the anterior temporal lobes [ATLs]) were reactivated at recall, especially when recall followed distraction. Moreover, activity in left VLPFC during encoding, left ATL during the delay, and left hippocampus during retrieval predicted recall success after distraction. Whereas shallow LOP and rehearsal-related areas supported active maintenance of one item in focal attention, the behavioral processes and neural substrates that support LTM supported recall of one item after it was displaced from focal attention.

Individuals with low working memory spans show greater interference from irrelevant information because of poor source monitoring, not greater activation.

Although individuals with high and low working memory (WM) span appear to differ in the extent to which irrelevant information interferes with their performance on WM tasks, the locus of this interference is not clear. The present study investigated whether, when performing a WM task, high- and low-span individuals differ in the activation of formerly relevant, but now irrelevant items, and/or in their ability to correctly identify such irrelevant items. This was done in two experiments, both of which used modified complex WM span tasks. In Experiment 1, the span task included an embedded lexical decision task designed to obtain an implicit measure of the activation of both currently and formerly relevant items. In Experiment 2, the span task included an embedded recognition judgment task designed to obtain an explicit measure of both item and source recognition ability. The results of these experiments indicate that low-span individuals do not hold irrelevant information in a more active state in memory than high-span individuals, but rather that low-span individuals are significantly poorer at identifying such information as irrelevant at the time of retrieval. These results suggest that differences in the ability to monitor the source of information, rather than differences in the activation of irrelevant information, are the more important determinant of performance on WM tasks.

The short- and long-term fates of memory items retained outside the focus of attention.

When a test of working memory (WM) requires the retention of multiple items, a subset of them can be prioritized. Recent studies have shown that, although prioritized (i.e., attended) items are associated with active neural representations, unprioritized (i.e., unattended) memory items can be retained in WM despite the absence of such active representations, and with no decrement in their recognition if they are cued later in the trial. These findings raise two intriguing questions about the nature of the short-term retention of information outside the focus of attention. First, when the focus of attention shifts from items in WM, is there a loss of fidelity for those unattended memory items? Second, could the retention of unattended memory items be accomplished by long-term memory mechanisms? We addressed the first question by comparing the precision of recall of attended versus unattended memory items, and found a significant decrease in precision for unattended memory items, reflecting a degradation in the quality of those representations. We addressed the second question by asking subjects to perform a WM task, followed by a surprise memory test for the items that they had seen in the WM task. Long-term memory for unattended memory items from the WM task was not better than memory for items that had remained selected by the focus of attention in the WM task. These results show that unattended WM representations are degraded in quality and are not preferentially represented in long-term memory, as compared to attended memory items.

Prospective memory training in older adults and its relevance for successful aging.

In research on cognitive plasticity, two training approaches have been established: (1) training of strategies to improve performance in a given task (e.g., encoding strategies to improve episodic memory performance) and (2) training of basic cognitive processes (e.g., working memory, inhibition) that underlie a range of more complex cognitive tasks (e.g., planning) to improve both the training target and the complex transfer tasks. Strategy training aims to compensate or circumvent limitations in underlying processes, while process training attempts to augment or to restore these processes. Although research on both approaches has produced some promising findings, results are still heterogeneous and the impact of most training regimes for everyday life is unknown. We, therefore, discuss recent proposals of training regimes aiming to improve prospective memory (i.e., forming and realizing delayed intentions) as this type of complex cognition is highly relevant for independent living. Furthermore, prospective memory is associated with working memory and executive functions and age-related decline is widely reported. We review initial evidence suggesting that both training regimes (i.e., strategy and/or process training) can successfully be applied to improve prospective memory. Conceptual and methodological implications of the findings for research on age-related prospective memory and for training research in general are discussed.

Short-term retention of a single word relies on retrieval from long-term memory when both rehearsal and refreshing are disrupted.

Many working memory (WM) models propose that the focus of attention (or primary memory) has a capacity limit of one to four items, and therefore, that performance on WM tasks involves retrieving some items from long-term (or secondary) memory (LTM). In the present study, we present evidence suggesting that recall of even one item on a WM task can involve retrieving it from LTM. The WM task required participants to make a deep (living/nonliving) or shallow ("e"/no "e") level-of-processing (LOP) judgment on one word and to recall the word after a 10-s delay on each trial. During the delay, participants either rehearsed the word or performed an easy or a hard math task. When the to-be-remembered item could be rehearsed, recall was fast and accurate. When it was followed by a math task, recall was slower, error-prone, and benefited from a deeper LOP at encoding, especially for the hard math condition. The authors suggest that a covert-retrieval mechanism may have refreshed the item during easy math, and that the hard math condition shows that even a single item cannot be reliably held in WM during a sufficiently distracting task--therefore, recalling the item involved retrieving it from LTM. Additionally, performance on a final free recall (LTM) test was better for items recalled following math than following rehearsal, suggesting that initial recall following math involved elaborative retrieval from LTM, whereas rehearsal did not. The authors suggest that the extent to which performance on WM tasks involves retrieval from LTM depends on the amounts of disruption to both rehearsal and covert-retrieval/refreshing maintenance mechanisms.

Naturalistic assessments in virtual reality and in real life help resolve the age-prospective memory paradox.

Cognitive aging researchers have long reported "paradoxical" age differences in prospective memory (PM), with age deficits in laboratory settings and age benefits (or no deficits) in real-world settings. We propose a theoretical account that explains this "age-PM-paradox" as a consequence of both methodological factors and developmental changes in cognitive abilities and personality traits. To test this account, young and older adults performed a series of naturalistic PM tasks in the lab and real world. Age-related PM deficits were observed in both lab-based tasks where demands were implemented using virtual reality and in-person role-playing. In contrast, older adults performed equal to or better than young adults on both real-world tasks, where demands were implemented in participants' daily lives. Consistent with our proposed account, an index of these "paradoxical" effects was partially predicted by age-related differences in working memory, vigilance, agreeableness, and neuroticism, whose predictive utility varied across task settings.