Protein Phosphatase 1-Dependent Transcriptional Programs for Long-Term Memory and Plasticity

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Graff, Johannes; Koshibu, Kyoko; Jouvenceau, Anne; Dutar, Patrick; Mansuy, Isabelle M.

2010-01-01

Gene transcription is essential for the establishment and the maintenance of long-term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and…

Memory extinction entails the inhibition of the transcription factor NF-kappaB.

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Emiliano Merlo

Full Text Available In contextual memories, an association between a positive or negative reinforcement and the contextual cues where the reinforcement occurs is formed. The re-exposure to the context without reinforcement can lead to memory extinction or reconsolidation, depending on the number of events or duration of a single event of context re-exposure. Extinction involves the temporary waning of the previously acquired conditioned response. The molecular processes underlying extinction and the mechanisms which determine if memory will reconsolidate or extinguish after retrieval are not well characterized, particularly the role of transcription factors and gene expression. Here we studied the participation of a transcription factor, NF-kappaB, in memory extinction. In the crab context-signal memory, the activation of NF-kappaB plays a critical role in consolidation and reconsolidation, memory processes that are well characterized in this model. The administration of a NF-kappaB inhibitor, sulfasalazine prior to extinction session impeded spontaneous recovery. Moreover, reinstatement experiments showed that the original memory was not affected and that NF-kappaB inhibition by sulfasalazine impaired spontaneous recovery strengthening the ongoing memory extinction process. Interestingly, in animals with fully consolidated memory, a brief re-exposure to the training context induced neuronal NF-kappaB activation and reconsolidation, while prolonged re-exposure induced NF-kappaB inhibition and memory extinction. These data constitutes a novel insight into the molecular mechanisms involved in the switch between memory reconsolidation and extinction. Moreover, we propose the inhibition of NF-kappaB as the engaged mechanism underlying extinction, supporting a novel approach for the pharmacological enhancement of this memory process. The accurate description of the molecular mechanisms that support memory extinction is potentially useful for developing new strategies

p53 Maintains Genomic Stability by Preventing Interference between Transcription and Replication

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Constance Qiao Xin Yeo

2016-04-01

Full Text Available p53 tumor suppressor maintains genomic stability, typically acting through cell-cycle arrest, senescence, and apoptosis. We discovered a function of p53 in preventing conflicts between transcription and replication, independent of its canonical roles. p53 deficiency sensitizes cells to Topoisomerase (Topo II inhibitors, resulting in DNA damage arising spontaneously during replication. Topoisomerase IIα (TOP2A-DNA complexes preferentially accumulate in isogenic p53 mutant or knockout cells, reflecting an increased recruitment of TOP2A to regulate DNA topology. We propose that p53 acts to prevent DNA topological stress originating from transcription during the S phase and, therefore, promotes normal replication fork progression. Consequently, replication fork progression is impaired in the absence of p53, which is reversed by transcription inhibition. Pharmacologic inhibition of transcription also attenuates DNA damage and decreases Topo-II-DNA complexes, restoring cell viability in p53-deficient cells. Together, our results demonstrate a function of p53 that may underlie its role in tumor suppression.

Regulation of Memory Formation by the Transcription Factor XBP1

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Gabriela Martínez

2016-02-01

Full Text Available Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer’s disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR, mediating adaptation to endoplasmic reticulum (ER stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP, whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF, a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress.

Different gene-specific mechanisms determine the 'revised-response' memory transcription patterns of a subset of A. thaliana dehydration stress responding genes.

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Liu, Ning; Ding, Yong; Fromm, Michael; Avramova, Zoya

2014-05-01

Plants that have experienced several exposures to dehydration stress show increased resistance to future exposures by producing faster and/or stronger reactions, while many dehydration stress responding genes in Arabidopsis thaliana super-induce their transcription as a 'memory' from the previous encounter. A previously unknown, rather unusual, memory response pattern is displayed by a subset of the dehydration stress response genes. Despite robustly responding to a first stress, these genes return to their initial, pre-stressed, transcript levels during the watered recovery; surprisingly, they do not respond further to subsequent stresses of similar magnitude and duration. This transcriptional behavior defines the 'revised-response' memory genes. Here, we investigate the molecular mechanisms regulating this transcription memory behavior. Potential roles of abscisic acid (ABA), of transcription factors (TFs) from the ABA signaling pathways (ABF2/3/4 and MYC2), and of histone modifications (H3K4me3 and H3K27me3) as factors in the revised-response transcription memory patterns are elucidated. We identify the TF MYC2 as the critical component for the memory behavior of a specific subset of MYC2-dependent genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Memory-based attention capture when multiple items are maintained in visual working memory.

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Hollingworth, Andrew; Beck, Valerie M

2016-07-01

Efficient visual search requires that attention is guided strategically to relevant objects, and most theories of visual search implement this function by means of a target template maintained in visual working memory (VWM). However, there is currently debate over the architecture of VWM-based attentional guidance. We contrasted a single-item-template hypothesis with a multiple-item-template hypothesis, which differ in their claims about structural limits on the interaction between VWM representations and perceptual selection. Recent evidence from van Moorselaar, Theeuwes, and Olivers (2014) indicated that memory-based capture during search, an index of VWM guidance, is not observed when memory set size is increased beyond a single item, suggesting that multiple items in VWM do not guide attention. In the present study, we maximized the overlap between multiple colors held in VWM and the colors of distractors in a search array. Reliable capture was observed when 2 colors were held in VWM and both colors were present as distractors, using both the original van Moorselaar et al. singleton-shape search task and a search task that required focal attention to array elements (gap location in outline square stimuli). In the latter task, memory-based capture was consistent with the simultaneous guidance of attention by multiple VWM representations. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Feature bindings are maintained in visual short-term memory without sustained focused attention.

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Delvenne, Jean-François; Cleeremans, Axel; Laloyaux, Cédric

2010-01-01

Does the maintenance of feature bindings in visual short-term memory (VSTM) require sustained focused attention? This issue was investigated in three experiments, in which memory for single features (i.e., colors or shapes) was compared with memory for feature bindings (i.e., the link between the color and shape of an object). Attention was manipulated during the memory retention interval with a retro-cue, which allows attention to be directed and focused on a subset of memory items. The retro-cue was presented 700 ms after the offset of the memory display and 700 ms before the onset of the test display. If the maintenance of feature bindings - but not of individual features - in memory requires sustained focused attention, the retro-cue should not affect memory performance. Contrary to this prediction, we found that both memory for feature bindings and memory for individual features were equally improved by the retro-cue. Therefore, this finding does not support the view that the sustained focused attention is needed to properly maintain feature bindings in VSTM.

Developmental Improvement in Strategies to Maintain Verbal Information in Working Memory

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Oftinger, Anne-Laure; Camos, Valérie

2018-01-01

Although it has been proposed that maintenance of verbal information in adults' working memory relies on two strategies, articulatory rehearsal and attentional refreshing, little is known about the interplay of these strategies in children. To examine strategy changes around the age of seven, children were asked to maintain digits during a…

Savings Memory Is Accompanied by Transcriptional Changes That Persist beyond the Decay of Recall

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Perez, Leticia; Patel, Ushma; Rivota, Marissa; Calin-Jageman, Irina E.; Calin-Jageman, Robert J.

2018-01-01

Most long-term memories are forgotten. What happens, then, to the changes in neuronal gene expression that were initially required to encode and maintain the memory? Here we show that the decay of recall for long-term sensitization memory in "Aplysia" is accompanied both by a form of savings memory (easier relearning) and by persistent…

Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell identity.

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Finley, Lydia W S; Vardhana, Santosha A; Carey, Bryce W; Alonso-Curbelo, Direna; Koche, Richard; Chen, Yanyang; Wen, Duancheng; King, Bryan; Radler, Megan R; Rafii, Shahin; Lowe, Scott W; Allis, C David; Thompson, Craig B

2018-05-01

A robust network of transcription factors and an open chromatin landscape are hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4 has been implicated in stem cell maintenance, but the relative contribution of Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression. In metastable ESCs, Brd4 independence can be achieved by increased expression of pluripotency transcription factors, including STAT3, Nanog or Klf4, so long as the DNA methylcytosine oxidases Tet1 and Tet2 are present. These data reveal that Brd4 is not essential for ESC self-renewal. Rather, the levels of pluripotency transcription factor abundance and Tet1/2 function determine the extent to which bromodomain recognition of protein acetylation contributes to the maintenance of gene expression and cell identity.

The Role of Epigenetic Regulation in Transcriptional Memory in the Immune System.

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Woodworth, A M; Holloway, A F

The immune system is exquisitely poised to identify, respond to, and eradicate pathogens from the body, as well as to produce a more rapid and augmented response to a subsequent encounter with the pathogen. These cellular responses rely on the highly coordinated and rapid activation of gene expression programs as well as the ability of the cell to retain a memory of the initial gene response. It is clear that chromatin structure and epigenetic mechanisms play a crucial role in determining these gene responses, and in fact the immune system has proved an instructive model for investigating the multifaceted mechanisms through which the chromatin landscape contributes to gene expression programs. These mechanisms include modifications to the DNA and histone proteins, the positioning, composition, and remodeling of nucleosomes, as well as the formation of higher-order chromatin structures. Moreover, it is now apparent that epigenetic mechanisms also provide an instrument by which cells can retain memory of the initial transcriptional response, "priming" the genome so that it can respond more quickly to subsequent exposure to the signal. Here, we use the immune system as a model to demonstrate the complex interplay between transcription factors and the chromatin landscape required to orchestrate precise gene responses to external stimuli and further to demonstrate how these interactions can establish memory of past transcriptional events. We focus on what we have learnt from the immune system and how this can inform our understanding of other cellular systems. © 2017 Elsevier Inc. All rights reserved.

Working memory templates are maintained as feature-specific perceptual codes.

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Sreenivasan, Kartik K; Sambhara, Deepak; Jha, Amishi P

2011-07-01

Working memory (WM) representations serve as templates that guide behavior, but the neural basis of these templates remains elusive. We tested the hypothesis that WM templates are maintained by biasing activity in sensoriperceptual neurons that code for features of items being held in memory. Neural activity was recorded using event-related potentials (ERPs) as participants viewed a series of faces and responded when a face matched a target face held in WM. Our prediction was that if activity in neurons coding for the features of the target is preferentially weighted during maintenance of the target, then ERP activity evoked by a nontarget probe face should be commensurate with the visual similarity between target and probe. Visual similarity was operationalized as the degree of overlap in visual features between target and probe. A face-sensitive ERP response was modulated by target-probe similarity. Amplitude was largest for probes that were similar to the target, and decreased monotonically as a function of decreasing target-probe similarity. These results indicate that neural activity is weighted in favor of visual features that comprise an actively held memory representation. As such, our findings support the notion that WM templates rely on neural populations involved in forming percepts of memory items.

Integrated analysis of hematopoietic differentiation outcomes and molecular characterization reveals unbiased differentiation capacity and minor transcriptional memory in HPC/HSC-iPSCs.

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Gao, Shuai; Hou, Xinfeng; Jiang, Yonghua; Xu, Zijian; Cai, Tao; Chen, Jiajie; Chang, Gang

2017-01-23

Transcription factor-mediated reprogramming can reset the epigenetics of somatic cells into a pluripotency compatible state. Recent studies show that induced pluripotent stem cells (iPSCs) always inherit starting cell-specific characteristics, called epigenetic memory, which may be advantageous, as directed differentiation into specific cell types is still challenging; however, it also may be unpredictable when uncontrollable differentiation occurs. In consideration of biosafety in disease modeling and personalized medicine, the availability of high-quality iPSCs which lack a biased differentiation capacity and somatic memory could be indispensable. Herein, we evaluate the hematopoietic differentiation capacity and somatic memory state of hematopoietic progenitor and stem cell (HPC/HSC)-derived-iPSCs (HPC/HSC-iPSCs) using a previously established sequential reprogramming system. We found that HPC/HSCs are amenable to being reprogrammed into iPSCs with unbiased differentiation capacity to hematopoietic progenitors and mature hematopoietic cells. Genome-wide analyses revealed that no global epigenetic memory was detectable in HPC/HSC-iPSCs, but only a minor transcriptional memory of HPC/HSCs existed in a specific tetraploid complementation (4 N)-incompetent HPC/HSC-iPSC line. However, the observed minor transcriptional memory had no influence on the hematopoietic differentiation capacity, indicating the reprogramming of the HPC/HSCs was nearly complete. Further analysis revealed the correlation of minor transcriptional memory with the aberrant distribution of H3K27me3. This work provides a comprehensive framework for obtaining high-quality iPSCs from HPC/HSCs with unbiased hematopoietic differentiation capacity and minor transcriptional memory.

Blockade of intracellular Zn2+ signaling in the dentate gyrus erases recognition memory via impairment of maintained LTP.

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Tamano, Haruna; Minamino, Tatsuya; Fujii, Hiroaki; Takada, Shunsuke; Nakamura, Masatoshi; Ando, Masaki; Takeda, Atsushi

2015-08-01

There is no evidence on the precise role of synaptic Zn2+ signaling on the retention and recall of recognition memory. On the basis of the findings that intracellular Zn2+ signaling in the dentate gyrus is required for object recognition, short-term memory, the present study deals with the effect of spatiotemporally blocking Zn2+ signaling in the dentate gyrus after LTP induction and learning. Three-day-maintained LTP was impaired 1 day after injection of clioquinol into the dentate gyrus, which transiently reduced intracellular Zn2+ signaling in the dentate gyrus. The irreversible impairment was rescued not only by co-injection of ZnCl2 , which ameliorated the loss of Zn2+ signaling, but also by pre-injection of Jasplakinolide, a stabilizer of F-actin, prior to clioquinol injection. Simultaneously, 3-day-old space recognition memory was impaired 1 day after injection of clioquinol into the dentate gyrus, but not by pre-injection of Jasplakinolide. Jasplakinolide also rescued both impairments of 3-day-maintained LTP and 3-day-old memory after injection of ZnAF-2DA into the dentate gyrus, which blocked intracellular Zn2+ signaling in the dentate gyrus. The present paper indicates that the blockade and/or loss of intracellular Zn2+ signaling in the dentate gyrus coincidently impair maintained LTP and recognition memory. The mechanism maintaining LTP via intracellular Zn2+ signaling in dentate granule cells, which may be involved in the formation of F-actin, may retain space recognition memory. © 2015 Wiley Periodicals, Inc.

How Polycomb-Mediated Cell Memory Deals With a Changing Environment

KAUST Repository

Marasca, Federica

2018-03-09

Cells and tissues are continuously exposed to a changing microenvironment, hence the necessity of a flexible modulation of gene expression that in complex organism have been achieved through specialized chromatin mechanisms. Chromatin-based cell memory enables cells to maintain their identity by fixing lineage specific transcriptional programs, ensuring their faithful transmission through cell division; in particular PcG-based memory system evolved to maintain the silenced state of developmental and cell cycle genes. In evolution the complexity of this system have increased, particularly in vertebrates, indicating combinatorial and dynamic properties of Polycomb proteins, in some cases even overflowing outside the cell nucleus. Therefore, their function may not be limited to the imposition of rigid states of genetic programs, but on the ability to recognize signals and allow plastic transcriptional changes in response to different stimuli. Here, we discuss the most novel PcG mediated memory functions in facing and responding to the challenges posed by a fluctuating environment.

How Polycomb-Mediated Cell Memory Deals With a Changing Environment

KAUST Repository

Marasca, Federica; Bodega, Beatrice; Orlando, Valerio

2018-01-01

Cells and tissues are continuously exposed to a changing microenvironment, hence the necessity of a flexible modulation of gene expression that in complex organism have been achieved through specialized chromatin mechanisms. Chromatin-based cell memory enables cells to maintain their identity by fixing lineage specific transcriptional programs, ensuring their faithful transmission through cell division; in particular PcG-based memory system evolved to maintain the silenced state of developmental and cell cycle genes. In evolution the complexity of this system have increased, particularly in vertebrates, indicating combinatorial and dynamic properties of Polycomb proteins, in some cases even overflowing outside the cell nucleus. Therefore, their function may not be limited to the imposition of rigid states of genetic programs, but on the ability to recognize signals and allow plastic transcriptional changes in response to different stimuli. Here, we discuss the most novel PcG mediated memory functions in facing and responding to the challenges posed by a fluctuating environment.

The Calmodulin-Binding Transcription Activator CAMTA1 Is Required for Long-Term Memory Formation in Mice

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Bas-Orth, Carlos; Tan, Yan-Wei; Oliveira, Ana M. M.; Bengtson, C. Peter; Bading, Hilmar

2016-01-01

The formation of long-term memory requires signaling from the synapse to the nucleus to mediate neuronal activity-dependent gene transcription. Synapse-to-nucleus communication is initiated by influx of calcium ions through synaptic NMDA receptors and/or L-type voltage-gated calcium channels and involves the activation of transcription factors by…

Maintained LTP and Memory Are Lost by Zn2+ Influx into Dentate Granule Cells, but Not Ca2+ Influx.

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Takeda, Atsushi; Tamano, Haruna; Hisatsune, Marie; Murakami, Taku; Nakada, Hiroyuki; Fujii, Hiroaki

2018-02-01

The idea that maintained LTP and memory are lost by either increase in intracellular Zn 2+ in dentate granule cells or increase in intracellular Ca 2+ was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K + into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K + -induced increase in intracellular Zn 2+ but not high K + -induced increase in intracellular Ca 2+ . High K + -induced disturbances of LTP and intracellular Zn 2+ are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels. Furthermore, AMPA impaired maintained LTP and the impairment was also rescued by co-injection of CaEDTA, which blocked increase in intracellular Zn 2+ , but not increase in intracellular Ca 2+ . NMDA and glucocorticoid, which induced Zn 2+ release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn 2+ influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn 2+ influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca 2+ influx.

PKMzeta maintains 1-day- and 6-day-old long-term object location but not object identity memory in dorsal hippocampus.

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Hardt, Oliver; Migues, Paola V; Hastings, Margaret; Wong, Jacinda; Nader, Karim

2010-06-01

Continuous activity of the atypical protein kinase C isoform M zeta (PKMzeta) is necessary for maintaining long-term memory acquired in aversively or appetitively motivated associative learning tasks, such as active avoidance, aversive taste conditioning, auditory and contextual fear conditioning, radial arm maze, and watermaze. Whether unreinforced, nonassociative memory will also require PKMzeta for long-term maintenance is not known. Using recognition memory for object location and object identity, we found that inactivating PKMzeta in dorsal hippocampus abolishes 1-day and 6-day-old long-term recognition memory for object location, while recognition memory for object identity was not affected by this treatment. Memory for object location persisted for no more than 35 days after training. These results suggest that the dorsal hippocampus mediates long-term memory for where, but not what things have been encountered, and that PKMzeta maintains this type of spatial knowledge as long as the memory exists.

nalyot, a mutation of the Drosophila myb-related Adf1 transcription factor, disrupts synapse formation and olfactory memory.

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DeZazzo, J; Sandstrom, D; de Belle, S; Velinzon, K; Smith, P; Grady, L; DelVecchio, M; Ramaswami, M; Tully, T

2000-07-01

nalyot (nal) is a novel olfactory memory mutant of Drosophila, encoding Adf1, a myb-related transcription factor. Following extended training sessions, Adf1 mutants show normal early memory but defective longterm memory. Adf1 shows widespread spatiotemporal expression, yet mutant alleles reveal no discernible disruptions in gross morphology of the nervous system. Studies at the larval neuromuscular junction, however, reveal a role for Adf1 in the modulation of synaptic growth-in contrast to the role established for dCREB2 in the control of synaptic function (Davis et al., 1996). These findings suggest that Adf1 and dCREB2 regulate distinct transcriptional cascades involved in terminal stages of synapse maturation. More generally, Adf1 provides a novel link between molecular mechanisms of developmental and behavioral plasticity.

Histone Deacetylase Inhibition Induces Odor Preference Memory Extension and Maintains Enhanced AMPA Receptor Expression in the Rat Pup Model

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Bhattacharya, Sriya; Mukherjee, Bandhan; Doré, Jules J. E.; Yuan, Qi; Harley, Carolyn W.; McLean, John H.

2017-01-01

Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. We hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that have been hypothesized to support memory. We used an early odor preference learning model in…

Oct1 and OCA-B are selectively required for CD4 memory T cell function.

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Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N; Snook, Jeremy; Kuchroo, Vijay K; Yosef, Nir; Chan, Raymond C; Regev, Aviv; Williams, Matthew A; Tantin, Dean

2015-11-16

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4(+) T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4(+) T cell memory. © 2015 Shakya et al.

Memory responses of jasmonic acid-associated Arabidopsis genes to a repeated dehydration stress.

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Liu, Ning; Staswick, Paul E; Avramova, Zoya

2016-11-01

Dehydration stress activates numerous genes co-regulated by diverse signaling pathways. Upon repeated exposures, however, a subset of these genes does not respond maintaining instead transcription at their initial pre-stressed levels ('revised-response' genes). Most of these genes are involved in jasmonic acid (JA) biosynthesis, JA-signaling and JA-mediated stress responses. How these JA-associated genes are regulated to provide different responses to similar dehydration stresses is an enigma. Here, we investigate molecular mechanisms that contribute to this transcriptional behavior. The memory-mechanism is stress-specific: one exposure to dehydration stress or to abscisic acid (ABA) is required to prevent transcription in the second. Both ABA-mediated and JA-mediated pathways are critical for the activation of these genes, but the two signaling pathways interact differently during a single or multiple encounters with dehydration stress. Synthesis of JA during the first (S1) but not the second dehydration stress (S2) accounts for the altered transcriptional responses. We propose a model for these memory responses, wherein lack of MYC2 and of JA synthesis in S2 is responsible for the lack of expression of downstream genes. The similar length of the memory displayed by different memory-type genes suggests biological relevance for transcriptional memory as a gene-regulating mechanism during recurring bouts of drought. © 2016 John Wiley & Sons Ltd.

PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

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Peter Serrano

2008-12-01

Full Text Available How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta, an autonomously active atypical protein kinase C (PKC isoform critical for the maintenance of long-term potentiation (LTP. PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH and basolateral amygdala (BLA on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise

PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

Science.gov (United States)

Serrano, Peter; Friedman, Eugenia L; Kenney, Jana; Taubenfeld, Stephen M; Zimmerman, Joshua M; Hanna, John; Alberini, Cristina; Kelley, Ann E; Maren, Stephen; Rudy, Jerry W; Yin, Jerry C P; Sacktor, Todd C; Fenton, André A

2008-12-23

How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or

Transcriptional and physiological data reveal the dehydration memory behavior in switchgrass (Panicum virgatum L.).

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Zhang, Chao; Peng, Xi; Guo, Xiaofeng; Tang, Gaijuan; Sun, Fengli; Liu, Shudong; Xi, Yajun

2018-01-01

Switchgrass ( Panicum virgatum L.) is a model biofuel plant because of its high biomass, cellulose-richness, easy degradation to ethanol, and the availability of extensive genomic information. However, a little is currently known about the molecular responses of switchgrass plants to dehydration stress, especially multiple dehydration stresses. Studies on the transcriptional profiles of 35-day-old tissue culture plants revealed 741 dehydration memory genes. Gene Ontology and pathway analysis showed that these genes were enriched in phenylpropanoid biosynthesis, starch and sucrose metabolism, and plant hormone signal transduction. Further analysis of specific pathways combined with physiological data suggested that switchgrass improved its dehydration resistance by changing various aspects of its responses to secondary dehydration stress (D2), including the regulation of abscisic acid (ABA) and jasmonic acid (JA) biosynthesis and signal transduction, the biosynthesis of osmolytes (l-proline, stachyose and trehalose), energy metabolism (i.e., metabolic process relating to photosynthetic systems, glycolysis, and the TCA cycle), and lignin biosynthesis. The transcriptional data and chemical substance assays showed that ABA was significantly accumulated during both primary (D1) and secondary (D2) dehydration stresses, whereas JA accumulated during D1 but became significantly less abundant during D2. This suggests the existence of a complicated signaling network of plant hormones in response to repeated dehydration stresses. A homology analysis focusing on switchgrass, maize, and Arabidopsis revealed the conservation and species-specific distribution of dehydration memory genes. The molecular responses of switchgrass plants to successive dehydration stresses have been systematically characterized, revealing a previously unknown transcriptional memory behavior. These results provide new insights into the mechanisms of dehydration stress responses in plants. The genes and

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

Directory of Open Access Journals (Sweden)

Shusaku Uchida

2017-01-01

Full Text Available Summary: Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3-N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB, and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets. : Uchida et al. link CRTC1 synapse-to-nucleus shuttling in memory. Weak and strong training induce CRTC1 nuclear transport and transient Fgf1b transcription by a complex including CRTC1, CREB, and histone acetyltransferase CBP, whereas strong training alone maintains Fgf1b transcription through CRTC1-dependent substitution of KAT5 for CBP, leading to memory enhancement. Keywords: memory enhancement, long-term potentiation, hippocampus, nuclear transport, epigenetics, FGF1, CRTC1, KAT5/Tip60, HDAC3, CREB

Paradoxical role of an Egr transcription factor family member, Egr2/Krox20, in learning and memory

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Roseline Poirier

2007-12-01

Full Text Available It is well established that Egr1/zif268, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memories. Recently, the Egr3 family member has also been implicated in learning and memory. Because Egr family members encode closely related zinc-finger transcription factors sharing a highly homologous DNA binding domain that recognises the same DNA sequence, they may have related functions in brain. Another Egr family member expressed in brain, Egr2/Krox20 is known to be crucial for normal hindbrain development and has been implicated in several inherited peripheral neuropathies; however, due to Egr2-null mice perinatal lethality, its potential role in cognitive functions in the adult has not been yet explored. Here, we generated Egr2 conditional mutant mice allowing postnatal, forebrain-specific Cre-mediated Egr2 excision and tested homozygous, heterozygous and control littermates on a battery of behavioural tasks to evaluate motor capacity, exploratory behaviour, emotional reactivity and learning and memory performance in spatial and non-spatial tasks. Egr2-deficient mice had no sign of locomotor, exploratory or anxiety disturbances. Surprisingly, they also had no impairment in spatial learning and memory, taste aversion memory or fear memory using a trace conditioning paradigm. On the contrary, Egr2-deficient mice had improved performance in motor learning on a rotarod, and in object recognition memory. These results clearly do not extend the phenotypic consequences resulting from either Egr1 or Egr3 loss-of-function to Egr2. In contrast, they indicate that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain.

Upregulation of CREB-mediated transcription enhances both short- and long-term memory.

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Suzuki, Akinobu; Fukushima, Hotaka; Mukawa, Takuya; Toyoda, Hiroki; Wu, Long-Jun; Zhao, Ming-Gao; Xu, Hui; Shang, Yuze; Endoh, Kengo; Iwamoto, Taku; Mamiya, Nori; Okano, Emiko; Hasegawa, Shunsuke; Mercaldo, Valentina; Zhang, Yue; Maeda, Ryouta; Ohta, Miho; Josselyn, Sheena A; Zhuo, Min; Kida, Satoshi

2011-06-15

Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

Stress memory induced rearrangements of HSP transcription, photosystem II photochemistry and metabolism of tall fescue (Festuca arundinacea Schreb. in response to high-temperature stress

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Tao eHu

2015-06-01

Full Text Available When plants are pre-exposed to stress, they can produce some stable signals and physiological reactions that may be carried forward as ‘stress memory’. However, there is insufficient information about is known about plants’ stress memory responses mechanisms. Here, two tall fescue genotypes, heat-tolerant PI 574522 and heat-sensitive PI 512315, were subjected to recurring high-temperature pre-acclimation treatment. Two heat shock protein (HSP genes, LMW-HSP and HMW-HSP, exhibited transcriptional memory for their higher transcript abundance during one or more subsequent stresses (S2, S3, S4 relative to the first stress (S1, and basal transcript levels during the recovery states (R1, R2 and R3. Activated transcriptional memory from two trainable genes could persist up to 4 days, and induce higher thermotolerance in tall fescue. This was confirmed by greater turf quality and lower electrolyte leakage. Pre-acclimation treatment inhibited the decline at steps of O-J-I-P and energy transport fluxes in active Photosystem II reaction center (PSII RC for both tall fescue genotypes. The heat stress memory was associated with major shifts in leaf metabolite profiles. Furthermore, there was an exclusive increase in leaf organic acids (citric acid, malic acid, tris phosphoric acid, threonic acid, sugars (sucrose, glucose, idose, allose, talose, glucoheptose, tagatose, psicose, amino acids (serine, proline, pyroglutamic acid, glycine, alanine and one fatty acid (butanoic acid in pre-acclimated plants. These discoveries involved in transcriptional memory, PSII RC energy transport and metabolite profiles could provide new insights into the plant high–temperature response process.

The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts.

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Maléne E Lindholm

2016-09-01

Full Text Available Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity.

Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.

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Kozyrev, S A; Nikitin, V P

2013-03-01

We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.

A bilateral advantage for maintaining objects in visual short term memory.

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Holt, Jessica L; Delvenne, Jean-François

2015-01-01

Research has shown that attentional pre-cues can subsequently influence the transfer of information into visual short term memory (VSTM) (Schmidt, B., Vogel, E., Woodman, G., & Luck, S. (2002). Voluntary and automatic attentional control of visual working memory. Perception & Psychophysics, 64(5), 754-763). However, studies also suggest that those effects are constrained by the hemifield alignment of the pre-cues (Holt, J. L., & Delvenne, J.-F. (2014). A bilateral advantage in controlling access to visual short-term memory. Experimental Psychology, 61(2), 127-133), revealing better recall when distributed across hemifields relative to within a single hemifield (otherwise known as a bilateral field advantage). By manipulating the duration of the retention interval in a colour change detection task (1s, 3s), we investigated whether selective pre-cues can also influence how information is later maintained in VSTM. The results revealed that the pre-cues influenced the maintenance of the colours in VSTM, promoting consistent performance across retention intervals (Experiments 1 & 4). However, those effects were only shown when the pre-cues were directed to stimuli displayed across hemifields relative to stimuli within a single hemifield. Importantly, the results were not replicated when participants were required to memorise colours (Experiment 2) or locations (Experiment 3) in the absence of spatial pre-cues. Those findings strongly suggest that attentional pre-cues have a strong influence on both the transfer of information in VSTM and its subsequent maintenance, allowing bilateral items to better survive decay. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibition of Different Histone Acetyltransferases (HATs) Uncovers Transcription-Dependent and -Independent Acetylation-Mediated Mechanisms in Memory Formation

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Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

2016-01-01

Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied…

Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.

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Amanda L Kauffman

2010-05-01

Full Text Available Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR, exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.

Inhibition of transcription and translation in the striatum after memory reactivation: Lack of evidence of reconsolidation.

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Prado-Alcalá, Roberto A; Medina, Andrea Cristina; Bello-Medina, Paola C; Quirarte, Gina L

2017-07-01

It has been found that interference with neural activity after a consolidated memory is retrieved produces an amnestic state; this has been taken has indicative of destabilization of the memory trace that would have been produced by a process of reconsolidation (allowing for maintenance of the original trace). However, a growing body of evidence shows that this is not a reliable effect, and that it is dependent upon some experimental conditions, such as the age of the memory, memory reactivation procedures, the predictability of the reactivation stimulus, and strength of training. In some instances, where post-retrieval treatments induce a retention deficit (which would be suggestive of interference with reconsolidation), memory is rescued by simple passing of time or by repeated retention tests. We now report that post-training and post-retrieval inhibition of transcription and translation in dorsal striatum, a structure where both of these manipulations have not been studied, produce interference with consolidation and a transitory retention deficit, respectively. These results do not give support to the reconsolidation hypothesis and lead to the conclusion that the post-activation deficiencies are due to interference with retrieval of information. Copyright © 2016 Elsevier Inc. All rights reserved.

Maintaining the ties that bind: the role of an intermediate visual memory store in the persistence of awareness.

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Ferber, Susanne; Emrich, Stephen M

2007-03-01

Segregation and feature binding are essential to the perception and awareness of objects in a visual scene. When a fragmented line-drawing of an object moves relative to a background of randomly oriented lines, the previously hidden object is segregated from the background and consequently enters awareness. Interestingly, in such shape-from-motion displays, the percept of the object persists briefly when the motion stops, suggesting that the segregated and bound representation of the object is maintained in awareness. Here, we tested whether this persistence effect is mediated by capacity-limited working-memory processes, or by the amount of object-related information available. The experiments demonstrate that persistence is affected mainly by the proportion of object information available and is independent of working-memory limits. We suggest that this persistence effect can be seen as evidence for an intermediate, form-based memory store mediating between sensory and working memory.

Distinct Neural Substrates for Maintaining Locations and Spatial Relations in Working Memory

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Kara J Blacker

2016-11-01

Full Text Available Previous work has demonstrated a distinction between maintenance of two types of spatial information in working memory (WM: spatial locations and spatial relations. While a body of work has investigated the neural mechanisms of sensory-based information like spatial locations, little is known about how spatial relations are maintained in WM. In two experiments, we used fMRI to investigate the involvement of early visual cortex in the maintenance of spatial relations in WM. In both experiments, we found less quadrant-specific BOLD activity in visual cortex when a single spatial relation, compared to a single spatial location, was held in WM. Also across both experiments, we found a consistent set of brain regions that were differentially activated during maintenance of locations versus relations. Maintaining a location, compared to a relation, was associated with greater activity in typical spatial WM regions like posterior parietal cortex and prefrontal regions. Whereas maintaining a relation, compared to a location, was associated with greater activity in the parahippocampal gyrus and precuneus/retrosplenial cortex. Further, in Experiment 2 we manipulated WM load and included trials where participants had to maintain three spatial locations or relations. Under this high load condition, the regions sensitive to locations versus relations were somewhat different than under low load. We also identified regions that were sensitive to load specifically for location or relation maintenance, as well as overlapping regions sensitive to load more generally. These results suggest that the neural substrates underlying WM maintenance of spatial locations and relations are distinct from one another and that the neural representations of these distinct types of spatial information change with load.

Lateralized effects of orthographical irregularity and auditory memory load on the kinematics of transcription typewriting.

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Bloemsaat, Gijs; Van Galen, Gerard P; Meulenbroek, Ruud G J

2003-05-01

This study investigated the combined effects of orthographical irregularity and auditory memory load on the kinematics of finger movements in a transcription-typewriting task. Eight right-handed touch-typists were asked to type 80 strings of ten seven-letter words. In half the trials an irregularly spelt target word elicited a specific key press sequence of either the left or right index finger. In the other trials regularly spelt target words elicited the same key press sequence. An auditory memory load was added in half the trials by asking participants to remember the pitch of a tone during task performance. Orthographical irregularity was expected to slow down performance. Auditory memory load, viewed as a low level stressor, was expected to affect performance only when orthographically irregular words needed to be typed. The hypotheses were confirmed. Additional analysis showed differential effects on the left and right hand, possibly related to verbal-manual interference and hand dominance. The results are discussed in relation to relevant findings of recent neuroimaging studies.

ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis

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Moguche, Albanus O.; Shafiani, Shahin; Clemons, Corey; Larson, Ryan P.; Dinh, Crystal; Higdon, Lauren E.; Cambier, C.J.; Sissons, James R.; Gallegos, Alena M.; Fink, Pamela J.

2015-01-01

Immune control of persistent infection with Mycobacterium tuberculosis (Mtb) requires a sustained pathogen-specific CD4 T cell response; however, the molecular pathways governing the generation and maintenance of Mtb protective CD4 T cells are poorly understood. Using MHCII tetramers, we show that Mtb-specific CD4 T cells are subject to ongoing antigenic stimulation. Despite this chronic stimulation, a subset of PD-1+ cells is maintained within the lung parenchyma during tuberculosis (TB). When transferred into uninfected animals, these cells persist, mount a robust recall response, and provide superior protection to Mtb rechallenge when compared to terminally differentiated Th1 cells that reside preferentially in the lung-associated vasculature. The PD-1+ cells share features with memory CD4 T cells in that their generation and maintenance requires intrinsic Bcl6 and intrinsic ICOS expression. Thus, the molecular pathways required to maintain Mtb-specific CD4 T cells during ongoing infection are similar to those that maintain memory CD4 T cells in scenarios of antigen deprivation. These results suggest that vaccination strategies targeting the ICOS and Bcl6 pathways in CD4 T cells may provide new avenues to prevent TB. PMID:25918344

Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection.

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Shan, Liang; Deng, Kai; Gao, Hongbo; Xing, Sifei; Capoferri, Adam A; Durand, Christine M; Rabi, S Alireza; Laird, Gregory M; Kim, Michelle; Hosmane, Nina N; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B; Li, Linghua; Cai, Weiping; Ke, Ruian; Flavell, Richard A; Siliciano, Janet D; Siliciano, Robert F

2017-10-17

The latent reservoir for HIV-1 in resting memory CD4 + T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4 + T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4 + T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4 + T cells. Establishment of latent HIV-1 infection in CD4 + T could be inhibited by viral-specific CD8 + T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. Copyright © 2017. Published by Elsevier Inc.

Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor knock-out mice.

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Luis Segu

Full Text Available Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR(4, but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR(4 knock-out (KO and wild-type (WT mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR(4 control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR(4. Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR(4 KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT, the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4 KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR(4 KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR(4 to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR(4 aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR(4 mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.

Detailed sensory memory, sloppy working memory

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Ilja G Sligte

2010-10-01

Full Text Available Visual short-term memory (VSTM enables us to actively maintain information in mind for a brief period of time after stimulus disappearance. According to recent studies, VSTM consists of three stages - iconic memory, fragile VSTM, and visual working memory - with increasingly stricter capacity limits and progressively longer lifetimes. Still, the resolution (or amount of visual detail of each VSTM stage has remained unexplored and we test this in the present study. We presented people with a change detection task that measures the capacity of all three forms of VSTM, and we added an identification display after each change trial that required people to identify the pre-change object. Accurate change detection plus pre-change identification requires subjects to have a high-resolution representation of the pre-change object, whereas change detection or identification only can be based on the hunch that something has changed, without exactly knowing what was presented before. We observed that people maintained 6.1 objects in iconic memory, 4.6 objects in fragile VSTM and 2.1 objects in visual working memory. Moreover, when people detected the change, they could also identify the pre-change object on 88 percent of the iconic memory trials, on 71 percent of the fragile VSTM trials and merely on 53 percent of the visual working memory trials. This suggests that people maintain many high-resolution representations in iconic memory and fragile VSTM, but only one high-resolution object representation in visual working memory.

Detailed sensory memory, sloppy working memory.

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Sligte, Ilja G; Vandenbroucke, Annelinde R E; Scholte, H Steven; Lamme, Victor A F

2010-01-01

Visual short-term memory (VSTM) enables us to actively maintain information in mind for a brief period of time after stimulus disappearance. According to recent studies, VSTM consists of three stages - iconic memory, fragile VSTM, and visual working memory - with increasingly stricter capacity limits and progressively longer lifetimes. Still, the resolution (or amount of visual detail) of each VSTM stage has remained unexplored and we test this in the present study. We presented people with a change detection task that measures the capacity of all three forms of VSTM, and we added an identification display after each change trial that required people to identify the "pre-change" object. Accurate change detection plus pre-change identification requires subjects to have a high-resolution representation of the "pre-change" object, whereas change detection or identification only can be based on the hunch that something has changed, without exactly knowing what was presented before. We observed that people maintained 6.1 objects in iconic memory, 4.6 objects in fragile VSTM, and 2.1 objects in visual working memory. Moreover, when people detected the change, they could also identify the pre-change object on 88% of the iconic memory trials, on 71% of the fragile VSTM trials and merely on 53% of the visual working memory trials. This suggests that people maintain many high-resolution representations in iconic memory and fragile VSTM, but only one high-resolution object representation in visual working memory.

Detailed sensory memory, sloppy working memory

NARCIS (Netherlands)

Sligte, I.G.; Vandenbroucke, A.R.E.; Scholte, H.S.; Lamme, V.A.F.

2010-01-01

Visual short-term memory (VSTM) enables us to actively maintain information in mind for a brief period of time after stimulus disappearance. According to recent studies, VSTM consists of three stages - iconic memory, fragile VSTM, and visual working memory - with increasingly stricter capacity

High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

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Siersbæk, Majken; Varticovski, Lyuba; Yang, Shutong

2017-01-01

Abstract Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks...... for efficient treatment of early obesity-associated changes to hepatic complications by simple weight loss intervention without persistent reprograming of the liver transcriptome....

The transcription elongation factor Bur1-Bur2 interacts with replication protein A and maintains genome stability during replication stress

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Clausing, Emanuel; Mayer, Andreas; Chanarat, Sittinan

2010-01-01

Multiple DNA-associated processes such as DNA repair, replication, and recombination are crucial for the maintenance of genome integrity. Here, we show a novel interaction between the transcription elongation factor Bur1-Bur2 and replication protein A (RPA), the eukaryotic single-stranded DNA......-binding protein with functions in DNA repair, recombination, and replication. Bur1 interacted via its C-terminal domain with RPA, and bur1-¿C mutants showed a deregulated DNA damage response accompanied by increased sensitivity to DNA damage and replication stress as well as increased levels of persisting Rad52...... foci. Interestingly, the DNA damage sensitivity of an rfa1 mutant was suppressed by bur1 mutation, further underscoring a functional link between these two protein complexes. The transcription elongation factor Bur1-Bur2 interacts with RPA and maintains genome integrity during DNA replication stress....

How Polycomb-Mediated Cell Memory Deals With a Changing Environment: Variations in PcG complexes and proteins assortment convey plasticity to epigenetic regulation as a response to environment.

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Marasca, Federica; Bodega, Beatrice; Orlando, Valerio

2018-04-01

Cells and tissues are continuously exposed to a changing microenvironment, hence the necessity of a flexible modulation of gene expression that in complex organism have been achieved through specialized chromatin mechanisms. Chromatin-based cell memory enables cells to maintain their identity by fixing lineage specific transcriptional programs, ensuring their faithful transmission through cell division; in particular PcG-based memory system evolved to maintain the silenced state of developmental and cell cycle genes. In evolution the complexity of this system have increased, particularly in vertebrates, indicating combinatorial and dynamic properties of Polycomb proteins, in some cases even overflowing outside the cell nucleus. Therefore, their function may not be limited to the imposition of rigid states of genetic programs, but on the ability to recognize signals and allow plastic transcriptional changes in response to different stimuli. Here, we discuss the most novel PcG mediated memory functions in facing and responding to the challenges posed by a fluctuating environment. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Induction of latent memory for conditioned food aversion and its transformation into "active" state depend on translation and transcription processes.

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Solntseva, S V; Nikitin, V P

2014-05-01

Mechanisms of induction and retrieval of latent (hidden) memory for conditioned food aversion were investigated in snails. After initial training (single combination of a food stimulus with electric shock), aversive reactions to presentation of the conditioned food stimulus were not revealed. Repeated presentation of the stimuli in 12 days after the first combination was followed by the appearance of aversive food reactions that persisted for at least 14 days. Injections of inhibitors of protein (cycloheximide) or RNA (α-amanitin) synthesis immediately after the first or second combined presentation of the stimuli disturbed skill performance. We hypothesized that single combination of food and reinforcing stimuli led to translation- and transcription-dependent induction of latent conditioned food aversion memory. Transformation of this memory into an active state after repeated presentation of the stimulus combination also depends on the synthesis of new proteins and RNA.

Rapid changes in transcription profiles of the Plasmodium yoelii yir multigene family in clonal populations: lack of epigenetic memory?

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Deirdre Cunningham

Full Text Available The pir multigene family, found in the genomes of Plasmodium vivax, P. knowlesi and the rodent malaria species, encode variant antigens that could be targets of the immune response. Individual parasites of the rodent malaria Plasmodium yoelii, selected by micromanipulation, transcribe only 1 to 3 different pir (yir suggesting tight transcriptional control at the level of individual cells. Using microarray and quantitative RT-PCR, we show that despite this very restricted transcription in a single cell, many yir genes are transcribed throughout the intra-erythrocytic asexual cycle. The timing and level of transcription differs between genes, with some being more highly transcribed in ring and trophozoite stages, whereas others are more highly transcribed in schizonts. Infection of immunodeficient mice with single infected erythrocytes results in populations of parasites each with transcriptional profiles different from that of the parent parasite population and from each other. This drift away from the original 'set' of transcribed genes does not appear to follow a preset pattern and "epigenetic memory" of the yir transcribed in the parent parasite can be rapidly lost. Thus, regulation of pir gene transcription may be different from that of the well-characterised multigene family, var, of Plasmodium falciparum.

Dehydration stress memory genes of Zea mays; comparison with Arabidopsis thaliana

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2014-01-01

Background Pre-exposing plants to diverse abiotic stresses may alter their physiological and transcriptional responses to a subsequent stress, suggesting a form of “stress memory”. Arabidopsis thaliana plants that have experienced multiple exposures to dehydration stress display transcriptional behavior suggesting “memory” from an earlier stress. Genes that respond to a first stress by up-regulating or down-regulating their transcription but in a subsequent stress provide a significantly different response define the ‘memory genes’ category. Genes responding similarly to each stress form the ‘non-memory’ category. It is unknown whether such memory responses exists in other Angiosperm lineages and whether memory is an evolutionarily conserved response to repeated dehydration stresses. Results Here, we determine the transcriptional responses of maize (Zea mays L.) plants that have experienced repeated exposures to dehydration stress in comparison with plants encountering the stress for the first time. Four distinct transcription memory response patterns similar to those displayed by A. thaliana were revealed. The most important contribution is the evidence that monocot and eudicot plants, two lineages that have diverged 140 to 200 M years ago, display similar abilities to ‘remember’ a dehydration stress and to modify their transcriptional responses, accordingly. The highly sensitive RNA-Seq analyses allowed to identify genes that function similarly in the two lineages, as well as genes that function in species-specific ways. Memory transcription patterns indicate that the transcriptional behavior of responding genes under repeated stresses is different from the behavior during an initial dehydration stress, suggesting that stress memory is a complex phenotype resulting from coordinated responses of multiple signaling pathways. Conclusions Structurally related genes displaying the same memory responses in the two species would suggest conservation

Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

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E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

DNA Topoisomerases Maintain Promoters in a State Competent for Transcriptional Activation in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Pedersen, Jakob Madsen; Fredsøe, Jacob Christian; Rødgaard, Morten Terpager

2012-01-01

To investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings. The genome-wide studies show a general transcriptional down......-regulation upon lack of the enzymes, which correlates with gene activity but not gene length. Furthermore, our data reveal a distinct subclass of genes with a strong requirement for topoisomerases. These genes are characterized by high transcriptional plasticity, chromatin regulation, TATA box presence......-depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation...

Fluid consumption and taste novelty determines transcription temporal dynamics in the gustatory cortex

OpenAIRE

Inberg, Sharon; Jacob, Eyal; Elkobi, Alina; Edry, Efrat; Rappaport, Akiva; Simpson, T. Ian; Armstrong, J. Douglas; Shomron, Noam; Pasmanik-Chor, Metsada; Rosenblum, Kobi

2016-01-01

Background Novel taste memories, critical for animal survival, are consolidated to form long term memories which are dependent on translation regulation in the gustatory cortex (GC) hours following acquisition. However, the role of transcription regulation in the process is unknown. Results Here, we report that transcription in the GC is necessary for taste learning in rats, and that drinking and its consequences, as well as the novel taste experience, affect transcription in the GC during ta...

Detailed Sensory Memory, Sloppy Working Memory

OpenAIRE

Sligte, Ilja G.; Vandenbroucke, Annelinde R. E.; Scholte, H. Steven; Lamme, Victor A. F.

2010-01-01

Visual short-term memory (VSTM) enables us to actively maintain information in mind for a brief period of time after stimulus disappearance. According to recent studies, VSTM consists of three stages - iconic memory, fragile VSTM, and visual working memory - with increasingly stricter capacity limits and progressively longer lifetimes. Still, the resolution (or amount of visual detail) of each VSTM stage has remained unexplored and we test this in the present study. We presented people with a...

New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

Science.gov (United States)

Levy, Roi; Levitan, David; Susswein, Abraham J

2016-01-01

Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory. DOI: http://dx.doi.org/10.7554/eLife.17769.001 PMID:27919318

New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process.

Science.gov (United States)

Levy, Roi; Levitan, David; Susswein, Abraham J

2016-12-06

Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory.

CREB regulates spine density of lateral amygdala neurons: implications for memory allocation

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Derya eSargin

2013-12-01

Full Text Available Neurons may compete against one another for integration into a memory trace. Specifically, neurons in the lateral nucleus of the amygdala with relatively higher levels of CREB seem to be preferentially allocated to a fear memory trace, while neurons with relatively decreased CREB function seem to be excluded from a fear memory trace. CREB is a ubiquitous transcription factor that modulates many diverse cellular processes, raising the question as to which of these CREB-mediated processes underlie memory allocation. CREB is implicated in modulating dendritic spine number and morphology. As dendritic spines are intimately involved in memory formation, we investigated whether manipulations of CREB function alter spine number or morphology of neurons at the time of fear conditioning. We used viral vectors to manipulate CREB function in the lateral amygdala principal neurons in mice maintained in their homecages. At the time that fear conditioning normally occurs, we observed that neurons with high levels of CREB had more dendritic spines, while neurons with low CREB function had relatively fewer spines compared to control neurons. These results suggest that the modulation of spine density provides a potential mechanism for preferential allocation of a subset of neurons to the memory trace.

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

Science.gov (United States)

Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

Memory T follicular helper CD4 T cells

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J. Scott eHale

2015-02-01

Full Text Available T follicular helper (Tfh cells are the subset of CD4 T helper cells that are required for generation and maintenance of germinal center reactions and the generation of long-lived humoral immunity. This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and other molecules. Tfh cells are characterized by their expression of the chemokine receptor CXCR5, expression of the transcriptional repressor Bcl6, and their capacity to migrate to the follicle and promote germinal center B cell responses. Until recently, it remained unclear whether Tfh cells differentiated into memory cells and whether they maintain their Tfh commitment at the memory phase. This review will highlight several recent studies that support the idea of Tfh-committed CD4 T cells at the memory stage of the immune response. The implication of these findings is that memory Tfh cells retain their capacity to recall their Tfh-specific effector functions upon reactivation to provide help for B cell responses and play an important role in prime and boost vaccination or during recall responses to infection. The markers that are useful for distinguishing Tfh effector and memory cells, as well as the limitations of using these markers will be discussed. Tfh effector and memory generation, lineage maintenance, and plasticity relative to other T helper lineages (Th1, Th2, Th17, etc will also be discussed. Ongoing discoveries regarding the maintenance and lineage stability versus plasticity of memory Tfh cells will improve strategies that utilize CD4 T cell memory to modulate antibody responses during prime and boost vaccination.

Gestures maintain spatial imagery.

Science.gov (United States)

Wesp, R; Hesse, J; Keutmann, D; Wheaton, K

2001-01-01

Recent theories suggest alternatives to the commonly held belief that the sole role of gestures is to communicate meaning directly to listeners. Evidence suggests that gestures may serve a cognitive function for speakers, possibly acting as lexical primes. We observed that participants gestured more often when describing a picture from memory than when the picture was present and that gestures were not influenced by manipulating eye contact of a listener. We argue that spatial imagery serves a short-term memory function during lexical search and that gestures may help maintain spatial images. When spatial imagery is not necessary, as in conditions of direct visual stimulation, reliance on gestures is reduced or eliminated.

Fluid consumption and taste novelty determines transcription temporal dynamics in the gustatory cortex.

Science.gov (United States)

Inberg, Sharon; Jacob, Eyal; Elkobi, Alina; Edry, Efrat; Rappaport, Akiva; Simpson, T Ian; Armstrong, J Douglas; Shomron, Noam; Pasmanik-Chor, Metsada; Rosenblum, Kobi

2016-02-09

Novel taste memories, critical for animal survival, are consolidated to form long term memories which are dependent on translation regulation in the gustatory cortex (GC) hours following acquisition. However, the role of transcription regulation in the process is unknown. Here, we report that transcription in the GC is necessary for taste learning in rats, and that drinking and its consequences, as well as the novel taste experience, affect transcription in the GC during taste memory consolidation. We show differential effects of learning on temporal dynamics in set of genes in the GC, including Arc/Arg3.1, known to regulate the homeostasis of excitatory synapses. We demonstrate that in taste learning, transcription programs were activated following the physiological responses (i.e., fluid consumption following a water restriction regime, reward, arousal of the animal, etc.) and the specific information about a given taste (i.e., taste novelty). Moreover, the cortical differential prolonged kinetics of mRNA following novel versus familiar taste learning may represent additional novelty related molecular response, where not only the total amount, but also the temporal dynamics of transcription is modulated by sensory experience of novel information.

Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

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Hong SU

2013-03-01

Full Text Available Objective 　To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3 and Ac-H4 in human renal mesangial cell (HMCs as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods 　The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, high glucose group (HG, 25mmol/L D-glucose×2d, memory groups (M1, M2, M3, 25mmol/L D-glucose×2days + 5.5mmol/L D-glucose×3d, 6d or 9d, persisting normal glucose group (NG, 5.5mmol/L D-glucose×9d. ② Advanced glycation end products memory model: normal glucose group (NG, 5.5mmol/ L D-glucose×2d, NG+AGEs group (AGEs, 5.5mmol/L D-glucose+250µg/ml AGEs×2d; AGEs memory group (AGEs-M, 5.5mmol/L D-glucose + 250µg/ml AGEs×2d + 5.5mmol/L D-glucose×3d; BSA control group (NG+BSA, 5.5mmol/L D-glucose + 250µg/ml BSA×2d. ③ H2O2 was used to simulate oxidative stress memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, NG+H2O2 group (H2O2, 5.5mmol/L D-glucose +100µmol/L H2O2×30min; H2O2 memory group [(5.5mmol/ L D-glucose + 100µmol/L H2O2×30min + 5.5mmol/L D-glucose×3d]; normal glucose control group (NG3, 5.5mmol/L D-glucose×3d. ④ Transfection with PKCβ2 memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d; high glucose group (HG, 25mmol/L D-glucose×2d; memory group (M, 25mmol/L D-glucose×2d + 5.5mmol/L D-glucose×3d; Ad5-null memory group (HN, 25mmol/L D-glucose + Ad5-null×2d + 5.5mmol/L D-glucose×3d; PKCβ2 memory group (PO, 25mmol/L D-glucose + Ad5-PKCβ2×2d + 5.5mmol/L D-glucose×3d; inhibitor of PKCβ2 memory group (PI, 25mmol/L D-glucose×2d + 10µmol/L CGP53353 + 5.5mmol/L D-glucose×3d. The expression of intracellular reactive oxygen species (ROS was detected by fluorescence microscope and fluorescence microplate reader. The expression levels of p300, Ac-H3, Ac-H4 and PKCβ2 proteins were

A bilateral advantage for maintaining objects in visual short term memory

OpenAIRE

Holt, JL; Delvenne, JFCM

2015-01-01

Research has shown that attentional pre-cues can subsequently influence the transfer of information into visual short term memory (VSTM) (Schmidt, B., Vogel, E., Woodman, G., & Luck, S. (2002). Voluntary and automatic attentional control of visual working memory. Perception & Psychophysics, 64(5), 754–763). However, studies also suggest that those effects are constrained by the hemifield alignment of the pre-cues (Holt, J. L., & Delvenne, J.-F. (2014). A bilateral advantage in controlling acc...

Estrogen-induced transcription factor EGR1 regulates c-Kit transcription in the mouse uterus to maintain uterine receptivity for embryo implantation.

Science.gov (United States)

Park, Mira; Kim, Hye-Ryun; Kim, Yeon Sun; Yang, Seung Chel; Yoon, Jung Ah; Lyu, Sang Woo; Lim, Hyunjung Jade; Hong, Seok-Ho; Song, Haengseok

2018-07-15

Early growth response 1 (Egr1) is a key transcription factor that mediates the action of estrogen (E 2 ) to establish uterine receptivity for embryo implantation. However, few direct target genes of EGR1 have been identified in the uterus. Here, we demonstrated that E 2 induced EGR1-regulated transcription of c-Kit, which plays a crucial role in cell fate decisions. Spatiotemporal expression of c-Kit followed that of EGR1 in uteri of ovariectomized mice at various time points after E 2 treatment. E 2 activated ERK1/2 and p38 to induce EGR1, which then activated c-Kit expression in the uterus. EGR1 transfection produced rapid and transient induction of c-KIT in a time- and dose-dependent manner. Furthermore, luciferase assays to measure c-Kit promoter activity confirmed that a functional EGR1 binding site(s) (EBS) was located within -1 kb of the c-Kit promoter. Site-directed mutagenesis and chromatin immunoprecipitation-PCR for three putative EBS within -1 kb demonstrated that the EBS at -818/-805 was critical for EGR1-dependent c-Kit transcription. c-Kit expression was significantly increased in the uterus on day 4 and administration of Masitinib, a c-Kit inhibitor, effectively interfered with embryo implantation. Collectively, our results showed that estrogen induces transcription factor EGR1 to regulate c-Kit transcription for uterine receptivity for embryo implantation in the mouse uterus. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered Gradients of Glutamate and Gamma-Aminobutyric Acid Transcripts in the Cortical Visuospatial Working Memory Network in Schizophrenia.

Science.gov (United States)

Hoftman, Gil D; Dienel, Samuel J; Bazmi, Holly H; Zhang, Yun; Chen, Kehui; Lewis, David A

2018-04-15

Visuospatial working memory (vsWM), which is impaired in schizophrenia, requires information transfer across multiple nodes in the cerebral cortex, including visual, posterior parietal, and dorsolateral prefrontal regions. Information is conveyed across these regions via the excitatory projections of glutamatergic pyramidal neurons located in layer 3, whose activity is modulated by local inhibitory gamma-aminobutyric acidergic (GABAergic) neurons. Key properties of these neurons differ across these cortical regions. Consequently, in schizophrenia, alterations in the expression of gene products regulating these properties could disrupt vsWM function in different ways, depending on the region(s) affected. Here, we quantified the expression of markers of glutamate and GABA neurotransmission selectively in layer 3 of four cortical regions in the vsWM network from 20 matched pairs of schizophrenia and unaffected comparison subjects. In comparison subjects, levels of glutamate transcripts tended to increase, whereas GABA transcript levels tended to decrease, from caudal to rostral, across cortical regions of the vsWM network. Composite measures across all transcripts revealed a significant effect of region, with the glutamate measure lowest in the primary visual cortex and highest in the dorsolateral prefrontal cortex, whereas the GABA measure showed the opposite pattern. In schizophrenia subjects, the expression levels of many of these transcripts were altered. However, this disease effect differed across regions, such that the caudal-to-rostral increase in the glutamate measure was blunted and the caudal-to-rostral decline in the GABA measure was enhanced in the illness. Differential alterations in layer 3 glutamate and GABA neurotransmission across cortical regions may contribute to vsWM deficits in schizophrenia. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Manipulations of attention dissociate fragile visual short-term memory from visual working memory

NARCIS (Netherlands)

Vandenbroucke, A.R.E.; Sligte, I.G.; Lamme, V.A.F.

2011-01-01

People often rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). Traditionally, VSTM is thought to operate on either a short time-scale with high capacity - iconic memory - or a long time scale with small capacity - visual working memory. Recent research

AP1 transcription factors are required to maintain the peripheral taste system.

Science.gov (United States)

Shandilya, Jayasha; Gao, Yankun; Nayak, Tapan K; Roberts, Stefan G E; Medler, Kathryn F

2016-10-27

The sense of taste is used by organisms to achieve the optimal nutritional requirement and avoid potentially toxic compounds. In the oral cavity, taste receptor cells are grouped together in taste buds that are present in specialized taste papillae in the tongue. Taste receptor cells are the cells that detect chemicals in potential food items and transmit that information to gustatory nerves that convey the taste information to the brain. As taste cells are in contact with the external environment, they can be damaged and are routinely replaced throughout an organism's lifetime to maintain functionality. However, this taste cell turnover loses efficiency over time resulting in a reduction in taste ability. Currently, very little is known about the mechanisms that regulate the renewal and maintenance of taste cells. We therefore performed RNA-sequencing analysis on isolated taste cells from 2 and 6-month-old mice to determine how alterations in the taste cell-transcriptome regulate taste cell maintenance and function in adults. We found that the activator protein-1 (AP1) transcription factors (c-Fos, Fosb and c-Jun) and genes associated with this pathway were significantly downregulated in taste cells by 6 months and further declined at 12 months. We generated conditional c-Fos-knockout mice to target K14-expressing cells, including differentiating taste cells. c-Fos deletion caused a severe perturbation in taste bud structure and resulted in a significant reduction in the taste bud size. c-Fos deletion also affected taste cell turnover as evident by a decrease in proliferative marker, and upregulation of the apoptotic marker cleaved-PARP. Thus, AP1 factors are important regulators of adult taste cell renewal and their downregulation negatively impacts taste maintenance.

A Brain System for Auditory Working Memory.

Science.gov (United States)

Kumar, Sukhbinder; Joseph, Sabine; Gander, Phillip E; Barascud, Nicolas; Halpern, Andrea R; Griffiths, Timothy D

2016-04-20

The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance. Copyright © 2016 Kumar et al.

Transcriptional and Post-Transcriptional Mechanisms of the Development of Neocortical Lamination

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Tatiana Popovitchenko

2017-11-01

Full Text Available The neocortex is a laminated brain structure that is the seat of higher cognitive capacity and responses, long-term memory, sensory and emotional functions, and voluntary motor behavior. Proper lamination requires that progenitor cells give rise to a neuron, that the immature neuron can migrate away from its mother cell and past other cells, and finally that the immature neuron can take its place and adopt a mature identity characterized by connectivity and gene expression; thus lamination proceeds through three steps: genesis, migration, and maturation. Each neocortical layer contains pyramidal neurons that share specific morphological and molecular characteristics that stem from their prenatal birth date. Transcription factors are dynamic proteins because of the cohort of downstream factors that they regulate. RNA-binding proteins are no less dynamic, and play important roles in every step of mRNA processing. Indeed, recent screens have uncovered post-transcriptional mechanisms as being integral regulatory mechanisms to neocortical development. Here, we summarize major aspects of neocortical laminar development, emphasizing transcriptional and post-transcriptional mechanisms, with the aim of spurring increased understanding and study of its intricacies.

Working memory benefits creative insight, musical improvisation, and original ideation through maintained task-focused attention.

Science.gov (United States)

De Dreu, Carsten K W; Nijstad, Bernard A; Baas, Matthijs; Wolsink, Inge; Roskes, Marieke

2012-05-01

Anecdotes from creative eminences suggest that executive control plays an important role in creativity, but scientific evidence is sparse. Invoking the Dual Pathway to Creativity Model, the authors hypothesize that working memory capacity (WMC) relates to creative performance because it enables persistent, focused, and systematic combining of elements and possibilities (persistence). Study 1 indeed showed that under cognitive load, participants performed worse on a creative insight task. Study 2 revealed positive associations between time-on-task and creativity among individuals high but not low in WMC, even after controlling for general intelligence. Study 3 revealed that across trials, semiprofessional cellists performed increasingly more creative improvisations when they had high rather than low WMC. Study 4 showed that WMC predicts original ideation because it allows persistent (rather than flexible) processing. The authors conclude that WMC benefits creativity because it enables the individual to maintain attention focused on the task and prevents undesirable mind wandering.

Neuroimaging markers associated with maintenance of optimal memory performance in late-life.

Science.gov (United States)

Dekhtyar, Maria; Papp, Kathryn V; Buckley, Rachel; Jacobs, Heidi I L; Schultz, Aaron P; Johnson, Keith A; Sperling, Reisa A; Rentz, Dorene M

2017-06-01

Age-related memory decline has been well-documented; however, some individuals reach their 8th-10th decade while maintaining strong memory performance. To determine which demographic and biomarker factors differentiated top memory performers (aged 75+, top 20% for memory) from their peers and whether top memory performance was maintained over 3 years. Clinically normal adults (n=125, CDR=0; age: 79.5±3.57 years) from the Harvard Aging Brain Study underwent cognitive testing and neuroimaging (amyloid PET, MRI) at baseline and 3-year follow-up. Participants were grouped into Optimal (n=25) vs. Typical (n=100) performers using performance on 3 challenging memory measures. Non-parametric tests were used to compare groups. There were no differences in age, sex, or education between Optimal vs. Typical performers. The Optimal group performed better in Processing Speed (p=0.016) and Executive Functioning (pmemory performance while 7 declined. Non-Maintainers additionally declined in Executive Functioning but not Processing Speed. Longitudinally, there were no hippocampal volume differences between Maintainers and Non-Maintainers, however Non-Maintainers exhibited higher amyloid burden at baseline in contrast with Maintainers (p=0.008). Excellent memory performance in late life does not guarantee protection against cognitive decline. Those who maintain an optimal memory into the 8th and 9th decades may have lower levels of AD pathology. Copyright © 2017. Published by Elsevier Ltd.

Working-memory consolidation : Insights from studies on attention and working memory

NARCIS (Netherlands)

Ricker, Timothy; Nieuwenstein, Mark; Bayliss, Donna; Barrouillet, Pierre

2018-01-01

Working memory, the system that maintains a limited set of representations for immediate use in cognition, is a central part of human cognition. Three processes have recently been proposed to govern information storage in working memory: Consolidation, refreshing and removal. Here we discuss in

Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity

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Dane M. Newman

2016-09-01

Full Text Available How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning of CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show that lysine acetyltransferase 6A (KAT6A is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses during infection. KAT6A-deficient CD8+ T cells downregulated surface CD8 co-receptor expression during clonal expansion, a finding linked to reduced Cd8α transcripts and histone-H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in KAT6A-deficient T cells correlated with reduced TCR signaling intensity and accelerated contraction of the effector-like memory compartment, whereas the long-lived memory compartment appeared unaffected, a result phenocopied by the removal of the Cd8 E8I enhancer element. These findings suggest a direct role of CD8αβ co-receptor expression and histone acetylation in shaping functional diversity within the cytotoxic T cell pool.

Maintaining binding in working memory : Comparing the effects of intentional goals and incidental affordances

NARCIS (Netherlands)

Morey, Candice C.

Much research on memory for binding depends on incidental measures. However, if encoding associations benefits from conscious attention, then incidental measures of binding memory might not yield a sufficient understanding of how binding is accomplished. Memory for letters and spatial locations was

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

Science.gov (United States)

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to

Histone modifier, the gatekeeper of good memory

Institute of Scientific and Technical Information of China (English)

Zilong Qiu

2009-01-01

@@ How do we learn and how do we remember? Learning and memory has long been one of the most fascinating questions in biology. In the 1970s, Squire LR et aL provided evidence that gene expression processes are critical for memory by showing that memory consolidation is disrupted when gene transcription or translation is blocked during the learning process [1].

The CD8+ memory T-cell state of readiness is actively maintained and reversible

OpenAIRE

Allam, Atef; Conze, Dietrich B.; Giardino Torchia, Maria Letizia; Munitic, Ivana; Yagita, Hideo; Sowell, Ryan T.; Marzo, Amanda L.; Ashwell, Jonathan D.

2009-01-01

The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cy...

Altered gene regulation and synaptic morphology in Drosophila learning and memory mutants

Science.gov (United States)

Guan, Zhuo; Buhl, Lauren K.; Quinn, William G.; Littleton, J. Troy

2011-01-01

Genetic studies in Drosophila have revealed two separable long-term memory pathways defined as anesthesia-resistant memory (ARM) and long-lasting long-term memory (LLTM). ARM is disrupted in radish (rsh) mutants, whereas LLTM requires CREB-dependent protein synthesis. Although the downstream effectors of ARM and LLTM are distinct, pathways leading to these forms of memory may share the cAMP cascade critical for associative learning. Dunce, which encodes a cAMP-specific phosphodiesterase, and rutabaga, which encodes an adenylyl cyclase, both disrupt short-term memory. Amnesiac encodes a pituitary adenylyl cyclase-activating peptide homolog and is required for middle-term memory. Here, we demonstrate that the Radish protein localizes to the cytoplasm and nucleus and is a PKA phosphorylation target in vitro. To characterize how these plasticity pathways may manifest at the synaptic level, we assayed synaptic connectivity and performed an expression analysis to detect altered transcriptional networks in rutabaga, dunce, amnesiac, and radish mutants. All four mutants disrupt specific aspects of synaptic connectivity at larval neuromuscular junctions (NMJs). Genome-wide DNA microarray analysis revealed ∼375 transcripts that are altered in these mutants, suggesting defects in multiple neuronal signaling pathways. In particular, the transcriptional target Lapsyn, which encodes a leucine-rich repeat cell adhesion protein, localizes to synapses and regulates synaptic growth. This analysis provides insights into the Radish-dependent ARM pathway and novel transcriptional targets that may contribute to memory processing in Drosophila. PMID:21422168

Chewing Maintains Hippocampus-Dependent Cognitive Function.

Science.gov (United States)

Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2015-01-01

Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

Requirement for nuclear calcium signaling in Drosophila long-term memory.

Science.gov (United States)

Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

2013-05-07

Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

GoldiRunx and Remembering Cytotoxic Memory.

Science.gov (United States)

Mikami, Yohei; Kanno, Yuka

2018-04-17

The molecular basis for T cell memory differentiation remains elusive. Wang et al. (2018) identify Runx3 as an initiating transcription factor that specifies regulatory regions required for cytotoxic T cell (CTL) memory differentiation early after TCR signaling and constrains the ability of T-bet to drive terminal effector generation. Published by Elsevier Inc.

Acquired transcriptional programming in functional and exhausted virus-specific CD8 T cells.

Science.gov (United States)

Youngblood, Ben; Wherry, E John; Ahmed, Rafi

2012-01-01

Failure to control viral infections such as HIV results in T-cell receptor (TCR) and inhibitory receptor driven exhaustion of antigen-specific T cells. Persistent signaling by these receptors during chronic viral infection sculpts the transcriptional regulatory programs of virus-specific T cells. The resulting gene expression profile is tailored to temper the potentially damaging effector functions of cytotoxic T cells and adapt them to an antigen-rich and inflammation-rich environment. Here we review recent studies investigating mechanisms of transcriptional regulation of effector, functional memory, and exhausted T-cell functions during acute versus chronic infections. Patterns of gene expression in virus-specific CD8 T cells are a result of a combination of pro and inhibitory signals from antigen presentation (TCR-mediated) and co-inhibitory receptor ligation (PD-1, 2B4). Further, memory-specific transcriptional regulation of 2B4 expression and signaling impose a self-limiting secondary effector response to a prolonged viral infection. Additionally, differentiation of functional memory CD8 T cells is coupled with acquisition of a repressive epigenetic program for PD-1 expression. However, chronic infection provides a signal that blocks the acquisition of these epigenetic modifications reinforcing the suppression of cytotoxic lymphocyte (CTL) functions in exhausted cells. Current findings suggest that the mechanism(s) that delineate functional memory versus exhaustion are coupled with acquisition of transcriptional programs at the effector stage of differentiation, reinforced by cessation or persistence of TCR signaling.

Neuroepigenetic Regulation of Pathogenic Memories.

Science.gov (United States)

Sillivan, Stephanie E; Vaissière, Thomas; Miller, Courtney A

2015-01-01

Our unique collection of memories determines our individuality and shapes our future interactions with the world. Remarkable advances into the neurobiological basis of memory have identified key epigenetic mechanisms that support the stability of memory. Various forms of epigenetic regulation at the levels of DNA methylation, histone modification, and non-coding RNAs (ncRNAs) can modulate transcriptional and translational events required for memory processes. By changing the cellular profile in the brain's emotional, reward, and memory circuits, these epigenetic modifications have also been linked to perseverant, pathogenic memories. In this review, we will delve into the relevance of epigenetic dysregulation to pathogenic memory mechanisms by focusing on two neuropsychiatric disorders perpetuated by aberrant memory associations: substance use disorder (SUD) and post-traumatic stress disorder (PTSD). As our understanding improves, neuroepigenetic mechanisms may someday be harnessed to develop novel therapeutic targets for the treatment of these chronic, relapsing disorders.

Neuroepigenetic regulation of pathogenic memories

Directory of Open Access Journals (Sweden)

Stephanie E. Sillivan

2015-01-01

Full Text Available Our unique collection of memories determines our individuality and shapes our future interactions with the world. Remarkable advances into the neurobiological basis of memory have identified key epigenetic mechanisms that support the stability of memory. Various forms of epigenetic regulation at the levels of DNA methylation, histone modification, and noncoding RNAs can modulate transcriptional and translational events required for memory processes. By changing the cellular profile in the brain’s emotional, reward, and memory circuits, these epigenetic modifications have also been linked to perseverant, pathogenic memories. In this review, we will delve into the relevance of epigenetic dysregulation to pathogenic memory mechanisms by focusing on 2 neuropsychiatric disorders perpetuated by aberrant memory associations: substance use disorder and post-traumatic stress disorder. As our understanding improves, neuroepigenetic mechanisms may someday be harnessed to develop novel therapeutic targets for the treatment of these chronic, relapsing disorders.

Heartwarming memories: Nostalgia maintains physiological comfort.

Science.gov (United States)

Zhou, Xinyue; Wildschut, Tim; Sedikides, Constantine; Chen, Xiaoxi; Vingerhoets, Ad J J M

2012-08-01

Nostalgia, a sentimental longing or wistful affection for the past, is a predominantly positive and social emotion. Recent evidence suggests that nostalgia maintains psychological comfort. Here, we propose, and document in five methodologically diverse studies, a broader homeostatic function for nostalgia that also encompasses the maintenance of physiological comfort. We show that nostalgia--an emotion with a strong connotation of warmth--is triggered by coldness. Participants reported stronger nostalgia on colder (vs. warmer) days and in a cold (vs. neutral or warm) room. Nostalgia, in turn, modulates the interoceptive feeling of temperature. Higher levels of music-evoked nostalgia predicted increased physical warmth, and participants who recalled a nostalgic (vs. ordinary autobiographical) event perceived ambient temperature as higher. Finally, and consistent with the close central nervous system integration of temperature and pain sensations, participants who recalled a nostalgic (vs. ordinary autobiographical) event evinced greater tolerance to noxious cold.

The Scc2/Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

Science.gov (United States)

Lopez-Serra, Lidia; Kelly, Gavin; Patel, Harshil; Stewart, Aengus; Uhlmann, Frank

2014-01-01

The cohesin complex is at the heart of many chromosomal activities, including sister chromatid cohesion and transcriptional regulation1-3. Cohesin loading onto chromosomes depends on the Scc2/Scc4 cohesin loader complex4-6, but the chromatin features that form cohesin loading sites remain poorly understood. Here, we show that the RSC chromatin remodeling complex recruits budding yeast Scc2/Scc4 to broad nucleosome-free regions, that the cohesin loader itself helps to maintain. Consequently, inactivation of the cohesin loader or RSC complex have similar effects on nucleosome positioning, gene expression and sister chromatid cohesion. These results reveal an intimate link between local chromatin structure and higher order chromosome architecture. Our findings pertain to the similarities between two severe human disorders, Cornelia de Lange syndrome, caused by mutations in the human cohesin loader, and Coffin-Siris syndrome, resulting from mutations in human RSC complex components7-9. Both could arise from gene misregulation due to related changes in the nucleosome landscape. PMID:25173104

Strategies for improving memory: a randomized trial of memory groups for older people, including those with mild cognitive impairment.

Science.gov (United States)

Kinsella, Glynda J; Ames, David; Storey, Elsdon; Ong, Ben; Pike, Kerryn E; Saling, Michael M; Clare, Linda; Mullaly, Elizabeth; Rand, Elizabeth

2016-01-01

Governments are promoting the importance of maintaining cognitive health into older age to minimize risk of cognitive decline and dementia. Older people with amnestic mild cognitive impairment (aMCI) are particularly vulnerable to memory challenges in daily activities and are seeking ways to maintain independent living. To evaluate the effectiveness of memory groups for improving memory strategies and memory ability of older people, especially those with aMCI. 113 healthy older adults (HOA) and 106 adults with aMCI were randomized to a six-week memory group or a waitlist control condition. Outcome was evaluated through knowledge and use of memory strategies, memory ability (self-report and neuropsychological tests), and wellbeing. Assessments included a six-month follow-up. Using intention to treat analyses, there were intervention effects for HOA and aMCI groups in strategy knowledge (HOA: η2= 0.20; aMCI: η2= 0.06), strategy use (HOA: η2= 0.18; aMCI: η2= 0.08), and wellbeing (HOA: η2= 0.11; aMCI: η2= 0.05). There were also intervention effects in the HOA group, but not the aMCI group, in self-reported memory ability (η2= 0.06) and prospective memory tests (η2= 0.02). By six-month follow-up, gains were found on most HOA outcomes. In the aMCI group gains were found in strategy use, and by this stage, gains in prospective memory were also found. Memory groups can engage older people in techniques for maintaining cognitive health and improve memory performance, but more modest benefits are seen for older adults with aMCI.

Iconic memory requires attention

OpenAIRE

Persuh, Marjan; Genzer, Boris; Melara, Robert D.

2012-01-01

Two experiments investigated whether attention plays a role in iconic memory, employing either a change detection paradigm (Experiment 1) or a partial-report paradigm (Experiment 2). In each experiment, attention was taxed during initial display presentation, focusing the manipulation on consolidation of information into iconic memory, prior to transfer into working memory. Observers were able to maintain high levels of performance (accuracy of change detection or categorization) even when co...

Holding multiple items in short term memory: a neural mechanism.

Directory of Open Access Journals (Sweden)

Edmund T Rolls

Full Text Available Human short term memory has a capacity of several items maintained simultaneously. We show how the number of short term memory representations that an attractor network modeling a cortical local network can simultaneously maintain active is increased by using synaptic facilitation of the type found in the prefrontal cortex. We have been able to maintain 9 short term memories active simultaneously in integrate-and-fire simulations where the proportion of neurons in each population, the sparseness, is 0.1, and have confirmed the stability of such a system with mean field analyses. Without synaptic facilitation the system can maintain many fewer memories active in the same network. The system operates because of the effectively increased synaptic strengths formed by the synaptic facilitation just for those pools to which the cue is applied, and then maintenance of this synaptic facilitation in just those pools when the cue is removed by the continuing neuronal firing in those pools. The findings have implications for understanding how several items can be maintained simultaneously in short term memory, how this may be relevant to the implementation of language in the brain, and suggest new approaches to understanding and treating the decline in short term memory that can occur with normal aging.

Holding multiple items in short term memory: a neural mechanism.

Science.gov (United States)

Rolls, Edmund T; Dempere-Marco, Laura; Deco, Gustavo

2013-01-01

Human short term memory has a capacity of several items maintained simultaneously. We show how the number of short term memory representations that an attractor network modeling a cortical local network can simultaneously maintain active is increased by using synaptic facilitation of the type found in the prefrontal cortex. We have been able to maintain 9 short term memories active simultaneously in integrate-and-fire simulations where the proportion of neurons in each population, the sparseness, is 0.1, and have confirmed the stability of such a system with mean field analyses. Without synaptic facilitation the system can maintain many fewer memories active in the same network. The system operates because of the effectively increased synaptic strengths formed by the synaptic facilitation just for those pools to which the cue is applied, and then maintenance of this synaptic facilitation in just those pools when the cue is removed by the continuing neuronal firing in those pools. The findings have implications for understanding how several items can be maintained simultaneously in short term memory, how this may be relevant to the implementation of language in the brain, and suggest new approaches to understanding and treating the decline in short term memory that can occur with normal aging.

Holding Multiple Items in Short Term Memory: A Neural Mechanism

Science.gov (United States)

Rolls, Edmund T.; Dempere-Marco, Laura; Deco, Gustavo

2013-01-01

Human short term memory has a capacity of several items maintained simultaneously. We show how the number of short term memory representations that an attractor network modeling a cortical local network can simultaneously maintain active is increased by using synaptic facilitation of the type found in the prefrontal cortex. We have been able to maintain 9 short term memories active simultaneously in integrate-and-fire simulations where the proportion of neurons in each population, the sparseness, is 0.1, and have confirmed the stability of such a system with mean field analyses. Without synaptic facilitation the system can maintain many fewer memories active in the same network. The system operates because of the effectively increased synaptic strengths formed by the synaptic facilitation just for those pools to which the cue is applied, and then maintenance of this synaptic facilitation in just those pools when the cue is removed by the continuing neuronal firing in those pools. The findings have implications for understanding how several items can be maintained simultaneously in short term memory, how this may be relevant to the implementation of language in the brain, and suggest new approaches to understanding and treating the decline in short term memory that can occur with normal aging. PMID:23613789

Repeated Recall and PKM? Maintain Fear Memories in Juvenile Rats

Science.gov (United States)

Oliver, Chicora F.; Kabitzke, Patricia; Serrano, Peter; Egan, Laura J.; Barr, Gordon A.; Shair, Harry N.; Wiedenmayer, Christoph

2016-01-01

We examined the neural substrates of fear memory formation and maintenance when repeated recall was used to prevent forgetting in young animals. In contrast to adult rats, juveniles failed to show contextual fear responses at 4 d post-fear conditioning. Reconsolidation sessions 3 and 6 d after conditioning restored contextual fear responses in…

Dicer maintains the identity and function of proprioceptive sensory neurons.

Science.gov (United States)

O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

2017-03-01

Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, micro

The Benefit of Attention-to-Memory Depends on the Interplay of Memory Capacity and Memory Load

Science.gov (United States)

Lim, Sung-Joo; Wöstmann, Malte; Geweke, Frederik; Obleser, Jonas

2018-01-01

Humans can be cued to attend to an item in memory, which facilitates and enhances the perceptual precision in recalling this item. Here, we demonstrate that this facilitating effect of attention-to-memory hinges on the overall degree of memory load. The benefit an individual draws from attention-to-memory depends on her overall working memory performance, measured as sensitivity (d′) in a retroactive cue (retro-cue) pitch discrimination task. While listeners maintained 2, 4, or 6 auditory syllables in memory, we provided valid or neutral retro-cues to direct listeners’ attention to one, to-be-probed syllable in memory. Participants’ overall memory performance (i.e., perceptual sensitivity d′) was relatively unaffected by the presence of valid retro-cues across memory loads. However, a more fine-grained analysis using psychophysical modeling shows that valid retro-cues elicited faster pitch-change judgments and improved perceptual precision. Importantly, as memory load increased, listeners’ overall working memory performance correlated with inter-individual differences in the degree to which precision improved (r = 0.39, p = 0.029). Under high load, individuals with low working memory profited least from attention-to-memory. Our results demonstrate that retrospective attention enhances perceptual precision of attended items in memory but listeners’ optimal use of informative cues depends on their overall memory abilities. PMID:29520246

The Benefit of Attention-to-Memory Depends on the Interplay of Memory Capacity and Memory Load

Directory of Open Access Journals (Sweden)

Sung-Joo Lim

2018-02-01

Full Text Available Humans can be cued to attend to an item in memory, which facilitates and enhances the perceptual precision in recalling this item. Here, we demonstrate that this facilitating effect of attention-to-memory hinges on the overall degree of memory load. The benefit an individual draws from attention-to-memory depends on her overall working memory performance, measured as sensitivity (d′ in a retroactive cue (retro-cue pitch discrimination task. While listeners maintained 2, 4, or 6 auditory syllables in memory, we provided valid or neutral retro-cues to direct listeners’ attention to one, to-be-probed syllable in memory. Participants’ overall memory performance (i.e., perceptual sensitivity d′ was relatively unaffected by the presence of valid retro-cues across memory loads. However, a more fine-grained analysis using psychophysical modeling shows that valid retro-cues elicited faster pitch-change judgments and improved perceptual precision. Importantly, as memory load increased, listeners’ overall working memory performance correlated with inter-individual differences in the degree to which precision improved (r = 0.39, p = 0.029. Under high load, individuals with low working memory profited least from attention-to-memory. Our results demonstrate that retrospective attention enhances perceptual precision of attended items in memory but listeners’ optimal use of informative cues depends on their overall memory abilities.

BACH transcription factors in innate and adaptive immunity.

Science.gov (United States)

Igarashi, Kazuhiko; Kurosaki, Tomohiro; Roychoudhuri, Rahul

2017-07-01

BTB and CNC homology (BACH) proteins are transcriptional repressors of the basic region leucine zipper (bZIP) transcription factor family. Recent studies indicate widespread roles of BACH proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4 + regulatory T cells and macrophages. Here, we emphasize similarities at a molecular level in the cell-type-specific activities of BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions. The findings contribute to a general understanding of how transcriptional repressors shape lineage commitment and cell-type-specific functions through repression of alternative lineage programmes.

Working memory binding and episodic memory formation in aging, mild cognitive impairment, and Alzheimer's dementia

NARCIS (Netherlands)

Geldorp, B. van; Heringa, S.M.; Berg, E. van den; Olde Rikkert, M.G.M.; Biessels, G.J.; Kessels, R.P.C.

2015-01-01

INTRODUCTION: Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present

Light-dependent changes in psbD and psbC transcripts of barley chloroplasts: accumulation of two transcripts maintains psbD and psbC translation capability in mature chloroplasts.

OpenAIRE

Gamble, P E; Sexton, T B; Mullet, J E

1988-01-01

The psbD and psbC genes encode two polypeptides of Photosystem II. These genes are adjacent in the barley chloroplast genome and are part of a 5.7 kbp transcription unit. In dark-grown barley, four large transcripts hybridize to psbD and psbC; two additional transcripts hybridize to psbC. Illumination of 4.5-day-old dark-grown seedlings causes a decrease in the six psbD--psbC transcripts found in etioplasts and the accumulation of two different transcripts of 4.0 and 3.2 kb which hybridize to...

PKMzeta Maintains Spatial, Instrumental, and Classically Conditioned Long-Term Memories

Czech Academy of Sciences Publication Activity Database

Serrano, P.; Friedman, E.L.; Kenney, Jana; Taubenfeld, S.M.; Zimmerman, J.M.; Hanna, J.; Alberini, C.; Kelley, A.E.; Maren, S.; Rudy, J.W.; Yin, J.C.P.; Sacktor, T.C.; Fenton, A.A.

2008-01-01

Roč. 6, č. 12 (2008), s. 2698-2706 ISSN 1544-9173 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/06/1231 Institutional research plan: CEZ:AV0Z50110509 Keywords : PKMzeta * memory * LTP Subject RIV: FH - Neurology Impact factor: 12.683, year: 2008

Magnetic stimulation of the dorsolateral prefrontal cortex dissociates fragile visual short-term memory from visual working memory

NARCIS (Netherlands)

Sligte, I.G.; Wokke, M.E.; Tesselaar, J.P.; Scholte, H.S.; Lamme, V.A.F.

2011-01-01

To guide our behavior in successful ways, we often need to rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). While VSTM is usually broken down into iconic memory (brief and high-capacity store) and visual working memory (sustained, yet limited-capacity

Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

Directory of Open Access Journals (Sweden)

Joke J. F. A. Van Vugt

2015-09-01

Full Text Available Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata and C. rubecula, which lay their eggs in caterpillars of the large and small cabbage white butterfly. A successful egg laying event serves as an unconditioned stimulus in a classical conditioning paradigm, where plant odors become associated to the encounter of a suitable host caterpillar. Depending on the host species, the number of conditioning trials and the parasitic wasp species, three different types of transcription-dependent long-term memory (LTM and one type of transcription-independent, anesthesia-resistant memory (ARM can be distinguished. To identify transcripts underlying these differences in memory formation, we isolated mRNA from parasitic wasp heads at three different time points between induction and consolidation of each of the four memory types, and for each sample three biological replicates, where after strand-specific paired-end 100 bp deep sequencing. Transcriptomes were assembled de novo and differential expression was determined for each memory type and time point after conditioning, compared to unconditioned wasps. Most differentially expressed (DE genes and antisense transcripts were only DE in one of the LTM types. Among the DE genes that were DE in two or more LTM types, were many protein kinases and phosphatases, small GTPases, receptors and ion channels. Some genes were DE in opposing directions between any of the LTM memory types and ARM, suggesting that ARM in Cotesia requires the transcription of genes inhibiting LTM or vice versa. We discuss our findings in the context of neuronal functioning, including RNA splicing and transport, epigenetic regulation, neurotransmitter/peptide synthesis and antisense transcription. In

The lasting memory enhancements of retrospective attention

OpenAIRE

Reaves, Sarah; Strunk, Jonathan; Phillips, Shekinah; Verhaeghen, Paul; Duarte, Audrey

2016-01-01

Behavioral research has shown that spatial cues that orient attention toward task relevant items being maintained in visual short-term memory (VSTM) enhance item memory accuracy. However, it is unknown if these retrospective attentional cues (?retro-cues?) enhance memory beyond typical short-term memory delays. It is also unknown whether retro-cues affect the spatial information associated with VSTM representations. Emerging evidence suggests that processes that affect short-term memory maint...

Transcription arrest caused by long nascent RNA chains

DEFF Research Database (Denmark)

Bentin, Thomas; Cherny, Dmitry; Larsen, H Jakob

2004-01-01

on transcription. Using phage T3 RNA polymerase (T3 RNAP) and covalently closed circular (cccDNA) DNA templates that did not contain any strong termination signal, transcription was severely inhibited after a short period of time. Less than approximately 10% residual transcriptional activity remained after 10 min......The transcription process is highly processive. However, specific sequence elements encoded in the nascent RNA may signal transcription pausing and/or termination. We find that under certain conditions nascent RNA chains can have a strong and apparently sequence-independent inhibitory effect...... of incubation. The addition of RNase A almost fully restored transcription in a dose dependent manner. Throughout RNase A rescue, an elongation rate of approximately 170 nt/s was maintained and this velocity was independent of RNA transcript length, at least up to 6 kb. Instead, RNase A rescue increased...

Working memory binding and episodic memory formation in aging, mild cognitive impairment, and Alzheimer’s dementia

NARCIS (Netherlands)

Geldorp, B. van; Heringa, S.M.; Berg, E. van den; Olde Rikkert, M.G.M.; Biessels, G.J.; Kessels, R.P.C.

2015-01-01

Introduction: Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present

DNMT1 Maintains Progenitor Function in Self-Renewing Somatic Tissue

OpenAIRE

Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.

2010-01-01

Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation1,2. DNA methylation3,4,5 provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1)6,7 maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintena...

Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.

Directory of Open Access Journals (Sweden)

Kun Wei

Full Text Available In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE. Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.

Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.

Science.gov (United States)

Wei, Kun; Gao, Shilong; Zhong, Suchuan; Ma, Hong

2012-01-01

In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE). Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE) to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene.

Science.gov (United States)

Uchida, Shusaku; Teubner, Brett J W; Hevi, Charles; Hara, Kumiko; Kobayashi, Ayumi; Dave, Rutu M; Shintaku, Tatsushi; Jaikhan, Pattaporn; Yamagata, Hirotaka; Suzuki, Takayoshi; Watanabe, Yoshifumi; Zakharenko, Stanislav S; Shumyatsky, Gleb P

2017-01-10

Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3-N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB, and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Changing concepts of working memory

Science.gov (United States)

Ma, Wei Ji; Husain, Masud; Bays, Paul M

2014-01-01

Working memory is widely considered to be limited in capacity, holding a fixed, small number of items, such as Miller's ‘magical number’ seven or Cowan's four. It has recently been proposed that working memory might better be conceptualized as a limited resource that is distributed flexibly among all items to be maintained in memory. According to this view, the quality rather than the quantity of working memory representations determines performance. Here we consider behavioral and emerging neural evidence for this proposal. PMID:24569831

Fast, Accurate Memory Architecture Simulation Technique Using Memory Access Characteristics

OpenAIRE

小野, 貴継; 井上, 弘士; 村上, 和彰

2007-01-01

This paper proposes a fast and accurate memory architecture simulation technique. To design memory architecture, the first steps commonly involve using trace-driven simulation. However, expanding the design space makes the evaluation time increase. A fast simulation is achieved by a trace size reduction, but it reduces the simulation accuracy. Our approach can reduce the simulation time while maintaining the accuracy of the simulation results. In order to evaluate validity of proposed techniq...

H3K27me3 and H3K4me3 chromatin environment at super-induced dehydration stress memory genes of Arabidopsis thaliana.

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Liu, Ning; Fromm, Michael; Avramova, Zoya

2014-03-01

Pre-exposure to a stress may alter the plant's cellular, biochemical, and/or transcriptional responses during future encounters as a 'memory' from the previous stress. Genes increasing transcription in response to a first dehydration stress, but producing much higher transcript levels in a subsequent stress, represent the super-induced 'transcription memory' genes in Arabidopsis thaliana. The chromatin environment (histone H3 tri-methylations of Lys 4 and Lys 27, H3K4me3, and H3K27me3) studied at five dehydration stress memory genes revealed existence of distinct memory-response subclasses that responded differently to CLF deficiency and displayed different transcriptional activities during the watered recovery periods. Among the most important findings is the novel aspect of the H3K27me3 function observed at specific dehydration stress memory genes. In contrast to its well-known role as a chromatin repressive mechanism at developmentally regulated genes, H3K27me3 did not prevent transcription from the dehydration stress-responding genes. The high H3K27me3 levels present during transcriptionally inactive states did not interfere with the transition to active transcription and with H3K4me3 accumulation. H3K4me3 and H3K27me3 marks function independently and are not mutually exclusive at the dehydration stress-responding memory genes.

Role of the adhesion molecule F3/Contactin in synaptic plasticity and memory.

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Gulisano, Walter; Bizzoca, Antonella; Gennarini, Gianfranco; Palmeri, Agostino; Puzzo, Daniela

2017-06-01

Cell adhesion molecules (CAMs) have a pivotal role in building and maintaining synaptic structures during brain development participating in axonal elongation and pathfinding, glial guidance of neuronal migration, as well as myelination. CAMs expression persists in the adult brain particularly in structures undergoing postnatal neurogenesis and involved in synaptic plasticity and memory as the hippocampus. Among the neural CAMs, we have recently focused on F3/Contactin, a glycosylphosphatidyl inositol-anchored glycoprotein belonging to the immunoglobulin superfamily, involved in neuronal development, synaptic maintenance and organization of neuronal networks. Here, we discuss our recent data suggesting that F3/Contactin exerts a role in hippocampal synaptic plasticity and memory in adult and aged mice. In particular, we have studied long-term potentiation (LTP), spatial and object recognition memory, and phosphorylation of the transcription factor cAMP-Responsive-Element Binding protein (CREB) in a transgenic mouse model of F3/Contactin overexpression. We also investigated whether F3/Contactin might influence neuronal apoptosis and the production of amyloid-beta peptide (Aβ), known to be one of the main pathogenetic hallmarks of Alzheimer's disease (AD). In conclusion, a further understanding of F3/Contactin role in synaptic plasticity and memory might have interesting clinical outcomes in cognitive disorders, such as aging and AD, offering innovative therapeutic opportunities. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of transcriptional regulation in maintaining the availability of mycobacterial adenylate cyclases

Directory of Open Access Journals (Sweden)

Sarah J. Casey

2014-03-01

Full Text Available Mycobacterium species have a complex cAMP regulatory network indicated by the high number of adenylate cyclases annotated in their genomes. However the need for a high level of redundancy in adenylate cyclase genes remains unknown. We have used semiquantitiative RT-PCR to examine the expression of eight Mycobacterium smegmatis cyclases with orthologs in the human pathogen Mycobacterium tuberculosis, where cAMP has recently been shown to be important for virulence. All eight cyclases were transcribed in all environments tested, and only four demonstrated environmental-mediated changes in transcription. M. smegmatis genes MSMEG_0545 and MSMEG_4279 were upregulated during starvation conditions while MSMEG_0545 and MSMEG_4924 were downregulated in H2O2 and MSMEG_3780 was downregulated in low pH and starvation. Promoter fusion constructs containing M. tuberculosis H37Rv promoters showed consistent regulation compared to their M. smegmatis orthologs. Overall our findings indicate that while low levels of transcriptional regulation occur, regulation at the mRNA level does not play a major role in controlling cellular cyclase availability in a given environment.

The presence of lytic HSV-1 transcripts and clonally expanded T cells with a memory effector phenotype in human sensory ganglia.

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Derfuss, Tobias; Arbusow, Viktor; Strupp, Michael; Brandt, Thomas; Theil, Diethilde

2009-05-01

Herpes simplex virus type 1 (HSV-1) latent persistence in human trigeminal ganglia (TG) is accompanied by a chronic CD8 T-cell infiltration. Thus far, during HSV-1 latency only a single transcript, namely the latency-associated transcript (LAT), has been identified to be synthesized but not translated into a protein. In contrast, the chronic CD8 T-cell infiltration suggests that an antigen trigger must be present. The focus of the current work was to look for HSV-1 transcription activity as a potential trigger of the immune response and to demonstrate whether the immune cells are clonally expanded and have a phenotype that suggests that they have been triggered by viral antigen. By combining in situ hybridization, laser cutting microscopy, and single-cell real time RT-PCR, we demonstrated expression of the HSV-1 immediate early (IE) genes ICP0 and ICP4 in human trigeminal neurons. Using CDR3 spectratyping, we showed that the infiltrating T cells are clonally expanded, indicating an antigen-driven immune response. Moreover, the persisting CD8(+) T cells had prominent features of the memory effector phenotype. Chemokines CCL5 and CXCL10 were expressed by a subpopulation of infiltrating cells and the corresponding chemokine receptors CCR5 and CXCR3 were co-expressed on virtually all T cells bearing the CD8 phenotype. Thus, HSV-1 IE genes are expressed in human TG, and the infiltrating T cells bear several characteristics that suggest viral antigenic stimulation.

A mega-analysis of memory reports from eight peer-reviewed false memory implantation studies.

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Scoboria, Alan; Wade, Kimberley A; Lindsay, D Stephen; Azad, Tanjeem; Strange, Deryn; Ost, James; Hyman, Ira E

2017-02-01

Understanding that suggestive practices can promote false beliefs and false memories for childhood events is important in many settings (e.g., psychotherapeutic, medical, and legal). The generalisability of findings from memory implantation studies has been questioned due to variability in estimates across studies. Such variability is partly due to false memories having been operationalised differently across studies and to differences in memory induction techniques. We explored ways of defining false memory based on memory science and developed a reliable coding system that we applied to reports from eight published implantation studies (N = 423). Independent raters coded transcripts using seven criteria: accepting the suggestion, elaboration beyond the suggestion, imagery, coherence, emotion, memory statements, and not rejecting the suggestion. Using this scheme, 30.4% of cases were classified as false memories and another 23% were classified as having accepted the event to some degree. When the suggestion included self-relevant information, an imagination procedure, and was not accompanied by a photo depicting the event, the memory formation rate was 46.1%. Our research demonstrates a useful procedure for systematically combining data that are not amenable to meta-analysis, and provides the most valid estimate of false memory formation and associated moderating factors within the implantation literature to date.

Two memory associated genes regulated by amyloid precursor protein intracellular domain ovel insights into the pathogenesis of learning and memory impairment in Alzheimer's disease

Institute of Scientific and Technical Information of China (English)

Chuandong Zheng; Xi Gu; Zhimei Zhong; Rui Zhu; Tianming Gao; Fang Wang

2012-01-01

In this study, we employed chromatin immunoprecipitation, a useful method for studying the locations of transcription factors bound to specific DNA regions in specific cells, to investigate amyloid precursor protein intracellular domain binding sites in chromatin DNA from hippocampal neurons of rats, and to screen out five putative genes associated with the learning and memory functions. The promoter regions of the calcium/calmodulin-dependent protein kinase II alpha and glutamate receptor-2 genes were amplified by PCR from DNA products immunoprecipitated by amyloid precursor protein intracellular domain. An electrophoretic mobility shift assay and western blot analysis suggested that the promoter regions of these two genes associated with learning and memory were bound by amyloid precursor protein intracellular domain (in complex form). Our experimental findings indicate that the amyloid precursor protein intracellular domain is involved in the transcriptional regulation of learning- and memory-associated genes in hippocampal neurons. These data may provide new insights into the molecular mechanism underlying the symptoms of progressive memory loss in Alzheimer's disease.

Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

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Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

2007-01-01

The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

Characterization of the rapid transcriptional response to long-term sensitization training in Aplysia californica.

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Herdegen, Samantha; Holmes, Geraldine; Cyriac, Ashly; Calin-Jageman, Irina E; Calin-Jageman, Robert J

2014-12-01

We used a custom-designed microarray and quantitative PCR to characterize the rapid transcriptional response to long-term sensitization training in the marine mollusk Aplysia californica. Aplysia were exposed to repeated noxious shocks to one side of the body, a procedure known to induce a long-lasting, transcription-dependent increase in reflex responsiveness that is restricted to the side of training. One hour after training, pleural ganglia from the trained and untrained sides of the body were harvested; these ganglia contain the sensory nociceptors which help mediate the expression of long-term sensitization memory. Microarray analysis from 8 biological replicates suggests that long-term sensitization training rapidly regulates at least 81 transcripts. We used qPCR to test a subset of these transcripts and found that 83% were confirmed in the same samples, and 86% of these were again confirmed in an independent sample. Thus, our new microarray design shows strong convergent and predictive validity for analyzing the transcriptional correlates of memory in Aplysia. Fully validated transcripts include some previously identified as regulated in this paradigm (ApC/EBP and ApEgr) but also include novel findings. Specifically, we show that long-term sensitization training rapidly up-regulates the expression of transcripts which may encode Aplysia homologs of a C/EBPγ transcription factor, a glycine transporter (GlyT2), and a vacuolar-protein-sorting-associated protein (VPS36). Copyright © 2014 Elsevier Inc. All rights reserved.

PKA Increases in the Olfactory Bulb Act as Unconditioned Stimuli and Provide Evidence for Parallel Memory Systems: Pairing Odor with Increased PKA Creates Intermediate- and Long-Term, but Not Short-Term, Memories

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Grimes, Matthew T.; Harley, Carolyn W.; Darby-King, Andrea; McLean, John H.

2012-01-01

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and…

Long-term memory stabilized by noise-induced rehearsal.

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Wei, Yi; Koulakov, Alexei A

2014-11-19

Cortical networks can maintain memories for decades despite the short lifetime of synaptic strengths. Can a neural network store long-lasting memories in unstable synapses? Here, we study the effects of ongoing spike-timing-dependent plasticity (STDP) on the stability of memory patterns stored in synapses of an attractor neural network. We show that certain classes of STDP rules can stabilize all stored memory patterns despite a short lifetime of synapses. In our model, unstructured neural noise, after passing through the recurrent network connections, carries the imprint of all memory patterns in temporal correlations. STDP, combined with these correlations, leads to reinforcement of all stored patterns, even those that are never explicitly visited. Our findings may provide the functional reason for irregular spiking displayed by cortical neurons and justify models of system memory consolidation. Therefore, we propose that irregular neural activity is the feature that helps cortical networks maintain stable connections. Copyright © 2014 the authors 0270-6474/14/3415804-12$15.00/0.

DREAM Controls the On/Off Switch of Specific Activity-Dependent Transcription Pathways

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Mellström, Britt; Sahún, Ignasi; Ruiz-Nuño, Ana; Murtra, Patricia; Gomez-Villafuertes, Rosa; Savignac, Magali; Oliveros, Juan C.; Gonzalez, Paz; Kastanauskaite, Asta; Knafo, Shira; Zhuo, Min; Higuera-Matas, Alejandro; Errington, Michael L.; Maldonado, Rafael; DeFelipe, Javier; Jefferys, John G. R.; Bliss, Tim V. P.; Dierssen, Mara

2014-01-01

Changes in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstream regulatory element antagonist modulator), also known as calsenilin/KChIP-3 (K+ channel interacting protein 3), is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory. PMID:24366545

Shifting visual perspective during memory retrieval reduces the accuracy of subsequent memories.

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Marcotti, Petra; St Jacques, Peggy L

2018-03-01

Memories for events can be retrieved from visual perspectives that were never experienced, reflecting the dynamic and reconstructive nature of memories. Characteristics of memories can be altered when shifting from an own eyes perspective, the way most events are initially experienced, to an observer perspective, in which one sees oneself in the memory. Moreover, recent evidence has linked these retrieval-related effects of visual perspective to subsequent changes in memories. Here we examine how shifting visual perspective influences the accuracy of subsequent memories for complex events encoded in the lab. Participants performed a series of mini-events that were experienced from their own eyes, and were later asked to retrieve memories for these events while maintaining the own eyes perspective or shifting to an alternative observer perspective. We then examined how shifting perspective during retrieval modified memories by influencing the accuracy of recall on a final memory test. Across two experiments, we found that shifting visual perspective reduced the accuracy of subsequent memories and that reductions in vividness when shifting visual perspective during retrieval predicted these changes in the accuracy of memories. Our findings suggest that shifting from an own eyes to an observer perspective influences the accuracy of long-term memories.

Working Memory in the Service of Executive Control Functions.

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Mansouri, Farshad A; Rosa, Marcello G P; Atapour, Nafiseh

2015-01-01

Working memory is a type of short-term memory which has a crucial cognitive function that supports ongoing and upcoming behaviors, allowing storage of information across delay periods. The content of this memory may typically include tangible information about features such as the shape, color or texture of an object, and its location and motion relative to the body, as well as phonological information. The neural correlate of working memory has been found in different brain areas that are involved in organizing perceptual or motor functions. In particular, neuronal activity in prefrontal areas encodes task-related information corresponding to working memory across delay periods, and lesions in the prefrontal cortex severely affect the ability to retain this type of memory. Recent studies have further expanded the scope and possible role of working memory by showing that information of a more abstract nature (including a behavior-guiding rule, or the occurrence of a conflict in information processing) can also be maintained in short-term memory, and used for adjusting the allocation of executive control in dynamic environments. It has also been shown that neuronal activity in the prefrontal cortex encodes and maintains information about such abstract entities. These findings suggest that the prefrontal cortex plays crucial roles in the organization of goal-directed behavior by supporting many different mnemonic processes, which maintain a wide range of information required for the executive control of ongoing and upcoming behaviors.

Neural correlates of memory retrieval in the prefrontal cortex.

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Nácher, Verónica; Ojeda, Sabiela; Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Acuña, Carlos

2006-08-01

Working memory includes short-term representations of information that were recently experienced or retrieved from long-term representations of sensory stimuli. Evidence is presented here that working memory activates the same dorsolateral prefrontal cortex neurons that: (a) maintained recently perceived visual stimuli; and (b) retrieved visual stimuli from long-term memory (LTM). Single neuron activity was recorded in the dorsolateral prefrontal cortex while trained monkeys discriminated between two orientated lines shown sequentially, separated by a fixed interstimulus interval. This visual task required the monkey to compare the orientation of the second line with the memory trace of the first and to decide the relative orientation of the second. When the behavioural task required the monkey to maintain in working memory a first stimulus that continually changed from trial to trial, the discharge in these cells was related to the parameters--the orientation--of the memorized item. Then, what the monkey had to recall from memory was manipulated by switching to another task in which the first stimulus was not shown, and had to be retrieved from LTM. The discharge rates of the same neurons also varied depending on the parameters of the memorized stimuli, and their response was progressively delayed as the monkey performed the task. These results suggest that working memory activates dorsolateral prefrontal cortex neurons that maintain parametrical visual information in short-term and LTM, and that the contents of working memory cannot be limited to what has recently happened in the sensory environment.

Maintaining ancient organelles: mitochondrial biogenesis and maturation.

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Vega, Rick B; Horton, Julie L; Kelly, Daniel P

2015-05-22

The ultrastructure of the cardiac myocyte is remarkable for the high density of mitochondria tightly packed between sarcomeres. This structural organization is designed to provide energy in the form of ATP to fuel normal pump function of the heart. A complex system comprised of regulatory factors and energy metabolic machinery, encoded by both mitochondrial and nuclear genomes, is required for the coordinate control of cardiac mitochondrial biogenesis, maturation, and high-capacity function. This process involves the action of a transcriptional regulatory network that builds and maintains the mitochondrial genome and drives the expression of the energy transduction machinery. This finely tuned system is responsive to developmental and physiological cues, as well as changes in fuel substrate availability. Deficiency of components critical for mitochondrial energy production frequently manifests as a cardiomyopathic phenotype, underscoring the requirement to maintain high respiration rates in the heart. Although a precise causative role is not clear, there is increasing evidence that perturbations in this regulatory system occur in the hypertrophied and failing heart. This review summarizes current knowledge and highlights recent advances in our understanding of the transcriptional regulatory factors and signaling networks that serve to regulate mitochondrial biogenesis and function in the mammalian heart. © 2015 American Heart Association, Inc.

Working memory updating occurs independently of the need to maintain task-context: accounting for triggering updating in the AX-CPT paradigm.

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Kessler, Yoav; Baruchin, Liad J; Bouhsira-Sabag, Anat

2017-01-01

Theoretical models suggest that maintenance and updating are two functional states of working memory (WM), which are controlled by a gate between perceptual information and WM representations. Opening the gate enables updating WM with input, while closing it enables keeping the maintained information shielded from interference. However, it is still unclear when gate opening takes place, and what is the external signal that triggers it. A version of the AX-CPT paradigm was used to examine a recent proposal in the literature, suggesting that updating is triggered whenever the maintenance of the context is necessary for task performance (context-dependent tasks). In four experiments using this paradigm, we show that (1) a task-switching cost takes place in both context-dependent and context-independent trials; (2) task-switching is additive to the dependency effect, and (3) unlike switching cost, the dependency effect is not affected by preparation and, therefore, does not reflect context-updating. We suggest that WM updating is likely to be triggered by a simple mechanism that occurs in each trial of the task regardless of whether maintaining the context is needed or not. The implications for WM updating and its relationship to task-switching are discussed.

Manipulations of attention dissociate fragile visual short-term memory from visual working memory.

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Vandenbroucke, Annelinde R E; Sligte, Ilja G; Lamme, Victor A F

2011-05-01

People often rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). Traditionally, VSTM is thought to operate on either a short time-scale with high capacity - iconic memory - or a long time scale with small capacity - visual working memory. Recent research suggests that in addition, an intermediate stage of memory in between iconic memory and visual working memory exists. This intermediate stage has a large capacity and a lifetime of several seconds, but is easily overwritten by new stimulation. We therefore termed it fragile VSTM. In previous studies, fragile VSTM has been dissociated from iconic memory by the characteristics of the memory trace. In the present study, we dissociated fragile VSTM from visual working memory by showing a differentiation in their dependency on attention. A decrease in attention during presentation of the stimulus array greatly reduced the capacity of visual working memory, while this had only a small effect on the capacity of fragile VSTM. We conclude that fragile VSTM is a separate memory store from visual working memory. Thus, a tripartite division of VSTM appears to be in place, comprising iconic memory, fragile VSTM and visual working memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

Spatial working memory maintenance: does attention play a role?

NARCIS (Netherlands)

Chan, L.K.; Hayward, W.G.; Theeuwes, J.

2009-01-01

Recent studies have proposed that a common mechanism may underlie spatial attention and spatial working memory. One proposal is that spatial working memory is maintained by attention-based rehearsal [Awh, E., Jonides, J., & Reuter-Lorenz, P. A. (1998). Rehearsal in spatial working memory. Journal of

Effects of load on the guidance of visual attention from working memory.

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Zhang, Bao; Zhang, John X; Huang, Sai; Kong, Lingyue; Wang, Suiping

2011-12-08

An active recent line of research on working memory and attention has shown that the visual attention can be top-down guided by working memory contents. The present study examined whether the guidance effect is modulated by memory load, i.e., the amount of information maintained in working memory. In a set of three experiments, participants were asked to perform a visual search task while maintaining several objects in working memory. The memory-driven attentional guidance effect was observed in all experiments when there were spare working memory resources. When memory load was increased from one item to two items, there was no sign that the guidance effect was attenuated. When load was further increased to four items, the guidance effect disappeared completely, indicating a clear impact of memory load on attentional guidance. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Effects of Feedback on Memory Strategies of Younger and Older Adults.

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Zhang, Fan; Zhang, Xin; Luo, Meng; Geng, Haiyan

2016-01-01

Existing literature suggests that feedback could effectively reduce false memories in younger adults. However, it is unclear whether memory performance in older adults also might be affected by feedback. The current study tested the hypothesis that older adults can use immediate feedback to adjust their memory strategy, similar to younger adults, but after feedback is removed, older adults may not be able to maintain using the memory strategy. Older adults will display more false memories than younger adults due to a reduction in attentional resources. In Study 1, both younger and older adults adjusted gist processing and item-specific processing biases based on the feedback given (i.e., biased and objective feedback). In Study 2 after the feedback was removed, only younger adults with full attention were able to maintain the feedback-shaped memory strategy; whereas, both younger adults with divided attention and older adults had increased false memories after feedback was removed. The findings suggest that environmental support helps older adults as well as younger adults to adopt a memory strategy that demands high attentional resources, but when the support is removed, older adults can no longer maintain such a strategy.

HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

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Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation

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McQuown, Susan C.; Barrett, Ruth M.; Matheos, Dina P.; Post, Rebecca J.; Rogge, George A.; Alenghat, Theresa; Mullican, Shannon E.; Jones, Steven; Rusche, James R.; Lazar, Mitchell A.; Wood, Marcelo A.

2011-01-01

Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyl-transerases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3–FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3–FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3–FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation. PMID:21228185

Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

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Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

2016-10-06

Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

RNA polymerase II transcriptional fidelity control and its functional interplay with DNA modifications

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Xu, Liang; Wang, Wei; Chong, Jenny; Shin, Ji Hyun; Xu, Jun; Wang, Dong

2016-01-01

Accurate genetic information transfer is essential for life. As a key enzyme involved in the first step of gene expression, RNA polymerase II (Pol II) must maintain high transcriptional fidelity while it reads along DNA template and synthesizes RNA transcript in a stepwise manner during transcription elongation. DNA lesions or modifications may lead to significant changes in transcriptional fidelity or transcription elongation dynamics. In this review, we will summarize recent progress towards understanding the molecular basis of RNA Pol II transcriptional fidelity control and impacts of DNA lesions and modifications on Pol II transcription elongation. PMID:26392149

Spatial specificity of working memory representations in the early visual cortex.

Science.gov (United States)

Pratte, Michael S; Tong, Frank

2014-03-19

Recent fMRI decoding studies have demonstrated that early retinotopic visual areas exhibit similar patterns of activity during the perception of a stimulus and during the maintenance of that stimulus in working memory. These findings provide support for the sensory recruitment hypothesis that the mechanisms underlying perception serve as a foundation for visual working memory. However, a recent study by Ester, Serences, and Awh (2009) found that the orientation of a peripheral grating maintained in working memory could be classified from both the contralateral and ipsilateral regions of the primary visual cortex (V1), implying that, unlike perception, feature-specific information was maintained in a nonretinotopic manner. Here, we evaluated the hypothesis that early visual areas can maintain information in a spatially specific manner and will do so if the task encourages the binding of feature information to a specific location. To encourage reliance on spatially specific memory, our experiment required observers to retain the orientations of two laterally presented gratings. Multivariate pattern analysis revealed that the orientation of each remembered grating was classified more accurately based on activity patterns in the contralateral than in the ipsilateral regions of V1 and V2. In contrast, higher extrastriate areas exhibited similar levels of performance across the two hemispheres. A time-resolved analysis further indicated that the retinotopic specificity of the working memory representation in V1 and V2 was maintained throughout the retention interval. Our results suggest that early visual areas provide a cortical basis for actively maintaining information about the features and locations of stimuli in visual working memory.

The Transcriptional Heat Shock Response of Salmonella Typhimurium Shows Hysteresis and Heated Cells Show Increased Resistance to Heat and Acid Stress

DEFF Research Database (Denmark)

Pin, C.; Hansen, Trine; Munoz-Cuevas, M.

2012-01-01

We investigated if the transcriptional response of Salmonella Typhimurium to temperature and acid variations was hysteretic, i.e. whether the transcriptional regulation caused by environmental stimuli showed memory and remained after the stimuli ceased. The transcriptional activity of non......, implying that down-regulation was significantly less synchronized than upregulation. The hysteretic transcriptional response to heat shock was accompanied by higher resistance to inactivation at 50uC as well as cross-resistance to inactivation at pH 3; however, growth rates and lag times at 43uC and at p......H 4.5 were not affected. The exposure to pH 5 only caused up-regulation of 12 genes and this response was neither hysteretic nor accompanied of increased resistance to inactivation conditions. Cellular memory at the transcriptional level may represent a mechanism of adaptation to the environment...

Dynamic analysis of stochastic transcription cycles.

Directory of Open Access Journals (Sweden)

Claire V Harper

2011-04-01

Full Text Available In individual mammalian cells the expression of some genes such as prolactin is highly variable over time and has been suggested to occur in stochastic pulses. To investigate the origins of this behavior and to understand its functional relevance, we quantitatively analyzed this variability using new mathematical tools that allowed us to reconstruct dynamic transcription rates of different reporter genes controlled by identical promoters in the same living cell. Quantitative microscopic analysis of two reporter genes, firefly luciferase and destabilized EGFP, was used to analyze the dynamics of prolactin promoter-directed gene expression in living individual clonal and primary pituitary cells over periods of up to 25 h. We quantified the time-dependence and cyclicity of the transcription pulses and estimated the length and variation of active and inactive transcription phases. We showed an average cycle period of approximately 11 h and demonstrated that while the measured time distribution of active phases agreed with commonly accepted models of transcription, the inactive phases were differently distributed and showed strong memory, with a refractory period of transcriptional inactivation close to 3 h. Cycles in transcription occurred at two distinct prolactin-promoter controlled reporter genes in the same individual clonal or primary cells. However, the timing of the cycles was independent and out-of-phase. For the first time, we have analyzed transcription dynamics from two equivalent loci in real-time in single cells. In unstimulated conditions, cells showed independent transcription dynamics at each locus. A key result from these analyses was the evidence for a minimum refractory period in the inactive-phase of transcription. The response to acute signals and the result of manipulation of histone acetylation was consistent with the hypothesis that this refractory period corresponded to a phase of chromatin remodeling which significantly

Noradrenergic System and Memory

KAUST Repository

Zenger, Manuel; Burlet-Godinot, Sophie; Petit, Jean-Marie; Magistretti, Pierre J.

2017-01-01

There is ample evidence indicating that noradrenaline plays an important role in memory mechanisms. Noradrenaline is thought to modulate these procsses through activation of adrenergic receptors in neurons. Astrocytes that form essential partners for synaptic function, also express alpha- and beta-adrenergic receptors. In astrocytes, noradrenaline triggers metabolic actions such as the glycogenolysis leading to an increase in l-lactate formation and release. l-Lactate can be used by neurons as a sourc of energy during memory tasks and can also induc transcription of plasticity genes in neurons. Activation of β-adrenergic receptors can also trigger gliotransmitter release resulting of intracllular calcium waves. These gliotransmitters modulate the synaptic activity and thereby can modulate long-term potentiation mechanisms. In summary, recnt evidencs indicate that noradrenaline exerts its memory-promoting effects through different modes of action both on neurons and astrocytes.

Noradrenergic System and Memory

KAUST Repository

Zenger, Manuel

2017-07-22

There is ample evidence indicating that noradrenaline plays an important role in memory mechanisms. Noradrenaline is thought to modulate these procsses through activation of adrenergic receptors in neurons. Astrocytes that form essential partners for synaptic function, also express alpha- and beta-adrenergic receptors. In astrocytes, noradrenaline triggers metabolic actions such as the glycogenolysis leading to an increase in l-lactate formation and release. l-Lactate can be used by neurons as a sourc of energy during memory tasks and can also induc transcription of plasticity genes in neurons. Activation of β-adrenergic receptors can also trigger gliotransmitter release resulting of intracllular calcium waves. These gliotransmitters modulate the synaptic activity and thereby can modulate long-term potentiation mechanisms. In summary, recnt evidencs indicate that noradrenaline exerts its memory-promoting effects through different modes of action both on neurons and astrocytes.

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains.

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Sudhakaran, Indulekha P; Ramaswami, Mani

2017-05-04

Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs

Art: a powerful tool for keeping memory alive

International Nuclear Information System (INIS)

Anon.

2015-01-01

According to Cecile Massart, a belgian visual artist, any radioactive waste disposal site has to be made very visible in order to preserve memory of the activities on the very long term and avoid dangerous excavations. Art has a role to play to maintain vivid this local memory by proposing works of art that reveal the very inside of the site making useless any digging. A complementary way to maintain local memory is to consider disposal sites as historical monuments that will glorify the use of nuclear energy that allowed humanity to keep on going forwards decades ago. This strategy of openness and transparency opposes the present approach of concealing disposal sites through landscaping. (A.C.)

Exploring self-defining memories in schizophrenia.

Science.gov (United States)

Raffard, Stéphane; D'Argembeau, Arnaud; Lardi, Claudia; Bayard, Sophie; Boulenger, Jean-Philippe; Van Der Linden, Martial

2009-01-01

Previous studies have shown that patients with schizophrenia are impaired in recalling specific events from their personal past. However, the relationship between autobiographical memory impairments and disturbance of the sense of identity in schizophrenia has not been investigated in detail. In this study the authors investigated schizophrenic patients' ability to recall self-defining memories; that is, memories that play an important role in building and maintaining the self-concept. Results showed that patients recalled as many specific self-defining memories as healthy participants. However, patients with schizophrenia exhibited an abnormal reminiscence bump and reported different types of thematic content (i.e., they recalled less memories about past achievements and more memories regarding hospitalisation and stigmatisation of illness). Furthermore, the findings suggest that impairments in extracting meaning from personal memories could represent a core disturbance of autobiographical memory in patients with schizophrenia.

Protein kinase M ζ and the maintenance of long-term memory.

Science.gov (United States)

Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

2016-10-01

Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Working memory and attentional bias on reinforcing efficacy of food.

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Carr, Katelyn A; Epstein, Leonard H

2017-09-01

Reinforcing efficacy of food, or the relationship between food prices and purchasing, is related to obesity status and energy intake in adults. Determining how to allocate resources for food is a decision making process influenced by executive functions. Attention to appetitive cues, as well as working memory capacity, or the ability to flexibly control attention while mentally retaining information, may be important executive functions involved in food purchasing decisions. In two studies, we examined how attention bias to food and working memory capacity are related to reinforcing efficacy of both high energy-dense and low energy-dense foods. The first study examined 48 women of varying body mass index (BMI) and found that the relationship between attentional processes and reinforcing efficacy was moderated by working memory capacity. Those who avoid food cues and had high working memory capacity had the lowest reinforcing efficacy, as compared to those with low working memory capacity. Study 2 systematically replicated the methods of study 1 with assessment of maintained attention in a sample of 48 overweight/obese adults. Results showed the relationship between maintained attention to food cues and reinforcing efficacy was moderated by working memory capacity. Those with a maintained attention to food and high working memory capacity had higher reinforcing efficacy than low working memory capacity individuals. These studies suggest working memory capacity moderated the relationship between different aspects of attention and food reinforcement. Understanding how decision making process are involved in reinforcing efficacy may help to identify future intervention targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

Science.gov (United States)

Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

2017-07-15

Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

Kinetics and clonality of immunological memory in humans.

Science.gov (United States)

Beverley, Peter C L

2004-10-01

T-cell immunological memory consists largely of clones of proliferating lymphocytes maintained by antigenic stimulation and the survival and proliferative effects of cytokines. The duration of survival of memory clones in humans is determine by the Hayflick limit on the number of cell divisions, the rate of cycling of memory cells and factors that control erosion of telomeres, including mechanisms that control telomerase.

HDAC Inhibition Modulates Hippocampus-Dependent Long-Term Memory for Object Location in a CBP-Dependent Manner

Science.gov (United States)

Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation…

Inhibition of connexin43 hemichannels impairs spatial short-term memory without affecting spatial working memory

Directory of Open Access Journals (Sweden)

Laura Walrave

2016-12-01

Full Text Available Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs. We here investigated whether interfering with connexin43 (Cx43 HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19 into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

Memory CD8 T cell inflation vs tissue-resident memory T cells: Same patrollers, same controllers?

Science.gov (United States)

Welten, Suzanne P M; Sandu, Ioana; Baumann, Nicolas S; Oxenius, Annette

2018-05-01

The induction of long-lived populations of memory T cells residing in peripheral tissues is of considerable interest for T cell-based vaccines, as they can execute immediate effector functions and thus provide protection in case of pathogen encounter at mucosal and barrier sites. Cytomegalovirus (CMV)-based vaccines support the induction and accumulation of a large population of effector memory CD8 T cells in peripheral tissues, in a process called memory inflation. Tissue-resident memory (T RM ) T cells, induced by various infections and vaccination regimens, constitute another subset of memory cells that take long-term residence in peripheral tissues. Both memory T cell subsets have evoked substantial interest in exploitation for vaccine purposes. However, a direct comparison between these two peripheral tissue-localizing memory T cell subsets with respect to their short- and long-term ability to provide protection against heterologous challenge is pending. Here, we discuss communalities and differences between T RM and inflationary CD8 T cells with respect to their development, maintenance, function, and protective capacity. In addition, we discuss differences and similarities between the transcriptional profiles of T RM and inflationary T cells, supporting the notion that they are distinct memory T cell populations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Working memory and Down syndrome.

Science.gov (United States)

Baddeley, A; Jarrold, C

2007-12-01

A brief account is given of the evolution of the concept of working memory from a unitary store into a multicomponent system. Four components are distinguished, the phonological loop which is responsible for maintaining speech-based information, the visuospatial sketchpad performing a similar function for visual information, the central executive which acts as an attentional control system, and finally a new component, the episodic buffer. The buffer comprises a temporary multidimensional store which is assumed to form an interface between the various subsystems of working memory, long-term memory, and perception. The operation of the model is then illustrated through an account of a research programme concerned with the analysis of working memory in Down syndrome.

Working memory binding and episodic memory formation in aging, mild cognitive impairment, and Alzheimer's dementia.

Science.gov (United States)

van Geldorp, Bonnie; Heringa, Sophie M; van den Berg, Esther; Olde Rikkert, Marcel G M; Biessels, Geert Jan; Kessels, Roy P C

2015-01-01

Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present study, we examined WM and episodic memory formation in normal aging and in patients with early Alzheimer's disease (mild cognitive impairment, MCI; and Alzheimer's dementia, AD). In the first study, 26 young adults (mean age 29.6 years) were compared to 18 middle-aged adults (mean age 52.2 years) and 25 older adults (mean age 72.8 years). We used an associative delayed-match-to-sample WM task, which requires participants to maintain two pairs of faces and houses presented on a computer screen for short (3 s) or long (6 s) maintenance intervals. After the WM task, an unexpected subsequent associative memory task was administered (two-alternative forced choice). In the second study, 27 patients with AD and 19 patients with MCI were compared to 25 older controls, using the same paradigm as that in Experiment 1. Older adults performed worse than both middle-aged and young adults. No effect of delay was observed in the healthy adults, and pairs that were processed during long maintenance intervals were not better remembered in the subsequent memory task. In the MCI and AD patients, longer maintenance intervals hampered the task performance. Also, both patient groups performed significantly worse than controls on the episodic memory task as well as the associative WM task. Aging and AD present with a decline in WM binding, a finding that extends similar results in episodic memory. Longer delays in the WM task did not affect episodic memory formation. We conclude that WM deficits are found when WM capacity is exceeded, which may occur during associative processing.

Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4 in Neurons and Promotes ATF4-Dependent Induction of Sesn2

Directory of Open Access Journals (Sweden)

Jin Liu

2018-03-01

Full Text Available Activating transcription factor 4 (ATF4 plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.

An integrative view of storage of low- and high-level visual dimensions in visual short-term memory.

Science.gov (United States)

Magen, Hagit

2017-03-01

Efficient performance in an environment filled with complex objects is often achieved through the temporal maintenance of conjunctions of features from multiple dimensions. The most striking finding in the study of binding in visual short-term memory (VSTM) is equal memory performance for single features and for integrated multi-feature objects, a finding that has been central to several theories of VSTM. Nevertheless, research on binding in VSTM focused almost exclusively on low-level features, and little is known about how items from low- and high-level visual dimensions (e.g., colored manmade objects) are maintained simultaneously in VSTM. The present study tested memory for combinations of low-level features and high-level representations. In agreement with previous findings, Experiments 1 and 2 showed decrements in memory performance when non-integrated low- and high-level stimuli were maintained simultaneously compared to maintaining each dimension in isolation. However, contrary to previous findings the results of Experiments 3 and 4 showed decrements in memory performance even when integrated objects of low- and high-level stimuli were maintained in memory, compared to maintaining single-dimension objects. Overall, the results demonstrate that low- and high-level visual dimensions compete for the same limited memory capacity, and offer a more comprehensive view of VSTM.

Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory.

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Kutlu, Munir Gunes; Gould, Thomas J

2016-03-01

The hippocampus is a key brain structure involved in synaptic plasticity associated with long-term declarative memory formation. Importantly, nicotine and activation of nicotinic acetylcholine receptors (nAChRs) can alter hippocampal plasticity and these changes may occur through modulation of hippocampal kinases and transcription factors. Hippocampal kinases such as cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinases (CAMKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and c-jun N-terminal kinase 1 (JNK1), and the transcription factor cAMP-response element-binding protein (CREB) that are activated either directly or indirectly by nicotine may modulate hippocampal plasticity and in parallel hippocampus-dependent learning and memory. Evidence suggests that nicotine may alter hippocampus-dependent learning by changing the time and magnitude of activation of kinases and transcription factors normally involved in learning and by recruiting additional cell signaling molecules. Understanding how nicotine alters learning and memory will advance basic understanding of the neural substrates of learning and aid in understanding mental disorders that involve cognitive and learning deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

What works in auditory working memory? A neural oscillations perspective.

Science.gov (United States)

Wilsch, Anna; Obleser, Jonas

2016-06-01

Working memory is a limited resource: brains can only maintain small amounts of sensory input (memory load) over a brief period of time (memory decay). The dynamics of slow neural oscillations as recorded using magneto- and electroencephalography (M/EEG) provide a window into the neural mechanics of these limitations. Especially oscillations in the alpha range (8-13Hz) are a sensitive marker for memory load. Moreover, according to current models, the resultant working memory load is determined by the relative noise in the neural representation of maintained information. The auditory domain allows memory researchers to apply and test the concept of noise quite literally: Employing degraded stimulus acoustics increases memory load and, at the same time, allows assessing the cognitive resources required to process speech in noise in an ecologically valid and clinically relevant way. The present review first summarizes recent findings on neural oscillations, especially alpha power, and how they reflect memory load and memory decay in auditory working memory. The focus is specifically on memory load resulting from acoustic degradation. These findings are then contrasted with contextual factors that benefit neural as well as behavioral markers of memory performance, by reducing representational noise. We end on discussing the functional role of alpha power in auditory working memory and suggest extensions of the current methodological toolkit. This article is part of a Special Issue entitled SI: Auditory working memory. Published by Elsevier B.V.

PKA increases in the olfactory bulb act as unconditioned stimuli and provide evidence for parallel memory systems: pairing odor with increased PKA creates intermediate- and long-term, but not short-term, memories.

Science.gov (United States)

Grimes, Matthew T; Harley, Carolyn W; Darby-King, Andrea; McLean, John H

2012-02-21

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and translation-dependent). Here, we use neonatal odor-preference learning to explore the role of olfactory bulb PKA in these three phases of mammalian memory. PKA activity increased normally in learning animals 10 min after a single training trial. Inhibition of PKA by Rp-cAMPs blocked intermediate-term and long-term memory, with no effect on short-term memory. PKA inhibition also prevented learning-associated CREB phosphorylation, a transcription factor implicated in long-term memory. When long-term memory was rescued through increased β-adrenoceptor activation, CREB phosphorylation was restored. Intermediate-term and long-term, but not short-term odor-preference memories were generated by pairing odor with direct PKA activation using intrabulbar Sp-cAMPs, which bypasses β-adrenoceptor activation. Higher levels of Sp-cAMPs enhanced memory by extending normal 24-h retention to 48-72 h. These results suggest that increased bulbar PKA is necessary and sufficient for the induction of intermediate-term and long-term odor-preference memory, and suggest that PKA activation levels also modulate memory duration. However, short-term memory appears to use molecular mechanisms other than the PKA/CREB pathway. These mechanisms, which are also recruited by β-adrenoceptor activation, must operate in parallel with PKA activation.

Visual Working Memory Storage Recruits Sensory Processing Areas

NARCIS (Netherlands)

Gayet, Surya; Paffen, Chris L E; Van der Stigchel, Stefan

Human visual processing is subject to a dynamic influx of visual information. Visual working memory (VWM) allows for maintaining relevant visual information available for subsequent behavior. According to the dominating view, VWM recruits sensory processing areas to maintain this visual information

Visual working memory storage recruits sensory processing areas

NARCIS (Netherlands)

Gayet, S.; Paffen, C.L.E.; Stigchel, S. van der

2018-01-01

Human visual processing is subject to a dynamic influx of visual information. Visual working memory (VWM) allows for maintaining relevant visual information available for subsequent behavior. According to the dominating view, VWM recruits sensory processing areas to maintain this visual information

Contribution of Oral Language Skills, Linguistic Skills, and Transcription Skills to Chinese Written Composition among Fourth-Grade Students

Science.gov (United States)

Yeung, Pui-sze; Ho, Connie Suk-han; Chan, David Wai-ock; Chung, Kevin Kien-hoa

2013-01-01

The present study aimed to investigate the contribution of oral language skills, linguistic skills, and transcription skills to Chinese written composition among Grade 4 students in Hong Kong. Measures assessing verbal working memory, oral language skills, linguistic skills (i.e., syntactic skills and discourse skills), transcription skills (i.e.,…

Visual working memory contaminates perception.

Science.gov (United States)

Kang, Min-Suk; Hong, Sang Wook; Blake, Randolph; Woodman, Geoffrey F

2011-10-01

Indirect evidence suggests that the contents of visual working memory may be maintained within sensory areas early in the visual hierarchy. We tested this possibility using a well-studied motion repulsion phenomenon in which perception of one direction of motion is distorted when another direction of motion is viewed simultaneously. We found that observers misperceived the actual direction of motion of a single motion stimulus if, while viewing that stimulus, they were holding a different motion direction in visual working memory. Control experiments showed that none of a variety of alternative explanations could account for this repulsion effect induced by working memory. Our findings provide compelling evidence that visual working memory representations directly interact with the same neural mechanisms as those involved in processing basic sensory events.

CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis

Science.gov (United States)

Oh, Kyoung-Jin; Han, Hye-Sook; Kim, Min-Jung; Koo, Seung-Hoi

2013-01-01

Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6 phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed. [BMB Reports 2013; 46(12): 567-574] PMID:24238363

Memory functions reveal structural properties of gene regulatory networks

Science.gov (United States)

Perez-Carrasco, Ruben

2018-01-01

Gene regulatory networks (GRNs) control cellular function and decision making during tissue development and homeostasis. Mathematical tools based on dynamical systems theory are often used to model these networks, but the size and complexity of these models mean that their behaviour is not always intuitive and the underlying mechanisms can be difficult to decipher. For this reason, methods that simplify and aid exploration of complex networks are necessary. To this end we develop a broadly applicable form of the Zwanzig-Mori projection. By first converting a thermodynamic state ensemble model of gene regulation into mass action reactions we derive a general method that produces a set of time evolution equations for a subset of components of a network. The influence of the rest of the network, the bulk, is captured by memory functions that describe how the subnetwork reacts to its own past state via components in the bulk. These memory functions provide probes of near-steady state dynamics, revealing information not easily accessible otherwise. We illustrate the method on a simple cross-repressive transcriptional motif to show that memory functions not only simplify the analysis of the subnetwork but also have a natural interpretation. We then apply the approach to a GRN from the vertebrate neural tube, a well characterised developmental transcriptional network composed of four interacting transcription factors. The memory functions reveal the function of specific links within the neural tube network and identify features of the regulatory structure that specifically increase the robustness of the network to initial conditions. Taken together, the study provides evidence that Zwanzig-Mori projections offer powerful and effective tools for simplifying and exploring the behaviour of GRNs. PMID:29470492

Store operations to maintain cache coherence

Energy Technology Data Exchange (ETDEWEB)

Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

2017-08-01

In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

Store operations to maintain cache coherence

Energy Technology Data Exchange (ETDEWEB)

Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

2017-09-12

In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

转录因子Egr-1参与长期性恐惧记忆和焦虑%Transcription factor Egr-1 is required for long-term fear memory and anxiety

Institute of Scientific and Technical Information of China (English)

Shanelle; W．Ko; 敖虎山; Amelia; Gallitano-Mendel; 邱长申; 魏峰; Jeffrey; Milbrandt; 卓敏

2005-01-01

The zinc finger transcription factor Egr-1 is critical for coupling extracellular signals to changes in cellular gene expression.In the hippocampus and amygdala, two major central regions for memory formation and storage, Egr-1 is up-regulated by long-term potentiation (LTP) and learning paradigms. Using Egr-1 knockout mice, we showed that Egr-1 was selectively required for late auditory fear memory while short term, trace and contextual memory were not affected. Additionally, synaptic potentiation induced by theta burst stimulation in the amygdala and auditory cortex was significantly reduced or blocked in Egr-1 knockout mice. Our study suggests that the transcription factor Egr-1 plays a selective role in late auditory fear memory.%锌指转录因子Egr-1在将细胞外信号和胞内基因表达的变化相耦联过程中发挥重要的作用.海马和杏仁体是记忆形成和储存的两个主要的脑区.在海马和杏仁体中,Egr-1可被长时程增强(long-term potentiation,LTP)和学习过程上调.在Egr-1敲除小鼠上观察到晚时相声音恐惧记忆受损,而短时的痕迹和场景记忆却不受影响;另外,在Egr-1敲除小鼠上,用thetaburst刺激杏仁体和听觉皮层所引起的突触增强被明显减弱或完全阻断.因此,我们的研究表明,转录因子Egr-1选择性地在晚时相听觉恐惧记忆中发挥作用.

Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory.

Science.gov (United States)

Penke, Zsuzsa; Morice, Elise; Veyrac, Alexandra; Gros, Alexandra; Chagneau, Carine; LeBlanc, Pascale; Samson, Nathalie; Baumgärtel, Karsten; Mansuy, Isabelle M; Davis, Sabrina; Laroche, Serge

2014-01-05

It is well established that Zif268/Egr1, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.

Distant memories: a prospective study of vantage point of trauma memories.

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Kenny, Lucy M; Bryant, Richard A; Silove, Derrick; Creamer, Mark; O'Donnell, Meaghan; McFarlane, Alexander C

2009-09-01

Adopting an observer perspective to recall trauma memories may function as a form of avoidance that maintains posttraumatic stress disorder (PTSD). We conducted a prospective study to analyze the relationship between memory vantage point and PTSD symptoms. Participants (N= 947) identified the vantage point of their trauma memory and reported PTSD symptoms within 4 weeks of the trauma; 730 participants repeated this process 12 months later. Initially recalling the trauma from an observer vantage point was related to more severe PTSD symptoms at that time and 12 months later. Shifting from a field to an observer perspective a year after trauma was associated with greater PTSD severity at 12 months. These results suggest that remembering trauma from an observer vantage point is related to both immediate and ongoing PTSD symptoms.

Upgrading the sleeping brain with targeted memory reactivation.

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Oudiette, Delphine; Paller, Ken A

2013-03-01

A fundamental feature of human memory is the propensity for beneficial changes in information storage after initial encoding. Recent research findings favor the possibility that memory consolidation during sleep is instrumental for actively maintaining the storehouse of memories that individuals carry through their lives. The information that ultimately remains available for retrieval may tend to be that which is reactivated during sleep. A novel source of support for this idea comes from demonstrations that neurocognitive processing during sleep can benefit memory storage when memories are covertly cued via auditory or olfactory stimulation. Investigations of these subtle manipulations of memory processing during sleep can help elucidate the mechanisms of memory preservation in the human brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription*

Science.gov (United States)

Nadkarni, Aditi; Burns, John A.; Gandolfi, Alberto; Chowdhury, Moinuddin A.; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E.; Scicchitano, David A.

2016-01-01

DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N6-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N6-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N6-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N6-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N6-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. PMID:26559971

SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin.

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Sun, Wei-Wei; Jiao, Shi; Sun, Li; Zhou, Zhaocai; Jin, Xia; Wang, Jian-Hua

2018-05-01

The postintegrational latency of HIV-1 is characterized by reversible silencing of long terminal repeat (LTR)-driven transcription of the HIV genome. It is known that the formation of repressive chromatin at the 5'-LTR of HIV-1 proviral DNA impedes viral transcription by blocking the recruitment of positive transcription factors. How the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. Elucidation of which chromatin reassembly factor mediates the reorganization of chromatin is likely to facilitate the understanding of the host's modulation of HIV-1 transcription and latency. Here we revealed that "Sad1 and UNC84 domain containing 2" (SUN2), an inner nuclear membrane protein, maintained the repressive chromatin and inhibited HIV LTR-driven transcription of proviral DNA through an association with lamin A/C. Specifically, lamin A/C tethered SUN2 to the nucleosomes 1 and 2 of the HIV-1 5'-LTR to block the initiation and elongation of HIV-1 transcription. SUN2 knockdown converted chromatin to an active form and thus enhanced the phosphorylation of RNA polymerase II and its recruitment to the 5'-LTR HIV-1 proviral DNA, leading to reactivation of HIV-1 from latency. Conversely, the exogenous factors such as tumor necrosis factor alpha (TNF-α) induced reactivation, and the replication of HIV-1 led to the disassociation between SUN2 and lamin A/C, suggesting that disruption of the association between SUN2 and lamin A/C to convert the repressive chromatin to the active form might be a prerequisite for the initiation of HIV-1 transcription and replication. Together, our findings indicate that SUN2 is a novel chromatin reassembly factor that helps to maintain chromatin in a repressive state and consequently inhibits HIV-1 transcription. IMPORTANCE Despite the successful use of scores of antiretroviral drugs, HIV latency poses a major impediment to virus eradication. Elucidation of the mechanism of latency facilitates the discovery of new

Global effects of the CSR-1 RNA interference pathway on transcriptional landscape

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Cecere, Germano; Hoersch, Sebastian; O’Keeffe, Sean; Sachidanandam, Ravi; Grishok, Alla

2014-01-01

Argonaute proteins and their small RNA co-factors short interfering RNAs (siRNAs) are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) antisense to germline transcripts and associates with chromatin in a siRNA-dependent manner. However, its role in gene expression regulation remains controversial. Here, we used a genome-wide profiling of nascent RNA transcripts to demonstrate that the CSR-1 RNAi pathway promotes sense-oriented Pol II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. Based on these findings, we propose that the CSR-1 pathway has a role in maintaining the directionality of active transcription thereby propagating the distinction between transcriptionally active and silent genomic regions. PMID:24681887

The Role of the Oculomotor System in Updating Visual-Spatial Working Memory across Saccades

OpenAIRE

Boon, Paul J.; Belopolsky, Artem V.; Theeuwes, Jan

2016-01-01

Visual-spatial working memory (VSWM) helps us to maintain and manipulate visual information in the absence of sensory input. It has been proposed that VSWM is an emergent property of the oculomotor system. In the present study we investigated the role of the oculomotor system in updating of spatial working memory representations across saccades. Participants had to maintain a location in memory while making a saccade to a different location. During the saccade the target was displaced, which ...

Working memory training improves visual short-term memory capacity.

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Schwarb, Hillary; Nail, Jayde; Schumacher, Eric H

2016-01-01

Since antiquity, philosophers, theologians, and scientists have been interested in human memory. However, researchers today are still working to understand the capabilities, boundaries, and architecture. While the storage capabilities of long-term memory are seemingly unlimited (Bahrick, J Exp Psychol 113:1-2, 1984), working memory, or the ability to maintain and manipulate information held in memory, seems to have stringent capacity limits (e.g., Cowan, Behav Brain Sci 24:87-185, 2001). Individual differences, however, do exist and these differences can often predict performance on a wide variety of tasks (cf. Engle What is working-memory capacity? 297-314, 2001). Recently, researchers have promoted the enticing possibility that simple behavioral training can expand the limits of working memory which indeed may also lead to improvements on other cognitive processes as well (cf. Morrison and Chein, Psychol Bull Rev 18:46-60 2011). However, initial investigations across a wide variety of cognitive functions have produced mixed results regarding the transferability of training-related improvements. Across two experiments, the present research focuses on the benefit of working memory training on visual short-term memory capacity-a cognitive process that has received little attention in the training literature. Data reveal training-related improvement of global measures of visual short-term memory as well as of measures of the independent sub-processes that contribute to capacity (Awh et al., Psychol Sci 18(7):622-628, 2007). These results suggest that the ability to inhibit irrelevant information within and between trials is enhanced via n-back training allowing for selective improvement on untrained tasks. Additionally, we highlight a potential limitation of the standard adaptive training procedure and propose a modified design to ensure variability in the training environment.

Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.

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Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

2016-07-26

PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis.

A novel Snf2 protein maintains trans-generational regulatory states established by paramutation in maize.

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Christopher J Hale

2007-10-01

Full Text Available Paramutations represent heritable epigenetic alterations that cause departures from Mendelian inheritance. While the mechanism responsible is largely unknown, recent results in both mouse and maize suggest paramutations are correlated with RNA molecules capable of affecting changes in gene expression patterns. In maize, multiple required to maintain repression (rmr loci stabilize these paramutant states. Here we show rmr1 encodes a novel Snf2 protein that affects both small RNA accumulation and cytosine methylation of a proximal transposon fragment at the Pl1-Rhoades allele. However, these cytosine methylation differences do not define the various epigenetic states associated with paramutations. Pedigree analyses also show RMR1 does not mediate the allelic interactions that typically establish paramutations. Strikingly, our mutant analyses show that Pl1-Rhoades RNA transcript levels are altered independently of transcription rates, implicating a post-transcriptional level of RMR1 action. These results suggest the RNA component of maize paramutation maintains small heterochromatic-like domains that can affect, via the activity of a Snf2 protein, the stability of nascent transcripts from adjacent genes by way of a cotranscriptional repression process. These findings highlight a mechanism by which alleles of endogenous loci can acquire novel expression patterns that are meiotically transmissible.

Modeling soil moisture memory in savanna ecosystems

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Gou, S.; Miller, G. R.

2011-12-01

Antecedent soil conditions create an ecosystem's "memory" of past rainfall events. Such soil moisture memory effects may be observed over a range of timescales, from daily to yearly, and lead to feedbacks between hydrological and ecosystem processes. In this study, we modeled the soil moisture memory effect on savanna ecosystems in California, Arizona, and Africa, using a system dynamics model created to simulate the ecohydrological processes at the plot-scale. The model was carefully calibrated using soil moisture and evapotranspiration data collected at three study sites. The model was then used to simulate scenarios with various initial soil moisture conditions and antecedent precipitation regimes, in order to study the soil moisture memory effects on the evapotranspiration of understory and overstory species. Based on the model results, soil texture and antecedent precipitation regime impact the redistribution of water within soil layers, potentially causing deeper soil layers to influence the ecosystem for a longer time. Of all the study areas modeled, soil moisture memory of California savanna ecosystem site is replenished and dries out most rapidly. Thus soil moisture memory could not maintain the high rate evapotranspiration for more than a few days without incoming rainfall event. On the contrary, soil moisture memory of Arizona savanna ecosystem site lasts the longest time. The plants with different root depths respond to different memory effects; shallow-rooted species mainly respond to the soil moisture memory in the shallow soil. The growing season of grass is largely depended on the soil moisture memory of the top 25cm soil layer. Grass transpiration is sensitive to the antecedent precipitation events within daily to weekly timescale. Deep-rooted plants have different responses since these species can access to the deeper soil moisture memory with longer time duration Soil moisture memory does not have obvious impacts on the phenology of woody plants

Conglomerate memory and cosmopolitanism

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Susannah Ryan

2016-01-01

Full Text Available Under what conditions do countries and cultures considered radically different find a basis for allegiance and kinship? What part does memory play in this process? This article responds to these questions in two ways: 1 Through Emmanuel Levinas and Hannah Arendt, I propose that when an other appears in empathetic discourses that both honor difference and cite shared human experiences, seemingly irreconcilable people can develop a sense of mutual responsibility and 2 Conglomerate memory, memories that fuse together others through common pains, contributes to such an appearance. To illustrate this point, I turn to Congolese voices as they are articulated in online American discourses; although currently, authors of online texts typically rely on traditional narrative forms that position Central Africa as incommensurate to Western civilizations, the Internet's worldwide accessibility and intertextual capacities render it a place primed for developing international collectives by connecting memories while maintaining difference.

Iconic memory requires attention.

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Persuh, Marjan; Genzer, Boris; Melara, Robert D

2012-01-01

Two experiments investigated whether attention plays a role in iconic memory, employing either a change detection paradigm (Experiment 1) or a partial-report paradigm (Experiment 2). In each experiment, attention was taxed during initial display presentation, focusing the manipulation on consolidation of information into iconic memory, prior to transfer into working memory. Observers were able to maintain high levels of performance (accuracy of change detection or categorization) even when concurrently performing an easy visual search task (low load). However, when the concurrent search was made difficult (high load), observers' performance dropped to almost chance levels, while search accuracy held at single-task levels. The effects of attentional load remained the same across paradigms. The results suggest that, without attention, participants consolidate in iconic memory only gross representations of the visual scene, information too impoverished for successful detection of perceptual change or categorization of features.

Iconic memory requires attention

Directory of Open Access Journals (Sweden)

Marjan ePersuh

2012-05-01

Full Text Available Two experiments investigated whether attention plays a role in iconic memory, employing either a change-detection paradigm (Experiment 1 or a partial-report paradigm (Experiment 2. In each experiment, attention was taxed during initial display presentation, focusing the manipulation on consolidation of information into iconic memory, prior to transfer into working memory. Observers were able to maintain high levels of performance (accuracy of change detection or categorization even when concurrently performing an easy visual search task (low load. However, when the concurrent search was made difficult (high load, observers’ performance dropped to almost chance levels, while search accuracy held at single-task levels. The effects of attentional load remained the same across paradigms. The results suggest that, without attention, participants consolidate in iconic memory only gross representations of the visual scene, information too impoverished for successful detection of perceptual change or categorization of features.

Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

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Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

2018-06-20

Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.

Science.gov (United States)

Cecere, Germano; Hoersch, Sebastian; O'Keeffe, Sean; Sachidanandam, Ravi; Grishok, Alla

2014-04-01

Argonaute proteins and their small RNA cofactors short interfering RNAs are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) that are antisense to germline transcripts. However, its role in gene expression regulation remains controversial. Here we used genome-wide profiling of nascent RNA transcripts and found that the CSR-1 RNA interference pathway promoted sense-oriented RNA polymerase II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. On the basis of these findings, we propose that the CSR-1 pathway helps maintain the directionality of active transcription, thereby propagating the distinction between transcriptionally active and silent genomic regions.

Multiple Systems of Spatial Memory: Evidence from Described Scenes

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Avraamides, Marios N.; Kelly, Jonathan W.

2010-01-01

Recent models in spatial cognition posit that distinct memory systems are responsible for maintaining transient and enduring spatial relations. The authors used perspective-taking performance to assess the presence of these enduring and transient spatial memories for locations encoded through verbal descriptions. Across 3 experiments, spatial…

Electroforming free resistive switching memory in two-dimensional VOx nanosheets

KAUST Repository

Hota, Mrinal Kanti; Nagaraju, Doddahalli H.; Hedhili, Mohamed N.; Alshareef, Husam N.

2015-01-01

, electroforming-free, low SET bias bipolar resistive switching memory performance with endurance for more than 100 cycles maintaining OFF/ON ratio of ∼60 times. These devices show better memory performance as compared to previously reported VOx thin film based

Appetitive Olfactory Learning and Long-Term Associative Memory in Caenorhabditis elegans

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Ichiro N. Maruyama

2017-05-01

Full Text Available Because of the relative simplicity of its nervous system, Caenorhabditis elegans is a useful model organism to study learning and memory at cellular and molecular levels. For appetitive conditioning in C. elegans, food has exclusively been used as an unconditioned stimulus (US. It may be difficult to analyze neuronal circuits for associative memory since food is a multimodal combination of olfactory, gustatory, and mechanical stimuli. Here, we report classical appetitive conditioning and associative memory in C. elegans, using 1-nonanol as a conditioned stimulus (CS, and potassium chloride (KCl as a US. Before conditioning, C. elegans innately avoided 1-nonanol, an aversive olfactory stimulus, and was attracted by KCl, an appetitive gustatory stimulus, on assay agar plates. Both massed training without an intertrial interval (ITI and spaced training with a 10-min ITI induced significant levels of memory of association regarding the two chemicals. Memory induced by massed training decayed within 6 h, while that induced by spaced training was retained for more than 6 h. Animals treated with inhibitors of transcription or translation formed the memory induced by spaced training less efficiently than untreated animals, whereas the memory induced by massed training was not significantly affected by such treatments. By definition, therefore, memories induced by massed training and spaced training are classified as short-term memory (STM and long-term memory (LTM, respectively. When animals conditioned by spaced training were exposed to 1-nonanol alone, their learning index was lower than that of untreated animals, suggesting that extinction learning occurs in C. elegans. In support of these results, C. elegans mutants defective in nmr-1, encoding an NMDA receptor subunit, formed both STM and LTM less efficiently than wild-type animals, while mutations in crh-1, encoding a ubiquitous transcription factor CREB required for memory consolidation, affected

Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze

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Kim Ryang

2011-02-01

Full Text Available Abstract Background Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory. Results We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1 and L-type voltage gated calcium channels (LVGCCs in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis. Conclusions Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

Commentary: cognitive-affective mechanisms and processes in autobiographical memory.

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Conway, Martin A

2003-03-01

This commentary highlights some of the interesting points to emerge from the preceding papers about the self, social, and directive functions of autobiographical memory. Additionally some cognitive functions are also considered and especially the way in which autobiographical memory supports, constrains, and maintains the goals of the self. Directions for future research into the self, social, directive, and cognitive-affective functions and processes of autobiographical memory are reviewed. Emphasis is placed on future research into the function of autobiographical memory in representations of attachment.

The Impact of Storage on Processing: How Is Information Maintained in Working Memory?

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Vergauwe, Evie; Camos, Valérie; Barrouillet, Pierre

2014-01-01

Working memory is typically defined as a system devoted to the simultaneous maintenance and processing of information. However, the interplay between these 2 functions is still a matter of debate in the literature, with views ranging from complete independence to complete dependence. The time-based resource-sharing model assumes that a central…

Epigenetic landscapes reveal transcription factors regulating CD8+ T cell differentiation

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Yu, Bingfei; Zhang, Kai; Milner, J. Justin; Toma, Clara; Chen, Runqiang; Scott-Browne, James P.; Pereira, Renata M.; Crotty, Shane; Chang, John T.; Pipkin, Matthew E.; Wang, Wei; Goldrath, Ananda W.

2017-01-01

Dynamic changes in the expression of transcription factors (TFs) can influence specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TF among differentially-fated precursor cells suggests additional underlying mechanisms. Here, we profiled genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8+ T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that TF expression and binding contributed to establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal novel TFs influencing the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8+ T cell differentiation, regulated the formation of terminal-effector and memory-precursor cell-fates, respectively. Our data define the epigenetic landscape of differentiation intermediates, facilitating identification of TFs with previously unappreciated roles in CD8+ T cell differentiation. PMID:28288100

Frequency shifting approach towards textual transcription of heartbeat sounds.

Science.gov (United States)

Arvin, Farshad; Doraisamy, Shyamala; Safar Khorasani, Ehsan

2011-10-04

Auscultation is an approach for diagnosing many cardiovascular problems. Automatic analysis of heartbeat sounds and extraction of its audio features can assist physicians towards diagnosing diseases. Textual transcription allows recording a continuous heart sound stream using a text format which can be stored in very small memory in comparison with other audio formats. In addition, a text-based data allows applying indexing and searching techniques to access to the critical events. Hence, the transcribed heartbeat sounds provides useful information to monitor the behavior of a patient for the long duration of time. This paper proposes a frequency shifting method in order to improve the performance of the transcription. The main objective of this study is to transfer the heartbeat sounds to the music domain. The proposed technique is tested with 100 samples which were recorded from different heart diseases categories. The observed results show that, the proposed shifting method significantly improves the performance of the transcription.

Frequency shifting approach towards textual transcription of heartbeat sounds

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Safar Khorasani Ehsan

2011-10-01

Full Text Available Abstract Auscultation is an approach for diagnosing many cardiovascular problems. Automatic analysis of heartbeat sounds and extraction of its audio features can assist physicians towards diagnosing diseases. Textual transcription allows recording a continuous heart sound stream using a text format which can be stored in very small memory in comparison with other audio formats. In addition, a text-based data allows applying indexing and searching techniques to access to the critical events. Hence, the transcribed heartbeat sounds provides useful information to monitor the behavior of a patient for the long duration of time. This paper proposes a frequency shifting method in order to improve the performance of the transcription. The main objective of this study is to transfer the heartbeat sounds to the music domain. The proposed technique is tested with 100 samples which were recorded from different heart diseases categories. The observed results show that, the proposed shifting method significantly improves the performance of the transcription.

Different effects of executive and visuospatial working memory on visual consciousness.

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De Loof, Esther; Poppe, Louise; Cleeremans, Axel; Gevers, Wim; Van Opstal, Filip

2015-11-01

Consciousness and working memory are two widely studied cognitive phenomena. Although they have been closely tied on a theoretical and neural level, empirical work that investigates their relation is largely lacking. In this study, the relationship between visual consciousness and different working memory components is investigated by using a dual-task paradigm. More specifically, while participants were performing a visual detection task to measure their visual awareness threshold, they had to concurrently perform either an executive or visuospatial working memory task. We hypothesized that visual consciousness would be hindered depending on the type and the size of the load in working memory. Results showed that maintaining visuospatial content in working memory hinders visual awareness, irrespective of the amount of information maintained. By contrast, the detection threshold was progressively affected under increasing executive load. Interestingly, increasing executive load had a generic effect on detection speed, calling into question whether its obstructing effect is specific to the visual awareness threshold. Together, these results indicate that visual consciousness depends differently on executive and visuospatial working memory.

Dissociation of active working memory and passive recognition in rhesus monkeys

OpenAIRE

Basile, Benjamin M.; Hampton, Robert R.

2012-01-01

Active cognitive control of working memory is central in most human memory models, but behavioral evidence for such control in nonhuman primates is absent and neurophysiological evidence, while suggestive, is indirect. We present behavioral evidence that monkey memory for familiar images is under active cognitive control. Concurrent cognitive demands during the memory delay impaired matching-to-sample performance for familiar images in a demand-dependent manner, indicating that maintaining th...

Cognitive neuroepigenetics: a role for epigenetic mechanisms in learning and memory.

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Day, Jeremy J; Sweatt, J David

2011-07-01

Although long-lasting behavioral memories have long been thought to require equally persistent molecular changes, little is known about the biochemical underpinnings of memory storage and maintenance. Increasing evidence now suggests that long-term behavioral change may be associated with epigenetic regulation of transcription in the central nervous system. In this review, we present evidence that changes in DNA methylation contribute to memory formation and maintenance, consider how DNA methylation affects readout of memory-related genes, and discuss how these changes may be important in the large-scale context of memory circuits. Finally, we discuss potential challenges involved in examining epigenetic changes in the brain and highlight how epigenetic mechanisms may be relevant for other cognitive processes. Copyright © 2010 Elsevier Inc. All rights reserved.

A working memory account of the interaction between numbers and spatial attention.

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van Dijck, Jean-Philippe; Abrahamse, Elger L; Acar, Freya; Ketels, Boris; Fias, Wim

2014-01-01

Rather than reflecting the long-term memory construct of a mental number line, it has been proposed that the relation between numbers and space is of a more temporary nature and constructed in working memory during task execution. In three experiments we further explored the viability of this working memory account. Participants performed a speeded dot detection task with dots appearing left or right, while maintaining digits or letters in working memory. Just before presentation of the dot, these digits or letters were used as central cues. These experiments show that the "attentional SNARC-effect" (where SNARC is the spatial-numerical association of response codes) is not observed when only the lastly perceived number cue--and no serially ordered sequence of cues--is maintained in working memory (Experiment 1). It is only when multiple items (numbers in Experiment 2; letters in Experiment 3) are stored in working memory in a serially organized way that the attentional cueing effect is observed as a function of serial working memory position. These observations suggest that the "attentional SNARC-effect" is strongly working memory based. Implications for theories on the mental representation of numbers are discussed.

Nobiletin improves emotional and novelty recognition memory but not spatial referential memory.

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Kang, Jiyun; Shin, Jung-Won; Kim, Yoo-Rim; Swanberg, Kelley M; Kim, Yooseung; Bae, Jae Ryong; Kim, Young Ki; Lee, Jinwon; Kim, Soo-Yeon; Sohn, Nak-Won; Maeng, Sungho

2017-01-01

How to maintain and enhance cognitive functions for both aged and young populations is a highly interesting subject. But candidate memory-enhancing reagents are tested almost exclusively on lesioned or aged animals. Also, there is insufficient information on the type of memory these reagents can improve. Working memory, located in the prefrontal cortex, manages short-term sensory information, but, by gaining significant relevance, this information is converted to long-term memory by hippocampal formation and/or amygdala, followed by tagging with space-time or emotional cues, respectively. Nobiletin is a product of citrus peel known for cognitive-enhancing effects in various pharmacological and neurodegenerative disease models, yet, it is not well studied in non-lesioned animals and the type of memory that nobiletin can improve remains unclear. In this study, 8-week-old male mice were tested using behavioral measurements for working, spatial referential, emotional and visual recognition memory after daily administration of nobiletin. While nobiletin did not induce any change of spontaneous activity in the open field test, freezing by fear conditioning and novel object recognition increased. However, the effectiveness of spatial navigation in the Y-maze and Morris water maze was not improved. These results mean that nobiletin can specifically improve memories of emotionally salient information associated with fear and novelty, but not of spatial information without emotional saliency. Accordingly, the use of nobiletin on normal subjects as a memory enhancer would be more effective on emotional types but may have limited value for the improvement of episodic memories.

Models of working memory:Mechanisms of active maintenance and executive control (1999 Models of working memory:Mechanisms of active maintenance and executive control (1999

Directory of Open Access Journals (Sweden)

Augusto Buchweitz

2008-04-01

Full Text Available What is working memory, anyway?’ Despite the seminal definition (Baddeley & Hitch 1974; Daneman & Carpenter 1980 of working memory (WM being the system or mechanism at the basis of maintaining task-relevant information during the performance of a cognitive task (p. 1, and despite the familiarity of the term, addressing the question of what WM really is does not seem to be in the same ballpark of easily-put answers; it is not even in the same league. What is working memory, anyway?’ Despite the seminal definition (Baddeley & Hitch 1974; Daneman & Carpenter 1980 of working memory (WM being the system or mechanism at the basis of maintaining task-relevant information during the performance of a cognitive task (p. 1, and despite the familiarity of the term, addressing the question of what WM really is does not seem to be in the same ballpark of easily-put answers; it is not even in the same league.

Long-term pitch memory for music recordings is related to auditory working memory precision.

Science.gov (United States)

Van Hedger, Stephen C; Heald, Shannon Lm; Nusbaum, Howard C

2018-04-01

Most individuals have reliable long-term memories for the pitch of familiar music recordings. This pitch memory (1) appears to be normally distributed in the population, (2) does not depend on explicit musical training and (3) only seems to be weakly related to differences in listening frequency estimates. The present experiment was designed to assess whether individual differences in auditory working memory could explain variance in long-term pitch memory for music recordings. In Experiment 1, participants first completed a musical note adjustment task that has been previously used to assess working memory of musical pitch. Afterward, participants were asked to judge the pitch of well-known music recordings, which either had or had not been shifted in pitch. We found that performance on the pitch working memory task was significantly related to performance in the pitch memory task using well-known recordings, even when controlling for overall musical experience and familiarity with each recording. In Experiment 2, we replicated these findings in a separate group of participants while additionally controlling for fluid intelligence and non-pitch-based components of auditory working memory. In Experiment 3, we demonstrated that participants could not accurately judge the pitch of unfamiliar recordings, suggesting that our method of pitch shifting did not result in unwanted acoustic cues that could have aided participants in Experiments 1 and 2. These results, taken together, suggest that the ability to maintain pitch information in working memory might lead to more accurate long-term pitch memory.

Working Memory Capacity and Fluid Intelligence: Maintenance and Disengagement.

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Shipstead, Zach; Harrison, Tyler L; Engle, Randall W

2016-11-01

Working memory capacity and fluid intelligence have been demonstrated to be strongly correlated traits. Typically, high working memory capacity is believed to facilitate reasoning through accurate maintenance of relevant information. In this article, we present a proposal reframing this issue, such that tests of working memory capacity and fluid intelligence are seen as measuring complementary processes that facilitate complex cognition. Respectively, these are the ability to maintain access to critical information and the ability to disengage from or block outdated information. In the realm of problem solving, high working memory capacity allows a person to represent and maintain a problem accurately and stably, so that hypothesis testing can be conducted. However, as hypotheses are disproven or become untenable, disengaging from outdated problem solving attempts becomes important so that new hypotheses can be generated and tested. From this perspective, the strong correlation between working memory capacity and fluid intelligence is due not to one ability having a causal influence on the other but to separate attention-demanding mental functions that can be contrary to one another but are organized around top-down processing goals. © The Author(s) 2016.

Enhancing memory self-efficacy during menopause through a group memory strategies program.

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Unkenstein, Anne E; Bei, Bei; Bryant, Christina A

2017-05-01

Anxiety about memory during menopause can affect quality of life. We aimed to improve memory self-efficacy during menopause using a group memory strategies program. The program was run five times for a total of 32 peri- and postmenopausal women, age between 47 and 60 years, recruited from hospital menopause and gynecology clinics. The 4-week intervention consisted of weekly 2-hour sessions, and covered how memory works, memory changes related to ageing, health and lifestyle factors, and specific memory strategies. Memory contentment (CT), reported frequency of forgetting (FF), use of memory strategies, psychological distress, and attitude toward menopause were measured. A double-baseline design was applied, with outcomes measured on two baseline occasions (1-month prior [T1] and in the first session [T2]), immediately postintervention (T3), and 3-month postintervention (T4). To describe changes in each variable between time points paired sample t tests were conducted. Mixed-effects models comparing the means of random slopes from T2 to T3 with those from T1 to T2 were conducted for each variable to test for treatment effects. Examination of the naturalistic changes in outcome measures from T1 to T2 revealed no significant changes (all Ps > 0.05). CT, reported FF, and use of memory strategies improved significantly more from T2 to T3, than from T1 to T2 (all Ps attitude toward menopause nor psychological distress improved significantly more postintervention than during the double-baseline (all Ps > 0.05). Improvements in reported CT and FF were maintained after 3 months. The use of group interventions to improve memory self-efficacy during menopause warrants continued evaluation.

How to assess gaming-induced benefits on attention and working memory

OpenAIRE

Mishra, Jyoti; Bavelier, Daphné; Gazzaley, Adam

2012-01-01

Our daily actions are driven by our goals in the moment, constantly forcing us to choose among various options. Attention and working memory are key enablers of that process. Attention allows for selective processing of goal-relevant information and rejecting task-irrelevant information. Working memory functions to maintain goal-relevant information in memory for brief periods of time for subsequent recall and/or manipulation. Efficient attention and working memory thus support the best extra...

Rethinking Materiality, Memory and Identity

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Tracy Ireland

2016-12-01

Full Text Available This introductory article  considers and questions exactly how materials and people constitute social worlds and relationships which sustain identity and memory and, in turn, the social and political structures or norms that these attachments invest in, stabilise and maintain.

Neural circuit mechanisms of short-term memory

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Goldman, Mark

Memory over time scales of seconds to tens of seconds is thought to be maintained by neural activity that is triggered by a memorized stimulus and persists long after the stimulus is turned off. This presents a challenge to current models of memory-storing mechanisms, because the typical time scales associated with cellular and synaptic dynamics are two orders of magnitude smaller than this. While such long time scales can easily be achieved by bistable processes that toggle like a flip-flop between a baseline and elevated-activity state, many neuronal systems have been observed experimentally to be capable of maintaining a continuum of stable states. For example, in neural integrator networks involved in the accumulation of evidence for decision making and in motor control, individual neurons have been recorded whose activity reflects the mathematical integral of their inputs; in the absence of input, these neurons sustain activity at a level proportional to the running total of their inputs. This represents an analog form of memory whose dynamics can be conceptualized through an energy landscape with a continuum of lowest-energy states. Such continuous attractor landscapes are structurally non-robust, in seeming violation of the relative robustness of biological memory systems. In this talk, I will present and compare different biologically motivated circuit motifs for the accumulation and storage of signals in short-term memory. Challenges to generating robust memory maintenance will be highlighted and potential mechanisms for ameliorating the sensitivity of memory networks to perturbations will be discussed. Funding for this work was provided by NIH R01 MH065034, NSF IIS-1208218, Simons Foundation 324260, and a UC Davis Ophthalmology Research to Prevent Blindness Grant.

Consciousness and working memory: Current trends and research perspectives.

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Velichkovsky, Boris B

2017-10-01

Working memory has long been thought to be closely related to consciousness. However, recent empirical studies show that unconscious content may be maintained within working memory and that complex cognitive computations may be performed on-line. This promotes research on the exact relationships between consciousness and working memory. Current evidence for working memory being a conscious as well as an unconscious process is reviewed. Consciousness is shown to be considered a subset of working memory by major current theories of working memory. Evidence for unconscious elements in working memory is shown to come from visual masking and attentional blink paradigms, and from the studies of implicit working memory. It is concluded that more research is needed to explicate the relationship between consciousness and working memory. Future research directions regarding the relationship between consciousness and working memory are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic algorithms with memory- and elitism-based immigrants in dynamic environments.

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Yang, Shengxiang

2008-01-01

In recent years the genetic algorithm community has shown a growing interest in studying dynamic optimization problems. Several approaches have been devised. The random immigrants and memory schemes are two major ones. The random immigrants scheme addresses dynamic environments by maintaining the population diversity while the memory scheme aims to adapt genetic algorithms quickly to new environments by reusing historical information. This paper investigates a hybrid memory and random immigrants scheme, called memory-based immigrants, and a hybrid elitism and random immigrants scheme, called elitism-based immigrants, for genetic algorithms in dynamic environments. In these schemes, the best individual from memory or the elite from the previous generation is retrieved as the base to create immigrants into the population by mutation. This way, not only can diversity be maintained but it is done more efficiently to adapt genetic algorithms to the current environment. Based on a series of systematically constructed dynamic problems, experiments are carried out to compare genetic algorithms with the memory-based and elitism-based immigrants schemes against genetic algorithms with traditional memory and random immigrants schemes and a hybrid memory and multi-population scheme. The sensitivity analysis regarding some key parameters is also carried out. Experimental results show that the memory-based and elitism-based immigrants schemes efficiently improve the performance of genetic algorithms in dynamic environments.

Revealing hidden states in visual working memory using electroencephalography

NARCIS (Netherlands)

Wolff, Michael J.; Ding, Jacqueline; Myers, Nicholas E.; Stokes, Mark G.

2015-01-01

It is often assumed that information in visual working memory (vWM) is maintained via persistent activity. However, recent evidence indicates that information in vWM could be maintained in an effectively "activity-silent" neural state. Silent vWM is consistent with recent cognitive and neural

Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription.

Science.gov (United States)

Nadkarni, Aditi; Burns, John A; Gandolfi, Alberto; Chowdhury, Moinuddin A; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E; Scicchitano, David A

2016-01-08

DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N(6)-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N(6)-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N(6)-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N(6)-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N(6)-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.

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Noyan, Kajsa; Nguyen, Son; Betts, Michael R; Sönnerborg, Anders; Buggert, Marcus

2018-01-01

Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (programmed cell death-1, CTLA-4, and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART. We found that the co-expression pattern of inhibitory receptors was significantly reduced in ELCs compared with HIV-1 cART-treated and viremic subjects, and similar to healthy controls. Markers associated with T cell exhaustion varied among different memory CD4+ T cell subsets and highest levels were found mainly on transitional memory T cells. CD4+ T cells co-expressing all inhibitory markers were positively correlated to T cell activation (CD38+ HLA-DR+) as well as the transcription factors Helios and FoxP3. Finally, clinical parameters such as CD4 count, HIV-1 viral load, and the CD4/CD8 ratio all showed significant associations with CD4+ T cell exhaustion. We demonstrate that ELCs are able to maintain lower levels of CD4+ T cell exhaustion despite years of ongoing viral replication compared with successfully cART-treated subjects. Our findings suggest that ELCs harbor a "healthy" state of inhibitory receptor expression on CD4+ T cells that might play part in maintenance of their control status.

The lasting memory enhancements of retrospective attention.

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Reaves, Sarah; Strunk, Jonathan; Phillips, Shekinah; Verhaeghen, Paul; Duarte, Audrey

2016-07-01

Behavioral research has shown that spatial cues that orient attention toward task relevant items being maintained in visual short-term memory (VSTM) enhance item memory accuracy. However, it is unknown if these retrospective attentional cues ("retro-cues") enhance memory beyond typical short-term memory delays. It is also unknown whether retro-cues affect the spatial information associated with VSTM representations. Emerging evidence suggests that processes that affect short-term memory maintenance may also affect long-term memory (LTM) but little work has investigated the role of attention in LTM. In the current event-related potential (ERP) study, we investigated the duration of retrospective attention effects and the impact of retrospective attention manipulations on VSTM representations. Results revealed that retro-cueing improved both VSTM and LTM memory accuracy and that posterior maximal ERPs observed during VSTM maintenance predicted subsequent LTM performance. N2pc ERPs associated with attentional selection were attenuated by retro-cueing suggesting that retrospective attention may disrupt maintenance of spatial configural information in VSTM. Collectively, these findings suggest that retrospective attention can alter the structure of memory representations, which impacts memory performance beyond short-term memory delays. Copyright © 2016 Elsevier B.V. All rights reserved.

The lasting memory enhancements of retrospective attention

Science.gov (United States)

Reaves, Sarah; Strunk, Jonathan; Phillips, Shekinah; Verhaeghen, Paul; Duarte, Audrey

2016-01-01

Behavioral research has shown that spatial cues that orient attention toward task relevant items being maintained in visual short-term memory (VSTM) enhance item memory accuracy. However, it is unknown if these retrospective attentional cues (“retro-cues”) enhance memory beyond typical short-term memory delays. It is also unknown whether retro-cues affect the spatial information associated with VSTM representations. Emerging evidence suggests that processes that affect short-term memory maintenance may also affect long-term memory (LTM) but little work has investigated the role of attention in LTM. In the current event-related potential (ERP) study, we investigated the duration of retrospective attention effects and the impact of retrospective attention manipulations on VSTM representations. Results revealed that retro-cueing improved both VSTM and LTM memory accuracy and that posterior maximal ERPs observed during VSTM maintenance predicted subsequent LTM performance. N2pc ERPs associated with attentional selection were attenuated by retro-cueing suggesting that retrospective attention may disrupt maintenance of spatial configural information in VSTM. Collectively, these findings suggest that retrospective attention can alter the structure of memory representations, which impacts memory performance beyond short-term memory delays. PMID:27038756

Visual Working Memory Is Independent of the Cortical Spacing Between Memoranda.

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Harrison, William J; Bays, Paul M

2018-03-21

The sensory recruitment hypothesis states that visual short-term memory is maintained in the same visual cortical areas that initially encode a stimulus' features. Although it is well established that the distance between features in visual cortex determines their visibility, a limitation known as crowding, it is unknown whether short-term memory is similarly constrained by the cortical spacing of memory items. Here, we investigated whether the cortical spacing between sequentially presented memoranda affects the fidelity of memory in humans (of both sexes). In a first experiment, we varied cortical spacing by taking advantage of the log-scaling of visual cortex with eccentricity, presenting memoranda in peripheral vision sequentially along either the radial or tangential visual axis with respect to the fovea. In a second experiment, we presented memoranda sequentially either within or beyond the critical spacing of visual crowding, a distance within which visual features cannot be perceptually distinguished due to their nearby cortical representations. In both experiments and across multiple measures, we found strong evidence that the ability to maintain visual features in memory is unaffected by cortical spacing. These results indicate that the neural architecture underpinning working memory has properties inconsistent with the known behavior of sensory neurons in visual cortex. Instead, the dissociation between perceptual and memory representations supports a role of higher cortical areas such as posterior parietal or prefrontal regions or may involve an as yet unspecified mechanism in visual cortex in which stimulus features are bound to their temporal order. SIGNIFICANCE STATEMENT Although much is known about the resolution with which we can remember visual objects, the cortical representation of items held in short-term memory remains contentious. A popular hypothesis suggests that memory of visual features is maintained via the recruitment of the same neural

Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

DEFF Research Database (Denmark)

Ly, Donald L.; Waheed, Faiza; Lodyga, Monika

2013-01-01

Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactiv......Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin......-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus...... in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF...

A single cis element maintains repression of the key developmental regulator Gata2.

Directory of Open Access Journals (Sweden)

Jonathan W Snow

2010-09-01

Full Text Available In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans-acting factors functioning through dispersed cis elements. It is not understood whether these elements function collectively to confer transcriptional regulation, or individually to control specific aspects of activation or repression, such as initiation versus maintenance. Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2, which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. We engineered mice lacking a single cis element -1.8 kb upstream of the Gata2 transcriptional start site. Although Gata2 is normally repressed in late-stage erythroblasts, the -1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. Our findings demonstrate that the -1.8 kb site selectively maintains repression, confers a specific histone modification pattern and expels RNA Polymerase II from the locus. These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed.

NiTi bonded space regainer/maintainer

Directory of Open Access Journals (Sweden)

Negi K

2010-06-01

Full Text Available Early orthodontic interventions are often initiated in the developing dentition to promote favorable developmental changes. Interceptive orthodontic can eliminate or reduce the severity of a developing malocclusion, the complexity of orthodontic treatment, overall treatment time and cost. Premature loss of deciduous tooth or teeth can often destroy the integrity of normal occlusion. There are many space regaining and maintaining devices mentioned in literature. In this article, I present a simple space regaining method by a piece of nickel titanium (NiTi wire bonded between the teeth in active loop form, and the unique shape memory property of NiTi wire will upright or move the teeth and the lost space can be regained easily.

Epigenetic mechanisms in experience-driven memory formation and behavior

Science.gov (United States)

Puckett, Rosemary E; Lubin, Farah D

2011-01-01

Epigenetic mechanisms have long been associated with the regulation of gene-expression changes accompanying normal neuronal development and cellular differentiation; however, until recently these mechanisms were believed to be statically quiet in the adult brain. Behavioral neuroscientists have now begun to investigate these epigenetic mechanisms as potential regulators of gene-transcription changes in the CNS subserving synaptic plasticity and long-term memory (LTM) formation. Experimental evidence from learning and memory animal models has demonstrated that active chromatin remodeling occurs in terminally differentiated postmitotic neurons, suggesting that these molecular processes are indeed intimately involved in several stages of LTM formation, including consolidation, reconsolidation and extinction. Such chromatin modifications include the phosphorylation, acetylation and methylation of histone proteins and the methylation of associated DNA to subsequently affect transcriptional gene readout triggered by learning. The present article examines how such learning-induced epigenetic changes contribute to LTM formation and influence behavior. In particular, this article is a survey of the specific epigenetic mechanisms that have been demonstrated to regulate gene expression for both transcription factors and growth factors in the CNS, which are critical for LTM formation and storage, as well as how aberrant epigenetic processing can contribute to psychological states such as schizophrenia and drug addiction. Together, the findings highlighted in this article support a novel role for epigenetic mechanisms in the adult CNS serving as potential key molecular regulators of gene-transcription changes necessary for LTM formation and adult behavior. PMID:22126252

Effects of working memory contents and perceptual load on distractor processing: When a response-related distractor is held in working memory.

Science.gov (United States)

Koshino, Hideya

2017-01-01

Working memory and attention are closely related. Recent research has shown that working memory can be viewed as internally directed attention. Working memory can affect attention in at least two ways. One is the effect of working memory load on attention, and the other is the effect of working memory contents on attention. In the present study, an interaction between working memory contents and perceptual load in distractor processing was investigated. Participants performed a perceptual load task in a standard form in one condition (Single task). In the other condition, a response-related distractor was maintained in working memory, rather than presented in the same stimulus display as a target (Dual task). For the Dual task condition, a significant compatibility effect was found under high perceptual load; however, there was no compatibility effect under low perceptual load. These results suggest that the way the contents of working memory affect visual search depends on perceptual load. Copyright © 2016 Elsevier B.V. All rights reserved.

Polyphonic Piano Transcription with a Note-Based Music Language Model

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Qi Wang

2018-03-01

Full Text Available This paper proposes a note-based music language model (MLM for improving note-level polyphonic piano transcription. The MLM is based on the recurrent structure, which could model the temporal correlations between notes in music sequences. To combine the outputs of the note-based MLM and acoustic model directly, an integrated architecture is adopted in this paper. We also propose an inference algorithm, in which the note-based MLM is used to predict notes at the blank onsets in the thresholding transcription results. The experimental results show that the proposed inference algorithm improves the performance of note-level transcription. We also observe that the combination of the restricted Boltzmann machine (RBM and recurrent structure outperforms a single recurrent neural network (RNN or long short-term memory network (LSTM in modeling the high-dimensional note sequences. Among all the MLMs, LSTM-RBM helps the system yield the best results on all evaluation metrics regardless of the performance of acoustic models.

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

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Kosan, Christian; Godmann, Maren

2016-01-01

All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

Directory of Open Access Journals (Sweden)

Christian Kosan

2016-01-01

Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

The DNA replication checkpoint directly regulates MBF-dependent G1/S transcription.

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Dutta, Chaitali; Patel, Prasanta K; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

2008-10-01

The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G(1)/S transcriptional program by directly regulating MBF, the G(1)/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G(1)/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G(1)/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes.

Effects of motor congruence on visual working memory.

Science.gov (United States)

Quak, Michel; Pecher, Diane; Zeelenberg, Rene

2014-10-01

Grounded-cognition theories suggest that memory shares processing resources with perception and action. The motor system could be used to help memorize visual objects. In two experiments, we tested the hypothesis that people use motor affordances to maintain object representations in working memory. Participants performed a working memory task on photographs of manipulable and nonmanipulable objects. The manipulable objects were objects that required either a precision grip (i.e., small items) or a power grip (i.e., large items) to use. A concurrent motor task that could be congruent or incongruent with the manipulable objects caused no difference in working memory performance relative to nonmanipulable objects. Moreover, the precision- or power-grip motor task did not affect memory performance on small and large items differently. These findings suggest that the motor system plays no part in visual working memory.

Neural Plasticity and Memory: Is Memory Encoded in Hydrogen Bonding Patterns?

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Amtul, Zareen; Rahman, Atta-Ur

2016-02-01

Current models of memory storage recognize posttranslational modification vital for short-term and mRNA translation for long-lasting information storage. However, at the molecular level things are quite vague. A comprehensive review of the molecular basis of short and long-lasting synaptic plasticity literature leads us to propose that the hydrogen bonding pattern at the molecular level may be a permissive, vital step of memory storage. Therefore, we propose that the pattern of hydrogen bonding network of biomolecules (glycoproteins and/or DNA template, for instance) at the synapse is the critical edifying mechanism essential for short- and long-term memories. A novel aspect of this model is that nonrandom impulsive (or unplanned) synaptic activity functions as a synchronized positive-feedback rehearsal mechanism by revising the configurations of the hydrogen bonding network by tweaking the earlier tailored hydrogen bonds. This process may also maintain the elasticity of the related synapses involved in memory storage, a characteristic needed for such networks to alter intricacy and revise endlessly. The primary purpose of this review is to stimulate the efforts to elaborate the mechanism of neuronal connectivity both at molecular and chemical levels. © The Author(s) 2014.

Role of Prefrontal Persistent Activity in Working Memory

Science.gov (United States)

Riley, Mitchell R.; Constantinidis, Christos

2016-01-01

The prefrontal cortex is activated during working memory, as evidenced by fMRI results in human studies and neurophysiological recordings in animal models. Persistent activity during the delay period of working memory tasks, after the offset of stimuli that subjects are required to remember, has traditionally been thought of as the neural correlate of working memory. In the last few years several findings have cast doubt on the role of this activity. By some accounts, activity in other brain areas, such as the primary visual and posterior parietal cortex, is a better predictor of information maintained in visual working memory and working memory performance; dynamic patterns of activity may convey information without requiring persistent activity at all; and prefrontal neurons may be ill-suited to represent non-spatial information about the features and identity of remembered stimuli. Alternative interpretations about the role of the prefrontal cortex have thus been suggested, such as that it provides a top-down control of information represented in other brain areas, rather than maintaining a working memory trace itself. Here we review evidence for and against the role of prefrontal persistent activity, with a focus on visual neurophysiology. We show that persistent activity predicts behavioral parameters precisely in working memory tasks. We illustrate that prefrontal cortex represents features of stimuli other than their spatial location, and that this information is largely absent from early cortical areas during working memory. We examine memory models not dependent on persistent activity, and conclude that each of those models could mediate only a limited range of memory-dependent behaviors. We review activity decoded from brain areas other than the prefrontal cortex during working memory and demonstrate that these areas alone cannot mediate working memory maintenance, particularly in the presence of distractors. We finally discuss the discrepancy between

Retrieval-Induced Inhibition in Short-Term Memory.

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Kang, Min-Suk; Choi, Joongrul

2015-07-01

We used a visual illusion called motion repulsion as a model system for investigating competition between two mental representations. Subjects were asked to remember two random-dot-motion displays presented in sequence and then to report the motion directions for each. Remembered motion directions were shifted away from the actual motion directions, an effect similar to the motion repulsion observed during perception. More important, the item retrieved second showed greater repulsion than the item retrieved first. This suggests that earlier retrieval exerted greater inhibition on the other item being held in short-term memory. This retrieval-induced motion repulsion could be explained neither by reduced cognitive resources for maintaining short-term memory nor by continued inhibition between short-term memory representations. These results indicate that retrieval of memory representations inhibits other representations in short-term memory. We discuss mechanisms of retrieval-induced inhibition and their implications for the structure of memory. © The Author(s) 2015.

[Pain and emotional dysregulation: Cellular memory due to pain].

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Narita, Minoru; Watanabe, Moe; Hamada, Yusuke; Tamura, Hideki; Ikegami, Daigo; Kuzumaki, Naoko; Igarashi, Katsuhide

2015-08-01

Genetic factors are involved in determinants for the risk of psychiatric disorders, and neurological and neurodegenerative diseases. Chronic pain stimuli and intense pain have effects at a cellular and/or gene expression level, and will eventually induce "cellular memory due to pain", which means that tissue damage, even if only transient, can elicit epigenetically abnormal transcription/translation and post-translational modification in related cells depending on the degree or kind of injury or associated conditions. Such cell memory/transformation due to pain can cause an abnormality in a fundamental intracellular response, such as a change in the three-dimensional structure of DNA, transcription, or translation. On the other hand, pain is a multidimensional experience with sensory-discriminative and motivational-affective components. Recent human brain imaging studies have examined differences in activity in the nucleus accumbens between controls and patients with chronic pain, and have revealed that the nucleus accumbens plays a role in predicting the value of a noxious stimulus and its offset, and in the consequent changes in the motivational state. In this review, we provide a very brief overview of a comprehensive understanding of chronic pain associated with emotional dysregulation due to transcriptional regulation, epigenetic modification and miRNA regulation.

The Focus of Spatial Attention Determines the Number and Precision of Face Representations in Working Memory.

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Towler, John; Kelly, Maria; Eimer, Martin

2016-06-01

The capacity of visual working memory for faces is extremely limited, but the reasons for these limitations remain unknown. We employed event-related brain potential measures to demonstrate that individual faces have to be focally attended in order to be maintained in working memory, and that attention is allocated to only a single face at a time. When 2 faces have to be memorized simultaneously in a face identity-matching task, the focus of spatial attention during encoding predicts which of these faces can be successfully maintained in working memory and matched to a subsequent test face. We also show that memory representations of attended faces are maintained in a position-dependent fashion. These findings demonstrate that the limited capacity of face memory is directly linked to capacity limits of spatial attention during the encoding and maintenance of individual face representations. We suggest that the capacity and distribution of selective spatial attention is a dynamic resource that constrains the capacity and fidelity of working memory for faces. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The neuronal PAS domain protein 4 (Npas4 is required for new and reactivated fear memories.

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Jonathan E Ploski

Full Text Available The Neuronal PAS domain protein 4 (Npas4 is a neuronal activity-dependent immediate early gene that has recently been identified as a transcription factor which regulates the transcription of genes that control inhibitory synapse development and synaptic plasticity. The role Npas4 in learning and memory, however, is currently unknown. Here, we systematically examine the role of Npas4 in auditory Pavlovian fear conditioning, an amygdala-dependent form of emotional learning. In our first series of experiments, we show that Npas4 mRNA and protein are regulated in the rat lateral nucleus of the amygdala (LA in a learning-dependent manner. Further, knockdown of Npas4 protein in the LA via adeno-associated viral (AAV mediated gene delivery of RNAi was observed to impair fear memory formation, while innate fear and the expression of fear memory were not affected. In our second series of experiments, we show that Npas4 protein is regulated in the LA by retrieval of an auditory fear memory and that knockdown of Npas4 in the LA impairs retention of a reactivated, but not a non-reactivated, fear memory. Collectively, our findings provide the first comprehensive look at the functional role of Npas4 in learning and memory.

Machine Learning Analysis Identifies Drosophila Grunge/Atrophin as an Important Learning and Memory Gene Required for Memory Retention and Social Learning.

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Kacsoh, Balint Z; Greene, Casey S; Bosco, Giovanni

2017-11-06

High-throughput experiments are becoming increasingly common, and scientists must balance hypothesis-driven experiments with genome-wide data acquisition. We sought to predict novel genes involved in Drosophila learning and long-term memory from existing public high-throughput data. We performed an analysis using PILGRM, which analyzes public gene expression compendia using machine learning. We evaluated the top prediction alongside genes involved in learning and memory in IMP, an interface for functional relationship networks. We identified Grunge/Atrophin ( Gug/Atro ), a transcriptional repressor, histone deacetylase, as our top candidate. We find, through multiple, distinct assays, that Gug has an active role as a modulator of memory retention in the fly and its function is required in the adult mushroom body. Depletion of Gug specifically in neurons of the adult mushroom body, after cell division and neuronal development is complete, suggests that Gug function is important for memory retention through regulation of neuronal activity, and not by altering neurodevelopment. Our study provides a previously uncharacterized role for Gug as a possible regulator of neuronal plasticity at the interface of memory retention and memory extinction. Copyright © 2017 Kacsoh et al.

Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory.

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Kojima, Nobuhiko; Borlikova, Gilyana; Sakamoto, Toshiro; Yamada, Kazuyuki; Ikeda, Toshio; Itohara, Shigeyoshi; Niki, Hiroaki; Endo, Shogo

2008-06-18

Long-lasting neuronal plasticity as well as long-term memory (LTM) requires de novo synthesis of proteins through dynamic regulation of gene expression. cAMP-responsive element (CRE)-mediated gene transcription occurs in an activity-dependent manner and plays a pivotal role in neuronal plasticity and LTM in a variety of species. To study the physiological role of inducible cAMP early repressor (ICER), a CRE-mediated gene transcription repressor, in neuronal plasticity and LTM, we generated two types of ICER mutant mice: ICER-overexpressing (OE) mice and ICER-specific knock-out (KO) mice. Both ICER-OE and ICER-KO mice show no apparent abnormalities in their development and reproduction. A comprehensive battery of behavioral tests revealed no robust changes in locomotor activity, sensory and motor functions, and emotional responses in the mutant mice. However, long-term conditioned fear memory was attenuated in ICER-OE mice and enhanced in ICER-KO mice without concurrent changes in short-term fear memory. Furthermore, ICER-OE mice exhibited retardation of kindling development, whereas ICER-KO mice exhibited acceleration of kindling. These results strongly suggest that ICER negatively regulates the neuronal processes required for long-term fear memory and neuronal plasticity underlying kindling epileptogenesis, possibly through suppression of CRE-mediated gene transcription.

The scope and control of attention: Sources of variance in working memory capacity.

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Chow, Michael; Conway, Andrew R A

2015-04-01

Working memory capacity is a strong positive predictor of many cognitive abilities, across various domains. The pattern of positive correlations across domains has been interpreted as evidence for a unitary source of inter-individual differences in behavior. However, recent work suggests that there are multiple sources of variance contributing to working memory capacity. The current study (N = 71) investigates individual differences in the scope and control of attention, in addition to the number and resolution of items maintained in working memory. Latent variable analyses indicate that the scope and control of attention reflect independent sources of variance and each account for unique variance in general intelligence. Also, estimates of the number of items maintained in working memory are consistent across tasks and related to general intelligence whereas estimates of resolution are task-dependent and not predictive of intelligence. These results provide insight into the structure of working memory, as well as intelligence, and raise new questions about the distinction between number and resolution in visual short-term memory.

Working memory deficits in adults with ADHD: is there evidence for subtype differences?

OpenAIRE

Schweitzer, Julie B; Hanford, Russell B; Medoff, Deborah R

2006-01-01

Abstract Background Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, ...

The Role of Actin Cytoskeleton in Dendritic Spines in the Maintenance of Long-Term Memory.

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Basu, Sreetama; Lamprecht, Raphael

2018-01-01

Evidence indicates that long-term memory formation involves alterations in synaptic efficacy produced by modifications in neural transmission and morphology. However, it is not clear how such alterations induced by learning, that encode memory, are maintained over long period of time to preserve long-term memory. This is especially intriguing as the half-life of most of the proteins that underlie such changes is usually in the range of hours to days and these proteins may change their location over time. In this review we describe studies that indicate the involvement of dendritic spines in memory formation and its maintenance. These studies show that learning leads to changes in the number and morphology of spines. Disruption in spines morphology or manipulations that lead to alteration in their number after consolidation are associated with impairment in memory maintenance. We further ask how changes in dendritic spines morphology, induced by learning and reputed to encode memory, are maintained to preserve long-term memory. We propose a mechanism, based on studies described in the review, whereby the actin cytoskeleton and its regulatory proteins involved in the initial alteration in spine morphology induced by learning are also essential for spine structural stabilization that maintains long-term memory. In this model glutamate receptors and other synaptic receptors activation during learning leads to the creation of new actin cytoskeletal scaffold leading to changes in spines morphology and memory formation. This new actin cytoskeletal scaffold is preserved beyond actin and its regulatory proteins turnover and dynamics by active stabilization of the level and activity of actin regulatory proteins within these memory spines.

'Memory and molecular turnover,' 30 years after inception.

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Meagher, Richard B

2014-01-01

In 1984 Sir Francis Crick hypothesized that memory is recorded in the brain as reversible modifications to DNA and protein, but acknowledged that most biomolecules turn over too rapidly to account for long-term memories. To accommodate this possible paradox he modeled an enzymatic mechanism to maintain modifications on hemi-modified multimeric symmetrical molecules. While studies on the turnover of chromatin modifications that may be involved in memory are in their infancy, an exploration of his model in the light of modern epigenetics produced somewhat surprising results. The molecular turnover rates for two classes of chromatin modifications believed to record and store durable memories were approximated from experiments using diverse approaches and were found to be remarkably short. The half-lives of DNA cytosine methylation and post-translationally modified nucleosomal histones are measured in hours and minutes, respectively, for a subset of sites on chromatin controlling gene expression. It appears likely that the turnover of DNA methylation in the brain and in neurons, in particular, is even more rapid than in other cell types and organs, perhaps accommodating neuronal plasticity, learning, and memory. The machinery responsible for the rapid turnover of DNA methylation and nucleosomal histone modifications is highly complex, partially redundant, and appears to act in a sequence specific manner. Molecular symmetry plays an important part in maintaining site-specific turnover, but its particular role in memory maintenance is unknown. Elucidating Crick's paradox, the contradiction between rapid molecular turnover of modified biomolecules and long-term memory storage, appears fundamental to understanding cognitive function and neurodegenerative disease.

The impact of auditory working memory training on the fronto-parietal working memory network.

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Schneiders, Julia A; Opitz, Bertram; Tang, Huijun; Deng, Yuan; Xie, Chaoxiang; Li, Hong; Mecklinger, Axel

2012-01-01

Working memory training has been widely used to investigate working memory processes. We have shown previously that visual working memory benefits only from intra-modal visual but not from across-modal auditory working memory training. In the present functional magnetic resonance imaging study we examined whether auditory working memory processes can also be trained specifically and which training-induced activation changes accompany theses effects. It was investigated whether working memory training with strongly distinct auditory materials transfers exclusively to an auditory (intra-modal) working memory task or whether it generalizes to a (across-modal) visual working memory task. We used adaptive n-back training with tonal sequences and a passive control condition. The memory training led to a reliable training gain. Transfer effects were found for the (intra-modal) auditory but not for the (across-modal) visual transfer task. Training-induced activation decreases in the auditory transfer task were found in two regions in the right inferior frontal gyrus. These effects confirm our previous findings in the visual modality and extents intra-modal effects in the prefrontal cortex to the auditory modality. As the right inferior frontal gyrus is frequently found in maintaining modality-specific auditory information, these results might reflect increased neural efficiency in auditory working memory processes. Furthermore, task-unspecific (amodal) activation decreases in the visual and auditory transfer task were found in the right inferior parietal lobule and the superior portion of the right middle frontal gyrus reflecting less demand on general attentional control processes. These data are in good agreement with amodal activation decreases within the same brain regions on a visual transfer task reported previously.

The impact of auditory working memory training on the fronto-parietal working memory network

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Schneiders, Julia A.; Opitz, Bertram; Tang, Huijun; Deng, Yuan; Xie, Chaoxiang; Li, Hong; Mecklinger, Axel

2012-01-01

Working memory training has been widely used to investigate working memory processes. We have shown previously that visual working memory benefits only from intra-modal visual but not from across-modal auditory working memory training. In the present functional magnetic resonance imaging study we examined whether auditory working memory processes can also be trained specifically and which training-induced activation changes accompany theses effects. It was investigated whether working memory training with strongly distinct auditory materials transfers exclusively to an auditory (intra-modal) working memory task or whether it generalizes to a (across-modal) visual working memory task. We used adaptive n-back training with tonal sequences and a passive control condition. The memory training led to a reliable training gain. Transfer effects were found for the (intra-modal) auditory but not for the (across-modal) visual transfer task. Training-induced activation decreases in the auditory transfer task were found in two regions in the right inferior frontal gyrus. These effects confirm our previous findings in the visual modality and extents intra-modal effects in the prefrontal cortex to the auditory modality. As the right inferior frontal gyrus is frequently found in maintaining modality-specific auditory information, these results might reflect increased neural efficiency in auditory working memory processes. Furthermore, task-unspecific (amodal) activation decreases in the visual and auditory transfer task were found in the right inferior parietal lobule and the superior portion of the right middle frontal gyrus reflecting less demand on general attentional control processes. These data are in good agreement with amodal activation decreases within the same brain regions on a visual transfer task reported previously. PMID:22701418

Maintenance of auditory-nonverbal information in working memory.

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Soemer, Alexander; Saito, Satoru

2015-12-01

According to the multicomponent view of working memory, both auditory-nonverbal information and auditory-verbal information are stored in a phonological code and are maintained by an articulation-based rehearsal mechanism (Baddeley, 2012). Two experiments have been carried out to investigate this hypothesis using sound materials that are difficult to label verbally and difficult to articulate. Participants were required to maintain 2 to 4 sounds differing in timbre over a delay of up to 12 seconds while performing different secondary tasks. While there was no convincing evidence for articulatory rehearsal as a main maintenance mechanism for auditory-nonverbal information, the results suggest that processes similar or identical to auditory imagery might contribute to maintenance. We discuss the implications of these results for multicomponent models of working memory.

Epigenetic regulation and chromatin remodeling in learning and memory.

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Kim, Somi; Kaang, Bong-Kiun

2017-01-13

Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.

NMDA Receptor- and ERK-Dependent Histone Methylation Changes in the Lateral Amygdala Bidirectionally Regulate Fear Memory Formation

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Gupta-Agarwal, Swati; Jarome, Timothy J.; Fernandez, Jordan; Lubin, Farah D.

2014-01-01

It is well established that fear memory formation requires de novo gene transcription in the amygdala. We provide evidence that epigenetic mechanisms in the form of histone lysine methylation in the lateral amygdala (LA) are regulated by NMDA receptor (NMDAR) signaling and involved in gene transcription changes necessary for fear memory…

Working Memory and Down Syndrome

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Baddeley, A.; Jarrold, C.

2007-01-01

A brief account is given of the evolution of the concept of working memory from a unitary store into a multicomponent system. Four components are distinguished, the phonological loop which is responsible for maintaining speech-based information, the visuospatial sketchpad performing a similar function for visual information, the central executive…

Short-term memory in the service of executive control functions

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Farshad Alizadeh Mansouri

2015-12-01

Full Text Available Short-term memory is a crucial cognitive function for supporting on-going and upcoming behaviours, allowing storage of information across delay periods. The content of this memory may typically include tangible information about features such as the shape, colour or texture of an object, its location and motion relative to the body, or phonological information. The neural correlate of these short-term memories has been found in different brain areas involved in organizing perceptual or motor functions. In particular, neuronal activity in different prefrontal areas encodes task-related information corresponding to short-term memory across delay periods, and lesions in the prefrontal cortex severely affect the ability to hold this type of memory. Recent studies have further expanded the scope and possible role of short-term memory by showing that information of abstract entities such as a behaviour-guiding rule, or the occurrence of a conflict in information processing; can also be maintained in short-term memory and used for adjusting the allocation of executive control in dynamic environments. It has also been shown that neuronal activity in the dorsolateral prefrontal and orbitofrontal cortices encodes information about such abstract entities. These findings suggest that the prefrontal cortex plays crucial roles in organizing goal-directed behaviour by supporting various mnemonic processes that maintain a wide range of information in the service of executive control of on-going or upcoming behaviour.

Age-Related Decline of Precision and Binding in Visual Working Memory

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2013-01-01

Working memory declines with normal aging, but the nature of this impairment is debated. Studies based on detecting changes to arrays of visual objects have identified two possible components to age-related decline: a reduction in the number of items that can be stored, or a deficit in maintaining the associations (bindings) between individual object features. However, some investigations have reported intact binding with aging, and specific deficits arising only in Alzheimer’s disease. Here, using a recently developed continuous measure of recall fidelity, we tested the precision with which adults of different ages could reproduce from memory the orientation and color of a probed array item. The results reveal a further component of cognitive decline: an age-related decrease in the resolution with which visual information can be maintained in working memory. This increase in recall variability with age was strongest under conditions of greater memory load. Moreover, analysis of the distribution of errors revealed that older participants were more likely to incorrectly report one of the unprobed items in memory, consistent with an age-related increase in misbinding. These results indicate a systematic decline with age in working memory resources that can be recruited to store visual information. The paradigm presented here provides a sensitive index of both memory resolution and feature binding, with the potential for assessing their modulation by interventions. The findings have implications for understanding the mechanisms underpinning working memory deficits in both health and disease. PMID:23978008

Transcription of tandemly repetitive DNA: functional roles.

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Biscotti, Maria Assunta; Canapa, Adriana; Forconi, Mariko; Olmo, Ettore; Barucca, Marco

2015-09-01

A considerable fraction of the eukaryotic genome is made up of satellite DNA constituted of tandemly repeated sequences. These elements are mainly located at centromeres, pericentromeres, and telomeres and are major components of constitutive heterochromatin. Although originally satellite DNA was thought silent and inert, an increasing number of studies are providing evidence on its transcriptional activity supporting, on the contrary, an unexpected dynamicity. This review summarizes the multiple structural roles of satellite noncoding RNAs at chromosome level. Indeed, satellite noncoding RNAs play a role in the establishment of a heterochromatic state at centromere and telomere. These highly condensed structures are indispensable to preserve chromosome integrity and genome stability, preventing recombination events, and ensuring the correct chromosome pairing and segregation. Moreover, these RNA molecules seem to be involved also in maintaining centromere identity and in elongation, capping, and replication of telomere. Finally, the abnormal variation of centromeric and pericentromeric DNA transcription across major eukaryotic lineages in stress condition and disease has evidenced the critical role that these transcripts may play and the potentially dire consequences for the organism.

Single Canonical Model of Reflexive Memory and Spatial Attention

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Patel, Saumil S.; Red, Stuart; Lin, Eric; Sereno, Anne B.

2015-01-01

Many neurons in the dorsal and ventral visual stream have the property that after a brief visual stimulus presentation in their receptive field, the spiking activity in these neurons persists above their baseline levels for several seconds. This maintained activity is not always correlated with the monkey’s task and its origin is unknown. We have previously proposed a simple neural network model, based on shape selective neurons in monkey lateral intraparietal cortex, which predicts the valence and time course of reflexive (bottom-up) spatial attention. In the same simple model, we demonstrate here that passive maintained activity or short-term memory of specific visual events can result without need for an external or top-down modulatory signal. Mutual inhibition and neuronal adaptation play distinct roles in reflexive attention and memory. This modest 4-cell model provides the first simple and unified physiologically plausible mechanism of reflexive spatial attention and passive short-term memory processes. PMID:26493949

Single Canonical Model of Reflexive Memory and Spatial Attention.

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Patel, Saumil S; Red, Stuart; Lin, Eric; Sereno, Anne B

2015-10-23

Many neurons in the dorsal and ventral visual stream have the property that after a brief visual stimulus presentation in their receptive field, the spiking activity in these neurons persists above their baseline levels for several seconds. This maintained activity is not always correlated with the monkey's task and its origin is unknown. We have previously proposed a simple neural network model, based on shape selective neurons in monkey lateral intraparietal cortex, which predicts the valence and time course of reflexive (bottom-up) spatial attention. In the same simple model, we demonstrate here that passive maintained activity or short-term memory of specific visual events can result without need for an external or top-down modulatory signal. Mutual inhibition and neuronal adaptation play distinct roles in reflexive attention and memory. This modest 4-cell model provides the first simple and unified physiologically plausible mechanism of reflexive spatial attention and passive short-term memory processes.

Spatial attention interacts with serial-order retrieval from verbal working memory.

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van Dijck, Jean-Philippe; Abrahamse, Elger L; Majerus, Steve; Fias, Wim

2013-09-01

The ability to maintain the serial order of events is recognized as a major function of working memory. Although general models of working memory postulate a close link between working memory and attention, such a link has so far not been proposed specifically for serial-order working memory. The present study provided the first empirical demonstration of a direct link between serial order in verbal working memory and spatial selective attention. We show that the retrieval of later items of a sequence stored in working memory-compared with that of earlier items-produces covert attentional shifts toward the right. This observation suggests the conceptually surprising notion that serial-order working memory, even for nonspatially defined verbal items, draws on spatial attention.

Effects of heavy particle irradiation and diet on object recognition memory in rats

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Rabin, Bernard M.; Carrihill-Knoll, Kirsty; Hinchman, Marie; Shukitt-Hale, Barbara; Joseph, James A.; Foster, Brian C.

2009-04-01

On long-duration missions to other planets astronauts will be exposed to types and doses of radiation that are not experienced in low earth orbit. Previous research using a ground-based model for exposure to cosmic rays has shown that exposure to heavy particles, such as 56Fe, disrupts spatial learning and memory measured using the Morris water maze. Maintaining rats on diets containing antioxidant phytochemicals for 2 weeks prior to irradiation ameliorated this deficit. The present experiments were designed to determine: (1) the generality of the particle-induced disruption of memory by examining the effects of exposure to 56Fe particles on object recognition memory; and (2) whether maintaining rats on these antioxidant diets for 2 weeks prior to irradiation would also ameliorate any potential deficit. The results showed that exposure to low doses of 56Fe particles does disrupt recognition memory and that maintaining rats on antioxidant diets containing blueberry and strawberry extract for only 2 weeks was effective in ameliorating the disruptive effects of irradiation. The results are discussed in terms of the mechanisms by which exposure to these particles may produce effects on neurocognitive performance.

Working Memory Capacity and Focused and Sustained Attention

National Research Council Canada - National Science Library

Engle, Randall

2003-01-01

.... We see WM as a system consisting of those long-term memory traces active above threshold, the procedures and skills necessary to achieve and maintain that activation and, what we call executive...

The distribution and the functions of autobiographical memories: Why do older adults remember autobiographical memories from their youth?

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Wolf, Tabea; Zimprich, Daniel

2016-09-01

In the present study, the distribution of autobiographical memories was examined from a functional perspective: we examined whether the extent to which long-term autobiographical memories were rated as having a self-, a directive, or a social function affects the location (mean age) and scale (standard deviation) of the memory distribution. Analyses were based on a total of 5598 autobiographical memories generated by 149 adults aged between 50 and 81 years in response to 51 cue-words. Participants provided their age at the time when the recalled events had happened and rated how frequently they recall these events for self-, directive, and social purposes. While more frequently using autobiographical memories for self-functions was associated with an earlier mean age, memories frequently shared with others showed a narrower distribution around a later mean age. The directive function, by contrast, did not affect the memory distribution. The results strengthen the assumption that experiences from an individual's late adolescence serve to maintain a sense of self-continuity throughout the lifespan. Experiences that are frequently shared with others, in contrast, stem from a narrow age range located in young adulthood.

Working Memory Benefits Creative Insight, Musical Improvisation, and Original Ideation Through Maintained Task-Focused Attention

NARCIS (Netherlands)

De Dreu, Carsten K. W.; Nijstad, Bernard A.; Baas, Matthijs; Wolsink, Inge; Roskes, Marieke

Anecdotes from creative eminences suggest that executive control plays an important role in creativity, but scientific evidence is sparse. Invoking the Dual Pathway to Creativity Model, the authors hypothesize that working memory capacity (WMC) relates to creative performance because it enables

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

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Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Selection on Coding and Regulatory Variation Maintains Individuality in Major Urinary Protein Scent Marks in Wild Mice.

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Michael J Sheehan

2016-03-01

Full Text Available Recognition of individuals by scent is widespread across animal taxa. Though animals can often discriminate chemical blends based on many compounds, recent work shows that specific protein pheromones are necessary and sufficient for individual recognition via scent marks in mice. The genetic nature of individuality in scent marks (e.g. coding versus regulatory variation and the evolutionary processes that maintain diversity are poorly understood. The individual signatures in scent marks of house mice are the protein products of a group of highly similar paralogs in the major urinary protein (Mup gene family. Using the offspring of wild-caught mice, we examine individuality in the major urinary protein (MUP scent marks at the DNA, RNA and protein levels. We show that individuality arises through a combination of variation at amino acid coding sites and differential transcription of central Mup genes across individuals, and we identify eSNPs in promoters. There is no evidence of post-transcriptional processes influencing phenotypic diversity as transcripts accurately predict the relative abundance of proteins in urine samples. The match between transcripts and urine samples taken six months earlier also emphasizes that the proportional relationships across central MUP isoforms in urine is stable. Balancing selection maintains coding variants at moderate frequencies, though pheromone diversity appears limited by interactions with vomeronasal receptors. We find that differential transcription of the central Mup paralogs within and between individuals significantly increases the individuality of pheromone blends. Balancing selection on gene regulation allows for increased individuality via combinatorial diversity in a limited number of pheromones.

Expertise for upright faces improves the precision but not the capacity of visual working memory.

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Lorenc, Elizabeth S; Pratte, Michael S; Angeloni, Christopher F; Tong, Frank

2014-10-01

Considerable research has focused on how basic visual features are maintained in working memory, but little is currently known about the precision or capacity of visual working memory for complex objects. How precisely can an object be remembered, and to what extent might familiarity or perceptual expertise contribute to working memory performance? To address these questions, we developed a set of computer-generated face stimuli that varied continuously along the dimensions of age and gender, and we probed participants' memories using a method-of-adjustment reporting procedure. This paradigm allowed us to separately estimate the precision and capacity of working memory for individual faces, on the basis of the assumptions of a discrete capacity model, and to assess the impact of face inversion on memory performance. We found that observers could maintain up to four to five items on average, with equally good memory capacity for upright and upside-down faces. In contrast, memory precision was significantly impaired by face inversion at every set size tested. Our results demonstrate that the precision of visual working memory for a complex stimulus is not strictly fixed but, instead, can be modified by learning and experience. We find that perceptual expertise for upright faces leads to significant improvements in visual precision, without modifying the capacity of working memory.

Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy

Science.gov (United States)

Solomon, Ajantha; Ghneim, Khader; Ahlers, Jeffrey; Cameron, Mark J.; Smith, Miranda Z.; Spelman, Tim; McMahon, James; Velayudham, Pushparaj; Brown, Gregor; Roney, Janine; Watson, Jo; Prince, Miles H.; Hoy, Jennifer F.; Chomont, Nicolas; Fromentin, Rémi; Procopio, Francesco A.; Zeidan, Joumana; Palmer, Sarah; Odevall, Lina; Johnstone, Ricky W.; Martin, Ben P.; Sinclair, Elizabeth; Deeks, Steven G.; Hazuda, Daria J.; Cameron, Paul U.; Sékaly, Rafick-Pierre; Lewin, Sharon R.

2014-01-01

Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells. Trial Registration ClinicalTrials.gov NCT01365065 PMID:25393648

Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy.

Directory of Open Access Journals (Sweden)

Julian H Elliott

2014-10-01

Full Text Available Human immunodeficiency virus (HIV persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART. The primary endpoint was change in cell associated unspliced (CA-US HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065. Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90% with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1. CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.ClinicalTrials.gov NCT01365065.

Social Working Memory: Neurocognitive networks and plasticity

OpenAIRE

Meyer, Meghan Leigh

2014-01-01

The social world is incredibly complex and the ability to keep track of various pieces of social information at once is imperative for success as a social species. Yet, how humans manage social information in mind has to date remained a mystery. On the one hand, psychological models of working memory, or the ability to maintain and manipulate information in mind, suggest that managing social information in mind would rely on generic working memory processes. However, recent research in social...

Is gene transcription involved in seed dry after-ripening?

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Patrice Meimoun

Full Text Available Orthodox seeds are living organisms that survive anhydrobiosis and may display dormancy, an inability to germinate at harvest. Seed germination potential can be acquired during a prolonged period of dry storage called after-ripening. The aim of this work was to determine if gene transcription is an underlying regulatory mechanism for dormancy alleviation during after-ripening. To identify changes in gene transcription strictly associated with the acquisition of germination potential but not with storage, we used seed storage at low relative humidity that maintains dormancy as control. Transcriptome profiling was performed using DNA microarray to compare change in gene transcript abundance between dormant (D, after-ripened non-dormant (ND and after-ripened dormant seeds (control, C. Quantitative real-time polymerase chain reaction (qPCR was used to confirm gene expression. Comparison between D and ND showed the differential expression of 115 probesets at cut-off values of two-fold change (p<0.05. Comparisons between both D and C with ND in transcript abundance showed that only 13 transcripts, among 115, could be specific to dormancy alleviation. qPCR confirms the expression pattern of these transcripts but without significant variation between conditions. Here we show that sunflower seed dormancy alleviation in the dry state is not related to regulated changes in gene expression.

Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.

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Yu, Bingfei; Zhang, Kai; Milner, J Justin; Toma, Clara; Chen, Runqiang; Scott-Browne, James P; Pereira, Renata M; Crotty, Shane; Chang, John T; Pipkin, Matthew E; Wang, Wei; Goldrath, Ananda W

2017-05-01

Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8 + T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8 + T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal key TFs that influence the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8 + T cell differentiation, regulated the formation of terminal-effector cell fates and memory-precursor cell fates, respectively. Our data define the epigenetic landscape of differentiation intermediates and facilitate the identification of TFs with previously unappreciated roles in CD8 + T cell differentiation.

In vitro synthesis of biologically active transcripts of tomato black ring virus satellite RNA.

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Greif, C; Hemmer, O; Demangeat, G; Fritsch, C

1990-04-01

Synthetic transcripts of tomato black ring virus satellite RNA (TBRV satRNA), isolate L, were prepared from cDNA cloned in the Bluescribe transcription vector. Transcripts with 49 (T49L) or two (T2GL) extra nucleotides at their 5' ends and 42 extra nucleotides at their 3' ends were able to induce, but to different extents, the synthesis in vitro of the satRNA-encoded 48K protein. However, when inoculated into Chenopodium quinoa together with TBRV L genomic RNAs, only T2GL was biologically active, in the presence or absence of a 5' cap analogue in the transcription reactions. Analysis of the 5' and 3' termini of the satRNA isolated from plants showed that nonviral extensions were not maintained in the transcript progeny.

Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory.

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Vetere, Gisella; Barbato, Christian; Pezzola, Silvia; Frisone, Paola; Aceti, Massimiliano; Ciotti, MariaTeresa; Cogoni, Carlo; Ammassari-Teule, Martine; Ruberti, Francesca

2014-12-01

Post-transcriptional gene regulation mediated by microRNAs (miRNAs) is implicated in memory formation; however, the function of miR-92 in this regulation is uncharacterized. The present study shows that training mice in contextual fear conditioning produces a transient increase in miR-92 levels in the hippocampus and decreases several miR-92 gene targets, including: (i) the neuronal Cl(-) extruding K(+) Cl(-) co-transporter 2 (KCC2) protein; (ii) the cytoplasmic polyadenylation protein (CPEB3), an RNA-binding protein regulator of protein synthesis in neurons; and (iii) the transcription factor myocyte enhancer factor 2D (MEF2D), one of the MEF2 genes which negatively regulates memory-induced structural plasticity. Selective inhibition of endogenous miR-92 in CA1 hippocampal neurons, by a sponge lentiviral vector expressing multiple sequences imperfectly complementary to mature miR-92 under the control of the neuronal specific synapsin promoter, leads to up-regulation of KCC2, CPEB3 and MEF2D, impairs contextual fear conditioning, and prevents a memory-induced increase in the spine density. Taken together, the results indicate that neuronal-expressed miR-92 is an endogenous fine regulator of contextual fear memory in mice. © 2014 Wiley Periodicals, Inc.

High density submicron magnetoresistive random access memory (invited)

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Tehrani, S.; Chen, E.; Durlam, M.; DeHerrera, M.; Slaughter, J. M.; Shi, J.; Kerszykowski, G.

1999-04-01

Various giant magnetoresistance material structures were patterned and studied for their potential as memory elements. The preferred memory element, based on pseudo-spin valve structures, was designed with two magnetic stacks (NiFeCo/CoFe) of different thickness with Cu as an interlayer. The difference in thickness results in dissimilar switching fields due to the shape anisotropy at deep submicron dimensions. It was found that a lower switching current can be achieved when the bits have a word line that wraps around the bit 1.5 times. Submicron memory elements integrated with complementary metal-oxide-semiconductor (CMOS) transistors maintained their characteristics and no degradation to the CMOS devices was observed. Selectivity between memory elements in high-density arrays was demonstrated.

Basic leucine zipper protein Cnc-C is a substrate and transcriptional regulator of the Drosophila 26S proteasome.

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Grimberg, Kristian Björk; Beskow, Anne; Lundin, Daniel; Davis, Monica M; Young, Patrick

2011-02-01

While the 26S proteasome is a key proteolytic complex, little is known about how proteasome levels are maintained in higher eukaryotic cells. Here we describe an RNA interference (RNAi) screen of Drosophila melanogaster that was used to identify transcription factors that may play a role in maintaining levels of the 26S proteasome. We used an RNAi library against 993 Drosophila transcription factor genes to identify genes whose suppression in Schneider 2 cells stabilized a ubiquitin-green fluorescent protein reporter protein. This screen identified Cnc (cap 'n' collar [CNC]; basic region leucine zipper) as a candidate transcriptional regulator of proteasome component expression. In fact, 20S proteasome activity was reduced in cells depleted of cnc. Immunoblot assays against proteasome components revealed a general decline in both 19S regulatory complex and 20S proteasome subunits after RNAi depletion of this transcription factor. Transcript-specific silencing revealed that the longest of the seven transcripts for the cnc gene, cnc-C, was needed for proteasome and p97 ATPase production. Quantitative reverse transcription-PCR confirmed the role of Cnc-C in activation of transcription of genes encoding proteasome components. Expression of a V5-His-tagged form of Cnc-C revealed that the transcription factor is itself a proteasome substrate that is stabilized when the proteasome is inhibited. We propose that this single cnc gene in Drosophila resembles the ancestral gene family of mammalian nuclear factor erythroid-derived 2-related transcription factors, which are essential in regulating oxidative stress and proteolysis.

A Common Neural Substrate for Language Production and Verbal Working Memory

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Acheson, Daniel J.; Hamidi, Massihullah; Binder, Jeffrey R.; Postle, Bradley R.

2011-01-01

Verbal working memory (VWM), the ability to maintain and manipulate representations of speech sounds over short periods, is held by some influential models to be independent from the systems responsible for language production and comprehension [e.g., Baddeley, A. D. "Working memory, thought, and action." New York, NY: Oxford University Press,…

Activation of Gαq Signaling Enhances Memory Consolidation and Slows Cognitive Decline.

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Arey, Rachel N; Stein, Geneva M; Kaletsky, Rachel; Kauffman, Amanda; Murphy, Coleen T

2018-05-02

Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function G αq signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes. Enhanced G αq signaling in the AWC sensory neuron is both necessary and sufficient for improved memory and increased AIM CREB activity, and activation of G αq specifically in aged animals rescues the ability to form memory. Activation of G αq in AWC sensory neurons non-cell autonomously induces consolidation after one CS-US pairing, enabling both cognitive function maintenance with age and restoration of memory function in animals with impaired memory performance without decreased longevity. Copyright © 2018 Elsevier Inc. All rights reserved.

The Impact of Auditory Working Memory Training on the Fronto-Parietal Working Memory Network

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Julia eSchneiders

2012-06-01

Full Text Available Working memory training has been widely used to investigate working memory processes. We have shown previously that visual working memory benefits only from intra-modal visual but not from across-modal auditory working memory training. In the present functional magnetic resonance imaging study we examined whether auditory working memory processes can also be trained specifically and which training-induced activation changes accompany theses effects. It was investigated whether working memory training with strongly distinct auditory materials transfers exclusively to an auditory (intra-modal working memory task or whether it generalizes to an (across-modal visual working memory task. We used an adaptive n-back training with tonal sequences and a passive control condition. The memory training led to a reliable training gain. Transfer effects were found for the (intra-modal auditory but not for the (across-modal visual 2-back task. Training-induced activation changes in the auditory 2-back task were found in two regions in the right inferior frontal gyrus. These effects confirm our previous findings in the visual modality and extends intra-modal effects to the auditory modality. These results might reflect increased neural efficiency in auditory working memory processes as in the right inferior frontal gyrus is frequently found in maintaining modality-specific auditory information. By this, these effects are analogical to the activation decreases in the right middle frontal gyrus for the visual modality in our previous study. Furthermore, task-unspecific (across-modal activation decreases in the visual and auditory 2-back task were found in the right inferior parietal lobule and the superior portion of the right middle frontal gyrus reflecting less demands on general attentional control processes. These data are in good agreement with across-modal activation decreases within the same brain regions on a visual 2-back task reported previously.

Attention is required for maintenance of feature binding in visual working memory

OpenAIRE

Zokaei, Nahid; Heider, Maike; Husain, Masud

2013-01-01

Working memory and attention are intimately connected. However, understanding the relationship between the two is challenging. Currently, there is an important controversy about whether objects in working memory are maintained automatically or require resources that are also deployed for visual or auditory attention. Here we investigated the effects of loading attention resources on precision of visual working memory, specifically on correct maintenance of feature-bound objects, using a dual-...

The histone deacetylase HDAC4 regulates long-term memory in Drosophila.

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Fitzsimons, Helen L; Schwartz, Silvia; Given, Fiona M; Scott, Maxwell J

2013-01-01

A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs) correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation.

Stability of discrete memory states to stochastic fluctuations in neuronal systems

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Miller, Paul; Wang, Xiao-Jing

2014-01-01

Noise can degrade memories by causing transitions from one memory state to another. For any biological memory system to be useful, the time scale of such noise-induced transitions must be much longer than the required duration for memory retention. Using biophysically-realistic modeling, we consider two types of memory in the brain: short-term memories maintained by reverberating neuronal activity for a few seconds, and long-term memories maintained by a molecular switch for years. Both systems require persistence of (neuronal or molecular) activity self-sustained by an autocatalytic process and, we argue, that both have limited memory lifetimes because of significant fluctuations. We will first discuss a strongly recurrent cortical network model endowed with feedback loops, for short-term memory. Fluctuations are due to highly irregular spike firing, a salient characteristic of cortical neurons. Then, we will analyze a model for long-term memory, based on an autophosphorylation mechanism of calcium/calmodulin-dependent protein kinase II (CaMKII) molecules. There, fluctuations arise from the fact that there are only a small number of CaMKII molecules at each postsynaptic density (putative synaptic memory unit). Our results are twofold. First, we demonstrate analytically and computationally the exponential dependence of stability on the number of neurons in a self-excitatory network, and on the number of CaMKII proteins in a molecular switch. Second, for each of the two systems, we implement graded memory consisting of a group of bistable switches. For the neuronal network we report interesting ramping temporal dynamics as a result of sequentially switching an increasing number of discrete, bistable, units. The general observation of an exponential increase in memory stability with the system size leads to a trade-off between the robustness of memories (which increases with the size of each bistable unit) and the total amount of information storage (which decreases

Autoradiographic study of transcription during early germination of Zea mays embryos maintained in situ

International Nuclear Information System (INIS)

Deltour, Roger

1979-01-01

Recovery of RNA synthesis was studied by autoradiography in primary root of Zea mays embryos germinating at 16 0 C. [H 3 ] uridine was provided to embryos maintained in situ. During the first 4hrs of germination the cell radioactivity is located almost exclusively in the extranucleolar chromatin. These observations agree well with previous results obtained when [H 3 ] uridine was provided to isolated embryos [fr

Magnetic stimulation of the dorsolateral prefrontal cortex dissociates fragile visual short-term memory from visual working memory.

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Sligte, Ilja G; Wokke, Martijn E; Tesselaar, Johannes P; Scholte, H Steven; Lamme, Victor A F

2011-05-01

To guide our behavior in successful ways, we often need to rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). While VSTM is usually broken down into iconic memory (brief and high-capacity store) and visual working memory (sustained, yet limited-capacity store), recent studies have suggested the existence of an additional and intermediate form of VSTM that depends on activity in extrastriate cortex. In previous work, we have shown that this fragile form of VSTM can be dissociated from iconic memory. In the present study, we provide evidence that fragile VSTM is different from visual working memory as magnetic stimulation of the right dorsolateral prefrontal cortex (DLPFC) disrupts visual working memory, while leaving fragile VSTM intact. In addition, we observed that people with high DLPFC activity had superior working memory capacity compared to people with low DLPFC activity, and only people with high DLPFC activity really showed a reduction in working memory capacity in response to magnetic stimulation. Altogether, this study shows that VSTM consists of three stages that have clearly different characteristics and rely on different neural structures. On the methodological side, we show that it is possible to predict individual susceptibility to magnetic stimulation based on functional MRI activity. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Superior intraparietal sulcus controls the variability of visual working memory precision

NARCIS (Netherlands)

Galeano Weber, E.M.; Peters, B.; Hahn, T.; Bledowski, C.; Fiebach, C.J.

2016-01-01

Limitations of working memory (WM) capacity depend strongly on the cognitive resources that are available for maintaining WM contents in an activated state. Increasing the number of items to be maintained in WM was shown to reduce the precision of WM and to increase the variability of WM precision

New insight into transcription of human endogenous retroviral elements

Czech Academy of Sciences Publication Activity Database

Pačes, Jan; Huang, Y.T.; Pačes, Václav; Rídl, Jakub; Chang, C.M.

2013-01-01

Roč. 30, č. 3 (2013), s. 314-318 ISSN 1871-6784 R&D Projects: GA ČR GCP305/10/J052 Grant - others:Chang Gung Memorial Hospital(TW) CMRPD170233; NSCNHRI Taiwan(TW) NSC 97-2314-B-182-001-MY2; NSCNHRI Taiwan(TW) NSC 99-2314-B-182-024-MY3; NSCNHRI Taiwan(TW) NSC 99-2923-B-182-001-MY3 Institutional support: RVO:68378050 Keywords : HERV * transcription * tissue-specific Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.106, year: 2013

Shifting visual perspective during retrieval shapes autobiographical memories.

Science.gov (United States)

St Jacques, Peggy L; Szpunar, Karl K; Schacter, Daniel L

2017-03-01

The dynamic and flexible nature of memories is evident in our ability to adopt multiple visual perspectives. Although autobiographical memories are typically encoded from the visual perspective of our own eyes they can be retrieved from the perspective of an observer looking at our self. Here, we examined the neural mechanisms of shifting visual perspective during long-term memory retrieval and its influence on online and subsequent memories using functional magnetic resonance imaging (fMRI). Participants generated specific autobiographical memories from the last five years and rated their visual perspective. In a separate fMRI session, they were asked to retrieve the memories across three repetitions while maintaining the same visual perspective as their initial rating or by shifting to an alternative perspective. Visual perspective shifting during autobiographical memory retrieval was supported by a linear decrease in neural recruitment across repetitions in the posterior parietal cortices. Additional analyses revealed that the precuneus, in particular, contributed to both online and subsequent changes in the phenomenology of memories. Our findings show that flexibly shifting egocentric perspective during autobiographical memory retrieval is supported by the precuneus, and suggest that this manipulation of mental imagery during retrieval has consequences for how memories are retrieved and later remembered. Copyright © 2017 Elsevier Inc. All rights reserved.

Theoretical analysis of the evolution of immune memory

Directory of Open Access Journals (Sweden)

Magnus Carsten

2010-12-01

Full Text Available Abstract Background The ability of an immune system to remember pathogens improves the chance of the host to survive a second exposure to the same pathogen. This immunological memory has evolved in response to the pathogen environment of the hosts. In vertebrates, the memory of previous infection is physiologically accomplished by the development of memory T and B cells. Many questions concerning the generation and maintenance of immunological memory are still debated. Is there a limit to how many memory cells a host can generate and maintain? If there is a limit, how should new cells be incorporated into a filled memory compartment? And how many different pathogens should the immune system remember? Results In this study, we examine how memory traits evolve as a response to different pathogen environments using an individual-based model. We find that even without a cost related to the maintenance of a memory pool, the positive effect of bigger memory pool sizes saturates. The optimal diversity of a limited memory pool is determined by the probability of re-infection, rather than by the prevalence of a pathogen in the environment, or the frequency of exposure. Conclusions Relating immune memory traits to the pathogen environment of the hosts, our population biological framework sheds light on the evolutionary determinants of immune memory.

How autobiographical memories can support episodic recall: transfer and maintenance effect of memory training with old-old low-autonomy adults.

Science.gov (United States)

Carretti, Barbara; Facchini, Giulia; Nicolini, Chiara

2011-02-01

A large body of research has demonstrated that, although specific memory activities can enhance the memory performance of healthy older adults, the extent of the increment is negatively associated with age. Conversely, few studies have examined the case of healthy elderly people not living alone. This study has two mains goals: to understand whether older adults with limited autonomy can benefit from activities devoted to increasing their episodic memory performance, and to test the efficacy of a memory training program based on autobiographical memories, in terms of transfer and maintenance effect. We postulated that being able to rely on stable autobiographical memories (intrinsically associated with emotions) would be a valuable memory aid. Memory training was given to healthy older adults (aged 75-85) living in a retirement home. Two programs were compared: in the first, participants were primed to recall autobiographical memories around certain themes, and then to complete a set of episodic memory tasks (experimental group); in the second, participants were only given the episodic tasks (control group). Both groups improved their performance from pre- to post-test. However, the experimental group reported a greater feeling of well-being after the training, and maintained the training gains relating to episodic performance after three months. Our findings suggest that specific memory activities are beneficial to elderly people living in a retirement home context. In addition, training based on reactivation of autobiographical memories is shown to produce a long-lasting effect on memory performance.

A dream model: Reactivation and re-encoding mechanisms for sleep-dependent memory consolidation

NARCIS (Netherlands)

Kachergis, G.E.; Kleijn, R. de; Hommel, B.; Papafragou, A.; Grodner, D.; Mirman, D.; Trueswell, J.

2016-01-01

We humans spend almost a third of our lives asleep, and there is mounting evidence that sleep not only maintains, but actually improves many of our cognitive functions. Memory consolidation - the process of crystallizing and integrating memories into knowledge and skills - is particularly benefitted

Working memory capacity predicts conflict-task performance

NARCIS (Netherlands)

Gulbinaite, Rasa; Johnson, Addie

The relationship between the ability to maintain task goals and working memory capacity (WMC) is firmly established, but evidence for WMC-related differences in conflict processing is mixed. We investigated whether WMC (measured using two complex-span tasks) mediates differences in adjustments of

Attention is required for maintenance of feature binding in visual working memory.

Science.gov (United States)

Zokaei, Nahid; Heider, Maike; Husain, Masud

2014-01-01

Working memory and attention are intimately connected. However, understanding the relationship between the two is challenging. Currently, there is an important controversy about whether objects in working memory are maintained automatically or require resources that are also deployed for visual or auditory attention. Here we investigated the effects of loading attention resources on precision of visual working memory, specifically on correct maintenance of feature-bound objects, using a dual-task paradigm. Participants were presented with a memory array and were asked to remember either direction of motion of random dot kinematograms of different colour, or orientation of coloured bars. During the maintenance period, they performed a secondary visual or auditory task, with varying levels of load. Following a retention period, they adjusted a coloured probe to match either the motion direction or orientation of stimuli with the same colour in the memory array. This allowed us to examine the effects of an attention-demanding task performed during maintenance on precision of recall on the concurrent working memory task. Systematic increase in attention load during maintenance resulted in a significant decrease in overall working memory performance. Changes in overall performance were specifically accompanied by an increase in feature misbinding errors: erroneous reporting of nontarget motion or orientation. Thus in trials where attention resources were taxed, participants were more likely to respond with nontarget values rather than simply making random responses. Our findings suggest that resources used during attention-demanding visual or auditory tasks also contribute to maintaining feature-bound representations in visual working memory-but not necessarily other aspects of working memory.

Evidence of gradual loss of precision for simple features and complex objects in visual working memory.

Science.gov (United States)

Rademaker, Rosanne L; Park, Young Eun; Sack, Alexander T; Tong, Frank

2018-03-01

Previous studies have suggested that people can maintain prioritized items in visual working memory for many seconds, with negligible loss of information over time. Such findings imply that working memory representations are robust to the potential contaminating effects of internal noise. However, once visual information is encoded into working memory, one might expect it to inevitably begin degrading over time, as this actively maintained information is no longer tethered to the original perceptual input. Here, we examined this issue by evaluating working memory for single central presentations of an oriented grating, color patch, or face stimulus, across a range of delay periods (1, 3, 6, or 12 s). We applied a mixture-model analysis to distinguish changes in memory precision over time from changes in the frequency of outlier responses that resemble random guesses. For all 3 types of stimuli, participants exhibited a clear and consistent decline in the precision of working memory as a function of temporal delay, as well as a modest increase in guessing-related responses for colored patches and face stimuli. We observed a similar loss of precision over time while controlling for temporal distinctiveness. Our results demonstrate that visual working memory is far from lossless: while basic visual features and complex objects can be maintained in a quite stable manner over time, these representations are still subject to noise accumulation and complete termination. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A direct comparison of short-term audiomotor and visuomotor memory.

Science.gov (United States)

Ward, Amanda M; Loucks, Torrey M; Ofori, Edward; Sosnoff, Jacob J

2014-04-01

Audiomotor and visuomotor short-term memory are required for an important variety of skilled movements but have not been compared in a direct manner previously. Audiomotor memory capacity might be greater to accommodate auditory goals that are less directly related to movement outcome than for visually guided tasks. Subjects produced continuous isometric force with the right index finger under auditory and visual feedback. During the first 10 s of each trial, subjects received continuous auditory or visual feedback. For the following 15 s, feedback was removed but the force had to be maintained accurately. An internal effort condition was included to test memory capacity in the same manner but without external feedback. Similar decay times of ~5-6 s were found for vision and audition but the decay time for internal effort was ~4 s. External feedback thus provides an advantage in maintaining a force level after feedback removal, but may not exclude some contribution from a sense of effort. Short-term memory capacity appears longer than certain previous reports but there may not be strong distinctions in capacity across different sensory modalities, at least for isometric force.

Reconciling conflicting electrophysiological findings on the guidance of attention by working memory.

Science.gov (United States)

Carlisle, Nancy B; Woodman, Geoffrey F

2013-10-01

Maintaining a representation in working memory has been proposed to be sufficient for the execution of top-down attentional control. Two recent electrophysiological studies that recorded event-related potentials (ERPs) during similar paradigms have tested this proposal, but have reported contradictory findings. The goal of the present study was to reconcile these previous reports. To this end, we used the stimuli from one study (Kumar, Soto, & Humphreys, 2009) combined with the task manipulations from the other (Carlisle & Woodman, 2011b). We found that when an item matching a working memory representation was presented in a visual search array, we could use ERPs to quantify the size of the covert attention effect. When the working memory matches were consistently task-irrelevant, we observed a weak attentional bias to these items. However, when the same item indicated the location of the search target, we found that the covert attention effect was approximately four times larger. This shows that simply maintaining a representation in working memory is not equivalent to having a top-down attentional set for that item. Our findings indicate that high-level goals mediate the relationship between the contents of working memory and perceptual attention.

Remembered but Unused: The Accessory Items in Working Memory that Do Not Guide Attention

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Peters, Judith C.; Goebel, Rainer; Roelfsema, Pieter R.

2009-01-01

If we search for an item, a representation of this item in our working memory guides attention to matching items in the visual scene. We can hold multiple items in working memory. Do all these items guide attention in parallel? We asked participants to detect a target object in a stream of objects while they maintained a second item in memory for…

Short-term blueberry-enriched diet prevents and reverses object recognition memory loss in aging rats.

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Malin, David H; Lee, David R; Goyarzu, Pilar; Chang, Yu-Hsuan; Ennis, Lalanya J; Beckett, Elizabeth; Shukitt-Hale, Barbara; Joseph, James A

2011-03-01

Previously, 4 mo of a blueberry-enriched (BB) antioxidant diet prevented impaired object recognition memory in aging rats. Experiment 1 determined whether 1- and 2-mo BB diets would have a similar effect and whether the benefits would disappear promptly after terminating the diets. Experiment 2 determined whether a 1-mo BB diet could subsequently reverse existing object memory impairment in aging rats. In experiment 1, Fischer-344 rats were maintained on an appropriate control diet or on 1 or 2 mo of the BB diet before testing object memory at 19 mo postnatally. In experiment 2, rats were tested for object recognition memory at 19 mo and again at 20 mo after 1 mo of maintenance on a 2% BB or control diet. In experiment 1, the control group performed no better than chance, whereas the 1- and 2-mo BB diet groups performed similarly and significantly better than controls. The 2-mo BB-diet group, but not the 1-mo group, maintained its performance over a subsequent month on a standard laboratory diet. In experiment 2, the 19-mo-old rats performed near chance. At 20 mo of age, the rats subsequently maintained on the BB diet significantly increased their object memory scores, whereas the control diet group exhibited a non-significant decline. The change in object memory scores differed significantly between the two diet groups. These results suggest that a considerable degree of age-related object memory decline can be prevented and reversed by brief maintenance on BB diets. Copyright © 2011 Elsevier Inc. All rights reserved.

Localization of RNA transcription sites in insect oocytes using microinjections of 5-bromouridine 5'-triphosphate.

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Dmitry Bogolyubov

2007-06-01

Full Text Available In the present study we used 5-bromouridine 5'-triphosphate (BrUTP microinjections to localize the transcription sites in oocytes of insects with different types of the ovarium structure: panoistic, meroistic polytrophic, and meroistic telotrophic. We found that in an insect with panoistic ovaries (Acheta domesticus, oocyte nuclei maintain their transcription activity during the long period of oocyte growth. In insects with meroistic ovaries (Tenebrio molitor and Panorpa communis, early oocyte chromosomes were found to be transcriptionally active, and some transcription activity still persist while the karyosphere, a compact structure formed by all condensed oocyte chromosomes, begins to develop. At the latest stages of karyosphere development, no anti-Br-RNA signal was registered in the karyosphere.

Time of Day Influences Memory Formation and dCREB2 Proteins in Drosophila

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Robin eFropf

2014-03-01

Full Text Available Many biological phenomena oscillate under the control of the circadian system, exhibiting peaks and troughs of activity across the day/night cycle. In most animal models, memory formation also exhibits this property, but the underlying neuronal and molecular mechanisms remain unclear. The dCREB2 transcription factor shows circadian regulated oscillations in its activity, and has been shown to be important for both circadian biology and memory formation. We show that the time-of-day (TOD of behavioral training affects Drosophila memory formation. dCREB2 exhibits complex changes in protein levels across the daytime and nighttime, and these changes in protein abundance are likely to contribute to oscillations in dCREB2 activity and TOD effects on memory formation.

The role of prefrontal cortex in working memory: a mini review

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Antonio Homero Lara

2015-12-01

Full Text Available A prominent account of prefrontal cortex (PFC function is that single neurons within the PFC maintain representations of task-relevant stimuli in working memory. Evidence for this view comes from studies in which subjects hold a stimulus across a delay lasting up to several seconds. Persistent elevated activity in the PFC has been observed in animal models as well as in humans performing these tasks. This persistent activity has been interpreted as evidence for the encoding of the stimulus itself in working memory. However, recent findings have posed a challenge to this notion. A number of recent studies have examined neural data from the PFC and posterior sensory areas, both at the single neuron level in primates, and at a larger scale in humans, and have failed to find encoding of stimulus information in the PFC during tasks with a substantial working memory component. Strong stimulus related information, however, was seen in posterior sensory areas. These results suggest that delay period activity in the PFC might be better understood not as a signature of memory storage per se, but as a top down signal that influences posterior sensory areas where the actual working memory representations are maintained.

Transcriptional regulator-mediated activation of adaptation genes triggers CRISPR de novo spacer acquisition

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Liu, Tao; Li, Yingjun; Wang, Xiaodi

2015-01-01

Acquisition of de novo spacer sequences confers CRISPR-Cas with a memory to defend against invading genetic elements. However, the mechanism of regulation of CRISPR spacer acquisition remains unknown. Here we examine the transcriptional regulation of the conserved spacer acquisition genes in Type I......, it was demonstrated that the transcription level of csa1, cas1, cas2 and cas4 was significantly enhanced in a csa3a-overexpression strain and, moreover, the Csa1 and Cas1 protein levels were increased in this strain. Furthermore, we demonstrated the hyperactive uptake of unique spacers within both CRISPR loci...... in the presence of the csa3a overexpression vector. The spacer acquisition process is dependent on the CCN PAM sequence and protospacer selection is random and non-directional. These results suggested a regulation mechanism of CRISPR spacer acquisition where a single transcriptional regulator senses the presence...

[Memory transfer in cerebellar motor learning].

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Nagao, Soichi

2012-01-01

Most of our motor skills are acquired through learning. Experiments of gain adaptation of ocular reflexes have consistently suggested that the memory of adaptation is initially formed in the cerebellar cortex, and is transferred to the cerebellar (vestibular) nuclei for consolidation to long-term memory after repetitions of training. We have recently developed a new system to evaluate the motor learning in human subjects using prism adaptation of hand reaching movement, by referring to the prism adaptation of dart throwing of Martin et al. (1996). In our system, the subject views the small target presented in the touch-panel screen, and touches it with his/her finger without direct visual feedback. After 15-30 trials of touching wearing prisms, an adaptation occurs in healthy subjects: they became able to touch the target correctly. Meanwhile, such an adaptation was impaired in patients of cerebellar disease. We have proposed a model of human prism adaptation that the memory of adaptation is initially encoded in the cerebellar cortex, and is later transferred to the cerebellar nuclei after repetitions of training. The memory in the cerebellar cortex may be formed and extinguished independently of the memory maintained in the cerebellar nuclei, and these two memories work cooperatively.

Hippocampal function is not required for the precision of remote place memory

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Kitamura Takashi

2012-02-01

Full Text Available Abstract Background During permanent memory formation, recall of acquired place memories initially depends on the hippocampus and eventually become hippocampus-independent with time. It has been suggested that the quality of original place memories also transforms from a precise form to a less precise form with similar time course. The question arises of whether the quality of original place memories is determined by brain regions on which the memory depends. Results To directly test this idea, we introduced a new procedure: a non-associative place recognition memory test in mice. Combined with genetic and pharmacological approaches, our analyses revealed that place memory is precisely maintained for 28 days, although the recall of place memory shifts from hippocampus-dependent to hippocampus-independent with time. Moreover, the inactivation of the hippocampal function does not inhibit the precision of remote place memory. Conclusion These results indicate that the quality of place memories is not determined by brain regions on which the memory depends.

GOTHIC memory management : a multiprocessor shared single level store

OpenAIRE

Michel , Béatrice

1990-01-01

Gothic purpose is to build an object-oriented fault-tolerant distributed operating system for a local area network of multiprocessor workstations. This paper describes Gothic memory manager. It realizes the sharing of the secondary memory space between any process running on the Gothic system. Processes on different processors can communicate by sharing permanent information. The manager implements a shared single level storage with an invalidation protocol working on disk-pages to maintain s...

Individualism-collectivism and interpersonal memory guidance of attention

OpenAIRE

He, Xun; Sebanz, N.; Sui, J.; Humphreys, G. W.

2014-01-01

Recently it has been shown that the allocation of attention by a participant in a visual search task can be affected by memory items that have to be maintained by a co-actor, when similar tasks are jointly engaged by dyads (He, Lever, & Humphreys, 2011). In the present study we examined the contribution of individualism-collectivism to this ‘interpersonal memory guidance’ effect. Actors performed visual search while a preview image was either held by the critical participant, held by a co-act...

Does selection against transcriptional interference shape retroelement-free regions in mammalian genomes?

DEFF Research Database (Denmark)

Mourier, Tobias; Willerslev, Eske

2008-01-01

in generating and maintaining retroelement-free regions in the human genome. METHODOLOGY/PRINCIPAL FINDINGS: Based on the known transcriptional properties of retroelements, we expect long interspersed elements (LINEs) to be able to display a high degree of transcriptional interference. In contrast, we expect......BACKGROUND: Eukaryotic genomes are scattered with retroelements that proliferate through retrotransposition. Although retroelements make up around 40 percent of the human genome, large regions are found to be completely devoid of retroelements. This has been hypothesised to be a result of genomic...... activity of LINEs has been identified previously. CONCLUSIONS/SIGNIFICANCE: Our observations are consistent with the notion that selection against transcriptional interference has contributed to the maintenance and/or generation of retroelement-free regions in the human genome....

Dysfunction of the RAR/RXR signaling pathway in the forebrain impairs hippocampal memory and synaptic plasticity

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Nomoto Masanori

2012-02-01

Full Text Available Abstract Background Retinoid signaling pathways mediated by retinoic acid receptor (RAR/retinoid × receptor (RXR-mediated transcription play critical roles in hippocampal synaptic plasticity. Furthermore, recent studies have shown that treatment with retinoic acid alleviates age-related deficits in hippocampal long-term potentiation (LTP and memory performance and, furthermore, memory deficits in a transgenic mouse model of Alzheimer's disease. However, the roles of the RAR/RXR signaling pathway in learning and memory at the behavioral level have still not been well characterized in the adult brain. We here show essential roles for RAR/RXR in hippocampus-dependent learning and memory. In the current study, we generated transgenic mice in which the expression of dominant-negative RAR (dnRAR could be induced in the mature brain using a tetracycline-dependent transcription factor and examined the effects of RAR/RXR loss. Results The expression of dnRAR in the forebrain down-regulated the expression of RARβ, a target gene of RAR/RXR, indicating that dnRAR mice exhibit dysfunction of the RAR/RXR signaling pathway. Similar with previous findings, dnRAR mice displayed impaired LTP and AMPA-mediated synaptic transmission in the hippocampus. More importantly, these mutant mice displayed impaired hippocampus-dependent social recognition and spatial memory. However, these deficits of LTP and memory performance were rescued by stronger conditioning stimulation and spaced training, respectively. Finally, we found that pharmacological blockade of RARα in the hippocampus impairs social recognition memory. Conclusions From these observations, we concluded that the RAR/RXR signaling pathway greatly contributes to learning and memory, and LTP in the hippocampus in the adult brain.

Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

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Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

2013-01-01

Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

The histone deacetylase HDAC4 regulates long-term memory in Drosophila.

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Helen L Fitzsimons

Full Text Available A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation.

Interactions between visual working memory representations.

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Bae, Gi-Yeul; Luck, Steven J

2017-11-01

We investigated whether the representations of different objects are maintained independently in working memory or interact with each other. Observers were shown two sequentially presented orientations and required to reproduce each orientation after a delay. The sequential presentation minimized perceptual interactions so that we could isolate interactions between memory representations per se. We found that similar orientations were repelled from each other whereas dissimilar orientations were attracted to each other. In addition, when one of the items was given greater attentional priority by means of a cue, the representation of the high-priority item was not influenced very much by the orientation of the low-priority item, but the representation of the low-priority item was strongly influenced by the orientation of the high-priority item. This indicates that attention modulates the interactions between working memory representations. In addition, errors in the reported orientations of the two objects were positively correlated under some conditions, suggesting that representations of distinct objects may become grouped together in memory. Together, these results demonstrate that working-memory representations are not independent but instead interact with each other in a manner that depends on attentional priority.

Memory: Enduring Traces of Perceptual and Reflective Attention

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Chun, Marvin M.; Johnson, Marcia K.

2011-01-01

Attention and memory are typically studied as separate topics, but they are highly intertwined. Here we discuss the relation between memory and two fundamental types of attention: perceptual and reflective. Memory is the persisting consequence of cognitive activities initiated by and/or focused on external information from the environment (perceptual attention) and initiated by and/or focused on internal mental representations (reflective attention). We consider three key questions for advancing a cognitive neuroscience of attention and memory: To what extent do perception and reflection share representational areas? To what extent are the control processes that select, maintain, and manipulate perceptual and reflective information subserved by common areas and networks? During perception and reflection, to what extent are common areas responsible for binding features together to create complex, episodic memories and for reviving them later? Considering similarities and differences in perceptual and reflective attention helps integrate a broad range of findings and raises important unresolved issues. PMID:22099456

Memory: enduring traces of perceptual and reflective attention.

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Chun, Marvin M; Johnson, Marcia K

2011-11-17

Attention and memory are typically studied as separate topics, but they are highly intertwined. Here we discuss the relation between memory and two fundamental types of attention: perceptual and reflective. Memory is the persisting consequence of cognitive activities initiated by and/or focused on external information from the environment (perceptual attention) and initiated by and/or focused on internal mental representations (reflective attention). We consider three key questions for advancing a cognitive neuroscience of attention and memory: to what extent do perception and reflection share representational areas? To what extent are the control processes that select, maintain, and manipulate perceptual and reflective information subserved by common areas and networks? During perception and reflection, to what extent are common areas responsible for binding features together to create complex, episodic memories and for reviving them later? Considering similarities and differences in perceptual and reflective attention helps integrate a broad range of findings and raises important unresolved issues. Copyright © 2011 Elsevier Inc. All rights reserved.

Individual differences in children's working memory and writing skill.

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Swanson, H L; Berninger, V W

1996-11-01

The purpose of this research is to address (a) whether individual differences in working memory (WM) and writing are related to a general or process-specific system, (b) whether WM tasks operate independently of phonological short-term memory (STM) on measures of writing and reading, and (c) whether working memory predicts variance in writing beyond that predicted by reading alone. The present study correlated several WM and phonological STM measures with writing and reading measures. The study showed among the memory measures that a four-factor model reflecting phonological STM, verbal WM span, executive processing, and visual-spatial WM span best fit the multivariate data set. Working memory was correlated significantly with a number of writing measures, particularly those related to text generation. WM measures contributed unique variance to writing that was independent of reading skill, and STM measures best predicted transcription processes and reading recognition, whereas WM measures best predicted text generation and reading comprehension. Both verbal and visual-spatial working memory measures predicted reading comprehension, whereas only WM measures that reflect executive processing significantly predicted writing. In general, the results suggest that individual differences in children's writing reflect a specific capacity system, whereas reading comprehension draws upon a multiple capacity system.

Cycle accurate and cycle reproducible memory for an FPGA based hardware accelerator

Science.gov (United States)

Asaad, Sameh W.; Kapur, Mohit

2016-03-15

A method, system and computer program product are disclosed for using a Field Programmable Gate Array (FPGA) to simulate operations of a device under test (DUT). The DUT includes a device memory having a number of input ports, and the FPGA is associated with a target memory having a second number of input ports, the second number being less than the first number. In one embodiment, a given set of inputs is applied to the device memory at a frequency Fd and in a defined cycle of time, and the given set of inputs is applied to the target memory at a frequency Ft. Ft is greater than Fd and cycle accuracy is maintained between the device memory and the target memory. In an embodiment, a cycle accurate model of the DUT memory is created by separating the DUT memory interface protocol from the target memory storage array.

Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function

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Andrew J. Kennedy

2016-09-01

Full Text Available Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS, which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/− mice have enhanced long-term potentiation in the CA1 area of the hippocampus. In translationally oriented studies, we found that small-molecule HDAC inhibitors normalized hippocampal LTP and memory recall. A comprehensive set of next-generation sequencing experiments of hippocampal mRNA and methylated DNA isolated from Tcf4-deficient and WT mice before or shortly after experiential learning, with or without administration of vorinostat, identified “memory-associated” genes modulated by HDAC inhibition and dysregulated by Tcf4 haploinsufficiency. Finally, we observed that Hdac2 isoform-selective knockdown was sufficient to rescue memory deficits in Tcf4(+/− mice.

Attention is required for maintenance of feature binding in visual working memory

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Heider, Maike; Husain, Masud

2013-01-01

Working memory and attention are intimately connected. However, understanding the relationship between the two is challenging. Currently, there is an important controversy about whether objects in working memory are maintained automatically or require resources that are also deployed for visual or auditory attention. Here we investigated the effects of loading attention resources on precision of visual working memory, specifically on correct maintenance of feature-bound objects, using a dual-task paradigm. Participants were presented with a memory array and were asked to remember either direction of motion of random dot kinematograms of different colour, or orientation of coloured bars. During the maintenance period, they performed a secondary visual or auditory task, with varying levels of load. Following a retention period, they adjusted a coloured probe to match either the motion direction or orientation of stimuli with the same colour in the memory array. This allowed us to examine the effects of an attention-demanding task performed during maintenance on precision of recall on the concurrent working memory task. Systematic increase in attention load during maintenance resulted in a significant decrease in overall working memory performance. Changes in overall performance were specifically accompanied by an increase in feature misbinding errors: erroneous reporting of nontarget motion or orientation. Thus in trials where attention resources were taxed, participants were more likely to respond with nontarget values rather than simply making random responses. Our findings suggest that resources used during attention-demanding visual or auditory tasks also contribute to maintaining feature-bound representations in visual working memory—but not necessarily other aspects of working memory. PMID:24266343

Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning.

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Ganguly, Krishnendu; Rejmak, Emilia; Mikosz, Marta; Nikolaev, Evgeni; Knapska, Ewelina; Kaczmarek, Leszek

2013-07-19

Memory formation requires learning-based molecular and structural changes in neurons, whereas matrix metalloproteinase (MMP) 9 is involved in the synaptic plasticity by cleaving extracellular matrix proteins and, thus, is associated with learning processes in the mammalian brain. Because the mechanisms of MMP-9 transcription in the brain are poorly understood, this study aimed to elucidate regulation of MMP-9 gene expression in the mouse brain after fear learning. We show here that contextual fear conditioning markedly increases MMP-9 transcription, followed by enhanced enzymatic levels in the three major brain structures implicated in fear learning, i.e. the amygdala, hippocampus, and prefrontal cortex. To reveal the role of AP-1 transcription factor in MMP-9 gene expression, we have used reporter gene constructs with specifically mutated AP-1 gene promoter sites. The constructs were introduced into the medial prefrontal cortex of neonatal mouse pups by electroporation, and the regulation of MMP-9 transcription was studied after contextual fear conditioning in the adult animals. Specifically, -42/-50- and -478/-486-bp AP-1 binding motifs of the mouse MMP-9 promoter sequence have been found to play a major role in MMP-9 gene activation. Furthermore, increases in MMP-9 gene promoter binding by the AP-1 transcription factor proteins c-Fos and c-Jun have been demonstrated in all three brain structures under investigation. Hence, our results suggest that AP-1 acts as a positive regulator of MMP-9 transcription in the brain following fear learning.

The Relationship between Processing and Storage in Working Memory Span: Not Two Sides of the Same Coin

Science.gov (United States)

Maehara, Yukio; Saito, Satoru

2007-01-01

In working memory (WM) span tests, participants maintain memory items while performing processing tasks. In this study, we examined the impact of task processing requirements on memory-storage activities, looking at the stimulus order effect and the impact of storage requirements on processing activities, testing the processing time effect in WM…

Training of attention and memory deficits in children with acquired brain injury

DEFF Research Database (Denmark)

Madsen Sjö, Nina; Spellerberg, Stine Marie; Weidner, Susanne

2010-01-01

supervision in the school-setting maintains the child’s motivation throughout the training programme and (3) whether positive changes in memory, attention and executive functions are found with this implementation of the training method. Methods: Seven children with memory and ⁄ or attention deficits after......) sustaining of motivation and (3) improvements in learning and memory.......This pilot study concerns cognitive rehabilitation of children with acquired brain injury (ABI). Aim: The aim is threefold; to determine (1) whether the Amsterdam Memory and Attention Training for Children (AMAT-C) programme for children with ABI can be integrated in the child’s school, (2) whether...

Bystander chronic infection negatively impacts development of CD8+ T cell memory

Science.gov (United States)

Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

2014-01-01

Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

Effects of working memory load on visual selective attention: Behavioral and electrophysiological evidence

OpenAIRE

Nikki ePratt; Adrian eWilloughby; Diane eSwick; Diane eSwick

2011-01-01

Working memory and attention interact in a way that enables us to focus on relevant items and maintain current goals. The influence of working memory on attention has been noted in several studies using dual task designs. Multitasking increases the demands on working memory and reduces the amount of resources available for cognitive control functions such as resolving stimulus conflict. However, few studies have investigated the temporal activation of the cortex while multitasking. The pre...

Effects of Working Memory Load on Visual Selective Attention: Behavioral and Electrophysiological Evidence

OpenAIRE

Pratt, Nikki; Willoughby, Adrian; Swick, Diane

2011-01-01

Working memory and attention interact in a way that enables us to focus on relevant items and maintain current goals. The influence of working memory on attention has been noted in several studies using dual task designs. Multitasking increases the demands on working memory and reduces the amount of resources available for cognitive control functions such as resolving stimulus conflict. However, few studies have investigated the temporal activation of the cortex while multitasking. The presen...

Updating working memory in aircraft noise and speech causes different fMRI activations

OpenAIRE

Sætrevik, Bjørn; Sörqvist, Patrik

2014-01-01

The present study used fMRI/BOLD neuroimaging to investigate how visual-verbal working memory is updated when exposed to three different background-noise conditions: speech noise, aircraft noise and silence. The number-updating task that was used can distinguish between ?substitution processes,? which involve adding new items to the working memory representation and suppressing old items, and ?exclusion processes,? which involve rejecting new items and maintaining an intact memory set. The cu...

Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

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Guiqin He

2017-11-01

Full Text Available In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs remains unclear. Cyclin-dependent kinases (Cdks are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH and the only known Cdk-activating kinase (CAK in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS and prevented the formation of long-term memories.

The influence of Markov decision process structure on the possible strategic use of working memory and episodic memory.

Science.gov (United States)

Zilli, Eric A; Hasselmo, Michael E

2008-07-23

Researchers use a variety of behavioral tasks to analyze the effect of biological manipulations on memory function. This research will benefit from a systematic mathematical method for analyzing memory demands in behavioral tasks. In the framework of reinforcement learning theory, these tasks can be mathematically described as partially-observable Markov decision processes. While a wealth of evidence collected over the past 15 years relates the basal ganglia to the reinforcement learning framework, only recently has much attention been paid to including psychological concepts such as working memory or episodic memory in these models. This paper presents an analysis that provides a quantitative description of memory states sufficient for correct choices at specific decision points. Using information from the mathematical structure of the task descriptions, we derive measures that indicate whether working memory (for one or more cues) or episodic memory can provide strategically useful information to an agent. In particular, the analysis determines which observed states must be maintained in or retrieved from memory to perform these specific tasks. We demonstrate the analysis on three simplified tasks as well as eight more complex memory tasks drawn from the animal and human literature (two alternation tasks, two sequence disambiguation tasks, two non-matching tasks, the 2-back task, and the 1-2-AX task). The results of these analyses agree with results from quantitative simulations of the task reported in previous publications and provide simple indications of the memory demands of the tasks which can require far less computation than a full simulation of the task. This may provide a basis for a quantitative behavioral stoichiometry of memory tasks.

The influence of Markov decision process structure on the possible strategic use of working memory and episodic memory.

Directory of Open Access Journals (Sweden)

Eric A Zilli

2008-07-01

Full Text Available Researchers use a variety of behavioral tasks to analyze the effect of biological manipulations on memory function. This research will benefit from a systematic mathematical method for analyzing memory demands in behavioral tasks. In the framework of reinforcement learning theory, these tasks can be mathematically described as partially-observable Markov decision processes. While a wealth of evidence collected over the past 15 years relates the basal ganglia to the reinforcement learning framework, only recently has much attention been paid to including psychological concepts such as working memory or episodic memory in these models. This paper presents an analysis that provides a quantitative description of memory states sufficient for correct choices at specific decision points. Using information from the mathematical structure of the task descriptions, we derive measures that indicate whether working memory (for one or more cues or episodic memory can provide strategically useful information to an agent. In particular, the analysis determines which observed states must be maintained in or retrieved from memory to perform these specific tasks. We demonstrate the analysis on three simplified tasks as well as eight more complex memory tasks drawn from the animal and human literature (two alternation tasks, two sequence disambiguation tasks, two non-matching tasks, the 2-back task, and the 1-2-AX task. The results of these analyses agree with results from quantitative simulations of the task reported in previous publications and provide simple indications of the memory demands of the tasks which can require far less computation than a full simulation of the task. This may provide a basis for a quantitative behavioral stoichiometry of memory tasks.

Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

Science.gov (United States)

Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

2016-07-01

Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

The simian immunodeficiency virus targets central cell cycle functions through transcriptional repression in vivo.

Directory of Open Access Journals (Sweden)

Carl-Magnus Hogerkorp

Full Text Available A massive and selective loss of CD4+ memory T cells occurs during the acute phase of immunodeficiency virus infections. The mechanism of this depletion is poorly understood but constitutes a key event with implications for progression. We assessed gene expression of purified T cells in Rhesus Macaques during acute SIVmac239 infection in order to define mechanisms of pathogenesis. We observe a general transcriptional program of over 1,600 interferon-stimulated genes induced in all T cells by the infection. Furthermore, we identify 113 transcriptional changes that are specific to virally infected cells. A striking downregulation of several key cell cycle regulator genes was observed and shared promotor-region E2F binding sites in downregulated genes suggested a targeted transcriptional control of an E2F regulated cell cycle program. In addition, the upregulation of the gene for the fundamental regulator of RNA polymerase II, TAF7, demonstrates that viral interference with the cell cycle and transcriptional regulation programs may be critical components during the establishment of a pathogenic infection in vivo.

Gut memories do not fade: epigenetic regulation of lasting gut homing receptor expression in CD4+ memory T cells.

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Szilagyi, B A; Triebus, J; Kressler, C; de Almeida, M; Tierling, S; Durek, P; Mardahl, M; Szilagyi, A; Floess, S; Huehn, J; Syrbe, U; Walter, J; Polansky, J K; Hamann, A

2017-11-01

The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α 4 β 7 was found in CD8 + T cells, questioning the concept. We now demonstrate that α 4 β 7 expression in murine CD4 + memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments. Repetitive rounds of RA treatment enhanced the stability of de novo induced α 4 β 7 . A novel enhancer element in the murine Itga4 locus was identified that showed, correlating to stability, selective DNA demethylation in mucosa-seeking memory cells and methylation-dependent transcriptional activity in a reporter gene assay. This implies that epigenetic mechanisms contribute to the stabilization of α 4 β 7 expression. Analogous DNA methylation patterns could be observed in the human ITGA4 locus, suggesting that its epigenetic regulation is conserved between mice and men. These data prove that mucosa-specific homing mediated by α 4 β 7 is imprinted in CD4 + memory T cells, reinstating the validity of the concept of "topographical memory" for mucosal tissues, and imply a critical role of epigenetic mechanisms.

Social working memory: Neurocognitive networks and directions for future research

Directory of Open Access Journals (Sweden)

Meghan L Meyer

2012-12-01

Full Text Available Navigating the social world requires the ability to maintain and manipulate information about people’s beliefs, traits, and mental states. We characterize this capacity as social working memory. To date, very little research has explored this phenomenon, in part because of the assumption that general working memory systems would support working memory for social information. Various lines of research, however, suggest that social cognitive processing relies on a neurocognitive network (i.e., the ‘mentalizing network’ that is functionally distinct from, and considered antagonistic with, the canonical working memory network. Here, we review evidence suggesting that demanding social cognition requires social working memory and that both the mentalizing and canonical working memory neurocognitive networks support social working memory. The neural data run counter to the common finding of parametric decreases in mentalizing regions as a function of working memory demand and suggest that the mentalizing network can support demanding cognition, when it is demanding social cognition. Implications for individual differences in social cognition and pathologies of social cognition are discussed.

Two-way shape memory behavior of shape memory polyurethanes with a bias load

International Nuclear Information System (INIS)

Hong, Seok Jin; Yu, Woong-Ryeol; Youk, Ji Ho

2010-01-01

Thermo-responsive shape memory polyurethane (SMPU) is a smart material that can respond to external heat by changing its macroscopic shape from a temporary configuration to a memorized permanent one. The temporary shape can be processed using mechanical forces above a certain temperature (the transition temperature) and can be maintained until the material acquires a certain thermal energy. Thereafter, the material will recover its memorized permanent shape. However, it is unclear what will occur if the thermal energy is then dissipated, i.e., the material temperature decreases. There are two possibilities: the material will respond to the dissipated energy, resulting in another macroscopic shape change; or nothing will happen beyond the thermal contraction. The former is called two-way shape memory (TWSM) behavior and the latter is called one-way shape memory behavior. This paper reports novel findings showing that TWSM behavior can be imparted to SMPUs using a thermo-mechanical treatment, i.e., imposing a constant stress on them after their temporary shaping. A series of experiments were carried out to characterize the TWSM behavior of SMPUs and to explain its mechanism

Hemispheric Asymmetries in Discourse Processing: Evidence from False Memories for Lists and Texts

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Ben-Artzi, Elisheva; Faust, Miriam; Moeller, Edna

2009-01-01

Previous research suggests that the right hemisphere (RH) may contribute uniquely to discourse and text processing by activating and maintaining a wide range of meanings, including more distantly related meanings. The present study used the word-lists false memory paradigm [Roediger, H. L., III, & McDermott, K. B. (1995). "Creating false memories:…

Interplay of DNA repair with transcription: from structures to mechanisms.

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Deaconescu, Alexandra M; Artsimovitch, Irina; Grigorieff, Nikolaus

2012-12-01

Many DNA transactions are crucial for maintaining genomic integrity and faithful transfer of genetic information but remain poorly understood. An example is the interplay between nucleotide excision repair (NER) and transcription, also known as transcription-coupled DNA repair (TCR). Discovered decades ago, the mechanisms for TCR have remained elusive, not in small part due to the scarcity of structural studies of key players. Here we summarize recent structural information on NER/TCR factors, focusing on bacterial systems, and integrate it with existing genetic, biochemical, and biophysical data to delineate the mechanisms at play. We also review emerging, alternative modalities for recruitment of NER proteins to DNA lesions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Do the Contents of Visual Working Memory Automatically Influence Attentional Selection During Visual Search?

OpenAIRE

Woodman, Geoffrey F.; Luck, Steven J.

2007-01-01

In many theories of cognition, researchers propose that working memory and perception operate interactively. For example, in previous studies researchers have suggested that sensory inputs matching the contents of working memory will have an automatic advantage in the competition for processing resources. The authors tested this hypothesis by requiring observers to perform a visual search task while concurrently maintaining object representations in visual working memory. The hypothesis that ...

Aging increases cell-to-cell transcriptional variability upon immune stimulation.

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Martinez-Jimenez, Celia Pilar; Eling, Nils; Chen, Hung-Chang; Vallejos, Catalina A; Kolodziejczyk, Aleksandra A; Connor, Frances; Stojic, Lovorka; Rayner, Timothy F; Stubbington, Michael J T; Teichmann, Sarah A; de la Roche, Maike; Marioni, John C; Odom, Duncan T

2017-03-31

Aging is characterized by progressive loss of physiological and cellular functions, but the molecular basis of this decline remains unclear. We explored how aging affects transcriptional dynamics using single-cell RNA sequencing of unstimulated and stimulated naïve and effector memory CD4 + T cells from young and old mice from two divergent species. In young animals, immunological activation drives a conserved transcriptomic switch, resulting in tightly controlled gene expression characterized by a strong up-regulation of a core activation program, coupled with a decrease in cell-to-cell variability. Aging perturbed the activation of this core program and increased expression heterogeneity across populations of cells in both species. These discoveries suggest that increased cell-to-cell transcriptional variability will be a hallmark feature of aging across most, if not all, mammalian tissues. Copyright © 2017, American Association for the Advancement of Science.

Multiplicity detector using a glow-discharge memory

International Nuclear Information System (INIS)

Mulera, T.; Elola, M.; Perez-Mendez, V.; Wiedenbeck, P.

1981-04-01

It has been proposed to eliminate the x-y cor relation ambiguities introduced by multiple tracks in a wire chamber by using the chamber itself as a memory. Hits in the chamber itself ignite glow discharges storing the x-y location of the hits in a correlated fashion. Glow ignition may be achieved by employing a multi-step avalanche chamber above a memory gap. Correlation is maintained during readout by successively pulsing each hit wire in one coordinate and sensing transmissions through glows in the other coordinate. Prototypes constructed by the authors are discussed along with the associated high voltage and readout systems

Organizer-Derived WOX5 Signal Maintains Root Columella Stem Cells through Chromatin-Mediated Repression of CDF4 Expression.

NARCIS (Netherlands)

Pi, L.; Graaff, van der E.; Llavata Peris, C.I.; Weijers, D.; Henning, L.; Groot, de E.; Laux, T.

2015-01-01

Stem cells in plants and animals are maintained pluripotent by signals from adjacent niche cells. In plants, WUSCHEL HOMEOBOX (WOX) transcription factors are central regulators of stem cell maintenance in different meristem types, yet their molecular mode of action has remained elusive. Here we show

Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

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Orsini, Caitlin A.; Maren, Stephen

2012-01-01

Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

Memory for conversation and the development of common ground.

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McKinley, Geoffrey L; Brown-Schmidt, Sarah; Benjamin, Aaron S

2017-11-01

Efficient conversation is guided by the mutual knowledge, or common ground, that interlocutors form as a conversation progresses. Characterized from the perspective of commonly used measures of memory, efficient conversation should be closely associated with item memory-what was said-and context memory-who said what to whom. However, few studies have explicitly probed memory to evaluate what type of information is maintained following a communicative exchange. The current study examined how item and context memory relate to the development of common ground over the course of a conversation, and how these forms of memory vary as a function of one's role in a conversation as speaker or listener. The process of developing common ground was positively related to both item and context memory. In addition, content that was spoken was remembered better than content that was heard. Our findings illustrate how memory assessments can complement language measures by revealing the impact that basic conversational processes have on memory for what has been discussed. By taking this approach, we show that not only does the process of forming common ground facilitate communication in the present, but it also promotes an enduring record of that event, facilitating conversation into the future.

Stimulus-specific suppression preserves information in auditory short-term memory.

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Linke, Annika C; Vicente-Grabovetsky, Alejandro; Cusack, Rhodri

2011-08-02

Philosophers and scientists have puzzled for millennia over how perceptual information is stored in short-term memory. Some have suggested that early sensory representations are involved, but their precise role has remained unclear. The current study asks whether auditory cortex shows sustained frequency-specific activation while sounds are maintained in short-term memory using high-resolution functional MRI (fMRI). Investigating short-term memory representations within regions of human auditory cortex with fMRI has been difficult because of their small size and high anatomical variability between subjects. However, we overcame these constraints by using multivoxel pattern analysis. It clearly revealed frequency-specific activity during the encoding phase of a change detection task, and the degree of this frequency-specific activation was positively related to performance in the task. Although the sounds had to be maintained in memory, activity in auditory cortex was significantly suppressed. Strikingly, patterns of activity in this maintenance period correlated negatively with the patterns evoked by the same frequencies during encoding. Furthermore, individuals who used a rehearsal strategy to remember the sounds showed reduced frequency-specific suppression during the maintenance period. Although negative activations are often disregarded in fMRI research, our findings imply that decreases in blood oxygenation level-dependent response carry important stimulus-specific information and can be related to cognitive processes. We hypothesize that, during auditory change detection, frequency-specific suppression protects short-term memory representations from being overwritten by inhibiting the encoding of interfering sounds.

Rescripting Early Memories Linked to Negative Images in Social Phobia: A Pilot Study

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Wild, Jennifer; Hackmann, Ann; Clark, David M.

2008-01-01

Negative self-images are a maintaining factor in social phobia. A retrospective study (Hackmann, A., Clark, D.M., McManus, F. (2000). Recurrent images and early memories in social phobia. Behaviour Research and Therapy, 38, 601-610) suggested that the images may be linked to early memories of unpleasant social experiences. This preliminary study…

EMSAR: estimation of transcript abundance from RNA-seq data by mappability-based segmentation and reclustering.

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Lee, Soohyun; Seo, Chae Hwa; Alver, Burak Han; Lee, Sanghyuk; Park, Peter J

2015-09-03

RNA-seq has been widely used for genome-wide expression profiling. RNA-seq data typically consists of tens of millions of short sequenced reads from different transcripts. However, due to sequence similarity among genes and among isoforms, the source of a given read is often ambiguous. Existing approaches for estimating expression levels from RNA-seq reads tend to compromise between accuracy and computational cost. We introduce a new approach for quantifying transcript abundance from RNA-seq data. EMSAR (Estimation by Mappability-based Segmentation And Reclustering) groups reads according to the set of transcripts to which they are mapped and finds maximum likelihood estimates using a joint Poisson model for each optimal set of segments of transcripts. The method uses nearly all mapped reads, including those mapped to multiple genes. With an efficient transcriptome indexing based on modified suffix arrays, EMSAR minimizes the use of CPU time and memory while achieving accuracy comparable to the best existing methods. EMSAR is a method for quantifying transcripts from RNA-seq data with high accuracy and low computational cost. EMSAR is available at https://github.com/parklab/emsar.

Temporal Prediction Errors Affect Short-Term Memory Scanning Response Time.

Science.gov (United States)

Limongi, Roberto; Silva, Angélica M

2016-11-01

The Sternberg short-term memory scanning task has been used to unveil cognitive operations involved in time perception. Participants produce time intervals during the task, and the researcher explores how task performance affects interval production - where time estimation error is the dependent variable of interest. The perspective of predictive behavior regards time estimation error as a temporal prediction error (PE), an independent variable that controls cognition, behavior, and learning. Based on this perspective, we investigated whether temporal PEs affect short-term memory scanning. Participants performed temporal predictions while they maintained information in memory. Model inference revealed that PEs affected memory scanning response time independently of the memory-set size effect. We discuss the results within the context of formal and mechanistic models of short-term memory scanning and predictive coding, a Bayes-based theory of brain function. We state the hypothesis that our finding could be associated with weak frontostriatal connections and weak striatal activity.

Social working memory: neurocognitive networks and directions for future research.

Science.gov (United States)

Meyer, Meghan L; Lieberman, Matthew D

2012-01-01

Navigating the social world requires the ability to maintain and manipulate information about people's beliefs, traits, and mental states. We characterize this capacity as social working memory (SWM). To date, very little research has explored this phenomenon, in part because of the assumption that general working memory systems would support working memory for social information. Various lines of research, however, suggest that social cognitive processing relies on a neurocognitive network (i.e., the "mentalizing network") that is functionally distinct from, and considered antagonistic with, the canonical working memory network. Here, we review evidence suggesting that demanding social cognition requires SWM and that both the mentalizing and canonical working memory neurocognitive networks support SWM. The neural data run counter to the common finding of parametric decreases in mentalizing regions as a function of working memory demand and suggest that the mentalizing network can support demanding cognition, when it is demanding social cognition. Implications for individual differences in social cognition and pathologies of social cognition are discussed.

Experimental Incubations Elicit Profound Changes in Community Transcription in OMZ Bacterioplankton

Science.gov (United States)

Stewart, Frank J.; Dalsgaard, Tage; Young, Curtis R.; Thamdrup, Bo; Revsbech, Niels Peter; Ulloa, Osvaldo; Canfield, Don E.; DeLong, Edward F.

2012-01-01

Sequencing of microbial community RNA (metatranscriptome) is a useful approach for assessing gene expression in microorganisms from the natural environment. This method has revealed transcriptional patterns in situ, but can also be used to detect transcriptional cascades in microcosms following experimental perturbation. Unambiguously identifying differential transcription between control and experimental treatments requires constraining effects that are simply due to sampling and bottle enclosure. These effects remain largely uncharacterized for “challenging” microbial samples, such as those from anoxic regions that require special handling to maintain in situ conditions. Here, we demonstrate substantial changes in microbial transcription induced by sample collection and incubation in experimental bioreactors. Microbial communities were sampled from the water column of a marine oxygen minimum zone by a pump system that introduced minimal oxygen contamination and subsequently incubated in bioreactors under near in situ oxygen and temperature conditions. Relative to the source water, experimental samples became dominated by transcripts suggestive of cell stress, including chaperone, protease, and RNA degradation genes from diverse taxa, with strong representation from SAR11-like alphaproteobacteria. In tandem, transcripts matching facultative anaerobic gammaproteobacteria of the Alteromonadales (e.g., Colwellia) increased 4–13 fold up to 43% of coding transcripts, and encoded a diverse gene set suggestive of protein synthesis and cell growth. We interpret these patterns as taxon-specific responses to combined environmental changes in the bioreactors, including shifts in substrate or oxygen availability, and minor temperature and pressure changes during sampling with the pump system. Whether such changes confound analysis of transcriptional patterns may vary based on the design of the experiment, the taxonomic composition of the source community, and on the

Evolution of transcriptional enhancers and animal diversity

Science.gov (United States)

Rubinstein, Marcelo; de Souza, Flávio S. J.

2013-01-01

Deciphering the genetic bases that drive animal diversity is one of the major challenges of modern biology. Although four decades ago it was proposed that animal evolution was mainly driven by changes in cis-regulatory DNA elements controlling gene expression rather than in protein-coding sequences, only now are powerful bioinformatics and experimental approaches available to accelerate studies into how the evolution of transcriptional enhancers contributes to novel forms and functions. In the introduction to this Theme Issue, we start by defining the general properties of transcriptional enhancers, such as modularity and the coexistence of tight sequence conservation with transcription factor-binding site shuffling as different mechanisms that maintain the enhancer grammar over evolutionary time. We discuss past and current methods used to identify cell-type-specific enhancers and provide examples of how enhancers originate de novo, change and are lost in particular lineages. We then focus in the central part of this Theme Issue on analysing examples of how the molecular evolution of enhancers may change form and function. Throughout this introduction, we present the main findings of the articles, reviews and perspectives contributed to this Theme Issue that together illustrate some of the great advances and current frontiers in the field. PMID:24218630

A-type nuclear lamins act as transcriptional repressors when targeted to promoters

International Nuclear Information System (INIS)

Lee, Damian C.; Welton, K. Linnea; Smith, Erica D.; Kennedy, Brian K.

2009-01-01

Regions of heterochromatin are often found at the periphery of the mammalian nucleus, juxtaposed to the nuclear lamina. Genes in these regions are likely maintained in a transcriptionally silent state, although other locations at the nuclear periphery associated with nuclear pores are sites of active transcription. As primary components of the nuclear lamina, A- and B-type nuclear lamins are intermediate filament proteins that interact with DNA, histones and known transcriptional repressors, leading to speculation that they may promote establishment of repressive domains. However, no direct evidence of a role for nuclear lamins in transcriptional repression has been reported. Here we find that human lamin A, when expressed in yeast and cultured human cells as a fusion protein to the Gal4 DNA-binding domain (DBD), can mediate robust transcriptional repression of promoters with Gal4 binding sites. Full repression by lamin A requires both the coiled-coil rod domain and the C-terminal tail domain. In human cells, other intermediate filament proteins such as lamin B and vimentin are unable to confer robust repression as Gal4-DBD fusions, indicating that this property is specific to A-type nuclear lamins. These findings indicate that A-type lamins can promote transcriptional repression when in proximity of a promoter

Human T Cell Memory: A Dynamic View

Directory of Open Access Journals (Sweden)

Derek C. Macallan

2017-02-01

Full Text Available Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy.

Highly Stretchable Non-volatile Nylon Thread Memory

Science.gov (United States)

Kang, Ting-Kuo

2016-04-01

Integration of electronic elements into textiles, to afford e-textiles, can provide an ideal platform for the development of lightweight, thin, flexible, and stretchable e-textiles. This approach will enable us to meet the demands of the rapidly growing market of wearable-electronics on arbitrary non-conventional substrates. However the actual integration of the e-textiles that undergo mechanical deformations during both assembly and daily wear or satisfy the requirements of the low-end applications, remains a challenge. Resistive memory elements can also be fabricated onto a nylon thread (NT) for e-textile applications. In this study, a simple dip-and-dry process using graphene-PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) ink is proposed for the fabrication of a highly stretchable non-volatile NT memory. The NT memory appears to have typical write-once-read-many-times characteristics. The results show that an ON/OFF ratio of approximately 103 is maintained for a retention time of 106 s. Furthermore, a highly stretchable strain and a long-term digital-storage capability of the ON-OFF-ON states are demonstrated in the NT memory. The actual integration of the knitted NT memories into textiles will enable new design possibilities for low-cost and large-area e-textile memory applications.

Neuroepigenetics of memory formation and impairment: the role of microRNAs.

Science.gov (United States)

Saab, Bechara J; Mansuy, Isabelle M

2014-05-01

MicroRNAs (miRNAs) are a class of short non-coding RNAs that primarily regulate protein synthesis through reversible translational repression or mRNA degradation. MiRNAs can act by translational control of transcription factors or via direct action on the chromatin, and thereby contribute to the non-genetic control of gene-environment interactions. MiRNAs that regulate components of pathways required for learning and memory further modulate the influence of epigenetics on cognition in the normal and diseased brain. This review summarizes recent data exemplifying the known roles of miRNAs in memory formation in different model organisms, and describes how neuronal plasticity regulates miRNA biogenesis, activity and degradation. It also examines the relevance of miRNAs for memory impairment in human, using recent clinical observations related to neurodevelopmental and neurodegenerative diseases, and discusses the potential mechanisms by which these miRNAs may contribute to memory disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Temporal compression in episodic memory for real-life events.

Science.gov (United States)

Jeunehomme, Olivier; Folville, Adrien; Stawarczyk, David; Van der Linden, Martial; D'Argembeau, Arnaud

2018-07-01

Remembering an event typically takes less time than experiencing it, suggesting that episodic memory represents past experience in a temporally compressed way. Little is known, however, about how the continuous flow of real-life events is summarised in memory. Here we investigated the nature and determinants of temporal compression by directly comparing memory contents with the objective timing of events as measured by a wearable camera. We found that episodic memories consist of a succession of moments of prior experience that represent events with varying compression rates, such that the density of retrieved information is modulated by goal processing and perceptual changes. Furthermore, the results showed that temporal compression rates remain relatively stable over one week and increase after a one-month delay, particularly for goal-related events. These data shed new light on temporal compression in episodic memory and suggest that compression rates are adaptively modulated to maintain current goal-relevant information.

Remifentanil maintains lower initial delayed nonmatching-to-sample accuracy compared to food pellets in male rhesus monkeys.

Science.gov (United States)

Hutsell, Blake A; Banks, Matthew L

2017-12-01

Emerging human laboratory and preclinical drug self-administration data suggest that a history of contingent abused drug exposure impairs performance in operant discrimination procedures, such as delayed nonmatching-to-sample (DNMTS), that are hypothesized to assess components of executive function. However, these preclinical discrimination studies have exclusively used food as the reinforcer and the effects of drugs as reinforcers in these operant procedures are unknown. The present study determined effects of contingent intravenous remifentanil injections on DNMTS performance hypothesized to assess 1 aspect of executive function, working memory. Daily behavioral sessions consisted of 2 components with sequential intravenous remifentanil (0, 0.01-1.0 μg/kg/injection) or food (0, 1-10 pellets) availability in nonopioid dependent male rhesus monkeys (n = 3). Remifentanil functioned as a reinforcer in the DNMTS procedure. Similar delay-dependent DNMTS accuracy was observed under both remifentanil- and food-maintained components, such that higher accuracies were maintained at shorter (0.1-1.0 s) delays and lower accuracies approaching chance performance were maintained at longer (10-32 s) delays. Remifentanil maintained significantly lower initial DNMTS accuracy compared to food. Reinforcer magnitude was not an important determinant of DNMTS accuracy for either remifentanil or food. These results extend the range of experimental procedures under which drugs function as reinforcers. Furthermore, the selective remifentanil-induced decrease in initial DNMTS accuracy is consistent with a selective impairment of attentional, but not memorial, processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Where do we store the memory representations that guide attention?

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Woodman, Geoffrey F.; Carlisle, Nancy B.; Reinhart, Robert M. G.

2013-01-01

During the last decade one of the most contentious and heavily studied topics in the attention literature has been the role that working memory representations play in controlling perceptual selection. The hypothesis has been advanced that to have attention select a certain perceptual input from the environment, we only need to represent that item in working memory. Here we summarize the work indicating that the relationship between what representations are maintained in working memory and what perceptual inputs are selected is not so simple. First, it appears that attentional selection is also determined by high-level task goals that mediate the relationship between working memory storage and attentional selection. Second, much of the recent work from our laboratory has focused on the role of long-term memory in controlling attentional selection. We review recent evidence supporting the proposal that working memory representations are critical during the initial configuration of attentional control settings, but that after those settings are established long-term memory representations play an important role in controlling which perceptual inputs are selected by mechanisms of attention. PMID:23444390

Functions of autobiographical memory in Taiwanese and American emerging adults.

Science.gov (United States)

Liao, Hsiao-Wen; Bluck, Susan; Alea, Nicole; Cheng, Ching-Ling

2016-01-01

The study addresses cultural and person-level factors contributing to emerging adult's use of memory to serve adaptive functions. The focus is on three functions: self-continuity, social-bonding and directing-behaviour. Taiwanese (N = 85, 52 women) and American (N = 95, 51 women) emerging adults completed the Thinking about Life Experiences scale, and measures of trait personality, self-concept clarity and future time perspective. Findings show that individuals from both cultures use memory to serve these three functions, but Taiwanese individuals use memory more frequently than Americans to maintain self-continuity. Culture also interacted with person-level factors: in Taiwan, but not America, memory is more frequently used to create self-continuity in individuals high in conscientiousness. Across cultures, having lower self-concept clarity was related to greater use of memory to create self-continuity. Findings are discussed in terms of how memory serves functions in context and specific aspects of the Taiwanese and American cultural context that may predict the functional use of memory in emerging adulthood.

Taste and odor recognition memory: the emotional flavor of life.

Science.gov (United States)

Miranda, Maria Isabel

2012-01-01

In recent years, our knowledge of the neurobiology of taste and smell has greatly increased; by using several learning models, we now have a better understanding of the behavioral and neurochemical basis of memory recognition. Studies have provided new evidence of some processes that depend on prior experience with the specific combination of sensory stimuli. This review contains recent research related to taste and odor recognition memory, and the goal is to highlight the role of two prominent brain structures, the insular cortex and the amygdala. These structures have an important function during learning and memory and have been associated with the differences in learning induced by the diverse degrees of emotion during taste/odor memory formation, either aversive or appetitive or when taste and odor are combined and/or potentiated.Therefore, this review includes information about certain neurochemical transmitters and their interactions during appetitive or aversive taste memory formation,taste-potentiated odor aversion memory, and conditioned odor aversion, which might be able to maintain the complex processes necessary for flavor recognition memory.

Genetic algorithms with memory- and elitism-based immigrants in dynamic environments

OpenAIRE

Yang, S

2008-01-01

Copyright @ 2008 by the Massachusetts Institute of Technology In recent years the genetic algorithm community has shown a growing interest in studying dynamic optimization problems. Several approaches have been devised. The random immigrants and memory schemes are two major ones. The random immigrants scheme addresses dynamic environments by maintaining the population diversity while the memory scheme aims to adapt genetic algorithms quickly to new environments by reusing historical inform...

Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

Science.gov (United States)

Matamales, Miriam

2012-12-19

Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

Postnatal TLR2 activation impairs learning and memory in adulthood.

Science.gov (United States)

Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

2015-08-01

Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences.

Science.gov (United States)

Donzis, Elissa J; Tronson, Natalie C

2014-11-01

This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of multiplexed reading scheme on nanocrossbar memristor memory's scalability

International Nuclear Information System (INIS)

Zhu Xuan; Tang Yu-Hua; Wu Jun-Jie; Yi Xun; Wu Chun-Qing

2014-01-01

Nanocrossbar is a potential memory architecture to integrate memristor to achieve large scale and high density memory. However, based on the currently widely-adopted parallel reading scheme, scalability of the nanocrossbar memory is limited, since the overhead of the reading circuits is in proportion with the size of the nanocrossbar component. In this paper, a multiplexed reading scheme is adopted as the foundation of the discussion. Through HSPICE simulation, we reanalyze scalability of the nanocrossbar memristor memory by investigating the impact of various circuit parameters on the output voltage swing as the memory scales to larger size. We find that multiplexed reading maintains sufficient noise margin in large size nanocrossbar memristor memory. In order to improve the scalability of the memory, memristors with nonlinear I—V characteristics and high LRS (low resistive state) resistance should be adopted. (interdisciplinary physics and related areas of science and technology)

Enhanced dimension-specific visual working memory in grapheme–color synesthesia☆

Science.gov (United States)

Terhune, Devin Blair; Wudarczyk, Olga Anna; Kochuparampil, Priya; Cohen Kadosh, Roi

2013-01-01

There is emerging evidence that the encoding of visual information and the maintenance of this information in a temporarily accessible state in working memory rely on the same neural mechanisms. A consequence of this overlap is that atypical forms of perception should influence working memory. We examined this by investigating whether having grapheme–color synesthesia, a condition characterized by the involuntary experience of color photisms when reading or representing graphemes, would confer benefits on working memory. Two competing hypotheses propose that superior memory in synesthesia results from information being coded in two information channels (dual-coding) or from superior dimension-specific visual processing (enhanced processing). We discriminated between these hypotheses in three n-back experiments in which controls and synesthetes viewed inducer and non-inducer graphemes and maintained color or grapheme information in working memory. Synesthetes displayed superior color working memory than controls for both grapheme types, whereas the two groups did not differ in grapheme working memory. Further analyses excluded the possibilities of enhanced working memory among synesthetes being due to greater color discrimination, stimulus color familiarity, or bidirectionality. These results reveal enhanced dimension-specific visual working memory in this population and supply further evidence for a close relationship between sensory processing and the maintenance of sensory information in working memory. PMID:23892185

Flash memory management system and method utilizing multiple block list windows

Science.gov (United States)

Chow, James (Inventor); Gender, Thomas K. (Inventor)

2005-01-01

The present invention provides a flash memory management system and method with increased performance. The flash memory management system provides the ability to efficiently manage and allocate flash memory use in a way that improves reliability and longevity, while maintaining good performance levels. The flash memory management system includes a free block mechanism, a disk maintenance mechanism, and a bad block detection mechanism. The free block mechanism provides efficient sorting of free blocks to facilitate selecting low use blocks for writing. The disk maintenance mechanism provides for the ability to efficiently clean flash memory blocks during processor idle times. The bad block detection mechanism provides the ability to better detect when a block of flash memory is likely to go bad. The flash status mechanism stores information in fast access memory that describes the content and status of the data in the flash disk. The new bank detection mechanism provides the ability to automatically detect when new banks of flash memory are added to the system. Together, these mechanisms provide a flash memory management system that can improve the operational efficiency of systems that utilize flash memory.

Mitochondrial nad2 gene is co-transcripted with CMS-associated orfB gene in cytoplasmic male-sterile stem mustard (Brassica juncea).

Science.gov (United States)

Yang, Jing-Hua; Zhang, Ming-Fang; Yu, Jing-Quan

2009-02-01

The transcriptional patterns of mitochondrial respiratory related genes were investigated in cytoplasmic male-sterile and fertile maintainer lines of stem mustard, Brassica juncea. There were numerous differences in nad2 (subunit 2 of NADH dehydrogenase) between stem mustard CMS and its maintainer line. One novel open reading frame, hereafter named orfB gene, was located at the downstream of mitochondrial nad2 gene in the CMS. The novel orfB gene had high similarity with YMF19 family protein, orfB in Raphanus sativus, Helianthus annuus, Nicotiana tabacum and Beta vulgaris, orfB-CMS in Daucus carota, atp8 gene in Arabidopsis thaliana, 5' flanking of orf224 in B. napus (nap CMS) and 5' flanking of orf220 gene in CMS Brassica juncea. Three copies probed by specific fragment (amplified by primers of nad2F and nad2R from CMS) were found in the CMS line following Southern blotting digested with HindIII, but only a single copy in its maintainer line. Meanwhile, two transcripts were shown in the CMS line following Northern blotting while only one transcript was detected in the maintainer line, which were probed by specific fragment (amplified by primers of nad2F and nad2R from CMS). Meanwhile, the expression of nad2 gene was reduced in CMS bud compared to that in its maintainer line. We thus suggested that nad2 gene may be co-transcripted with CMS-associated orfB gene in the CMS. In addition, the specific fragment that was amplified by primers of nad2F and nad2R just spanned partial sequences of nad2 gene and orfB gene. Such alterations in the nad2 gene would impact the activity of NADH dehydrogenase, and subsequently signaling, inducing the expression of nuclear genes involved in male sterility in this type of cytoplasmic male sterility.

Electroforming free resistive switching memory in two-dimensional VOx nanosheets

KAUST Repository

Hota, Mrinal Kanti

2015-10-21

We report two-dimensional VOx nanosheets containing multi-oxidation states (V5+, V4+, and V3+), prepared by a hydrothermal process for potential applications in resistive switching devices. The experimental results demonstrate a highly reproducible, electroforming-free, low SET bias bipolar resistive switching memory performance with endurance for more than 100 cycles maintaining OFF/ON ratio of ∼60 times. These devices show better memory performance as compared to previously reported VOx thin film based devices. The memory mechanism in VOx is proposed to be originated from the migration of oxygen vacancies/ions, an influence of the bottom electrode and existence of multi-oxidation states.

Autobiographical memory for the differential diagnosis of cognitive pathology in aging.

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Meléndez, Juan C; Redondo, Rita; Torres, Marta; Mayordomo, Teresa; Sales, Alicia

2016-11-01

The present study distinguishes three memory stages across the lifespan, and aims to compare episodic and semantic autobiographical memory in healthy older adults, with amnesic mild cognitive impairment, and with Alzheimer's disease. This information can offer evidence about the way semantic and episodic autobiographical memory work, and how the disease affects them. The sample was composed of 56 people, all aged over 60 years; 15 with amnestic mild cognitive impairment, 12 with Alzheimer's disease and 29 healthy older people. Participants were evaluated with the Autobiographical Memory Interview. A mixed anova showed significant main effects of memory and time-period, and significant interactions of memory × group, time-period × group and memory × time × group. Assessment of autobiographical memory provides information to differentiate amnestic mild cognitive impairment patients from Alzheimer's disease patients. Although the decline in episodic memory starts with the onset of the disease, semantic memory is maintained until moderate stages of dementia. Geriatr Gerontol Int 2016; 16:1220-1225. © 2015 Japan Geriatrics Society.

The brain decade in debate: I. Neurobiology of learning and memory

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Baddeley A.

2000-01-01

Full Text Available This article is a transcription of an electronic symposium in which some active researchers were invited by the Brazilian Society for Neuroscience and Behavior (SBNeC to discuss the last decade's advances in neurobiology of learning and memory. The way different parts of the brain are recruited during the storage of different kinds of memory (e.g., short-term vs long-term memory, declarative vs procedural memory and even the property of these divisions were discussed. It was pointed out that the brain does not really store memories, but stores traces of information that are later used to create memories, not always expressing a completely veridical picture of the past experienced reality. To perform this process different parts of the brain act as important nodes of the neural network that encode, store and retrieve the information that will be used to create memories. Some of the brain regions are recognizably active during the activation of short-term working memory (e.g., prefrontal cortex, or the storage of information retrieved as long-term explicit memories (e.g., hippocampus and related cortical areas or the modulation of the storage of memories related to emotional events (e.g., amygdala. This does not mean that there is a separate neural structure completely supporting the storage of each kind of memory but means that these memories critically depend on the functioning of these neural structures. The current view is that there is no sense in talking about hippocampus-based or amygdala-based memory since this implies that there is a one-to-one correspondence. The present question to be solved is how systems interact in memory. The pertinence of attributing a critical role to cellular processes like synaptic tagging and protein kinase A activation to explain the memory storage processes at the cellular level was also discussed.

Persistent increased PKMζ in long-term and remote spatial memory.

Science.gov (United States)

Hsieh, Changchi; Tsokas, Panayiotis; Serrano, Peter; Hernández, A Iván; Tian, Dezhi; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2017-02-01

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance. Copyright © 2016. Published by Elsevier Inc.

Maintenance and manipulation of information in schizophrenia: further evidence for impairment in the central executive component of working memory.

Science.gov (United States)

Kim, Junghoon; Glahn, David C; Nuechterlein, Keith H; Cannon, Tyrone D

2004-06-01

Impairments in working memory (WM) have been proposed to underlie various cognitive and functional impairments in schizophrenia. However, the nature and extent of the dysfunction remain unclear. The present study attempted to examine the integrity of sub-components of working memory in schizophrenia within the framework of the multiple-component working memory model proposed by Baddeley. Two sets of visuospatial and verbal delayed-response tasks were developed which had comparable formats and difficulties across domains. In Experiment 1, demands on the central executive (CE) were manipulated by requiring subjects either (1) to simultaneously maintain and transform information (maintenance-and-manipulation condition) or (2) just to maintain this information (maintenance-only condition). In Experiment 2, the amount of information to be maintained over the delay was parametrically varied to evaluate demands on the temporary maintenance component of working memory. Patients (N=16) performed worse than controls (N=16) in both conditions of Experiment 1; however, simultaneous maintenance and manipulation was associated with a significantly greater performance reduction in the patients. In Experiment 2, both patients (N=15) and controls (N=15) declined in performance, at equivalent rates, with increasing memory load. Parallel findings were observed for the verbal and visuospatial tasks. These results suggest that while both maintenance and central executive aspects of working memory are impaired in schizophrenic patients, the central executive may be more severely affected.

Working memory and organizational skills problems in ADHD.

Science.gov (United States)

Kofler, Michael J; Sarver, Dustin E; Harmon, Sherelle L; Moltisanti, Allison; Aduen, Paula A; Soto, Elia F; Ferretti, Nicole

2018-01-01

This study tested model-driven predictions regarding working memory's role in the organizational problems associated with ADHD. Children aged 8-13 (M = 10.33, SD = 1.42) with and without ADHD (N = 103; 39 girls; 73% Caucasian/Non-Hispanic) were assessed on multiple, counterbalanced working memory tasks. Parents and teachers completed norm-referenced measures of organizational problems (Children's Organizational Skills Scale; COSS). Results confirmed large magnitude working memory deficits (d = 1.24) and organizational problems in ADHD (d = 0.85). Bias-corrected, bootstrapped conditional effects models linked impaired working memory with greater parent- and teacher-reported inattention, hyperactivity/impulsivity, and organizational problems. Working memory predicted organization problems across all parent and teacher COSS subscales (R 2  = .19-.23). Approximately 38%-57% of working memory's effect on organization problems was conveyed by working memory's association with inattentive behavior. Unique effects of working memory remained significant for both parent- and teacher-reported task planning, as well as for teacher-reported memory/materials management and overall organization problems. Attention problems uniquely predicted worse organizational skills. Hyperactivity was unrelated to parent-reported organizational skills, but predicted better teacher-reported task planning. Children with ADHD exhibit multisetting, broad-based organizational impairment. These impaired organizational skills are attributable in part to performance deficits secondary to working memory dysfunction, both directly and indirectly via working memory's role in regulating attention. Impaired working memory in ADHD renders it extraordinarily difficult for these children to consistently anticipate, plan, enact, and maintain goal-directed actions. © 2017 Association for Child and Adolescent Mental Health.

The relationships between memory systems and sleep stages.

Science.gov (United States)

Rauchs, Géraldine; Desgranges, Béatrice; Foret, Jean; Eustache, Francis

2005-06-01

Sleep function remains elusive despite our rapidly increasing comprehension of the processes generating and maintaining the different sleep stages. Several lines of evidence support the hypothesis that sleep is involved in the off-line reprocessing of recently-acquired memories. In this review, we summarize the main results obtained in the field of sleep and memory consolidation in both animals and humans, and try to connect sleep stages with the different memory systems. To this end, we have collated data obtained using several methodological approaches, including electrophysiological recordings of neuronal ensembles, post-training modifications of sleep architecture, sleep deprivation and functional neuroimaging studies. Broadly speaking, all the various studies emphasize the fact that the four long-term memory systems (procedural memory, perceptual representation system, semantic and episodic memory, according to Tulving's SPI model; Tulving, 1995) benefit either from non-rapid eye movement (NREM) (not just SWS) or rapid eye movement (REM) sleep, or from both sleep stages. Tulving's classification of memory systems appears more pertinent than the declarative/non-declarative dichotomy when it comes to understanding the role of sleep in memory. Indeed, this model allows us to resolve several contradictions, notably the fact that episodic and semantic memory (the two memory systems encompassed in declarative memory) appear to rely on different sleep stages. Likewise, this model provides an explanation for why the acquisition of various types of skills (perceptual-motor, sensory-perceptual and cognitive skills) and priming effects, subserved by different brain structures but all designated by the generic term of implicit or non-declarative memory, may not benefit from the same sleep stages.

Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function.

Science.gov (United States)

Kennedy, Andrew J; Rahn, Elizabeth J; Paulukaitis, Brynna S; Savell, Katherine E; Kordasiewicz, Holly B; Wang, Jing; Lewis, John W; Posey, Jessica; Strange, Sarah K; Guzman-Karlsson, Mikael C; Phillips, Scott E; Decker, Kyle; Motley, S Timothy; Swayze, Eric E; Ecker, David J; Michael, Todd P; Day, Jeremy J; Sweatt, J David

2016-09-06

Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/-) mice have enhanced long-term potentiation in the CA1 area of the hippocampus. In translationally oriented studies, we found that small-molecule HDAC inhibitors normalized hippocampal LTP and memory recall. A comprehensive set of next-generation sequencing experiments of hippocampal mRNA and methylated DNA isolated from Tcf4-deficient and WT mice before or shortly after experiential learning, with or without administration of vorinostat, identified "memory-associated" genes modulated by HDAC inhibition and dysregulated by Tcf4 haploinsufficiency. Finally, we observed that Hdac2 isoform-selective knockdown was sufficient to rescue memory deficits in Tcf4(+/-) mice. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Sleep, Memory & Brain Rhythms.

Science.gov (United States)

Watson, Brendon O; Buzsáki, György

2015-01-01

Sleep occupies roughly one-third of our lives, yet the scientific community is still not entirely clear on its purpose or function. Existing data point most strongly to its role in memory and homeostasis: that sleep helps maintain basic brain functioning via a homeostatic mechanism that loosens connections between overworked synapses, and that sleep helps consolidate and re-form important memories. In this review, we will summarize these theories, but also focus on substantial new information regarding the relation of electrical brain rhythms to sleep. In particular, while REM sleep may contribute to the homeostatic weakening of overactive synapses, a prominent and transient oscillatory rhythm called "sharp-wave ripple" seems to allow for consolidation of behaviorally relevant memories across many structures of the brain. We propose that a theory of sleep involving the division of labor between two states of sleep-REM and non-REM, the latter of which has an abundance of ripple electrical activity-might allow for a fusion of the two main sleep theories. This theory then postulates that sleep performs a combination of consolidation and homeostasis that promotes optimal knowledge retention as well as optimal waking brain function.

miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb

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Zeyu Chen

2017-09-01

Full Text Available MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified. Without miR-150, c-Myb was upregulated and anti-apoptotic targets of c-Myb, such as Bcl-2 and Bcl-xL, were also increased, suggesting a miR-150-c-Myb survival circuit during memory CD8 T cell development. Indeed, overexpression of non-repressible c-Myb rescued the memory CD8 T cell defects caused by overexpression of miR-150. Overall, these results identify a key role for miR-150 in memory CD8 T cells through a c-Myb-controlled enhanced survival circuit.

dFOXO Activates Large and Small Heat Shock Protein Genes in Response to Oxidative Stress to Maintain Proteostasis in Drosophila.

Science.gov (United States)

Donovan, Marissa R; Marr, Michael T

2016-09-02

Maintaining protein homeostasis is critical for survival at the cellular and organismal level (Morimoto, R. I. (2011) Cold Spring Harb. Symp. Quant. Biol. 76, 91-99). Cells express a family of molecular chaperones, the heat shock proteins, during times of oxidative stress to protect against proteotoxicity. We have identified a second stress responsive transcription factor, dFOXO, that works alongside the heat shock transcription factor to activate transcription of both the small heat shock protein and the large heat shock protein genes. This expression likely protects cells from protein misfolding associated with oxidative stress. Here we identify the regions of the Hsp70 promoter essential for FOXO-dependent transcription using in vitro methods and find a physiological role for FOXO-dependent expression of heat shock proteins in vivo. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The role of central attention in retrieval from visual short-term memory.

Science.gov (United States)

Magen, Hagit

2017-04-01

The role of central attention in visual short-term memory (VSTM) encoding and maintenance is well established, yet its role in retrieval has been largely unexplored. This study examined the involvement of central attention in retrieval from VSTM using a dual-task paradigm. Participants performed a color change-detection task. Set size varied between 1 and 3 items, and the memory sample was maintained for either a short or a long delay period. A secondary tone discrimination task was introduced at the end of the delay period, shortly before the appearance of a central probe, and occupied central attention while participants were searching within VSTM representations. Similarly to numerous previous studies, reaction time increased as a function of set size reflecting the occurrence of a capacity-limited memory search. When the color targets were maintained over a short delay, memory was searched for the most part without the involvement of central attention. However, with a longer delay period, the search relied entirely on the operation of central attention. Taken together, this study demonstrates that central attention is involved in retrieval from VSTM, but the extent of its involvement depends on the duration of the delay period. Future studies will determine whether the type of memory search (parallel or serial) carried out during retrieval depends on the nature of the attentional mechanism involved the task.

The (gradual) rise of memory inflation.

Science.gov (United States)

Klenerman, Paul

2018-05-01

Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8 + T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to "exhaustion" the repeated antigen encounters experienced by CD8 + T cells lead to development of a robust T-cell population structure which maintains functionality and size. In this review, I will discuss how the ideas around this form of memory have evolved over time and some new models which can help explain how these populations are induced and sustained. These models are relevant to immunity against persistent viruses, to novel vaccine strategies and to concepts about aging. © 2018 The Author. Immunological Reviews Published by John Wiley & Sons Ltd.

The transcriptional landscape

DEFF Research Database (Denmark)

Nielsen, Henrik

2011-01-01

The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein coding...... regions, the map of transcripts is very complex due to small transcripts from the flanking ends of the transcription unit, the use of multiple start and stop sites for the main transcript, production of multiple functional RNA molecules from the same primary transcript, and RNA molecules made...... by independent transcription from within the unit. In genomic regions separating those that encode proteins or highly abundant RNA molecules with known function, transcripts are generally of low abundance and short-lived. In most of these cases, it is unclear to what extent a function is related to transcription...

Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

Science.gov (United States)

White, André O.; Wood, Marcelo A.

2013-01-01

It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. PMID:24149059

Limits to the usability of iconic memory.

Science.gov (United States)

Rensink, Ronald A

2014-01-01

Human vision briefly retains a trace of a stimulus after it disappears. This trace-iconic memory-is often believed to be a surrogate for the original stimulus, a representational structure that can be used as if the original stimulus were still present. To investigate its nature, a flicker-search paradigm was developed that relied upon a full scan (rather than partial report) of its contents. Results show that for visual search it can indeed act as a surrogate, with little cost for alternating between visible and iconic representations. However, the duration over which it can be used depends on the type of task: some tasks can use iconic memory for at least 240 ms, others for only about 190 ms, while others for no more than about 120 ms. The existence of these different limits suggests that iconic memory may have multiple layers, each corresponding to a particular level of the visual hierarchy. In this view, the inability to use a layer of iconic memory may reflect an inability to maintain feedback connections to the corresponding representation.

Effects of working memory load on visual selective attention: Behavioral and electrophysiological evidence

Directory of Open Access Journals (Sweden)

Nikki ePratt

2011-06-01

Full Text Available Working memory and attention interact in a way that enables us to focus on relevant items and maintain current goals. The influence of working memory on attention has been noted in several studies using dual task designs. Multitasking increases the demands on working memory and reduces the amount of resources available for cognitive control functions such as resolving stimulus conflict. However, few studies have investigated the temporal activation of the cortex while multitasking. The present study addresses the extent to which working memory load influences early (P1 and late (P300 attention-sensitive event-related potential (ERP components using a dual task paradigm. Participants performed an arrow flanker task alone (single task condition or concurrently with a Sternberg memory task (dual task condition. In the flanker task, participants responded to the direction of a central arrow surrounded by congruent or incongruent arrows. In the dual task condition, participants were presented with a Sternberg task that consisted of either 4 or 7 consonants to remember prior to a short block of flanker trials. Participants were slower and less accurate on incongruent versus congruent trials. Furthermore, accuracy on incongruent trials was reduced in both dual task conditions. Likewise, P300 amplitude to incongruent flanker stimuli decreased when working memory load increased. These findings suggest that interference from incongruent flankers was more difficult to suppress when working memory was taxed. In addition, P1 amplitude was diminished on all flanker trials in the dual task condition. This result indicates that top-down attentional control over early visual processing is diminished by increasing demands on working memory. Both the behavioral and electrophysiological results suggest that working memory is critical in maintaining attentional focus and resolving conflict.

Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family.

Science.gov (United States)

Schmidt, A; Vogel, R; Holloway, M K; Rutledge, S J; Friedman, O; Yang, Z; Rodan, G A; Friedman, E

1999-09-10

LXR and PPAR receptors belong to the nuclear receptor superfamily of transcriptional activating factors. Using ligand-dependent transcription assays, we found that 5-tetradecyloxy-2-furancarboxylic acid (TOFA) transactivates chimeric receptors composed of the glucocorticoid receptor DNA binding domain and the ligand binding regions of PPARalpha, PPARbeta (NUC-1) and LXRbeta (NER) receptors. In the same assays, ligands for PPARs (oleic acid, WY-14643 and L-631,033) and LXRs (hydroxycholesterols) maintain their respective receptor selectivity. TOFA and hydroxycholesterols also stimulate transcription from a minimal fibrinogen promoter that is under the control of AP-1 or NF-kappaB transcription factor binding sites. In addition to their effects on transcription, these LXRbeta activators induce neuronal differentiation in rat pheochromocytoma cells. TOFA and the natural LXR agonist, 22 (R)-hydroxycholesterol, stimulate neurite outgrowth in 55 and 28% of cells, respectively. No neurite outgrowth was induced by the related 22(S)-hydroxycholesterol, which does not activate the LXR family. These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells.

Does selection against transcriptional interference shape retroelement-free regions in mammalian genomes?

Directory of Open Access Journals (Sweden)

Tobias Mourier

Full Text Available BACKGROUND: Eukaryotic genomes are scattered with retroelements that proliferate through retrotransposition. Although retroelements make up around 40 percent of the human genome, large regions are found to be completely devoid of retroelements. This has been hypothesised to be a result of genomic regions being intolerant to insertions of retroelements. The inadvertent transcriptional activity of retroelements may affect neighbouring genes, which in turn could be detrimental to an organism. We speculate that such retroelement transcription, or transcriptional interference, is a contributing factor in generating and maintaining retroelement-free regions in the human genome. METHODOLOGY/PRINCIPAL FINDINGS: Based on the known transcriptional properties of retroelements, we expect long interspersed elements (LINEs to be able to display a high degree of transcriptional interference. In contrast, we expect short interspersed elements (SINEs to display very low levels of transcriptional interference. We find that genomic regions devoid of long interspersed elements (LINEs are enriched for protein-coding genes, but that this is not the case for regions devoid of short interspersed elements (SINEs. This is expected if genes are subject to selection against transcriptional interference. We do not find microRNAs to be associated with genomic regions devoid of either SINEs or LINEs. We further observe an increased relative activity of genes overlapping LINE-free regions during early embryogenesis, where activity of LINEs has been identified previously. CONCLUSIONS/SIGNIFICANCE: Our observations are consistent with the notion that selection against transcriptional interference has contributed to the maintenance and/or generation of retroelement-free regions in the human genome.

As Working Memory Grows: A Developmental Account of Neural Bases of Working Memory Capacity in 5- to 8-Year Old Children and Adults.

Science.gov (United States)

Kharitonova, Maria; Winter, Warren; Sheridan, Margaret A

2015-09-01

Working memory develops slowly: Even by age 8, children are able to maintain only half the number of items that adults can remember. Neural substrates that support performance on working memory tasks also have a slow developmental trajectory and typically activate to a lesser extent in children, relative to adults. Little is known about why younger participants elicit less neural activation. This may be due to maturational differences, differences in behavioral performance, or both. Here we investigate the neural correlates of working memory capacity in children (ages 5-8) and adults using a visual working memory task with parametrically increasing loads (from one to four items) using fMRI. This task allowed us to estimate working memory capacity limit for each group. We found that both age groups increased the activation of frontoparietal networks with increasing working memory loads, until working memory capacity was reached. Because children's working memory capacity limit was half of that for adults, the plateau occurred at lower loads for children. Had a parametric increase in load not been used, this would have given an impression of less activation overall and less load-dependent activation for children relative to adults. Our findings suggest that young children and adults recruit similar frontoparietal networks at working memory loads that do not exceed capacity and highlight the need to consider behavioral performance differences when interpreting developmental differences in neural activation.

Large Capacity of Conscious Access for Incidental Memories in Natural Scenes.

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Kaunitz, Lisandro N; Rowe, Elise G; Tsuchiya, Naotsugu

2016-09-01

When searching a crowd, people can detect a target face only by direct fixation and attention. Once the target is found, it is consciously experienced and remembered, but what is the perceptual fate of the fixated nontarget faces? Whereas introspection suggests that one may remember nontargets, previous studies have proposed that almost no memory should be retained. Using a gaze-contingent paradigm, we asked subjects to visually search for a target face within a crowded natural scene and then tested their memory for nontarget faces, as well as their confidence in those memories. Subjects remembered up to seven fixated, nontarget faces with more than 70% accuracy. Memory accuracy was correlated with trial-by-trial confidence ratings, which implies that the memory was consciously maintained and accessed. When the search scene was inverted, no more than three nontarget faces were remembered. These findings imply that incidental memory for faces, such as those recalled by eyewitnesses, is more reliable than is usually assumed. © The Author(s) 2016.

Neuro-Cognitive Intervention for Working Memory: Preliminary Results and Future Directions.

Science.gov (United States)

Bree, Kathleen D; Beljan, Paul

2016-01-01

Definitions of working memory identify it as a function of the executive function system in which an individual maintains two or more pieces of information in mind and uses that information simultaneously for some purpose. In academics, working memory is necessary for a variety of functions, including attending to the information one's teacher presents and then using that information simultaneously for problem solving. Research indicates difficulties with working memory are observed in children with mathematics learning disorder (MLD) and reading disorders (RD). To improve working memory and other executive function difficulties, and as an alternative to medication treatments for attention and executive function disorders, the Motor Cognition(2)® (MC(2)®)program was developed. Preliminary research on this program indicates statistically significant improvements in working memory, mathematics, and nonsense word decoding for reading. Further research on the MC(2)® program and its impact on working memory, as well as other areas of executive functioning, is warranted.

Temporal structure in neuronal activity during working memory in Macaque parietal cortex

CERN Document Server

Pesaran, B; Sahami, M; Mitra, P; Andersen, R A

2000-01-01

A number of cortical structures are reported to have elevated single unit firing rates sustained throughout the memory period of a working memory task. How the nervous system forms and maintains these memories is unknown but reverberating neuronal network activity is thought to be important. We studied the temporal structure of single unit (SU) activity and simultaneously recorded local field potential (LFP) activity from area LIP in the inferior parietal lobe of two awake macaques during a memory-saccade task. Using multitaper techniques for spectral analysis, which play an important role in obtaining the present results, we find elevations in spectral power in a 50--90 Hz (gamma) frequency band during the memory period in both SU and LFP activity. The activity is tuned to the direction of the saccade providing evidence for temporal structure that codes for movement plans during working memory. We also find SU and LFP activity are coherent during the memory period in the 50--90 Hz gamma band and no consisten...

The transcriptional programme of the androgen receptor (AR) in prostate cancer.

Science.gov (United States)

Lamb, Alastair D; Massie, Charlie E; Neal, David E

2014-03-01

The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors. © 2013 The Authors. BJU International © 2013 BJU International.

A transcription activator-like effector (TALE) induction system mediated by proteolysis.

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Copeland, Matthew F; Politz, Mark C; Johnson, Charles B; Markley, Andrew L; Pfleger, Brian F

2016-04-01

Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications owing to their customizable DNA-binding specificity. In this work we expanded the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded after induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator-agnostic.

A loss in the family: silence, memory, and narrative identity after bereavement.

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Baddeley, Jenna; Singer, Jefferson A

2010-02-01

Grief theories have converged on the idea that the sharing of autobiographical memory narratives of loss and of the deceased person, especially within the family, is a major way to maintain and/or reconfigure a healthy sense of identity after a loss. In contrast, we examine unspoken memory-the withholding of socially sharing autobiographical memories about the loss and the departed family member-as a way to either conserve an existing narrative identity or assert a new narrative identity. Depending on its context and function, silence about memory can play either a positive or negative role in an individual griever's ongoing narrative identity, as well as in the larger family narrative in which the griever's identity is embedded.

MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells.

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Li, Chen Xi; Talele, Nilesh P; Boo, Stellar; Koehler, Anne; Knee-Walden, Ericka; Balestrini, Jenna L; Speight, Pam; Kapus, Andras; Hinz, Boris

2017-03-01

Expansion on stiff culture substrates activates pro-fibrotic cell programs that are retained by mechanical memory. Here, we show that priming on physiologically soft silicone substrates suppresses fibrogenesis and desensitizes mesenchymal stem cells (MSCs) against subsequent mechanical activation in vitro and in vivo, and identify the microRNA miR-21 as a long-term memory keeper of the fibrogenic program in MSCs. During stiff priming, miR-21 levels were gradually increased by continued regulation through the acutely mechanosensitive myocardin-related transcription factor-A (MRTF-A/MLK-1) and remained high over 2 weeks after removal of the mechanical stimulus. Knocking down miR-21 once by the end of the stiff-priming period was sufficient to erase the mechanical memory and sensitize MSCs to subsequent exposure to soft substrates. Soft priming and erasing mechanical memory following cell culture expansion protects MSCs from fibrogenesis in the host wound environment and increases the chances for success of MSC therapy in tissue-repair applications.

CREB binding protein is required for both short-term and long-term memory formation.

NARCIS (Netherlands)

Chen, G.; Zou, X.; Watanabe, H.; Deursen, J.M.A. van; Shen, J.

2010-01-01

CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated

Effect of Pentylenetetrazol on Morphine State-Dependent Memory in Rat

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Marziyeh Tavassoli

2017-09-01

Full Text Available Abstract Background: Learning and memory are among the higher functions of the brain. State-dependent memory (STM is a type of memory in which the recall of a learned behavior is happend only in the same sensory and physiologic condition in which the behavior is encoded. The STM is seen with some drugs, e.g. the morphine. The pentylenetetrazol (PTZ is a durg which is used for the induction of seizure in experimental models. Some studies have been revealed different effects of the PTZ on brain higher function (learning, memory …. The aim of present study was to explore the effect of PTZ on morphine-induced STM. Materials and Methods: In this study, male adult Wistar rats (190-220 g were used. Animals in 3 groups (n=8 during 3 sessions (learning/memory, STM and interaction were studied. During 48 hour (training and test the learning and memory of animals were studied in inhibitory avoidance apparatus. The step-through latency in the test day was used as a criterion for memory. Post-training injection of saline or morphine (2.5, 5 and 7.5 mg/kg-ip in different groups was carried out. In addition, the pre-test injection of morphine at the same doses was made to study the STM. Moreover, the interaction of pre-test single-dose PTZ (60 mg/kg-ip on STM was studied. The locomotion of the animals was measured using the open field. Results: The post-training injection of morphine (2.5, 5 and 7.5 mg/kg-ip impaired the inhibitory memory of rats compared to control group (p<0.001. The post-training and pre-test injections of the same dose of morphine (7.5 mg/kg-ip reversed the impaired memory compared to morphine (2.5 and 5 mg/kg-ip, (p<0.001. The pre-test PTZ (60 mg/kg-ip maintained the morphine (7.5 mg/kg-ip STM (p<0.001. Conclusion: The present study revealed that the post-training ip injection of different doses of morphine results in the impairment of inhibitory avoidance memory in rat. In addition, the pre-test injection of the same doses of morphine

Trees or Grids? Indexing Moving Objects in Main Memory

DEFF Research Database (Denmark)

Sidlauskas, Darius; Saltenis, Simonas; Christiansen, Christian Winther

2009-01-01

New application areas, such as location-based services, rely on the efficient management of large collections of mobile objects. Maintaining accurate, up-to-date positions of these objects results in massive update loads that must be supported by spatial indexing structures and main-memory indexes...... are usually necessary to provide high update performance. Traditionally, the R-tree and its variants were used for indexing spatial data, but most of the recent research assumes that a simple, uniform grid is the best choice for managing moving objects in main memory. We perform an extensive experimental...

MOSFET analog memory circuit achieves long duration signal storage

Science.gov (United States)

1966-01-01

Memory circuit maintains the signal voltage at the output of an analog signal amplifier when the input signal is interrupted or removed. The circuit uses MOSFET /Metal Oxide Semiconductor Field Effect Transistor/ devices as voltage-controlled switches, triggered by an external voltage-sensing device.

Brain activity related to working memory for temporal order and object information.

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Roberts, Brooke M; Libby, Laura A; Inhoff, Marika C; Ranganath, Charan

2017-06-08

Maintaining items in an appropriate sequence is important for many daily activities; however, remarkably little is known about the neural basis of human temporal working memory. Prior work suggests that the prefrontal cortex (PFC) and medial temporal lobe (MTL), including the hippocampus, play a role in representing information about temporal order. The involvement of these areas in successful temporal working memory, however, is less clear. Additionally, it is unknown whether regions in the PFC and MTL support temporal working memory across different timescales, or at coarse or fine levels of temporal detail. To address these questions, participants were scanned while completing 3 working memory task conditions (Group, Position and Item) that were matched in terms of difficulty and the number of items to be actively maintained. Group and Position trials probed temporal working memory processes, requiring the maintenance of hierarchically organized coarse and fine temporal information, respectively. To isolate activation related to temporal working memory, Group and Position trials were contrasted against Item trials, which required detailed working memory maintenance of visual objects. Results revealed that working memory encoding and maintenance of temporal information relative to visual information was associated with increased activation in dorsolateral PFC (DLPFC), and perirhinal cortex (PRC). In contrast, maintenance of visual details relative to temporal information was characterized by greater activation of parahippocampal cortex (PHC), medial and anterior PFC, and retrosplenial cortex. In the hippocampus, a dissociation along the longitudinal axis was observed such that the anterior hippocampus was more active for working memory encoding and maintenance of visual detail information relative to temporal information, whereas the posterior hippocampus displayed the opposite effect. Posterior parietal cortex was the only region to show sensitivity to temporal

A program for undergraduate research into the mechanisms of sensory coding and memory decay

Energy Technology Data Exchange (ETDEWEB)

Calin-Jageman, R J

2010-09-28

This is the final technical report for this DOE project, entitltled "A program for undergraduate research into the mechanisms of sensory coding and memory decay". The report summarizes progress on the three research aims: 1) to identify phyisological and genetic correlates of long-term habituation, 2) to understand mechanisms of olfactory coding, and 3) to foster a world-class undergraduate neuroscience program. Progress on the first aim has enabled comparison of learning-regulated transcripts across closely related learning paradigms and species, and results suggest that only a small core of transcripts serve truly general roles in long-term memory. Progress on the second aim has enabled testing of several mutant phenotypes for olfactory behaviors, and results show that responses are not fully consistent with the combinitoral coding hypothesis. Finally, 14 undergraduate students participated in this research, the neuroscience program attracted extramural funding, and we completed a successful summer program to enhance transitions for community-college students into 4-year colleges to persue STEM fields.

Control of crack pattern using memory effect of paste

International Nuclear Information System (INIS)

Nakahara, Akio; Shinohara, Yuu; Matsuo, Yousuke

2011-01-01

A densely packed colloidal suspension, called as a paste, remembers the direction of external mechanical fields, such as flow and vibration. When the pastes are dried, memories in pastes are visualized as macroscopically anisotropic crack patterns, such as lamellar, radial, ring and spiral. Here, we experimentally investigate how pastes remember such experiences by using paste with different size distribution of colloidal particles. We find that a paste with smaller particles have a better memory, in the sense it remembers external mechanical fields at smaller solid volume fraction, which implies that interparticle forces between colloidal particles play an important role in memory effects, causing a quantitative change in the phase diagram for the same material. This result supports the hypothesis that memories in pastes are maintained as microscopically anisotropic network structure of colloidal particles, connected via interparticle forces between colloidal particles, such as van der Waals interaction.

The nature of short-term consolidation in visual working memory.

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Ricker, Timothy J; Hardman, Kyle O

2017-11-01

Short-term consolidation is the process by which stable working memory representations are created. This process is fundamental to cognition yet poorly understood. The present work examines short-term consolidation using a Bayesian hierarchical model of visual working memory recall to determine the underlying processes at work. Our results show that consolidation functions largely through changing the proportion of memory items successfully maintained until test. Although there was some evidence that consolidation affects representational precision, this change was modest and could not account for the bulk of the consolidation effect on memory performance. The time course of the consolidation function and selective influence of consolidation on specific serial positions strongly indicates that short-term consolidation induces an attentional blink. The blink leads to deficits in memory for the immediately following item when time pressure is introduced. Temporal distinctiveness accounts of the consolidation process are tested and ruled out. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

On the law relating processing to storage in working memory.

Science.gov (United States)

Barrouillet, Pierre; Portrat, Sophie; Camos, Valérie

2011-04-01

Working memory is usually defined in cognitive psychology as a system devoted to the simultaneous processing and maintenance of information. However, although many models of working memory have been put forward during the last decades, they often leave underspecified the dynamic interplay between processing and storage. Moreover, the account of their interaction proposed by the most popular A. D. Baddeley and G. Hitch's (1974) multiple-component model is contradicted by facts, leaving unresolved one of the main issues of cognitive functioning. In this article, the author derive from the time-based resource-sharing model of working memory a mathematical function relating the cognitive load involved by concurrent processing to the amount of information that can be simultaneously maintained active in working memory. A meta-analysis from several experiments testing the effects of processing on storage corroborates the parameters of the predicted function, suggesting that it properly reflects the law relating the 2 functions of working memory. 2011 APA, all rights reserved

Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load

Science.gov (United States)

Burke, C. J.; Seifritz, E.; Tobler, P. N.

2017-01-01

Abstract Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain’s capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations. PMID:28462394

Enhanced dimension-specific visual working memory in grapheme-color synesthesia.

Science.gov (United States)

Terhune, Devin Blair; Wudarczyk, Olga Anna; Kochuparampil, Priya; Cohen Kadosh, Roi

2013-10-01

There is emerging evidence that the encoding of visual information and the maintenance of this information in a temporarily accessible state in working memory rely on the same neural mechanisms. A consequence of this overlap is that atypical forms of perception should influence working memory. We examined this by investigating whether having grapheme-color synesthesia, a condition characterized by the involuntary experience of color photisms when reading or representing graphemes, would confer benefits on working memory. Two competing hypotheses propose that superior memory in synesthesia results from information being coded in two information channels (dual-coding) or from superior dimension-specific visual processing (enhanced processing). We discriminated between these hypotheses in three n-back experiments in which controls and synesthetes viewed inducer and non-inducer graphemes and maintained color or grapheme information in working memory. Synesthetes displayed superior color working memory than controls for both grapheme types, whereas the two groups did not differ in grapheme working memory. Further analyses excluded the possibilities of enhanced working memory among synesthetes being due to greater color discrimination, stimulus color familiarity, or bidirectionality. These results reveal enhanced dimension-specific visual working memory in this population and supply further evidence for a close relationship between sensory processing and the maintenance of sensory information in working memory. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Relative Ease in Creating Detailed Orthographic Representations Contrasted with Severe Difficulties to Maintain Them in Long-term Memory Among Dyslexic Children.

Science.gov (United States)

Binamé, Florence; Danzio, Sophie; Poncelet, Martine

2015-11-01

Most research into orthographic learning abilities has been conducted in English with typically developing children using reading-based tasks. In the present study, we examined the abilities of French-speaking children with dyslexia to create novel orthographic representations for subsequent use in spelling and to maintain them in long-term memory. Their performance was compared with that of chronological age (CA)-matched and reading age (RA)-matched control children. We used an experimental task designed to provide optimal learning conditions (i.e. 10 spelling practice trials) ensuring the short-term acquisition of the spelling of the target orthographic word forms. After a 1-week delay, the long-term retention of the targets was assessed by a spelling post-test. Analysis of the results revealed that, in the short term, children with dyslexia learned the novel orthographic word forms well, only differing from both CA and RA controls on the initial decoding of the targets and from CA controls on the first two practice trials. In contrast, a dramatic drop was observed in their long-term retention relative to CA and RA controls. These results support the suggestion of the self-teaching hypothesis (Share, 1995) that initial errors in the decoding and spelling of unfamiliar words may hinder the establishment of fully specified novel orthographic representations. Copyright © 2015 John Wiley & Sons, Ltd.

Memory for performance feedback :a test of three self- motivation theories

OpenAIRE

Donlin, Joanne Mac

1990-01-01

The current study tests the adequacy of three self-motive theories to predict recall of performance feedback, memory sensitivity, and ratings of perceived accuracy. Self-enhancement (Jones, 1973) predicts individuals are motivated to maintain their self-esteem. Individuals will therefore recall positive relative to negative feedback and will rate positive feedback as more accurate. Self-consistency theory (Swann, 1985) predicts individuals are motivated to maintain their self-conceptions. The...

Maintained improvement in neurocognitive function in major depressive disorders 6 months after ECT

Directory of Open Access Journals (Sweden)

Christine Mohn

2016-12-01

Full Text Available Both impaired and improved cognitive function after electroconvulsive treatment (ECT in major depressive disorder (MDD patients may occur. We have previously found improved cognitive function 6 weeks after ECT in this group. The aim of this study was to report 6-month follow-up results from the same prospective project monitoring cognitive effects of ECT. Thirty-one patients with major depressive disorder were assessed with the MATRICS Consensus Cognitive Battery (MCCB, the Everyday Memory Questionnaire (EMQ, and the Montgomery-Åsberg Depression Rating Scale (MADRS prior to, 6 weeks, and 6 months after ECT.Compared to baseline, the Speed of Processing, Attention/Vigilance, and Reasoning/Problem Solving test results were significantly improved. The depression score was significantly reduced. There were no changes in subjective memory complaint. There were no significant relationship between the EMQ and the MCCB subtests, but a significant correlation between current depression level and the EMQ.Six months after ECT the cognitive improvement reported at 6 weeks follow-up was maintained and extended. The corresponding decrease in depressive symptoms and stability in subjectively reported memory complaints suggests that the antidepressant effects of ECT do not occur at the expense of cognitive function.

Strengthening of Fe-Mn-Si based shape memory alloys by grain size refinement

International Nuclear Information System (INIS)

Sato, A.; Masuya, T.; Kumai, S.; Inoue, A.

2000-01-01

Degree of the shape memory effect was measured either by bending, tensile and compression tests in the temperature range 77∝300 K. The yield stress increased substantially by the grain size refinement, yet maintaining a good shape memory effect. In addition to usual mentioned slow strain rate tests (about 10 -3 s -1 ), shape deformation was given at high strain rate (10 3 s -1 ) by hammering, in order to induce fine structure. It is also found that the shape memory effect under an opposing force was improved by the high-speed deformation. (orig.)

Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells.

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