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Recognition memory for studied words is determined by cortical activation differences at encoding but not during retrieval.

Prior work has shown that when responses to incidentally encoded words are sorted, subsequently remembered words elicit greater left prefrontal BOLD signal change relative to forgotten words. Similarly, low-frequency words elicit greater activation than high-frequency words in the same left prefrontal regions, contributing to their better subsequent memorability. This study examined the relative contribution of encoding and retrieval processes to the correct recognition of target words. A mixture of high- and low-frequency words was incidentally encoded. Scanning was performed at encoding as well as during retrieval. During encoding, greater activation in the left prefrontal and anterior cingulate regions predicted a higher proportion of hits for low-frequency words. However, data acquired during recognition showed that word frequency did not modulate activation in any of the areas tracking successful recognition. This result demonstrates that under some circumstances, the recognition of studied words is determined purely by processes that are active during encoding. In contrast to the finding for hits, activation associated with correctly rejected foils was modulated by word frequency, being higher for high-frequency words in the left lateral parietal and anterior prefrontal regions. These findings were replicated in two further experiments, one in which the number of test items at recognition was doubled and another where encoding strength for high-frequency words was varied (once vs. 10 times). These results indicate that word frequency modulates activity in the left lateral parietal and anterior prefrontal regions contingent on whether the item involved is correctly recognized as a target or a foil. This observation is consistent with a dual process account of episodic memory.

Adult↗

Functional connectivity reveals load dependent neural systems underlying encoding and maintenance in verbal working memory.

One of the main challenges in working memory research has been to understand the degree of separation and overlap between the neural systems involved in encoding and maintenance. In the current study we used a variable load version of the Sternberg item recognition test (two, four, six, or eight letters) and a functional connectivity method based on constrained principal component analysis to extract load-dependent neural systems underlying encoding and maintenance, and to characterize their anatomical overlap and functional interaction. Based on the pattern of functional connectivity, constrained principal component analysis identified a load-dependent encoding system comprising bilateral occipital (Brodmann's area (BA) 17, 18), bilateral superior parietal (BA 7), bilateral dorsolateral prefrontal (BA 46), and dorsal anterior cingulate (BA 24, 32) regions. For maintenance, in contrast, constrained principal component analysis identified a system that was characterized by both load-dependent increases and decreases in activation. The structures in this system jointly activated by maintenance load involved left posterior parietal (BA 40), left inferior prefrontal (BA 44), left premotor and supplementary motor areas (BA 6), and dorsal cingulate regions (BA 24, 32), while the regions displaying maintenance-load-dependent activity decreases involved bilateral occipital (BA 17, 18), posterior cingulate (BA 23) and rostral anterior cingulate/orbitofrontal (BA 10, 11, 32) regions. The correlation between the encoding and maintenance systems was strong and negative (Pearson's r = -.55), indicting that some regions important for visual processing during encoding displayed reduced activity during maintenance, while subvocal rehearsal and phonological storage regions important for maintenance showed a reduction in activity during encoding. In summary, our analyses suggest that separable and complementary subsystems underlie encoding and maintenance in verbal working memory, and they demonstrate how constrained principal component analysis can be employed to characterize neuronal systems and their functional contributions to higher-level cognition.

Adolescent↗

Differences of cerebral activation between superior and inferior learners during motor sequence encoding and retrieval.

Cerebral activation during memory encoding and retrieval might depend on subjects' learning capacity, either by corresponding to better performance in superior learners or by reflecting increased effort in inferior learners. To investigate these alternative hypotheses, the study compared cerebral activation during encoding and retrieval of a motor sequence in groups of subjects with superior and inferior learning performances. Ten healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a motor sequence encoding paradigm (i.e. finger tapping sequence) and a retrieval paradigm (i.e. reproduction of the learned sequence). Subjects were divided into superior and inferior learners according to the correctness of sequence reproduction during retrieval. During encoding, there was strong bilateral activation in the middle frontal gyrus, the supplementary motor area (SMA), the lateral parietal lobe and the cerebellum. During retrieval, again strong activation was found in identical areas of the prefrontal cortex, the parietal lobe and the cerebellum. During encoding, inferior learners showed more left-sided activations in the left middle frontal and inferior parietal gyri. Superior learners showed increased activation in the corresponding right-sided brain areas during encoding as well as during retrieval. Differences of cerebral activations in the prefrontal and parietal cortex during encoding and retrieval were found to be related to retrieval performance, i.e. success and effort. Further intervention studies are needed to assess whether these interindividual differences are the cause or the consequence of differences in memory performance.

Achievement↗

Enhanced functional recovery from spinal cord injury following intrathecal or intramuscular administration of poliovirus replicons encoding IL-10.

Poliovirus-based vectors (replicons) have been shown to maintain the in vitro tropism of poliovirus for motor neurons of the CNS. To determine if replicons could be effective for delivery of potentially beneficial proteins to the CNS, we have constructed and characterized a replicon encoding IL-10. IL-10 was rapidly produced in tissue culture cells following in vitro infection with replicons encoding IL-10. Intrathecal inoculation of replicons encoding IL-10 into the non-injured CNS of mice transgenic for the poliovirus receptor resulted in expression of IL-10 within motor neurons at 24-48 h post-inoculation, which subsided by 72-96 h post-inoculation. Single intrathecal or intramuscular injections of replicons were given following spinal cord trauma. Animals receiving replicons encoding IL-10 demonstrated a greater functional recovery in the first 24 h after injury that was maintained throughout the testing period. Compared to animals given replicons encoding gfp, CNS tissue from animals given replicons encoding IL-10 revealed extensive expression of IL-10 from astrocytes around the CNS lesion during the first week following injury. The expression of IL-10 from astrocytes also correlated with more resting microglia as opposed to the rounded activated microglia seen in animals given replicons encoding gfp. Results of these studies establish that replicons can be used to express biologically active molecules in motor neurons of the CNS and these biologically active molecules can have a direct effect on the CNS or induce a cascade of molecules that can influence the cellular composition and activation state of cells within the CNS.

Animals↗

The effects of divided attention during encoding and retrieval on amnesic patients' memory performance.

This study examined the effect of divided attention during encoding or retrieval on primary (recall) or secondary (button-pressing) task performance by amnesic patients and control subjects. Experiment 1 demonstrated that control subjects' recall was affected by divided attention during encoding but not during retrieval, while the amnesic patients' recall remained at the same low level for all conditions. Both groups showed a reduction in rate of button-pressing during encoding relative to their baseline levels and a further reduction during the retrieval interval. In Experiment 2, five learning trials, instead of just one, were presented. This acted to increase all subjects' recall and also had the effect of producing superior recall following free encoding relative to encoding during divided attention for the amnesic patients as well as for the control subjects. Button-pressing performance during the encoding interval increased to baseline for both groups during the five presentation trials, but there was no increase in the rate of button-pressing during the retrieval interval. Amnesic patients' normal attention to the primary task during encoding and retrieval was felt to have several implications for future neuroimaging tasks with these patients.

Aged↗

Localisation of Globodera pallida FMRFamide-related peptide encoding genes using in situ hybridisation.

The present study employed an in situ hybridisation technique to detect the expression of a number of FMRFamide-like peptide encoding (flp) genes, previously identified from Globodera pallida, in whole-mount preparations of the J(2) stage of this worm. gpflp-1, encoding the FMRFamide-related peptide (FaRP) KSAYMRFamide, was expressed in neurones associated with the circumpharyngeal nerve ring and specifically in a number of cell bodies in the lumbar ganglia of the perianal nerve ring. The lumbar ganglia and pre-anal ganglia along with the BDU neurones and a number of cells in the retrovesicular ganglion were observed to express gpflp-2, encoding KNKFEFIRFamide. gpflp-3 (encoding KHEYLRFamide) expression was localised to the anterior ganglion and a number of paired cells posterior to the circumpharyngeal nerve ring whilst expression of gpflp-4, encoding a number of -P(G/Q)VLRFamides, was localised to the retrovesicular ganglion. No expression of gpflp-5 was observed. Identification of the reactive cells has implicated distinct roles for the FaRPs encoded on these genes in regulation of both dorsal and ventral body wall muscles, the musculature of the vulva and in the function of a number of sensory structures in both the head and tail of G. pallida. Comparison with the expression patterns of analogous genes in Caenorhabditis elegans suggests that, whilst some of the encoded peptides are conserved between nematode species, their functions therein are distinct. Furthermore, the expression of some of these genes in a number of interneurones supports the idea that FaRPs fulfil neuromodulatory as well as neurotransmitter roles.

Amino Acid Sequence↗

The effect of encoding manipulations on neural correlates of episodic retrieval.

The present experiments investigated whether the neural correlates of explicit (conscious) retrieval from episodic memory vary qualitatively according to conditions at encoding, as is predicted by current views of the neural basis of memory retrieval. Event-related potential (ERP) correlates of word stem (e.g. MOT_) cued recall were compared for items studied under different encoding conditions. In Experiment 1, encoding was either 'shallow' or 'deep' whereas in Experiment 2 the presentation modality of the study items was either visual or auditory. In both experiments robust ERP memory effects were observed for stems completed with explicitly retrieved items from each encoding condition. The effects varied in their magnitude, such that they were largest when elicited by the more memorable class of item in each experiment. The scalp distributions of the effects did not differ according to encoding condition, a finding which offers no support for the view that retrieval involves the literal reinstatement of neural activity engaged at the time of encoding. The findings instead point to the existence of a set of retrieval operations that are engaged regardless of the conditions under which retrieved information is encoded.

Adolescent↗

A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA species by alternative polyadenylation, mRNA splicing and transcription initiation.

Human TRAF-3 is a signaling molecule that interacts with the cytoplasmic tails of CD40 and other TNF-receptor family members. TRAF-3 mRNA is expressed as two major classes of approximately 2 and 8 kb and a number of TRAF-3 encoding cDNA clones differ in discrete gene segments. Because this variety of mRNA species could result from mRNA processing events and/or multiple genes, the structure and localization of TRAF-3 encoding gene elements were determined. FISH and radiation hybrid mapping demonstrated that TRAF-3 is located at chromosome 14q32.3, approximately 1 Mb centromeric to the Ig heavy chain gene complex. Physical mapping of four overlapping genomic PAC clones established that TRAF-3 transcripts are encoded by a single gene, comprised of 13 exons and spanning 130 kb. Alternative polyadenylation in the mRNA segment encoded by exon 12 accounts for the difference between the 2 kb and the 8 kb classes of transcripts. Alternative mRNA splicing in the coding region (encoded by exons 3-12) generates transcripts which delete exons 8 (75 nt), 7+8 (156 nt) or 8+9 (168 nt) and that encode distinct protein isoforms (delta25, delta52 and delta56 aa, respectively). Alternative splicing of exon 2 (139 nt) and alternative transcriptional initiation result in mRNA species with distinct 5'UTRs. Together, these data indicate that a single TRAF-3 gene encodes a variety of mRNA species by a combination of alternative polyadenylation, alternative mRNA splicing and/or alternative initiation.

Alternative Splicing↗

Introns resolve the conflict between base order-dependent stem-loop potential and the encoding of RNA or protein: further evidence from overlapping genes.

Many eukaryotic genes are split into exons and introns, the latter being removed post-transcriptionally so that only exon sequences appear in cytoplasmic RNAs. Since introns appear in both protein-encoding RNAs and non-protein-coding RNAs, they interrupt genetic information per se, not just protein-encoding information. A DNA sequence has the potential to carry more than one type of genetic information, but different types may conflict. Thus, it has been proposed that introns arose because sequences were unable to contain concomitantly complete information for the encoding both of stem-loops and of cytoplasmic products (protein and/or RNA). Stem-loop potential is held to be selectively advantageous since it promotes the recombination-dependent correction of genetic errors. Stem-loop potential, the best local measure of which is base order-dependent stem-loop potential, tends to be less in exons than in introns. This is particularly evident in genes evolving rapidly under positive Darwinian selection, where the protein-encoding function is dominant. Evidence is now presented that the rare regions where genes overlap also impose excessive encoding demands so that the concomitant coding of base order-dependent stem-loop potential is decreased. Our results are consistent with the hypothesis that sequences with high stem-loop potential arose in the early 'RNA world'. Ancestors of modern genes would have entered this world when sequences (exons) encoding cytoplasmic products, were interspersed with sequences (introns) encoding selectively advantageous stem-loops. Purine-loading pressure would also have favoured intron formation.

Animals↗

The histone-like C-terminal extension in ribosomal protein S6 in Aedes and Anopheles mosquitoes is encoded within the distal portion of exon 3.

In eukaryotic cells, ribosomal protein S6 (RPS6) is the major phosphorylated protein on the small ribosomal subunit. In the mosquitoes Aedes aegypti and Aedes albopictus, the cDNA encoding RPS6 contains 300 additional nucleotides, relative to the Drosophila homolog. The additional sequence encodes a 100-amino acid, lysine-rich C-terminal extension of the RPS6 protein with 42-49% identity to histone H1 proteins from the chicken and other multicellular organisms. Using mass spectrometry we now show that the C-terminal extension predicted by the cDNA is present on RPS6 protein isolated from ribosomal subunits purified from Ae. albopictus cells. To expand our analysis beyond the genus Aedes, we cloned the rpS6 cDNA from an Anopheles stephensi mosquito cell line. The cDNA also encoded a lysine-rich C-terminal extension. However, in An. stephensi rpS6 the extension was approximately 70 amino acids longer than that in Ae. albopictus, and at the nucleotide level, it most closely resembled histone H1 proteins from the unicellular eukaryotes Leishmania and Chlamydomonas, and the bacterium Bordetella pertussis. To examine how the histone-like C-terminal extension is encoded in the genome, we used PCR-based approaches to obtain the genomic DNA sequence encoding Ae. aegypti and Ae. albopictus rpS6. The sequence encoding the histone-like C-terminal extension was contiguous with upstream coding sequence within a single open reading frame in Exon 3, indicating that the lysine-rich extension in mosquito RPS6 is not the result of an aberrant splicing event. An in silico investigation of the Anopheles gambiae genome based on the cDNA sequence from An. stephensi allowed us to map the An. gambiae gene to chromosome 2R, to deduce its exon-intron organization, and to confirm that Exon 3 encodes a C-terminal histone-like extension. Because the C-terminal extension is absent from Drosophila melanogaster, we examined a partial cDNA clone from a Psychodid fly, which shares a relatively recent common ancestor with the mosquitoes. The absence of the C-terminal extension in the Psychodid rpS6 cDNA suggests that the unusual RPS6 structure is restricted to a relatively small group of flies in the Nematocera.

Aedes↗

cDNAs encoding large venom proteins from the parasitoid wasp Pimpla hypochondriaca identified by random sequence analysis.

Venom from the parasitoid wasp Pimpla hypochondriaca contains numerous proteins, has potent in vitro anti-haemocytic properties, and disrupts host encapsulation responses. By sequencing 500 cDNAs randomly isolated from a venom gland library, we have identified 60 clones that encode proteins containing potential secretory signal sequences. To identify cDNAs encoding particular venom proteins, N-terminal amino acid sequences were determined for large (>30 kDa) venom proteins that had been separated using a combination of gel filtration and SDS-PAGE. We describe five of these cDNAs, which encoded residues that matched with the N-terminal sequences of previously undescribed venom proteins. cDNAs vpr1 and vpr3 encoded related proteins of approximately 32 kDa that were found in widely different fractions of gel filtration-separated venom. Neither vpr1 nor vpr3 were closely related to any other protein in the GenBank database, suggesting that they are highly specialised venom components. vpr2 encoded a 57-kDa polypeptide that was similar to a Drosophila protein, of unknown function, which lacks a signal sequence. A fourth clone, tre1, encoded a 61-kDa protein with extensive sequence similarity to trehalases. The 76-kDa sequence encoded by lac1 contained three regions which were very similar to histidine-rich copper-binding motifs, and could be aligned with the laccase from the fungus Coprinus cinereus. This study represents a significant step towards a holistic view of the molecular composition of a parasitoid wasp venom.

Amino Acid Sequence↗

Memory in multiple sclerosis: contextual encoding deficits.

Long-term memory (LTM) is one of the diverse cognitive functions adversely affected by multiple sclerosis (MS). The LTM deficits have often been attributed to failure of retrieval, whereas encoding processes are presumed intact. However, support for this view comes primarily from studies in which encoding and retrieval operations were not investigated systematically. In the current study, we used an encoding specificity paradigm to examine the robustness of encoding in MS and to specifically evaluate the impact of the disease on contextual memory. We hypothesized that persons with MS would exhibit a selective impairment in retrieving items from LTM when required to generate new cue-target associations at encoding, but not when cues held a strong preexisting relationship to the targets. The findings supported the hypotheses. We conclude that the mnemonic deficits associated with MS affect both encoding and retrieval. Specifically, problems with binding of contextual information at encoding impair effective retrieval of memories. Nonetheless, access to these memories can be gained through preexisting associations organized in the semantic network.

Adult↗

Effects of encoding the perceptual features of pictures on memory.

Four experiments investigated whether manipulations of type of encoding affects the likelihood of remembering pictures' visual details and their names. Using an incidental learning procedures, subjects were led to make judgments about pictures' colors, spatial orientations, or appropriateness in a scene. The results indicate that the nature of the memory test influences the effectiveness of different encoding conditions. Recall and recognition of pictures' names were best after subjects judged scene encodings, second best after they judged orientation, and poorest after they judged color. However, the results for the recognition of pictures' visual details were quite different. Analyses of d' suggested that type of encoding task had no effect on memory for visual details, whereas analysis of Pr (hit rate minus false-alarm rate) suggested that memory for visual details was impaired by conceptual encoding (judging the appropriateness of a picture in a scene). The results of one experiment demonstrated that these findings were not produced by variation in distinctiveness of the encoding questions. This pattern of findings implies that conceptual encoding facilitates retention of the names of the pictures at the cost of some loss in the ability to retain specific visual details.

Adult↗

Hierarchical encoding of behavior: translating perception into action.

People encode goal-directed behaviors, such as assembling an object, by segmenting them into discrete actions, organized as goal-subgoal hierarchies. Does hierarchical encoding contribute to observational learning? Participants in 3 experiments segmented an object assembly task into coarse and fine units of action and later performed it themselves. Hierarchical encoding, measured by segmentation patterns, correlated with more accurate and more hierarchically structured performance of the later assembly task. Furthermore, hierarchical encoding increased when participants (a) segmented coarse units first, (b) explicitly looked for hierarchical structure, and (c) described actions while segmenting them. Improving hierarchical encoding always led to improvements in learning, as well as a surprising shift toward encoding and executing actions from the actor's spatial perspective instead of the participants' own. Hierarchical encoding facilitates observational learning by organizing perceived actions into a representation that can serve as an action plan.

Awareness↗

Why distinctive information reduces false memories: evidence for both impoverished relational-encoding and distinctiveness heuristic accounts.

Two accounts explain why studying pictures reduces false memories within the Deese-Roediger-McDermott paradigm (J. Deese, 1959; H. L. Roediger & K. B. McDermott, 1995). The impoverished relational-encoding account suggests that studying pictures interferes with the encoding of relational information, which is the primary basis for false memories in this paradigm. Alternatively, the distinctiveness heuristic assumes that critical lures are actively withheld by the use of a retrieval strategy. When participants were given inclusion recall instructions to report studied items as well as related items, they still reported critical lures less often after picture encoding than they did after word encoding. As the impoverished relational-encoding account suggests, critical lures appear less likely to come to mind after picture encoding than they do after word encoding. However, the results from a postrecall recognition test provide evidence in favor of the distinctiveness heuristic.

Adult↗

TIR-X and TIR-NBS proteins: two new families related to disease resistance TIR-NBS-LRR proteins encoded in Arabidopsis and other plant genomes.

The Toll/interleukin-1 receptor (TIR) domain is found in one of the two large families of homologues of plant disease resistance proteins (R proteins) in Arabidopsis and other dicotyledonous plants. In addition to these TIR-NBS-LRR (TNL) R proteins, we identified two families of TIR-containing proteins encoded in the Arabidopsis Col-0 genome. The TIR-X (TX) family of proteins lacks both the nucleotide-binding site (NBS) and the leucine rich repeats (LRRs) that are characteristic of the R proteins, while the TIR-NBS (TN) proteins contain much of the NBS, but lack the LRR. In Col-0, the TX family is encoded by 27 genes and three pseudogenes; the TN family is encoded by 20 genes and one pseudogene. Using massively parallel signature sequencing (MPSS), expression was detected at low levels for approximately 85% of the TN-encoding genes. Expression was detected for only approximately 40% of the TX-encoding genes, again at low levels. Physical map data and phylogenetic analysis indicated that multiple genomic duplication events have increased the numbers of TX and TN genes in Arabidopsis. Genes encoding TX, TN and TNL proteins were demonstrated in conifers; TX and TN genes are present in very low numbers in grass genomes. The expression, prevalence, and diversity of TX and TN genes suggests that these genes encode functional proteins rather than resulting from degradation or deletions of TNL genes. These TX and TN proteins could be plant analogues of small TIR-adapter proteins that function in mammalian innate immune responses such as MyD88 and Mal.

Amino Acid Sequence↗

Quantum control mechanism analysis through field based Hamiltonian encoding.

Optimal control of quantum dynamics in the laboratory is proving to be increasingly successful. The control fields can be complex, and the mechanisms by which they operate have often remained obscure. Hamiltonian encoding (HE) has been proposed as a method for understanding mechanisms in quantum dynamics. In this context mechanism is defined in terms of the dominant quantum pathways leading to the final state of the controlled system. HE operates by encoding a special modulation into the Hamiltonian and decoding its signature in the dynamics to determine the dominant pathway amplitudes. Earlier work encoded the modulation directly into the Hamiltonian operators. This present work introduces the alternative scheme of field based HE, where the modulation is encoded into the control field and not directly into the Hamiltonian operators. This distinct form of modulation yields a new perspective on mechanism and is computationally faster than the earlier approach. Field based encoding is also an important step towards a laboratory based algorithm for HE as it is the only form of encoding that may be experimentally executed. HE is also extended to cover systems with noise and uncertainty and finally, a hierarchical algorithm is introduced to reveal mechanism in a stepwise fashion of ever increasing detail as desired. This new hierarchical algorithm is an improvement over earlier approaches to HE where the entire mechanism was determined in one stroke. The improvement comes from the use of less complex modulation schemes, which leads to fewer evaluations of Schrodinger's equation. A number of simulations are presented on simple systems to illustrate the new field based encoding technique for mechanism assessment.

Journal Article↗

[Leu5]enkephalin-encoding sequences are targets for a specific DNA-binding factor.

A DNA-binding factor with high affinity and specificity for the [Leu5]enkephalin-encoding sequences in the prodynorphin and proenkephalin genes has been characterized. The factor has the highest affinity for the [Leu5]-enkephalin-encoding sequence in the dynorphin B-encoding region of the prodynorphin gene, has relatively high affinity for other [Leu5]enkephalin-encoding sequences in the prodynorphin and proenkephalin genes, but has no apparent affinity for similar DNA sequences coding for [Met5]-enkephalin in the prodynorphin or proopiomelanocortin genes. The factor has been named [Leu5]enkephalin-encoding sequence DNA-binding factor (LEF). LEF has a nuclear localization and is composed of three subunits of about 60, 70, and 95 kDa, respectively. The highest levels were observed in rat testis, cerebellum, and spleen and were generally higher in late embryonal compared to newborn or adult animals. LEF activity was also recorded in human clonal tumor cell lines. LEF inhibited the transcription of reporter genes in artificial gene constructs where a [Leu5]enkephalin-encoding DNA fragment had been inserted between the transcription initiation site and the coding region of the reporter genes. These observations suggest that the [Leu5]enkephalin-encoding sequences in the prodynorphin and proenkephalin genes also have regulatory functions realized through interaction with a specific DNA-binding factor.

Aging↗