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Position-element association has been extensively investigated as a mechanism for serial order memory and has been widely implemented in models of short-term memory. This study examined whether and how the position-element association is learned as a form of long-term knowledge dissociated from other forms of knowledge such as sequence knowledge acquired in the Hebb list repetition paradigm. Laboratory learning experiments demonstrated that repeated exposure to a specific position-element association facilitated subsequent recall of the position-element association with experimental control of other aspects of to-be-learned statistical structure of the artificial phonotactics. The experiments also demonstrated that the positional frequency learning was more gradual than Hebb list learning, suggesting a dissociation of the two forms of learning. Functional roles of these two forms of learning were discussed. [ABSTRACT FROM AUTHOR]

Recent studies of short-term serial order memory have suggested that the maintenance of order information does not involve domain-specific processes. We carried out two dual-task experiments aimed at resolving several ambiguities in those studies. In our experiments, encoding and response of one serial reconstruction task was embedded within encoding and response of a concurrent serial reconstruction task. Order demands in both tasks were independently varied so as to find revealing patterns of interference between the two tasks. In Experiment 1, participants were to maintain and reconstruct the order of a list of verbal materials, while maintaining a list of spatial materials or vice-versa. Increasing the order demands in the outer reconstruction task resulted in small or non-reliable performance decrements in the embedded reconstruction task. Experiment 2 sought to compare these results against two same-domain baseline conditions (two verbal lists or two spatial lists). In all conditions, increasing order demands in the outer task resulted in small or non-reliable performance decrements in the embedded task. However, performance in the embedded tasks was generally lower in the same-domain baseline conditions than in the cross-domain conditions. We argue that the main effect of domain in Experiment 2 indicates the contribution of domain-specific processes to short-term serial order maintenance. In addition, we interpret the failure to find consistent cross-list interference irrespective of domain as indicating the involvement of grouping mechanisms in concurrently performed serial order tasks. [ABSTRACT FROM AUTHOR]

Highlights: [•] A speech-error induction technique revealed principles of serial order control. [•] The technique successfully induced within-word adjacent mora exchanges in Japanese. [•] The exchange errors indicate the temporal distance principle within a word. [•] Induced speech errors exhibited serial position effects. [•] The serial position effects indicate the edge principle within a word. [ABSTRACT FROM AUTHOR]

Abstract: We have shown in [1] that the invariant varieties of periodic points (IVPP) of all periods of some higher dimensional rational maps can be derived, iteratively, from the singularity confinement (SC). We generalize this algorithm, in this paper, to apply to any birational map, which has more invariants than the half of the dimension. [Copyright &y& Elsevier]

Abstract: Although an increasing number of studies on adults have indicated that working memory (WM) contributes to the ability to understand the mental states of others (i.e., theory of mind), the detailed mechanism by which WM contributes to successful reasoning has not previously been revealed. This study shows that WM modulates the degree of attribution of one''s own knowledge to others'' mental states. Participants were asked to read a story twice (Experiment 2) or as carefully as possible (Experiment 3) and to estimate the probability percentages of possible choices for a naive protagonist''s behavior. The participants were then asked to maintain either a two- or seven-letter alphabet string (i.e., a light or heavy WM load, respectively) during the probability estimation but not during the story comprehension. The results showed that compared to the participants with a light WM load, those with a heavy WM load estimated a significantly higher probability of the choice indicating that the protagonist would behave on the basis of a fact that the participants knew but the protagonist did not. This result indicates that WM moderates the extent to which adults attribute their own knowledge to others'' mental states. The role of WM in theory of mind and in heuristic strategy for making probability judgments was then discussed. [Copyright &y& Elsevier]

Abstract: In a series of three experiments, native speakers of Japanese performed serial ordered written recall of visually presented Japanese kanji characters that varied systematically in visual and phonological similarity. Overall effects of phonological similarity were observed for retention of serial order under silent reading in Experiments 1 and 3 and they disappeared in articulatory suppression conditions in Experiments 2 and 3. All three experiments showed main effects of visual similarity even in articulatory suppression conditions in Experiments 2 and 3. This indicated spontaneous use of visual codes in immediate serial recall. It is suggested that any models of serial order memory should incorporate domain specificity. [Copyright &y& Elsevier]

Abstract: 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 span tests. The stimulus order effect is a phenomenon whereby span scores are higher when span lists end with a shorter task than when they end with a longer task. The processing time effect refers to the phenomenon whereby the processing speed slows for the later processing positions in a list in WM span tests when participants have more memory items to remember. Two experiments demonstrated the domain-specific nature of the stimulus order effect, which was observed only when the processing and storage materials were in the same domain (either verbal or visuospatial domains), and the domain-general nature of the processing time effect, which was observed with any combination of processing and storage materials. Although the domain specificity of the stimulus order effect is compatible with the representation-based interference view proposed by Saito and Miyake [Saito, S., & Miyake, A. (2004). On the nature of forgetting and the processing-storage relationship in reading span performance. Journal of Memory and Language, 50, 425–443.], the domain generality of the processing time effect is inconsistent with their account and indicates the involvement of a central bottleneck in WM span performance. [Copyright &y& Elsevier]

Abstract: This study investigated the effects of association values and the influences of prosodic information on Japanese children''s repetition of nonwords with varying association values and with or without pitch accent. Fifteen 3- and 4-year-olds (mean age=4.42 years, range: 3.9–4.9) and nineteen 5- and 6-year-olds (mean age=5.71 years, range: 5.1–6.1) participated in this experiment. Concerning the nonword repetition scores, an effect of association value was found only in older children for consonants of nonwords only, whereas the effect of accent pattern was observed only in young children for both consonants and vowels of nonwords. The occurrences of both effects were connected to differences in the ages of the children and the types of phoneme in nonwords. We interpret these results in the context of the framework of phonological working memory. [Copyright &y& Elsevier]

Four experiments examined the nature of forgetting and the processing–storage relationship during performance on a prevalent working memory task, the reading span test. Using two different presentation paradigms, Experiments 1 and 2 replicated finding that the Short-Final lists, which presented a long sentence first and a short sentence last, led to better recall performance than the reverse-order Long-Final lists. This effect was still obtained when the retention duration for the target words was held constant and the amount of sentence processing required during that interval was varied (Experiment 3). However, the effect disappeared when the retention duration was varied while holding constant the amount of sentence processing required (Experiment 4). These results suggest that the amount of processing activities, not the sheer passage of time, may be the critical factor underlying the sentence order effect, thereby challenging purely time-based explanations of forgetting during reading span performance. In addition, the analysis of reading times (Experiment 1) revealed that the number of memory items had a subtle yet reliable negative effect on reading times, suggesting that the processing and storage requirements of the reading span test are not completely independent. [Copyright &y& Elsevier]

Engaging cognitive control is essential to flexibly adapt to constantly changing environments. However, relatively little is known about how prior task experience impacts on the engagement of cognitive control in novel task environments. We aimed to clarify how individuals learn and transfer the engagement of cognitive control with a focus on the hierarchical and temporal aspects of task knowledge. Highlighting two distinct cognitive control processes, the engagement of cognitive control in advance (proactive control) and in response to conflicts (reactive control), we conducted six preregistered online experiments with both adults (Experiment 1, 3, and 5: N = 71, N = 108, and N = 70) and 9- to 10-year-olds (Experiment 2, 4, 6: N = 69, N = 108, and N = 70). Using two different experimental paradigms, we demonstrated that prior task experience of engaging reactive control makes adults and 9-to 10-year-olds respond in a reactive way in a subsequent similar-structured condition with different stimuli in which proactive control could have been engaged. This indicates that individuals do learn knowledge about the temporal structure of task goal activation and, on occasion, negatively transfer this knowledge. Furthermore, individuals exhibited these negative transfer effects in a similar-structured condition with different task goals and stimuli, indicating that they learn hierarchically-structured task knowledge. The collective findings suggest a new way of understanding how hierarchical and temporal task knowledge influences the engagement of cognitive control and highlight potential mechanisms underlying the near transfer effects observed in cognitive control training. [ABSTRACT FROM AUTHOR]

Abstract: A remarkable cognitive ability in humans is the competency to use a wide variety of different tools. Two cortical regions, the anterior temporal lobes (ATL) and left inferior parietal lobule (IPL), have been proposed to make differential contributions to two kinds of knowledge about tools – function vs. manipulation. We used repetitive transcranial magnetic stimulation (rTMS) and two semantic decision tasks to assess the role of these regions in healthy participants. Participants made semantic decisions about the function (what for) or manipulation (how) of tools used in daily life. The stimulation of ATL resulted in longer responses for the “function” judgments, whilst stimulation of IPL yielded longer responses for the “manipulation” judgments. In line with the neuropsychological literature, these results are discussed within hub-and-spoke framework of semantic memory. [Copyright &y& Elsevier]

Active maintenance of goal representations is an integral part of our mental regulatory processes. Previous developmental studies have highlighted goal neglect, which is the phenomenon caused by a failure to maintain goal representations, and demonstrated developmental changes of the ability to maintain goal representations among preschoolers. Yet, few studies have explored the cognitive mechanisms underlying preschoolers' development of goal maintenance. The first aim of this study was to test whether working memory capacity and inhibitory control contribute to goal maintenance using a paradigm for measuring goal neglect. Moreover, although recent studies have shown that preschoolers recruit lateral prefrontal regions in performing executive functions tasks, they could not specify the neural underpinnings of goal maintenance. Thus, the second aim was to examine whether lateral prefrontal regions played a key role in maintaining goal representations using functional near-infrared spectroscopy. Our results showed that developmental differences in inhibitory control predicted the degree of goal neglect. It was also demonstrated that activation in the right prefrontal region was associated with children's successful avoidance of goal neglect. These findings offer important insights into the cognitive and neural underpinnings of goal maintenance in preschoolers. [ABSTRACT FROM AUTHOR]

Background This paper reports the protocol of a randomised, double-blind, placebo-controlled study to test the efficacy, safety, and tolerability of lubiprostone (LUB) vs. placebo on suppressing gut permeability in non-alcoholic fatty liver disease (NAFLD) patients with constipation. NAFLD, including non-alcoholic steatohepatitis (NASH), is a common chronic liver disorder. Progression is associated with increased gut permeability and gut-derived endotoxins. Most NAFLD/NASH clinical trial drugs aim to improve liver function or systemic metabolism. LUB is a type 2 chloride channel activator used as a laxative for the treatment of patients with constipation. LUB suppresses gut permeability induced by non-steroidal anti-inflammatory drugs in healthy volunteers and lowers blood endotoxin levels. There have been no clinical studies of LUB for NAFLD/NASH patients. Methods The study plans to enrol adult patients (20–85 years, planned enrolment, n  = 150; planned sample size, n  = 120) with NAFLD and constipation, alanine aminotransferase ≥40 IU/L, equivalent steatosis grade ≥1, and equivalent fibrosis stage <4 measured using non-invasive vibration-controlled transient elastography and magnetic resonance imaging. Participants will be randomly allocated into three groups: LUB 12 μg, LUB 24 μg, and a placebo group. Results The primary endpoint will be changes in alanine aminotransferase from baseline at 12 weeks. The main secondary endpoint will be changes in intestinal permeability from baseline at 12 weeks using the lactulose mannitol ratio. Conclusions This study will determine whether LUB improves gut permeability in NAFLD patients with constipation. Trial registration This trial is registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000026635). [ABSTRACT FROM AUTHOR]

Background & Aims The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is affected by epigenetic factors as well as by genetic variation. Methods We performed targeted-bisulfite sequencing to determine the levels of DNA methylation of 4 CpG islands (CpG99, CpG71, CpG26, and CpG101) in the regulatory regions of PNPLA3 , SAMM50 , PARVB variant 1, and PARVB variant 2, respectively. We compared the levels of methylation of DNA in the livers of the first and second sets of patients with mild (fibrosis stages 0 and 1) or advanced (fibrosis stages 2 to 4) NAFLD and in those of patients with mild (F0 to F2) or advanced (F3 and F4) chronic hepatitis C infection. The hepatic mRNA levels of PNPLA3 , SAMM50 , and PARVB were measured using qPCR. Results CpG26, which resides in the regulatory region of PARVB variant 1, was markedly hypomethylated in the livers of patients with advanced NAFLD. Conversely, CpG99 in the regulatory region of PNPLA3 was substantially hypermethylated in these patients. These differences in DNA methylation were replicated in a second set of patients with NAFLD or chronic hepatitis C. PNPLA3 mRNA levels in the liver of the same section of a biopsy specimen used for genomic DNA preparation were lower in patients with advanced NAFLD compared with those with mild NAFLD and correlated inversely with CpG99 methylation in liver DNA. Moreover, the levels of CpG99 methylation and PNPLA3 mRNA were affected by the rs738409 genotype. Conclusions Hypomethylation of CpG26 and hypermethylation of CpG99 may contribute to the severity of fibrosis in patients with NAFLD or chronic hepatitis C infection. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named 'BioKnife'), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-κB (NF-κB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GM), the most frequent primary malignant brain tumor, is highly invasive due to the expression of proteases, including urokinase-type plasminogen activator (uPA). Here, we show the potential of our new and powerful recombinant Sendai virus (rSeV) showing uPA-specific cell-to-cell fusion activity [rSeV/dMFct14 (uPA2), named 'BioKnife'] for GM treatment, an effect that was synergistically enhanced by arming BioKnife with the interferon-β (IFN-β) gene. BioKnife killed human GM cell lines efficiently in a uPA-dependent fashion, and this killing was prevented by PA inhibitor-1. Rat gliosarcoma 9L cells expressing both uPA and its functional receptor uPAR (9L-L/R) exhibited high uPA activity on the cellular surface and were highly susceptible to BioKnife. Although parent 9L cells (9L-P) were resistant to BioKnife and to BioKnife expressing IFN-β (BioKnife-IFNβ), cell-cell fusion of 9L-L/R strongly facilitated the expression of IFN-β, and in turn, IFN-β significantly accelerated the fusion activity of BioKnife. A similar synergy was seen in a rat orthotopic brain GM model with 9L-L/R in vivo; therefore, these results suggest that BioKnife-IFNβ may have significant potential to improve the survival of GM patients in a clinical setting. [ABSTRACT FROM AUTHOR]

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an α-glucosidase inhibitor. Methods: C57BL/6J mice were divided into five treatment groups as follows: basal diet (BD), high-fat diet (HFD) only, HFD with EZ (5mg/kg/day), HFD with AC (100mg/kg/day), and HFD with both EZ and AC for 24 weeks. Results: Long-term combination therapy with EZ and AC significantly reduced steatosis, inflammation and fibrosis in the liver, compared with long-term monotherapy with either drug, in an HFD-induced NAFLD mouse model; the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-α1 (PPAR-α1) in the liver, compared with either monotherapy, which may have led to the improvement in lipid metabolic disorder seen in this model. Conclusions: Combination therapy with EZ and AC for 24 weeks improved the histopathological findings in a mouse model of NAFLD. [Copyright &y& Elsevier]

Background/Aims: The aim of this study is to clarify the differences of host immune responses between acute self-limited and chronic persistent hepatitis B virus (HBV) infections by quantitative and qualitative analysis of HLA-A*2402-restricted HBV-specific CD8+ T cells.Methods: HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HBV were analyzed by flow cytometry using two HLA-A*2402–HBV peptide tetrameric complexes.Results: High numbers of HBV-specific CD8+ T cells were detected in acute phase PBMCs from most individuals with acute HBV infection while the number of these cells was greatly reduced in recovery phase PBMCs. HBV-specific CD8+ T cells were not detected in PBMCs from individuals with chronic HBV infection except for one patient during acute exacerbation. HBV-specific CD8+ T cells were induced by in vitro peptide stimulation in PBMCs from chronic HBV carriers with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. CD28CD45RA phenotype analysis showed that HBV-specific CD8+ T cells in acute phase PBMCs predominantly express a memory T cell phenotype.Conclusions: HBV-specific memory CD8+ T cells may play a crucial role in complete clearance of HBV from patients with acute HBV hepatitis. [Copyright &y& Elsevier]