392 research outputs found

    Effects of daytime food intake on memory consolidation during sleep or sleep deprivation.

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    Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin), the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD) could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory) and a list of semantically associated word pairs (declarative memory). After the learning period, standardized meals were administered, equaling either ∼50% or ∼150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG). Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also sensitive to the fluctuations in the energy state of the body

    Multiple Chemical Sensitivities Following Intolerance to Azo Dye in Sweets in a 5-year-old Girl

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    ABSTRACTBackgroundCases of multiple chemical sensitivities (MCS) have been reported predominantly in adult patients, but pediatric cases have rarely been reported.MethodsWe present a 5-year-old girl who suffered from recurrent reactions accompanied by urticaria, angioedema, headaches, dyspnea, loss of consciousness, and abdominal pain that were not eradicated, but were instead exacerbated, by various treatments with antihistamines and intravenous corticosteroids. Her diet diary revealed that symptoms occurred after ingestion of colorful sweets such as candies and jellybeans. Open challenge tests with food additives and nonsteroidal anti-inflammatory drugs (NSAIDs) were performed after elimination of these items. Skin prick tests using additives and NSAIDs, which were dissolved in saline, and prick-prick tests using candies and jellybeans, were carried out.ResultsOpen challenge tests with Tartrazine, aspirin and acetaminophen were positive, whereas skin prick tests using additives and NSAIDs and prick-prick tests using candies and jellybeans were all negative. Consequently, intolerance to azo dyes and NSAIDs such as aspirin was diagnosed. However, she appeared to react to multiple chemical odors such as those of cigarette smoke, disinfectant, detergent, cleaning compounds, perfume, and hairdressing, all while avoiding additives and NSAIDs. On the basis of her history and the neuro-ophthalmological abnormalities, a diagnosis of severe MCS was made and she was prescribed multiple vitamins and glutathione.ConclusionsThe present results suggest that in pediatric MCS, food and drug additives containing azo dyes might play important roles as elicitors

    Synoviolin is a Novel Pathogenic Factor of Arthropathy and Chronic Inflammation

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    Inflammation is classical pathogenic concept, but still very crucial for understanding many disorders even in twenty-first century. The purpose of inflammation is to eliminate the damaged tissues and to initiate tissue repair. By contrast, chronic inflammation leads to intractable diseases, including rheumatoid arthritis (RA), atherosclerosis, cancer, diabetes mellitus, and obesity. We recently cloned synoviolin, an E3 ubiquitin ligase, as an overexpressing molecule in rheumatoid synovium and has been verifying its critical roles in RA, inflammatory cytokine signaling, and fibrosis. Moreover, synoviolin-deficient mice exhibited severe anemia caused by defective nursing activity of erythrocytes in the fetal liver. This phenomenon resembles of RA that accelerates nursing activity. Our data indicate a close relationship between embryogenesis and RA. We successfully discovered synoviolin inhibitors, LS-101 and LS-102. These drugs have inhibitory effects to synoviolin in vitro and in vivo. We are now proceeding with the optimization of small compounds, and we hope our research will lead to the development of a new therapy for RA and fibrosis and other synoviolin-related diseases

    Ongoing Rapid Evolution of a Post-Y Region Revealed by Chromosome-Scale Genome Assembly of a Hexaploid Monoecious Persimmon (Diospyros kaki)

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    Plants have evolved sex chromosomes independently in many lineages, and loss of separate sexes can also occur. In this study, we assembled a monoecious recently hexaploidized persimmon (Diospyros kaki), in which the Y chromosome has lost the maleness-determining function. Comparative genomic analysis of D. kaki and its dioecious relatives uncovered the evolutionary process by which the nonfunctional Y chromosome (or Y-monoecy) was derived, which involved silencing of the sex-determining gene, OGI, approximately 2 million years ago. Analyses of the entire X and Y-monoecy chromosomes suggested that D. kaki's nonfunctional male-specific region of the Y chromosome (MSY), which we call a post-MSY, has conserved some characteristics of the original functional MSY. Specifically, comparing the functional MSY in Diospyros lotus and the nonfunctional "post-MSY" in D. kaki indicated that both have been rapidly rearranged, mainly via ongoing transposable element bursts, resembling structural changes often detected in Y-linked regions, some of which can enlarge the nonrecombining regions. The recent evolution of the post-MSY (and possibly also MSYs in dioecious Diospyros species) therefore probably reflects these regions' ancestral location in a pericentromeric region, rather than the presence of male-determining genes and/or genes controlling sexually dimorphic traits

    Molecular regulation of starch metabolism

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    Starch is the second most abundant biomass next to cellulose and composed of amylopectin, a highly branched glucan, and amylose, an essentially linear glucan. The former and the latter glucans usually account for approximately 65–85% and 15–35% of the total starch, respectively. During the last three decades the basic scheme of starch biosynthesis has been established based on numerous biochemical, genetic, and molecular biological approaches worldwide using a variety of higher plants and algae. It is well known that after the synthesis of ADPglucose by ADPglucose pyrophosphorylase (AGPase), amylopectin’s fne structure is formed by concerted actions of multiple isozymes from three classes of enzymes, starch synthase (SS), starch branching enzyme (BE), and starch debranching enzyme (DBE), and that amylose is synthesized by mainly granule-bound SS (GBSS). In addition to the roles of starch biosynthetic isozymes, the contributions of α-glucan phosphorylase, α-glucan, water dikinase, phosphoglucan, water dikinase, pyruvate, phosphate dikinase, α-amylase, and carbohydrate-binding modules have been documented. Information on the whole genome sequence and omics analyses are available in main plant species. All these results revealed the roles of key biosynthetic isozymes of SS, GBSS, BE, and DBE and subunits of AGPase to starch biosynthesis, and presently we know to what extent the fne structure of starch molecules and the internal structure and physicochemical properties of starch granules as well as starch amounts can be modifed in accord with the activity levels of these isozymes and subunits. However, in spite of numerous past investigations, the regulation of the network of enzymatic reactions has not been fully understood. To resolve the complex mechanisms, we need to examine several topics such as redundancy and supplementary functions of multiple isozymes, enzymeenzyme interaction(s), and regulatory factors controlling catalytic and specific activities of individual isozymes, temporal and spatial co-expression of multiple isozymes, post-translational modifcation of enzymatic capacities such as phosphorylation, glycosylation, and redox state. There are still lots of uncertainties in the understanding of the initiation of starch biosynthesis.Fil: Nakamura, Yasunori. Akita Prefectural University; JapónFil: Steup, Martin. Universitat Potsdam; AlemaniaFil: Colleoni, Christophe. Université de Lille; FranciaFil: Iglesias, Alberto Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Bao, Jinsong. Zhejiang University; ChinaFil: Fujita, Naoko. University of Guelph; CanadáFil: Tetlow, Ian. University of Guelph; Canad

    Molecular Mechanism Underlying Derepressed Male Production in Hexaploid Persimmon

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    Sex expression in plants is often flexible and contributes to the maintenance of genetic diversity within a species. In diploid persimmons (the genus Diospyros), the sexuality is controlled by the Y chromosome-encoded small-RNA gene, OGI, and its autosomal counterpart, MeGI. Hexaploid Oriental persimmon (Diospyros kaki) evolved more flexible sex expression, where genetically male individuals carrying OGI can produce both male and female flowers (monoecy). This is due to (semi-)inactivation of OGI by the Kali-SINE retrotransposon insertion on the promoter region and the resultant DNA methylations. Instead, flower sex determination in Oriental persimmon is also dependent on DNA methylation states of MeGI. Here, we focused on a cultivar, Kumemaru, which shows stable male flower production. Our results demonstrated that cv. Kumemaru carries OGI with Kali-SINE, which was highly methylated as well as in other monoecious cultivars; nevertheless, OGI gene could have a basal expression level. Transcriptomic analysis between cv. Kumemaru and 14 cultivars that predominantly produce female flowers showed differentially expressed genes (DEGs) specific to cv. Kumemaru, which is mainly involved in stress responses. Co-expression gene networks focusing on the DEGs also suggested the involvement of stress signals, mainly via gibberellin (GA), salicylic acid (SA), and especially jasmonic acid (JA) signal pathways. We also identified potential regulators of this co-expression module, represented by the TCP4 transcription factor. Furthermore, we attempted to identify cv. Kumemaru-specific transcript polymorphisms potentially contributing to derepressed OGI expression by cataloging subsequences (k-mers) in the transcriptomic reads from cv. Kumemaru and the other 14 female cultivars. Overall, although the direct genetic factor to activate OGI remains to be solved, our results implied the involvement of stress signals in the release of silenced OGI and the resultant continuous male production

    Rice Mutants Lacking Starch Synthase I or Branching Enzyme IIb Activity Altered Starch Biosynthetic Protein Complexes

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    Amylopectin, the major component of starch, is synthesized by synergistic activity of multiple isozymes of starch synthases (SSs) and branching enzymes (BEs). The frequency and length of amylopectin branches determine the functionality of starch. In the rice endosperm, BEIIb generates short side chains of amylopectin and SSI elongates those branches, which can be further elongated by SSIIa. Absence of these enzymes greatly affects amylopectin structure. SSI, SSIIa, and BEIIb associate with each other and with other starch biosynthetic enzymes although SSIIa is low activity in japonica rice. The aim of the current study was to understand how the activity of starch biosynthetic enzyme complexes is compensated in the absence of SSI or BEIIb, and whether the compensatory effects are different in the absence of BEIIb or in the presence of inactive BEIIb. Interactions between starch biosynthetic enzymes were analyzed using one ss1 null mutant and two be2b japonica rice mutants (a mutant producing inactive BEIIb and a mutant that did not produce BEIIb). Soluble proteins extracted from the developing rice seeds were separated by gel filtration chromatography. In the absence of BEIIb activity, BEIIa was eluted in a broad molecular weight range (60–700 kDa). BEIIa in the wild-type was eluted with a mass below 300 kDa. Further, majority of inactive BEIIb co-eluted with SSI, SSIIa, and BEI, in a mass fraction over 700 kDa, whereas only small amounts of these isozymes were found in the wild-type. Compared with the be2b lines, the ss1 mutant showed subtle differences in protein profiles, but the amounts of SSIIa, SSIVb, and BEI in the over-700–kDa fraction were elevated. Immunoprecipitation revealed reduced association of SSIIa and BEIIb in the ss1 mutant, while the association of BEIIb with SSI, SSIIa, SSIVb, BEI, and BEIIa were more pronounced in the be2b mutant that produced inactive BEIIb enzyme. Mass spectrometry and western blotting revealed that SSI, SSIIa, SSIIIa, BEI, BEIIa, starch phosphorylase 1, and pullulanase were bound to the starch granules in the be2b mutants, but not in the wild-type and ss1 mutant. These results will aid the understanding of the mechanism of amylopectin biosynthesis

    A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers

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    Previously, we clarified the surface antigen profiles of hepatic progenitor cells (HPCs) in fetal liver tissue as the CD49f+CD45−Thy1− cell fraction. However, these cells were a heterogeneous cell population containing various stages of differentiation. This study aimed to detect more immature HPCs, using a novel surface antigen, gp38. After the collagenase digestion of fetal livers harvested from E13.5 to E18.5 fetal mice, HPCs were obtained and divided into two subpopulations using flow cytometry: gp38-positive HPCs, and gp38-negative HPCs. Both types of HPCs were characterized by immunocytochemistry and RT-PCR. The proliferative activity was compared by BrdU incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) assay. Furthermore, the comprehensive gene expression was investigated by DNA microarray. Both types of HPCs expressed alpha-fetoprotein. However, the gp38-positive HPCs derived from E13.5 fetal livers did not express albumin or cytokeratin 19, while the gp38-negative HPCs did. DNA microarray revealed that some genes related to the Wnt signal pathway were up-regulated in the gp38-positive HPCs. Furthermore, Wnt3a had a proliferative effect on the gp38-positive HPCs. In conclusion, the gp38-positive HPCs derived from fetal liver tissue until E13.5 could therefore be candidates for hepatic stem cells in the fetal liver
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