221 research outputs found

    spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast

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    AbstractTelomeres are essential for genome integrity. scRap1 (S. cerevisiae Rap1) directly binds to telomeric DNA [1–3] and regulates telomere length and telomere position effect (TPE) [4–6] by recruiting two different groups of proteins to its RCT (Rap1 C-terminal) domain [7]. The first group, Rif1 and Rif2, regulates telomere length [8, 9]. The second group, Sir3 and Sir4 [10], is involved in heterochromatin formation [11–13]. On the other hand, human TRF1 and TRF2, as well as their fission yeast homolog, Taz1, directly bind to telomeric DNA [14–16] and negatively regulate telomere length [16–20]. Taz1 also plays important roles in TPE and meiosis [16, 20, 21]. Human Rap1, the ortholog of scRap1, negatively regulates telomere length and appears to be recruited to telomeres by interacting with TRF2 [7]. Here, we describe two novel fission yeast proteins, spRap1 (S. pombe Rap1) and spRif1 (S. pombe Rif1), which are orthologous to scRap1 and scRif1, respectively. spRap1 and spRif1 are independently recruited to telomeres by interacting with Taz1. The rap1 mutant is severely defective in telomere length control, TPE, and telomere clustering toward the spindle pole body (SPB) at the premeiotic horsetail stage, indicating that spRap1 has critical roles in these telomere functions. The rif1 mutant also shows some defects in telomere length control and meiosis. Our results indicate that Taz1 provides binding sites for telomere regulators, spRap1 and spRif1, which perform the essential telomere functions. This study establishes the similarity of telomere organization in fission yeast and humans

    A critique of the Maastricht road to European Monetary Union: Bringing labour market analysis back in.

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    This thesis criticises the current project of European Monetary Union, based on the Maastricht convergence criteria. It attempts to reinterpret the issue of economic convergence by looking into structural aspects from a political economic point of view. Taking a structural approach, I examine the socio-political sustainability of EMU. The thesis applies the theoretical framework set forth by the French regulation school. Drawing on the regulationists' notion of 'regime', the concept of structural / regime compatibility among member states is introduced. The need to study non-monetary regimes in assessing the viability of monetary union is stressed by drawing on the historical experiences of monetary unions in the 19th century - the Latin Monetary Union, the Scandinavian Monetary Union and the American Monetary Union. Among the non-monetary structural regimes, the examination of national labour market regimes is crucial. After the loss of exchange rates as a means of adjustment, labour market adjustment becomes the key in coping with asymmetric economic shocks. Labour market flexibility is considered to be the main weapon of adjustment in post-EMU Europe. The comparison of three main labour market regimes in Europe - France, Germany and Britain - shows that they diverge substantially in their adjustment mechanisms and in the nature of their flexibility. Following Robert Boyer, I argue that there is fundamental incompatibility in national ideologies, concepts and practices of labour market policies in Europe. Without a common labour market regime, such differences could lead to major tensions between the Anglo-Saxon model of'external flexibility' and the continental European model of 'internal flexibility'. The thesis aims to show where the difficulties lie for the management of the future 'Euroland', including Britain, in order to indicate the tremendous task facing European policy makers

    Morphological Markers of Chromosomal Instability

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    Cancer is characterized by genomic complexity and chromosomal instability (CIN). Atypical mitosis and nuclear atypia such as micronuclei have been reported as morphological characteristics of chromosomal instability. An atypical mitotic figure is defined as anything other than the typical form of normal mitosis, including multipolar, ring, dispersed, asymmetrical, and lag-type mitoses. A micronucleus is defined as the small nucleus that forms whenever a chromosome or its fragment is not incorporated into one of the daughter nuclei during cell division. A telomere plays a key role in chromosomal instability. Telomere dysfunction induces fusion of chromatids and chromosome missegregation and this phenomenon can be observed as abnormal mitotic figures and micronuclei. Detection of morphological markers of chromosomal instability using pathological specimens, even small biopsy or cytological specimens, may provide valuable information concerning the prognosis of cancers. Here, we discuss morphological assessment of chromosomal instability using routine pathological specimens

    Three-Dimensional Comparison in Palatal Forms Between Modified Presurgical Nasoalveolar Molding Plate and Hotz's Plate Applied to the Infants With Unilateral Cleft Lip and Palate

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    AbstractThe presurgical nasoalveolar molding plate appliance with stent (PNAM) extended from the palatal molding plate; to correct the nostril shape of infants with cleft lip and palate is well known. The PNAM appliance is based on the finding that a high degree of plasticity is maintained in the cartilage of infants during the first 6 weeks after birth. However, on the current PNAM protocol described by Grayson et al. the nasal stent is supposed to be an adjunct to the palatal molding plate after reducing the severity of the alveolar cleft width. We have used the modified Hotz's plate from the setup model and built up the nasal stent even before reducing the severity of the alveolar deformity. In this study we assess the effects of the modified Hotz's plate and the modified PNAM appliance for the alveolar and palatal form. The lateral deviation of the incisal point, the width of the palatal cleft, and the degree of curvature of the palatal vault were first evaluated on plaster models. The PNAM group is smaller on the lateral deviation of the incisal point than the modified Hotz's group. The decreased average width of the palatal cleft and curvature of the palate, was almost the same in both the modified Hotz's and PNAM groups. In comparison with the modified Hotz's plate, the modified PNAM appliance also improves the molding of the alveolar segments and reduces cleft width

    Recognition of Brain Wave Related to the Episode Memory by Deep Learning Methods

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    Hippocampus makes an important role of memory in the brain. In this chapter, a study of brain wave recognition using deep learning methods is introduced. The purpose of the study is to match the ripple-firings of the hippocampal activity to the episodic memories. In fact, brain spike signals of rats (300–10 kHz) were recorded and machine learning methods such as Convolutional Neural Networks (CNN), Support Vector Machine (SVM), a deep learning model VGG16, and combination models composed by CNN with SVM and VGG16 with SVM were adopted to be classifiers of the brain wave signals. Four kinds of episodic memories, that is, a male rat contacted with a female/male rat, contacted with a novel object, and an experience of restrain stress, were detected corresponding to the ripple waves of Multiple-Unit Activities (MUAs) of hippocampal CA1 neurons in male rats in the experiments. The experiment results showed the possibility of matching of ripple-like firing patterns of hippocampus to episodic memory activities of rats, and it suggests disorders of memory function may be found by the analysis of brain waves

    Regulated interaction between polypeptide chain elongation factor-1 complex with the 26S proteasome during Xenopus oocyte maturation

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    BACKGROUND: During Xenopus oocyte maturation, the amount of a 48 kDa protein detected in the 26S proteasome fraction (p48) decreased markedly during oocyte maturation to the low levels seen in unfertilized eggs. The results indicate that the interaction of at least one protein with the 26S proteasome changes during oocyte maturation and early development. An alteration in proteasome function may be important for the regulation of developmental events, such as the rapid cell cycle, in the early embryo. In this study, we identified p48. RESULTS: p48 was purified by conventional column chromatography. The resulting purified fraction contained two other proteins with molecular masses of 30 (p30) and 37 (p37) kDa. cDNAs encode elongation factor-1γ and δ were obtained by an immuno-screening method using polyclonal antibodies against purified p48 complex, which recognized p48 and p37. N-terminal amino acid sequence analysis of p30 revealed that it was identical to EF-1β. To identify the p48 complex bound to the 26S proteasome as EF-1βγδ, antibodies were raised against the components of purified p48 complex. Recombinant EF-1 β,γ and δ were expressed in Escherichia coli, and an antibody was raised against purified recombinant EF-1γ. Cross-reactivity of the antibodies toward the p48 complex and recombinant proteins showed it to be specific for each component. These results indicate that the p48 complex bound to the 26S proteasome is the EF-1 complex. MPF phosphorylated EF-1γ was shown to bind to the 26S proteasome. When EF-1γ is phosphorylated by MPF, the association is stabilized. CONCLUSION: p48 bound to the 26S proteasome is identified as the EF-1γ. EF-1 complex is associated with the 26S proteasome in Xenopus oocytes and the interaction is stabilized by MPF-mediated phosphorylation

    Mechanical homeostasis of liver sinusoid is involved in the initiation and termination of liver regeneration

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    Organogenesis and regeneration are fundamental for developmental progress and are associated with morphogenesis, size control and functional properties for whole-body homeostasis. The liver plays an essential role in maintaining homeostasis of the entire body through various functions, including metabolic functions, detoxification, and production of bile, via the three-dimensional spatial arrangement of hepatic lobules and has high regenerative capacity. The regeneration occurs as hypertrophy, which strictly controls the size and lobule structure. In this study, we established a three-dimensional sinusoidal network analysis method and determined valuable parameters after partial hepatectomy by comparison to the static phase of the liver. We found that mechanical homeostasis, which is crucial for organ morphogenesis and functions in various phenomena, plays essential roles in liver regeneration for both initiation and termination of liver regeneration, which is regulated by cytokine networks. Mechanical homeostasis plays critical roles in the initiation and termination of organogenesis, tissue repair and organ regeneration in coordination with cytokine networks
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