251 research outputs found

    Principal series of finite subgroups of SU(3)

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    We attempt to give a complete description of the "exceptional" finite subgroups Sigma(36x3), Sigma(72x3) and Sigma(216x3) of SU(3), with the aim to make them amenable to model building for fermion masses and mixing. The information on these groups which we derive contains conjugacy classes, proper normal subgroups, irreducible representations, character tables and tensor products of their three-dimensional irreducible representations. We show that, for these three exceptional groups, usage of their principal series, i.e. ascending chains of normal subgroups, greatly facilitates the computations and illuminates the relationship between the groups. As a preparation and testing ground for the usage of principal series, we study first the dihedral-like groups Delta(27) and Delta(54) because both are members of the principal series of the three groups discussed in the paper.Comment: 43 pages, no figures; typos corrected, clarifications and references added, version matches publication in J. Phys.

    Dynamic 3D Cell Rearrangements Guided by a Fibronectin Matrix Underlie Somitogenesis

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    Somites are transient segments formed in a rostro-caudal progression during vertebrate development. In chick embryos, segmentation of a new pair of somites occurs every 90 minutes and involves a mesenchyme-to-epithelium transition of cells from the presomitic mesoderm. Little is known about the cellular rearrangements involved, and, although it is known that the fibronectin extracellular matrix is required, its actual role remains elusive. Using 3D and 4D imaging of somite formation we discovered that somitogenesis consists of a complex choreography of individual cell movements. Epithelialization starts medially with the formation of a transient epithelium of cuboidal cells, followed by cell elongation and reorganization into a pseudostratified epithelium of spindle-shaped epitheloid cells. Mesenchymal cells are then recruited to this medial epithelium through accretion, a phenomenon that spreads to all sides, except the lateral side of the forming somite, which epithelializes by cell elongation and intercalation. Surprisingly, an important contribution to the somite epithelium also comes from the continuous egression of mesenchymal cells from the core into the epithelium via its apical side. Inhibition of fibronectin matrix assembly first slows down the rate, and then halts somite formation, without affecting pseudopodial activity or cell body movements. Rather, cell elongation, centripetal alignment, N-cadherin polarization and egression are impaired, showing that the fibronectin matrix plays a role in polarizing and guiding the exploratory behavior of somitic cells. To our knowledge, this is the first 4D in vivo recording of a full mesenchyme-to-epithelium transition. This approach brought new insights into this event and highlighted the importance of the extracellular matrix as a guiding cue during morphogenesis

    Comparative analysis of somitogenesis related genes of the hairy/Enhancer of split class in Fugu and zebrafish

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    BACKGROUND: Members of a class of bHLH transcription factors, namely the hairy (h), Enhancer of split (E(spl)) and hairy-related with YRPW motif (hey) (h/E(spl)/hey) genes are involved in vertebrate somitogenesis and some of them show cycling expression. By sequence comparison, identified orthologues of cycling somitogenesis genes from higher vertebrates do not show an appropriate expression pattern in zebrafish. The zebrafish genomic sequence is not available yet but the genome of Fugu rubripes was recently published. To allow comparative analysis, the currently known Her proteins from zebrafish were used to screen the genomic sequence database of Fugu rubripes. RESULTS: 20 h/E(spl)/hey-related genes were identified in Fugu, which is twice the number of corresponding zebrafish genes known so far. A novel class of c-Hairy proteins was identified in the genomes of Fugu and Tetraodon. A screen of the human genome database with the Fugu proteins yielded 10 h/E(spl)/hey-related genes. By analysing the upstream sequences of the c-hairy class genes in zebrafish, Fugu and Tetraodon highly similar sequence stretches were identified that harbour Suppressor of hairless paired binding sites (SPS). This motif was also discovered in the upstream sequences of the her1 gene in the examined fish species. Here, the Su(h) sites are separated by longer intervening sequences. CONCLUSIONS: Our study indicates that not all her homologues in zebrafish have been isolated. Comparison to the human genome suggests a selective duplication of h/E(spl) genes in pufferfish or loss of members of these genes during evolution to the human lineage

    Thyroid and pituitary gland development from hatching through metamorphosis of a teleost flatfish, the Atlantic halibut

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    Fish larval development, not least the spectacular process of flatfish metamorphosis, appears to be under complex endocrine control, many aspects of which are still not fully elucidated. In order to obtain data on the functional development of two major endocrine glands, the pituitary and the thyroid, during flatfish metamorphosis, histology, immunohistochemistry and in situ hybridization techniques were applied on larvae of the Atlantic halibut (Hippoglossus hippoglossus), a large, marine flatfish species, from hatching through metamorphosis. The material was obtained from a commercial hatchery. Larval age is defined as day-degrees (D =accumulated daily temperature from hatching). Sporadic thyroid follicles are first detected in larvae at 142 D (27 days post-hatch), prior to the completion of yolk sack absorption. Both the number and activity of the follicles increase markedly after yolk sack absorption and continue to do so during subsequent development. The larval triiodothyronine (T3) and thyroxine (T4) content increases, subsequent to yolk absorption, and coincides with the proliferation of thyroid follicles. A second increase of both T3 and T4 occurs around the start of metamorphosis and the T3 content further increases at the metamorphic climax. Overall, the T3 content is lower than T4. The pituitary gland can first be distinguished as a separate organ at the yolk sack stage. During subsequent development, the gland becomes more elongated and differentiates into neurohypophysis (NH), pars distalis (PD) and pars intermedia (PI). The first sporadic endocrine pituitary cells are observed at the yolk sack stage, somatotrophs (growth hormone producing cells) and somatolactotrophs (somatolactin producing cells) are first observed at 121 D (23 days post-hatch), and lactotrophs (prolactin producing cells) at 134 D (25 days post-hatch). Scarce thyrotrophs are evident after detection of the first thyroid follicles (142 D ), but coincident with a phase in which follicle number and activity increase (260 D ). The somatotrophs are clustered in the medium ventral region of the PD, lactotrophs in the anterior part of the PD and somatolactotrophs are scattered in the mid and posterior region of the pituitary. At around 600 D , coinciding with the start of metamorphosis, somatolactotrophs are restricted to the interdigitating tissue of the NH. During larval development, the pituitary endocrine cells become more numerous. The present data on thyroid development support the notion that thyroid hormones may play a significant role in Atlantic halibut metamorphosis. The time of appearance and the subsequent proliferation of pituitary somatotrophs, lactotrophs, somatolactotrophs and thyrotrophs indicate at which stages of larval development and metamorphosis these endocrine cells may start to play active regulatory roles.This work has been carried out within the projects ‘‘Endocrine Control as a Determinant of Larval Quality in Fish Aquaculture’’ (CT-96-1422) and ‘‘Arrested development: The Molecular and Endocrine Basis of Flatfish Metamorphosis’’ (Q5RS-2002-01192), with financial support from the Commission of the European Communities. However, it does not necessarily reflect the Commission’s views and in no way anticipates its future policy in this area. This project was further supported by the Swedish Council for Agricultural and Forestry Research and Pluriannual funding to CCMAR by the Portuguese Science and Technology Council

    The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors

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    <p><b>Abstract</b></p> <p>Background</p> <p>Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity.</p> <p>Methods</p> <p>Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with <it>ERBB2 </it>(231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2.</p> <p>Results</p> <p>The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly.</p> <p>Conclusions</p> <p>Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors.</p

    Identification of miRNA from Porphyra yezoensis by High-Throughput Sequencing and Bioinformatics Analysis

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    BACKGROUND: miRNAs are a class of non-coding, small RNAs that are approximately 22 nucleotides long and play important roles in the translational level regulation of gene expression by either directly binding or cleaving target mRNAs. The red alga, Porphyra yezoensis is one of the most important marine economic crops worldwide. To date, only a few miRNAs have been identified in green unicellar alga and there is no report about Porphyra miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: To identify miRNAs in Porphyra yezoensis, a small RNA library was constructed. Solexa technology was used to perform high throughput sequencing of the library and subsequent bioinformatics analysis to identify novel miRNAs. Specifically, 180,557,942 reads produced 13,324 unique miRNAs representing 224 conserved miRNA families that have been identified in other plants species. In addition, seven novel putative miRNAs were predicted from a limited number of ESTs. The potential targets of these putative miRNAs were also predicted based on sequence homology search. CONCLUSIONS/SIGNIFICANCE: This study provides a first large scale cloning and characterization of Porphyra miRNAs and their potential targets. These miRNAs belong to 224 conserved miRNA families and 7 miRNAs are novel in Porphyra. These miRNAs add to the growing database of new miRNA and lay the foundation for further understanding of miRNA function in the regulation of Porphyra yezoensis development

    Somitogenesis Clock-Wave Initiation Requires Differential Decay and Multiple Binding Sites for Clock Protein

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    Somitogenesis is a process common to all vertebrate embryos in which repeated blocks of cells arise from the presomitic mesoderm (PSM) to lay a foundational pattern for trunk and tail development. Somites form in the wake of passing waves of periodic gene expression that originate in the tailbud and sweep posteriorly across the PSM. Previous work has suggested that the waves result from a spatiotemporally graded control protein that affects the oscillation rate of clock-gene expression. With a minimally constructed mathematical model, we study the contribution of two control mechanisms to the initial formation of this gene-expression wave. We test four biologically motivated model scenarios with either one or two clock protein transcription binding sites, and with or without differential decay rates for clock protein monomers and dimers. We examine the sensitivity of wave formation with respect to multiple model parameters and robustness to heterogeneity in cell population. We find that only a model with both multiple binding sites and differential decay rates is able to reproduce experimentally observed waveforms. Our results show that the experimentally observed characteristics of somitogenesis wave initiation constrain the underlying genetic control mechanisms
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