11 research outputs found

    Galactic Phylogenetics

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    Phylogenetics is a widely used concept in evolutionary biology. It is the reconstruction of evolutionary history by building trees that represent branching patterns and sequences. These trees represent shared history, and it is our intention for this approach to be employed in the analysis of Galactic history. In Galactic archaeology the shared environment is the interstellar medium in which stars form and provides the basis for tree-building as a methodological tool. Using elemental abundances of solar-type stars as a proxy for DNA, we built in Jofre et al 2017 such an evolutionary tree to study the chemical evolution of the solar neighbourhood. In this proceeding we summarise these results and discuss future prospects.Comment: Contribution to IAU Symposium No. 334: Rediscovering our Galax

    Memetic algorithm with route decomposing for periodic capacitated arc routing problem

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    In this paper, the Periodic Capacitated Arc Routing Problem (PCARP) is investigated. PCARP is an extension of the well-known CARP from a single period to a multi-period horizon. In PCARP, two objectives are to be minimized. One is the number of required vehicles (nv), and the other is the total cost (tc). Due to the multi-period nature, given the same graph or road network, PCARP can have a much larger solution space than the single-period CARP counterpart. Furthermore, PCARP consists of an additional allocation sub-problem (of the days to serve the arcs), which is interdependent with the routing sub-problem. Although some attempts have been made for solving PCARP, more investigations are yet to be done to further improve their performance especially on large-scale problem instances. It has been shown that optimizing nv and tc separately (hierarchically) is a good way of dealing with the two objectives. In this paper, we further improve this strategy and propose a new Route Decomposition (RD) operator thereby. Then, the RD operator is integrated into a Memetic Algorithm (MA) framework for PCARP, in which novel crossover and local search operators are designed accordingly. In addition, to improve the search efficiency, a hybridized initialization is employed to generate an initial population consisting of both heuristic and random individuals. The MA with RD (MARD) was evaluated and compared with the state-of-the-art approaches on two benchmark sets of PCARP instances and a large data set which is based on a real-world road network. The experimental results suggest that MARD outperforms the compared state-of-the-art algorithms, and improves most of the best-known solutions. The advantage of MARD becomes more obvious when the problem size increases. Thus, MARD is particularly effective in solving large-scale PCARP instances. Moreover, the efficacy of the proposed RD operator in MARD has been empirically verified. Graphical abstract https://ars.els-cdn.com/content/image/1-s2.0-S1568494616304768-fx1_lrg.jpg © This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0

    HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and Mice

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    <div><p>Hereditary hearing loss is a clinically and genetically heterogeneous disorder. More than 80 genes have been implicated to date, and with the advent of targeted genomic enrichment and massively parallel sequencing (TGE+MPS) the rate of novel deafness-gene identification has accelerated. Here we report a family segregating post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL). After first excluding plausible variants in known deafness-causing genes using TGE+MPS, we completed whole exome sequencing in three hearing-impaired family members. Only a single variant, p.Arg185Pro in <i>HOMER2</i>, segregated with the hearing-loss phenotype in the extended family. This amino acid change alters a highly conserved residue in the coiled-coil domain of HOMER2 that is essential for protein multimerization and the HOMER2-CDC42 interaction. As a scaffolding protein, HOMER2 is involved in intracellular calcium homeostasis and cytoskeletal organization. Consistent with this function, we found robust expression in stereocilia of hair cells in the murine inner ear and observed that over-expression of mutant p.Pro185 <i>HOMER2</i> mRNA causes anatomical changes of the inner ear and neuromasts in zebrafish embryos. Furthermore, mouse mutants homozygous for the targeted deletion of <i>Homer2</i> present with early-onset rapidly progressive hearing loss. These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action.</p></div

    Homer2 expression in P2 mouse inner ear.

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    <p><b>(A</b>) Staining with F-actin shows three rows of OHCs and one row of IHCs in the cochlea. (<b>B</b>) Homer2 staining in the OHCs and IHCs shows localization to stereocilia. (<b>C</b>) Merged pictures showing co-localization of Homer2 with F-actin in HC stereocilia. (<b>D</b>) Zoomed view of OHCs shows pronounced localization of Homer2 to the tips of stereocilia. Scale bar represents 10μm.</p

    Pedigree, clinical data, HOMER2 mutation and protein structure.

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    <p><b>(A)</b> The pedigree of a five-generation family segregating progressive ADNSHL. DNA samples were obtained for 9 unaffected and 10 affected individuals. The partially filled symbol represents a two-year-old female who carries the <i>HOMER2</i> mutation but in whom a formal ABR has not been performed. Individuals who underwent TGE+MPS using either the deafness panel (OtoSCOPE) or WES are marked with an O or W, respectively. Genotypes of participating family members are shown below each symbol in single letter amino acid nomenclature: P for Proline and R for Arginine. (<b>B)</b> Age-related typical audiograms (ARTA). Binaural mean air conduction thresholds (dB HL) are presented for the ages 10–70 years. Hearing levels ranged from 0 to 120 dB depending on age and frequency; the annual threshold deterioration (ATD) was 1.2–1.6 dB/year at all frequencies. (<b>C)</b> Representative chromatograms from wild-type and mutant sequences. (<b>D)</b> Diagram of HOMER2 structure; the amino acid numbering indicates the beginning and end of the EVH1 and CC domains. The CC includes the CDC42 binding domain (CBD), Leucine Zipper-A (LZA) and Leucine Zipper-B (LZB). The position of the p.Arg185Pro mutation is shown in red.</p
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