442 research outputs found

    Combining genetic and geospatial analyses to infer population extinction in mygalomorph spiders endemic to the Los Angeles region. Anim

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    Abstract Although hyperdiverse groups like terrestrial arthropods are almost certainly severely impacted by habitat fragmentation and destruction, few studies have formally documented such effects. In this paper, we summarize the results of a multifaceted research approach to assess the magnitude and importance of anthropogenic population extinction on the narrowly endemic trapdoor spider genus Apomastus. We used geographical information systems modeling to reconstruct the likely historical distribution of Apomastus, and used molecular phylogeographic data to discern population genetic structure and detect genetic signatures of population extinction. In combination, these complementary lines of inference support direct observations of population extinction, and lead us to conclude that population extinction via urbanization has played an important role in defining the modern-day distribution of Apomastus species. This population loss implies coincident loss of genetic and adaptive diversity within this genus, and more generally, suggests a loss of ground-dwelling arthropod population diversity throughout the Los Angeles Basin. Strategies for minimizing this loss are proposed

    Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections

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    Copyright: © 2013 Baron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by ANR (ANR-07-BLAN-0214 and ANR-12-EMMA-00O7-01), CNRS and INRA. PvW was financially supported by the BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

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    Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

    From DNA sequence to application: possibilities and complications

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    The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

    Early neoplastic and metastatic mammary tumours of transgenic mice detected by 5-aminolevulinic acid-stimulated protoporphyrin IX accumulation

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    A photodynamic technique for human breast cancer detection founded upon the ability of tumour cells to rapidly accumulate the fluorescent product protoporphyrin IX (PpIX) has been applied to transgenic mouse models of mammary tumorigenesis. A major goal of this investigation was to determine whether mouse mammary tumours are reliable models of human disease in terms of PpIX accumulation, for future mechanistic and therapeutic studies. The haeme substrate 5-aminolevulinic acid (5-ALA) (200 mg kg−1) was administered to mouse strains that develop mammary tumours of various histological subtypes upon expression of the transgenic oncogenes HRAS, Polyoma Virus middle T antigen, or Simian Virus 40 large T antigen in the mammary gland. Early neoplastic lesions, primary tumours and metastases showed consistent and rapid PpIX accumulation compared to the normal surrounding tissues, as evidenced by red fluorescence (635 nm) when the tumours were directly illuminated with blue light (380–440 nm). Detection of mouse mammary tumours at the stage of ductal carcinoma in situ by red fluorescence emissions suggests that enhanced PpIX synthesis is a good marker for early tumorigenic processes in the mammary gland. We propose the mouse models provide an ideal experimental system for further investigation of the early diagnostic and therapeutic potential of 5-ALA-stimulated PpIX accumulation in human breast cancer patients

    PROTDES: CHARMM toolbox for computational protein design

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    We present an open-source software able to automatically mutate any residue positions and find the best aminoacids in an arbitrary protein structure without requiring pairwise approximations. Our software, PROTDES, is based on CHARMM and it searches automatically for mutations optimizing a protein folding free energy. PROTDES allows the integration of molecular dynamics within the protein design. We have implemented an heuristic optimization algorithm that iteratively searches the best aminoacids and their conformations for an arbitrary set of positions within a structure. Our software allows CHARMM users to perform protein design calculations and to create their own procedures for protein design using their own energy functions. We show this by implementing three different energy functions based on different solvent treatments: surface area accessibility, generalized Born using molecular volume and an effective energy function. PROTDES, a tutorial, parameter sets, configuration tools and examples are freely available at http://soft.synth-bio.org/protdes.html

    Exploring the Design Space of Static and Incremental Graph Connectivity Algorithms on GPUs

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    Connected components and spanning forest are fundamental graph algorithms due to their use in many important applications, such as graph clustering and image segmentation. GPUs are an ideal platform for graph algorithms due to their high peak performance and memory bandwidth. While there exist several GPU connectivity algorithms in the literature, many design choices have not yet been explored. In this paper, we explore various design choices in GPU connectivity algorithms, including sampling, linking, and tree compression, for both the static as well as the incremental setting. Our various design choices lead to over 300 new GPU implementations of connectivity, many of which outperform state-of-the-art. We present an experimental evaluation, and show that we achieve an average speedup of 2.47x speedup over existing static algorithms. In the incremental setting, we achieve a throughput of up to 48.23 billion edges per second. Compared to state-of-the-art CPU implementations on a 72-core machine, we achieve a speedup of 8.26--14.51x for static connectivity and 1.85--13.36x for incremental connectivity using a Tesla V100 GPU
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