1,117 research outputs found

    What are the Marital Problems of Happy Couples? A Multimethod, Two‐Sample Investigation

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162758/2/famp12483.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162758/1/famp12483_am.pd

    Programming patterns and design patterns in the introductory computer science course

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    Gain of Function Analysis Reveals Non-Redundant Roles for the Yersinia pestis Type III Secretion System Effectors YopJ, YopT, and YpkA [preprint]

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    Virulence of Yersinia pestis in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across Y. pestis strains, but three -- YopJ, YopT, and YpkA -- are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection. We found that a Y. pestis strain lacking YopJ, YopT, and YpkA is attenuated for virulence in mice, and that addition of any one of these effectors to this strain increases lethality significantly. YopJ, YopT, and YpkA likely contribute to virulence via distinct mechanisms. YopJ is uniquely able to cause macrophage cell death in vitro and to suppress accumulation of inflammatory cells to foci of bacterial growth in deep tissue, whereas YopT and YpkA cannot. The synthetic phenotypes that emerge when YopJ, YopT, and YpkA are removed in combination provide evidence that each enhances Y. pestis virulence, and that YopT and YpkA act through a mechanism distinct from that of YopJ

    Late‐ but not early‐onset blindness impairs the development of audio‐haptic multisensory integration

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    Integrating different senses to reduce sensory uncertainty and increase perceptual precision can have an important compensatory function for individuals with visual impairment and blindness. However, how visual impairment and blindness impact the development of optimal multisensory integration in the remaining senses is currently unknown. Here we first examined how audio‐haptic integration develops and changes across the life span in 92 sighted (blindfolded) individuals between 7 to 70 years of age. We used a child‐ friendly task in which participants had to discriminate different object sizes by touching them and/or listening to them. We assessed whether audio‐haptic performance resulted in a reduction of perceptual uncertainty compared to auditory‐only and haptic‐only performance as predicted by maximum‐likelihood estimation model. We then compared how this ability develops in 28 children and adults with different levels of visual experience, focussing on low‐vision individuals and blind individuals that lost their sight at different ages during development. Our results show that in sighted individuals, adult‐like audio‐haptic integration develops around 13‐15 years of age, and remains stable until late adulthood. While early‐blind individuals, even at the youngest ages, integrate audio‐haptic information in an optimal fashion, late‐blind individuals do not. Optimal integration in low‐vision individuals follows a similar developmental trajectory as that of sighted individuals. These findings demonstrate that visual experience is not necessary for optimal audio‐haptic integration to emerge, but that consistency of sensory information across development is key for the functional outcome of optimal multisensory integration

    Maintaining Ethical Standards during Conservation Crises

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    Many species at risk in Canada and globally are at or approaching a crisis, especially where little or nothing consequential is being done to prevent extirpation. Such is the case of endangered boreal caribou (Rangifer tarandus caribou) in southern Alberta, Canada. Expedient but inadequate emergency ‘fixes’ have been experimentally implemented to arrest their decline and potential extirpation, but use of these measures raises important ethical problems. In their study of the effects of killing wolves (Canis lupus) on the Little Smoky woodland caribou population, Hervieux et al. (2014a) employed lethal methods that included shooting a firearm from a helicopter and the use of strychnine baits. Both of these methods raise critical questions with regard to animal welfare. When it is necessary to kill an animal, reliable humane procedures must be used to avoid pain or distress, and produce rapid loss of consciousness until death occurs. Also relevant are formal approvals by government and institutional animal ethics committees that adhere to Canadian Council on Animal Care (CCAC) guidelines. Shooting a moving animal from a helicopter is prone to error and not conducive to shots that quickly render animals insensitive to pain or produce a consistently quick kill. Strychnine does not meet the CCAC’s criteria for an acceptable killing method, and is specifically prohibited as an injectable option for euthanizing animals. Its use under uncontrolled conditions at bait sites is likely even less suitable. In addition, the risks of non-lethal and painful injuries from this poison and associated deaths to large numbers of non-target animals clearly contravene the CCAC guidelines for wildlife research. This study did not meet the CCAC’s guidelines and did not adhere to the Canadian Journal of Zoology’s requirement that all research must be approved by an institutional animal care committee. More broadly, and regardless of the failure of formal safeguards and implicit justifications offered by authors, we should be concerned when researchers impose suffering on wild animals and advocate for such programs to continue. Based on an apparent lack of compliance with CCAC’s guidelines, we believe that this controversial study should never have taken place and should not have been published by the Canadian Journal of Zoology. Experiments that involve the intentional inhumane killing of animals violate the fundamental principles of ethical science and rightfully endanger the reputation of science and scientists, as well as the journals willing to publish them. We recommend that CCAC guidelines be further developed to clearly address field methods used in wildlife studies, namely the shooting of animals from a helicopter, and the use of strychnine in baits. Also, independent audits should be conducted to investigate individual researchers and their studies, and the journals that publish this work, to ensure that CCAC guidelines are properly followed, even by researchers who collaborate well after the animal-based procedures have been carried out

    The role of plant functional trade-offs for biodiversity changes and biome shifts under scenarios of global climatic change

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    The global geographic distribution of biodiversity and biomes is determined by species-specific physiological tolerances to climatic constraints. Current vegetation models employ empirical bioclimatic relationships to predict present-day vegetation patterns and to forecast biodiversity changes and biome shifts under climatic change. In this paper, we consider trade-offs in plant functioning and their responses under climatic changes to forecast and explain changes in plant functional richness and shifts in biome geographic distributions. <br><br> The Jena Diversity model (JeDi) simulates plant survival according to essential plant functional trade-offs, including ecophysiological processes such as water uptake, photosynthesis, allocation, reproduction and phenology. We use JeDi to quantify changes in plant functional richness and biome shifts between present-day and a range of possible future climates from two SRES emission scenarios (A2 and B1) and seven global climate models using metrics of plant functional richness and functional identity. <br><br> Our results show (i) a significant loss of plant functional richness in the tropics, (ii) an increase in plant functional richness at mid and high latitudes, and (iii) a pole-ward shift of biomes. While these results are consistent with the findings of empirical approaches, we are able to explain them in terms of the plant functional trade-offs involved in the allocation, metabolic and reproduction strategies of plants. We conclude that general aspects of plant physiological tolerances can be derived from functional trade-offs, which may provide a useful process- and trait-based alternative to bioclimatic relationships. Such a mechanistic approach may be particularly relevant when addressing vegetation responses to climatic changes that encounter novel combinations of climate parameters that do not exist under contemporary climate

    Genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of Yersinia pestis in deep tissue

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    Rapid growth in deep tissue is essential to the high virulence of Yersinia pestis, causative agent of plague. To better understand the mechanisms underlying this unusual ability, we used transposon mutagenesis and high-throughput sequencing (Tn-seq) to systematically probe the Y. pestis genome for elements contributing to fitness during infection. More than a million independent insertion mutants representing nearly 200,000 unique genotypes were generated in fully virulent Y. pestis. Each mutant in the library was assayed for its ability to proliferate in vitro on rich medium and in mice following intravenous injection. Virtually all genes previously established to contribute to virulence following intravenous infection showed significant fitness defects, with the exception of genes for yersiniabactin biosynthesis, which were masked by strong intercellular complementation effects. We also identified more than 30 genes with roles in nutrient acquisition and metabolism as experiencing strong selection during infection. Many of these genes had not previously been implicated in Y. pestis virulence. We further examined the fitness defects of strains carrying mutations in two such genes-encoding a branched-chain amino acid importer (brnQ) and a glucose importer (ptsG)-both in vivo and in a novel defined synthetic growth medium with nutrient concentrations matching those in serum. Our findings suggest that diverse nutrient limitations in deep tissue play a more important role in controlling bacterial infection than has heretofore been appreciated. Because much is known about Y. pestis pathogenesis, this study also serves as a test case that assesses the ability of Tn-seq to detect virulence genes. IMPORTANCE: Our understanding of the functions required by bacteria to grow in deep tissues is limited, in part because most growth studies of pathogenic bacteria are conducted on laboratory media that do not reflect conditions prevailing in infected animal tissues. Improving our knowledge of this aspect of bacterial biology is important as a potential pathway to the development of novel therapeutics. Yersinia pestis, the plague bacterium, is highly virulent due to its rapid dissemination and growth in deep tissues, making it a good model for discovering bacterial adaptations that promote rapid growth during infection. Using Tn-seq, a genome-wide fitness profiling technique, we identified several functions required for fitness of Y. pestis in vivo that were not previously known to be important. Most of these functions are needed to acquire or synthesize nutrients. Interference with these critical nutrient acquisition pathways may be an effective strategy for designing novel antibiotics and vaccines

    Do we enjoy what we sense and perceive?:A dissociation between aesthetic appreciation and basic perception of environmental objects or events

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    This integrative review rearticulates the notion of human aesthetics by critically appraising the conventional definitions, offerring a new, more comprehensive definition, and identifying the fundamental components associated with it. It intends to advance holistic understanding of the notion by differentiating aesthetic perception from basic perceptual recognition, and by characterizing these concepts from the perspective of information processing in both visual and nonvisual modalities. To this end, we analyze the dissociative nature of information processing in the brain, introducing a novel local-global integrative model that differentiates aesthetic processing from basic perceptual processing. This model builds on the current state of the art in visual aesthetics as well as newer propositions about nonvisual aesthetics. This model comprises two analytic channels: aesthetics-only channel and perception-to-aesthetics channel. The aesthetics-only channel primarily involves restricted local processing for quality or richness (e.g., attractiveness, beauty/prettiness, elegance, sublimeness, catchiness, hedonic value) analysis, whereas the perception-to-aesthetics channel involves global/extended local processing for basic feature analysis, followed by restricted local processing for quality or richness analysis. We contend that aesthetic processing operates independently of basic perceptual processing, but not independently of cognitive processing. We further conjecture that there might be a common faculty, labeled as aesthetic cognition faculty, in the human brain for all sensory aesthetics albeit other parts of the brain can also be activated because of basic sensory processing prior to aesthetic processing, particularly during the operation of the second channel. This generalized model can account not only for simple and pure aesthetic experiences but for partial and complex aesthetic experiences as well.</p

    DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile in \u3cem\u3eBorrelia burgdorferi\u3c/em\u3e

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    Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease, Borrelia burgdorferi B31, possesses two RM systems with N6-methyladenosine (m6A) MTase activity, which are encoded by the bbe02 gene located on linear plasmid lp25 and bbq67 on lp56. The specific recognition and/or methylation sequences had not been identified for either of these B. burgdorferi MTases, and it was not previously known whether these RM systems influence transcript levels. In the current study, single-molecule real-time sequencing was utilized to map genome-wide m6A sites and to identify consensus modified motifs in wild-type B. burgdorferi as well as MTase mutants lacking either the bbe02 gene alone or both bbe02 and bbq67 genes. Four novel conserved m6A motifs were identified and were fully attributable to the presence of specific MTases. Whole-genome transcriptome changes were observed in conjunction with the loss of MTase enzymes, indicating that DNA methylation by the RM systems has effects on gene expression. Genes with altered transcription in MTase mutants include those involved in vertebrate host colonization (e.g., rpoS regulon) and acquisition by/transmission from the tick vector (e.g., rrp1 and pdeB). The results of this study provide a comprehensive view of the DNA methylation pattern in B. burgdorferi, and the accompanying gene expression profiles add to the emerging body of research on RM systems and gene regulation in bacteria
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