390 research outputs found

    Temperature dependence of positron trapping at voids in metals

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    We report positron-lifetime measurements in void-containing aluminum samples, which show strong temperature dependence for the positron trapping probability. A theory is presented for the positron motion and trapping in a three-dimensional array of large voids, which compares favorably with the experimental data. It is shown that at low temperatures the trapping is transition limited and strongly temperature dependent with a crossover to diffusion-limited and weakly-temperature-dependent behavior at high temperatures.Peer reviewe

    A New Model for the Evolution of Carnivory in the Bladderwort Plant (Utricularia) : Adaptive Changes in Cytochrome c Oxidase (COX) Provide Respiratory Power

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    The evolution of carnivorous plants has been modeled as a selective tradeoff between photosynthetic costs and benefits in nutrient-poor habitats. Although possibly applicable for pitfall and flypaper trappers, more variables may be required for active trapping systems. Bladderwort (Utricularia) suction traps react to prey stimuli with an extremely rapid release of elastic instability. Trap setting requires considerable energy to engage an active ion transport process whereby water is pumped out through the thin bladder walls to create negative internal pressure. Accordingly, empirical estimates have shown that respiratory rates in bladders are far greater than in leafy structures. Cytochrome c oxidase (COX) is a multi-subunit enzyme that catalyzes the respiratory reduction of oxygen to water and couples this reaction to translocation of protons, generating a transmembrane electrochemical gradient that is used for the synthesis of adenosine triphosphate (ATP). We have previously demonstrated that two contiguous cysteine residues in helix 3 of COX subunit I (COX I) have evolved under positive Darwinian selection. This motif, absent in = 99.9 % of databased COX I proteins from eukaryotes, Archaea, and Bacteria, lies directly at the docking point of COX I helix 3 and cytochrome c . Modeling of bovine COX I suggests the possibility that a vicinal disulfide bridge at this position could cause premature helix termination. The helix 3–4 loop makes crucial contacts with the active site of COX, and we postulate that the C–C motif might cause a conformational change that decouples (or partly decouples) electron transport from proton pumping. Such decoupling would permit bladderworts to optimize power output (which equals energy times rate) during times of need, albeit with a 20 % reduction in overall energy efficiency of the respiratory chain. A new model for the evolution of bladderwort carnivory is proposed that includes respiration as an additional tradeoff parameter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74764/1/s-2006-924459.pd

    Polyglutamine variation in a flowering time protein correlates with island age in a Hawaiian plant radiation

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    <p>Abstract</p> <p>Background</p> <p>A controversial topic in evolutionary developmental biology is whether morphological diversification in natural populations can be driven by expansions and contractions of amino acid repeats in proteins. To promote adaptation, selection on protein length variation must overcome deleterious effects of multiple correlated traits (pleiotropy). Thus far, systems that demonstrate this capacity include only ancient or artificial morphological diversifications. The Hawaiian Islands, with their linear geological sequence, present a unique environment to study recent, natural radiations. We have focused our research on the Hawaiian endemic mints (Lamiaceae), a large and diverse lineage with paradoxically low genetic variation, in order to test whether a direct relationship between coding-sequence repeat diversity and morphological change can be observed in an actively evolving system.</p> <p>Results</p> <p>Here we show that in the Hawaiian mints, extensive polyglutamine (CAG codon repeat) polymorphism within a homolog of the pleiotropic flowering time protein and abscisic acid receptor FCA tracks the natural environmental cline of the island chain, consequent with island age, across a period of 5 million years. CAG expansions, perhaps following their natural tendency to elongate, are more frequent in colonists of recently-formed, nutrient-rich islands than in their forebears on older, nutrient-poor islands. Values for several quantitative morphological variables related to reproductive investment, known from Arabidopsis <it>fca </it>mutant studies, weakly though positively correlate with increasing glutamine tract length. Together with protein modeling of FCA, which indicates that longer polyglutamine tracts could induce suboptimally mobile functional domains, we suggest that CAG expansions may form slightly deleterious alleles (with respect to protein function) that become fixed in founder populations.</p> <p>Conclusion</p> <p>In the Hawaiian mint <it>FCA </it>system, we infer that contraction of slightly deleterious CAG repeats occurred because of competition for resources along the natural environmental cline of the island chain. The observed geographical structure of <it>FCA </it>variation and its correlation with morphologies expected from Arabidopsis mutant studies may indicate that developmental pleiotropy played a role in the diversification of the mints. This discovery is important in that it concurs with other suggestions that repetitive amino acid motifs might provide a mechanism for driving morphological evolution, and that variation at such motifs might permit rapid tuning to environmental change.</p

    Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature

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    We performed in vivo phage display in the stroke prone spontaneously hypertensive rat, a cardiovascular disease model, and the normotensive Wistar Kyoto rat to identify cardiac targeting peptides, and then assessed each in the context of viral gene delivery. We identified both common and strain-selective peptides, potentially indicating ubiquitous markers and those found selectively in dysfunctional microvasculature of the heart. We show the utility of the peptide, DDTRHWG, for targeted gene delivery in human cells and rats in vivo when cloned into the fiber protein of subgroup D adenovirus 19p. This study therefore identifies cardiac targeting peptides by in vivo phage display and the potential of a candidate peptide for vector targeting strategies

    Hepsin regulates TGF beta signaling via fibronectin proteolysis

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    Transforming growth factor-beta (TGF beta) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGF beta activity by acting as a storage compartment of latent-TGF beta, but how TGF beta is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGF beta signaling through the release of latent-TGF beta from the ECM storage compartment. Mammary glands in hepsin CRISPR knockout mice showed reduced TGF beta signaling and increased epithelial branching, accompanied by increased levels of fibronectin and latent-TGF beta 1, while overexpression of hepsin in mammary tumors increased TGF beta signaling. Cell-free and cell-based experiments showed that hepsin is capable of direct proteolytic cleavage of fibronectin but not latent-TGF beta and, importantly, that the ability of hepsin to activate TGF beta signaling is dependent on fibronectin. Altogether, this study demonstrates a role for hepsin as a regulator of the TGF beta pathway in the mammary gland via a novel mechanism involving proteolytic downmodulation of fibronectin.Peer reviewe

    Composition and Function of Haemolymphatic Tissues in the European Common Shrew

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    BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding
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