155 research outputs found

    Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host

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    Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as “infection resistance,” in which hosts delay or prevent infection, and “proliferation resistance,” in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h2 = 0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection-resistant animals thus appear to follow a “fast” pace-of-life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health—such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population

    Effect of alemtuzumab-based T-cell depletion on graft compositional change in vitro and immune reconstitution early after allogeneic stem cell transplantation

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    Background aims: To reduce the risk of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloSCT), T-cell depletion (TCD) of grafts can be performed by the addition of alemtuzumab (ALT) "to the bag" (in vitro) before transplantation. In this prospective study, the authors analyzed the effect of in vitro incubation with 20 mg ALT on the composition of grafts prior to graft infusion. Furthermore, the authors assessed whether graft composition at the moment of infusion was predictive for T-cell reconstitution and development of GVHD early after TCD alloSCT.Methods: Sixty granulocyte colony-stimulating factor-mobilized stem cell grafts were obtained from >= 9/10 HLA-matched related and unrelated donors. The composition of the grafts was analyzed by flow cytometry before and after in vitro incubation with ALT. T-cell reconstitution and incidence of severe GVHD were monitored until 12 weeks after transplantation.Results: In vitro incubation of grafts with 20 mg ALT resulted in an initial median depletion efficiency of T-cell receptor (TCR) alpha/beta T cells of 96.7% (range, 63.5-99.8%), followed by subsequent depletion in vivo. Graft volumes and absolute leukocyte counts of grafts before the addition of ALT were not predictive for the efficiency of TCR alpha/beta T-cell depletion. CD4(pos) T cells were depleted more efficiently than CD8(pos) T cells, and naive and regulatory T cells were depleted more efficiently than memory and effector T cells. This differential depletion of T-cell subsets was in line with their reported differential CD52 expression. In vitro depletion efficiencies and absolute numbers of (naive) TCR alpha/beta T cells in the grafts after ALT incubation were not predictive for T cell reconstitution or development of GVHD postalloSCT.Conclusions: The addition of ALT to the bag is an easy, fast and generally applicable strategy to prevent GVHD in patients receiving alloSCT after myeloablative or non-myeloablative conditioning because of the efficient differential depletion of donor-derived lymphocytes and T cells. (C) 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

    Effects of an anionic surfactant (FFD-6) on the energy and information flow between a primary producer (Scenedesmus obliquus) and a consumer (Daphnia magna)

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    The effects of a commercially available anionic surfactant solution (FFD-6) on growth and morphology of a common green alga (Scenedesmus obliquus) and on survival and clearance rates of the water flea Daphnia magna were studied. The surfactant-solution elicited a morphological response (formation of colonies) in Scenedesmus at concentrations of 10–100 μl l−1 that were far below the No Observed Effect Concentration (NOEC) value of 1,000 μl l−1 for growth inhibition. The NOEC-value of FFD-6 for colony-induction was 3 μl l−1. Daphnia survival was strongly affected by FFD-6, yielding LC50–24h and LC50–48h of 148 and 26 μl l−1, respectively. In addition, clearance rates of Daphnia feeding on unicellular Scenedesmus were inhibited by FFD-6, yielding a 50% inhibition (EC50–1.5h) at 5.2 μl l−1 with a NOEC of 0.5 μl l−1. When Daphnia were offered FFD-6-induced food in which eight-celled colonies (43 × 29 μm) were most abundant, clearance rates (~0.14 ml ind.−1 h−1) were only 25% the rates of animals that were offered non-induced unicellular (15 × 5 μm) Scenedesmus (~0.56 ml ind.−1 h−1). As FFD-6 concentrations in the treated food used in the experiments were far below the NOEC for clearance rate inhibition, it is concluded that the feeding rate depression was caused by the altered morphology of the Scenedesmus moving them out of the feeding window of the daphnids. The surfactant evoked a response in Scenedesmus that is similar to the natural chemically induced defensive reaction against grazers and could disrupt the natural information conveyance between these plankton organisms

    Kimberlites reveal 2.5-billion-year evolution of a deep, isolated mantle reservoir

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    The widely accepted paradigm of Earth's geochemical evolution states that the successive extraction of melts from the mantle over the past 4.5 billion years formed the continental crust, and produced at least one complementary melt-depleted reservoir that is now recognized as the upper-mantle source of mid-ocean-ridge basalts1. However, geochemical modelling and the occurrence of high 3He/4He (that is, primordial) signatures in some volcanic rocks suggest that volumes of relatively undifferentiated mantle may reside in deeper, isolated regions2. Some basalts from large igneous provinces may provide temporally restricted glimpses of the most primitive parts of the mantle3,4, but key questions regarding the longevity of such sources on planetary timescales—and whether any survive today—remain unresolved. Kimberlites, small-volume volcanic rocks that are the source of most diamonds, offer rare insights into aspects of the composition of the Earth’s deep mantle. The radiogenic isotope ratios of kimberlites of different ages enable us to map the evolution of this domain through time. Here we show that globally distributed kimberlites originate from a single homogeneous reservoir with an isotopic composition that is indicative of a uniform and pristine mantle source, which evolved in isolation over at least 2.5 billion years of Earth history—to our knowledge, the only such reservoir that has been identified to date. Around 200 million years ago, extensive volumes of the same source were perturbed, probably as a result of contamination by exogenic material. The distribution of affected kimberlites suggests that this event may be related to subduction along the margin of the Pangaea supercontinent. These results reveal a long-lived and globally extensive mantle reservoir that underwent subsequent disruption, possibly heralding a marked change to large-scale mantle-mixing regimes. These processes may explain why uncontaminated primordial mantle is so difficult to identify in recent mantle-derived melts

    Plutonic foundation of a slow-spreading ridge segment : oceanic core complex at Kane Megamullion, 23°30′N, 45°20′W

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    Author Posting. Š American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q05014, doi:10.1029/2007GC001645.We mapped the Kane megamullion, an oceanic core complex on the west flank of the Mid-Atlantic Ridge exposing the plutonic foundation of a ∟50 km long, second-order ridge segment. The complex was exhumed by long-lived slip on a normal-sense detachment fault at the base of the rift valley wall from ∟3.3 to 2.1 Ma (Williams, 2007). Mantle peridotites, gabbros, and diabase dikes are exposed in the detachment footwall and in outward facing high-angle normal fault scarps and slide-scar headwalls that cut through the detachment. These rocks directly constrain crustal architecture and the pattern of melt flow from the mantle to and within the lower crust. In addition, the volcanic carapace that originally overlay the complex is preserved intact on the conjugate African plate, so the complete internal and external architecture of the paleoridge segment can be studied. Seafloor spreading during formation of the core complex was highly asymmetric, and crustal accretion occurred largely in the footwall of the detachment fault exposing the core complex. Because additions to the footwall, both magmatic and amagmatic, are nonconservative, oceanic detachment faults are plutonic growth faults. A local volcano and fissure eruptions partially cover the northwestern quarter of the complex. This volcanism is associated with outward facing normal faults and possible, intersecting transform-parallel faults that formed during exhumation of the megamullion, suggesting the volcanics erupted off-axis. We find a zone of late-stage vertical melt transport through the mantle to the crust in the southern part of the segment marked by a ∟10 km wide zone of dunites that likely fed a large gabbro and troctolite intrusion intercalated with dikes. This zone correlates with the midpoint of a lineated axial volcanic high of the same age on the conjugate African plate. In the central region of the segment, however, primitive gabbro is rare, massive depleted peridotite tectonites abundant, and dunites nearly absent, which indicate that little melt crossed the crust-mantle boundary there. Greenschist facies diabase and pillow basalt hanging wall debris are scattered over the detachment surface. The diabase indicates lateral melt transport in dikes that fed the volcanic carapace away from the magmatic centers. At the northern edge of the complex (southern wall of the Kane transform) is a second magmatic center marked by olivine gabbro and minor troctolite intruded into mantle peridotite tectonite. This center varied substantially in size with time, consistent with waxing and waning volcanism near the transform as is also inferred from volcanic abyssal-hill relief on the conjugate African plate. Our results indicate that melt flow from the mantle focuses to local magmatic centers and creates plutonic complexes within the ridge segment whose position varies in space and time rather than fixed at a single central point. Distal to and between these complexes there may not be continuous gabbroic crust, but only a thin carapace of pillow lavas overlying dike complexes laterally fed from the magmatic centers. This is consistent with plate-driven flow that engenders local, stochastically distributed transient instabilities at depth in the partially molten mantle that fed the magmatic centers. Fixed boundaries, such as large-offset fracture zones, or relatively short segment lengths, however, may help to focus episodes of repeated melt extraction in the same location. While no previous model for ocean crust is like that inferred here, our observations do not invalidate them but rather extend the known diversity of ridge architecture.NSF Grants OCE-0118445, OCE-0624408 and OCE-0621660 supported this research. B. Tucholke was also supported by the Henry Bryant Bigelow Chair in Oceanography at Woods Hole Oceanographic Institution

    Knowledge translation on dementia: a cluster randomized trial to compare a blended learning approach with a "classical" advanced training in GP quality circles

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    <p>Abstract</p> <p>Background</p> <p>Thus far important findings regarding the dementia syndrome have been implemented into patients' medical care only inadequately. A professional training accounting for both, general practitioners' (GP) needs and learning preferences as well as care-relevant aspects could be a major step towards improving medical care. In the WIDA-study, entitled "Knowledge translation on dementia in general practice" two different training concepts are developed, implemented and evaluated. Both concepts are building on an evidence-based, GP-related dementia guideline and communicate the guideline's essential insights.</p> <p>Methods/Design</p> <p>Both development and implementation emphasize a procedure that is well-accepted in practice and, thus, can achieve a high degree of external validity. This is particularly guaranteed through the preparation of training material and the fact that general practitioners' quality circles (QC) are addressed. The evaluation of the two training concepts is carried out by comparing two groups of GPs to which several quality circles have been randomly assigned. The primary outcome is the GPs' knowledge gain. Secondary outcomes are designed to indicate the training's potential effects on the GPs' practical actions. In the first training concept (study arm A) GPs participate in a structured case discussion prepared for by internet-based learning material ("blended-learning" approach). The second training concept (study arm B) relies on frontal medical training in the form of a slide presentation and follow-up discussion ("classical" approach).</p> <p>Discussion</p> <p>This paper presents the outline of a cluster-randomized trial which has been peer reviewed and support by a national funding organization – Federal Ministry of Education and Research (BMBF) – and is approved by an ethics commission. The data collection has started in August 2006 and the results will be published independently of the study's outcome.</p> <p>Trial Registration</p> <p>Current Controlled Trials [ISRCTN36550981]</p
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