90 research outputs found

    The role of genetically engineered pigs in xenotransplantation research

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    There is a critical shortage in the number of deceased human organs that become available for the purposes of clinical transplantation. This problem might be resolved by the transplantation of organs from pigs genetically engineered to protect them from the human immune response. The pathobiological barriers to successful pig organ transplantation in primates include activation of the innate and adaptive immune systems, coagulation dysregulation and inflammation. Genetic engineering of the pig as an organ source has increased the survival of the transplanted pig heart, kidney, islet and corneal graft in non-human primates (NHPs) from minutes to months or occasionally years. Genetic engineering may also contribute to any physiological barriers that might be identified, as well as to reducing the risks of transfer of a potentially infectious micro-organism with the organ. There are now an estimated 40 or more genetic alterations that have been carried out in pigs, with some pigs expressing five or six manipulations. With the new technology now available, it will become increasingly common for a pig to express even more genetic manipulations, and these could be tested in the pig-to-NHP models to assess their efficacy and benefit. It is therefore likely that clinical trials of pig kidney, heart and islet transplantation will become feasible in the near futur

    Sowing the seeds or failing to blossom? A feasibility study of a simple ecotherapy-based intervention in women affected by breast cancer

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    Engaging in nature-based activities is recognised as providing the basis for easily accessible, cost-effective interventions which can have other important physical and psychological health outcomes. The aim of the reported feasibility study was to explore the acceptability and potential psychological benefits of a simple ecotherapy-based intervention for individuals affected by cancer. A total of seven women from an existing breast cancer support group agreed to take part in the study by cultivating and customising a garden bowl for three months, maintaining a diary, and participating in a focus group at the end of the project. The analysis of the focus group data revealed four main themes that suggested that the women found engaging with the intervention to be therapeutic on a number of different levels: reflecting their cancer journey, a source of positivity, making meaning through memories, and a sense of control provided by engagement with the intervention. Engagement with the diary-writing element of the intervention, however, was not as widely endorsed by the group, as participants were even reluctant to make use of an online forum to share experiences of engaging with the intervention. Overall, the study suggests that the flexibility of level of engagement with an intervention is an important factor in developing acceptable interventions, and that the value of targeted recruitment to improve engagement with novel interventions is paramoun

    Development of the catecholamine innervation of the supraoptic nucleus in the Brattleboro rat

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    The ontogenetic development of the noradrenergic innervation of the supraoptic nucleus was studied in the Brattleboro rat at late postcoital and early postnatal ages. This genetic mutant offers a useful model for analysis of neuronal development because of the absence of a specific peptide component of identifiable target neurons and has been used presently to eliminate the possibility that such substances are essential for the establishment of normal connectivity during postnatal development. In this model, catecholamine varicosities were seen in juxtaposition to vasopressin-deficient perikarya during the initial phases of postnatal development, but these varicosities gradually decreased in number suggesting the possibility that the target neuron peptide, or some functional aspect of the neuron, may be necessary for the normal maintenance of this neuronal interaction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24975/1/0000402.pd

    Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft

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    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and alpha CD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed alpha CD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of aCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days

    Environmental liability litigation could remedy biodiversity loss

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    Many countries allow lawsuits to hold responsible parties liable for the environmental harm they cause. Such litigation remains largely untested in most biodiversity hotspots and is rarely used in response to leading drivers of biodiversity loss, including illegal wildlife trade. Yet, liability litigation is a potentially ground-breaking conservation strategy to remedy harm to biodiversity by seeking legal remedies such as species rehabilitation, public apologies, habitat conservation and education, with the goal of making the injured parties ‘whole’. However, precedent cases, expert guidance, and experience to build such conservation lawsuits is nascent in most countries. We propose a simplified framework for developing conservation lawsuits across countries and conservation contexts. We explain liability litigation in terms of three dimensions: (1) defining the harm that occurred, (2) identifying appropriate remedies to that harm, and (3) understanding what remedies the law and courts will allow. We illustrate the framework via a hypothetical lawsuit against an illegal orangutan trader in Indonesia. We highlight that conservationists’ expertise is essential to characterizing harm and identifying remedies, and could more actively contribute to strategic, science-based litigation. This would identify priority contexts, target defendants responsible for egregious harm, propose novel and meaningful remedies, and build new transdisciplinary collaborations

    Subsurface scientific exploration of extraterrestrial environments (MINAR 5): analogue science, technology and education in the Boulby Mine, UK

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    The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation

    Changes in Prefrontal-Limbic Function in Major Depression after 15 Months of Long-Term Psychotherapy

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    Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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