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"Roberts, David"
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Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration
Rationale
Recent evidence indicates that the hypocretin/orexin system participates in the regulation of reinforcement and addiction processes. For example, manipulations that decrease hypocretin neurotransmission result in disruptions of neurochemical and behavioral responses to cocaine.
Objectives
To further assess the relationship between the hypocretin system and cocaine reinforcement, the current studies used microdialysis and
in vivo
voltammetry to examine the effects of hypocretin 1 on cocaine-induced enhancement of dopamine signaling in the nucleus accumbens core. Fixed ratio, discrete trials, and progressive ratio self-administration procedures were also used to assess whether hypocretin 1 promotes cocaine self-administration behavior.
Results
Infusions of hypocretin 1 into the ventral tegmental area increased the effects of cocaine on tonic and phasic dopamine signaling and increased the motivation to self-administer cocaine on the discrete trials and progressive ratio schedules.
Conclusions
Together with previous observations demonstrating that a hypocretin 1 receptor antagonist disrupts dopamine signaling and reduces self-administration of cocaine, the current observations further indicate that the hypocretin system participates in reinforcement processes likely through modulation of the mesolimbic dopamine system.
Journal Article
The more deceived
\"With Winston Churchill receiving unauthorised information on Britain's rearmament program, the Foreign Office brings in Lord Edward Corinth to investigate the leaks. However, Edward rapidly abandons the investigation to concentrate on the murder of a Foreign Office official, who might have been one of Churchill's sources. All too soon, he finds himself entangled in a web of deception threatening the very security of the United Kingdom. All too soon there is a second murder. Setting out for Spain to find the victim's son, Edward joins his friend Verity Browne, whom he fears is in extreme peril\"--Back cover.
Book
Dating first cases of COVID-19
Questions persist as to the origin of the COVID-19 pandemic. Evidence is building that its origin as a zoonotic spillover occurred prior to the officially accepted timing of early December, 2019. Here we provide novel methods to date the origin of COVID-19 cases. We show that six countries had exceptionally early cases, unlikely to represent part of their main case series. The model suggests a likely timing of the first case of COVID-19 in China as November 17 (95% CI October 4). Origination dates are discussed for the first five countries outside China and each continent. Results infer that SARS-CoV-2 emerged in China in early October to mid-November, and by January, had spread globally. This suggests an earlier and more rapid timeline of spread. Our study provides new approaches for estimating dates of the arrival of infectious diseases based on small samples that can be applied to many epidemiological situations.
Journal Article
Alone on the ice : the greatest survival story in the history of exploration
Describes the epic journey undertaken by Douglas Mawson, who suffered starvation, the loss of his team, and a crippling foot injury as he resorted to crawling back to base camp during the Australasian Antarctic Expedition of 1913.
Book
Liberal Peacebuilding and Global Governance
This book examines the limits to cosmopolitan liberal peacebuilding caused by its preoccupation with the values and assumptions of neoliberal global governance.
The peace people experience is determined by the processes privileged in peacebuilding. This book is about four things that shape the processes involved. First, it is a critique of orthodox postconflict peacebuilding. It takes the position that the present approach, although seemingly hegemonic, is routinely ignored or manipulated by elites and society and converted into a miasma that to some degree wastes the energies and opportunities involved. Second, it is about alternatives which invoke the kind of peace people might seek in postconflict places if they had more control over the process of peacebuilding, a notion referred to here as 'popular peace'. It is thus not the kind of critical work that some describe as 'reflexive anti-liberalism'. Rather, it seeks alternatives that are grounded in the lives of people in postconflict spaces and which also reflect some of the essential values of Liberalism. Third, it is about the role of both informal and formal actors, institutions and practices in the creation of such a peace. For instance, it is concerned with the legitimacy of informal practices that lie beyond Liberal tolerance and which are vital in the pursuit of everyday peace. Fourth, it is about a 'transversal' (rather than vertical or hierarchical) relationship of global and local governance in securing a peace that reflects the needs and values of both. In short, this work is a response to the substantial inconsistencies that appear between peacebuilding rhetoric and everyday outcomes in postconflict places.
This book will be of much interest to students of peacebuilding, post-conflict statebuilding, conflict studies, global governance and International Relations in general.
eBook
Hollow crown
\"October 1936. Joe Weaver, press magnate and close friend of the Royal family, calls for Lord Edward Corinth's help in recovering some missing letters, stolen from Wallis Simpson--the King's intimate friend. But there is no mystery about who has taken the correspondence: it is known to be Mrs. Harkness, Edward's close friend and His Majesty's former favourite. As what seemed a simple stolen property case is complicated by murder, Verity Browne joins Edward in the investigation at Haling, the country home of Conservative MP Leo Scannon, where Mrs. Harkness is a guest\"--Back cover.
Book
Biotic and Climatic Velocity Identify Contrasting Areas of Vulnerability to Climate Change
Metrics that synthesize the complex effects of climate change are essential tools for mapping future threats to biodiversity and predicting which species are likely to adapt in place to new climatic conditions, disperse and establish in areas with newly suitable climate, or face the prospect of extirpation. The most commonly used of such metrics is the velocity of climate change, which estimates the speed at which species must migrate over the earth's surface to maintain constant climatic conditions. However, \"analog-based\" velocities, which represent the actual distance to where analogous climates will be found in the future, may provide contrasting results to the more common form of velocity based on local climate gradients. Additionally, whereas climatic velocity reflects the exposure of organisms to climate change, resultant biotic effects are dependent on the sensitivity of individual species as reflected in part by their climatic niche width. This has motivated development of biotic velocity, a metric which uses data on projected species range shifts to estimate the velocity at which species must move to track their climatic niche. We calculated climatic and biotic velocity for the Western Hemisphere for 1961-2100, and applied the results to example ecological and conservation planning questions, to demonstrate the potential of such analog-based metrics to provide information on broad-scale patterns of exposure and sensitivity. Geographic patterns of biotic velocity for 2954 species of birds, mammals, and amphibians differed from climatic velocity in north temperate and boreal regions. However, both biotic and climatic velocities were greatest at low latitudes, implying that threats to equatorial species arise from both the future magnitude of climatic velocities and the narrow climatic tolerances of species in these regions, which currently experience low seasonal and interannual climatic variability. Biotic and climatic velocity, by approximating lower and upper bounds on migration rates, can inform conservation of species and locally-adapted populations, respectively, and in combination with backward velocity, a function of distance to a source of colonizers adapted to a site's future climate, can facilitate conservation of diversity at multiple scales in the face of climate change.
Journal Article
Functions of Thrombospondin-1 in the Tumor Microenvironment
The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. The diverse activities of thrombospondin-1 to regulate autophagy, senescence, stem cell maintenance, extracellular vesicle function, and metabolic responses to ischemic and genotoxic stress are mediated by several cell surface receptors and by regulating the functions of several secreted proteins. This review highlights progress in understanding thrombospondin-1 functions in cancer and the challenges that remain in harnessing its therapeutic potential.
Journal Article