1,651 research outputs found

    Is there a reliable taphonomic clock in the temperate North Atlantic? An example from a North Sea population of the mollusc Arctica islandica

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    This is the final version. Available on open access from Elsevier via the DOI in this recordTwo hundred and seventy-seven shells of the long-lived bivalve mollusc Arctica islandica, collected from the Fladen Ground, northern North Sea, were radiocarbon dated and their taphonomic condition assessed, in order to determine whether taphonomic condition might provide a reliable indication of time since the death of the animal. With nine stations from across the Fladen Ground sampled, some strong geographic biases in 14C ages were apparent, with living and modern (post-bomb pulse) material found in the northern part of the Fladen Ground while older material (first half of the last millennium and early Holocene/Lateglacial) was concentrated in the central and western sites. Samples from the south and east Fladen Ground were sparse and were dominated by material from the second half of the last millennium. This south-north distribution is interpreted as the result of environmental change over millennial time-scales in the North Sea causing a gradual northward shift of living A. islandica populations and is not thought to be related to post mortem transport of shells to the south and east. Taphonomic condition, assessed using discriminant analysis and principal component analysis of five characteristics (amount of remaining periostracum, presence and condition of the ligament, extent of erosion at the shell margin, amount of bioerosion, and nacre condition), appeared to be a generally unreliable indicator of time since the death of the animal. Based on these five taphonomic characteristics, discriminant analysis placed 81.1% of post-bomb shells, 39.6% of shells from the period 0–500 yr BP, 68.0% of shells from the period 500–1000 yr BP and 20.0% of shells from the Early Holocene/Late glacial group into the correct radiocarbon age grouping, providing no support for the idea that this method can be used to triage shells for chronology construction as an alternative to radiometric dating.Natural Environment Research Council (NERC

    Critical Essay: Organizational cognitive neuroscience drives theoretical progress, or: The curious case of the straw man murder:organizational cognitive neuroscience drives theoretical progress, or: The curious case of the straw man murder

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    In this critical essay, we respond to Lindebaum’s (2016) argument that neuroscientific methodologies and data have been accepted prematurely in proposing novel management theory. We acknowledge that building new management theories requires firm foundations. We also find his distinction between demand and supply side forces helpful as an analytical framework identifying the momentum for the contemporary production of management theory. Nevertheless, some of the arguments Lindebaum (2016) puts forward, on closer inspection, can be contested, especially those related to the supply side of organizational cognitive neuroscience (OCN) research: fMRI data, motherhood statements and ethical concerns. We put forward a more positive case for OCN methodologies and data, as well as clarifying exactly what OCN really means, and its consequences for the development of strong management theory

    In Vitro Proliferation of Adult Human Beta-Cells

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    A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide

    Trapped in the prison of the mind: notions of climate-induced (im)mobility decision-making and wellbeing from an urban informal settlement in Bangladesh

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    The concept of Trapped Populations has until date mainly referred to people ‘trapped’ in environmentally high-risk rural areas due to economic constraints. This article attempts to widen our understanding of the concept by investigating climate-induced socio-psychological immobility and its link to Internally Displaced People’s (IDPs) wellbeing in a slum of Dhaka. People migrated here due to environmental changes back on Bhola Island and named the settlement Bhola Slum after their home. In this way, many found themselves ‘immobile’ after having been mobile—unable to move back home, and unable to move to other parts of Dhaka, Bangladesh, or beyond. The analysis incorporates the emotional and psychosocial aspects of the diverse immobility states. Mind and emotion are vital to better understand people’s (im)mobility decision-making and wellbeing status. The study applies an innovative and interdisciplinary methodological approach combining Q-methodology and discourse analysis (DA). This mixed-method illustrates a replicable approach to capture the complex state of climate-induced (im)mobility and its interlinkages to people’s wellbeing. People reported facing non-economic losses due to the move, such as identity, honour, sense of belonging and mental health. These psychosocial processes helped explain why some people ended up ‘trapped’ or immobile. The psychosocial constraints paralysed them mentally, as well as geographically. More empirical evidence on how climate change influences people’s wellbeing and mental health will be important to provide us with insights in how to best support vulnerable people having faced climatic impacts, and build more sustainable climate policy frameworks

    Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study

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    OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p  22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well-tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families

    Defining the challenges and opportunities for using patient-derived models in prostate cancer research

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    BackgroundThere are relatively few widely used models of prostate cancer compared to other common malignancies. This impedes translational prostate cancer research because the range of models does not reflect the diversity of disease seen in clinical practice. In response to this challenge, research laboratories around the world have been developing new patient-derived models of prostate cancer, including xenografts, organoids, and tumor explants.MethodsIn May 2023, we held a workshop at the Monash University Prato Campus for researchers with expertise in establishing and using a variety of patient-derived models of prostate cancer. This review summarizes our collective ideas on how patient-derived models are currently being used, the common challenges, and future opportunities for maximizing their usefulness in prostate cancer research.ResultsAn increasing number of patient-derived models for prostate cancer are being developed. Despite their individual limitations and varying success rates, these models are valuable resources for exploring new concepts in prostate cancer biology and for preclinical testing of potential treatments. Here we focus on the need for larger collections of models that represent the changing treatment landscape of prostate cancer, robust readouts for preclinical testing, improved in vitro culture conditions, and integration of the tumor microenvironment. Additional priorities include ensuring model reproducibility, standardization, and replication, and streamlining the exchange of models and data sets among research groups.ConclusionsThere are several opportunities to maximize the impact of patient-derived models on prostate cancer research. We must develop large, diverse and accessible cohorts of models and more sophisticated methods for emulating the intricacy of patient tumors. In this way, we can use the samples that are generously donated by patients to advance the outcomes of patients in the future

    Shwachman-Bodian-Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia.

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    Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase inactivated in many cancers including acute myeloid leukaemia (AML). Activation of PP2A is emerging as a therapeutic strategy, however the mechanisms underpinning PP2A inhibition are not well understood. Using myeloid progenitor cells harbouring oncogenic mutant c-KIT and characterised by PP2A inhibition, we have identified the ribosome biogenesis protein SBDS, as a target of the PP2A activating drugs FTY720 and AAL(S). We show SBDS binds to PP2A complexes comprised of the B55α regulatory subunit of PP2A. shRNA mediated knockdown of SBDS increased PP2A activity and induced apoptosis. At diagnosis, AML patients expressed significantly more SBDS mRNA than healthy controls, with relapsed patients expressing significantly more SBDS mRNA than both healthy controls and patients at diagnosis. Together, our data presents a role for SBDS in the dysregulation of PP2A in AML
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