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"Hall, Catherine"
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More than just summed neuronal activity: how multiple cell types shape the BOLD response
Functional neuroimaging techniques are widely applied to investigations of human cognition and disease. The most commonly used among these is blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. The BOLD signal occurs because neural activity induces an increase in local blood supply to support the increased metabolism that occurs during activity. This supply usually outmatches demand, resulting in an increase in oxygenated blood in an active brain region, and a corresponding decrease in deoxygenated blood, which generates the BOLD signal. Hence, the BOLD response is shaped by an integration of local oxygen use, through metabolism, and supply, in the blood. To understand what information is carried in BOLD signals, we must understand how several cell types in the brain—local excitatory neurons, inhibitory neurons, astrocytes and vascular cells (pericytes, vascular smooth muscle and endothelial cells), and their modulation by ascending projection neurons—contribute to both metabolism and haemodynamic changes. Here, we review the contributions of each cell type to the regulation of cerebral blood flow and metabolism, and discuss situations where a simplified interpretation of the BOLD response as reporting local excitatory activity may misrepresent important biological phenomena, for example with regards to arousal states, ageing and neurological disease. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Journal Article
Diffusing the legal conceptions of the global south and decolonizing international law: crystallizing animal rights through inter-judicial dialogue
Global environmental law is characterized by Eurocentric cultural paradigms that perceive humanity as external and superior to Nature. This supremacy over Nature reflects a legacy of Western colonial domination. Accordingly, environmental regulations have been complicit in sustaining the paradigms that have given rise to the Anthropocene. It is against this backdrop that this article seeks to investigate how global environmental law could engage in transformative reform by embracing Southern epistemologies, particularly through the legal subjectivisation of Nature, i.e. by conceptualizing Nature as subjects of rights. Rooted in Indigenous worldviews, the emerging Rights of Nature movement provides a critical opportunity to re-envision global environmental law through historically colonized and marginalized forms of knowledge. In particular, this article explores the instrumentality of litigation to act as a catalyst for diffusing Southern conceptions in Eurocentric legal cultures to decolonize international law. This article specifically analyzes the animal rights dimension of the broader Rights of Nature paradigm. It argues that the recent wave of litigation awarding rights to animals - primarily in the Global South - reflects an evolving inter-judicial dialogue between domestic judges, whose interactions could potentially feed into a cosmopolitan global jurisprudence for animal rights in a bottom-up manner, which captures the plurality of ways of understanding and conceptualizing Nature.
Journal Article
Learning and teaching community-based research : linking pedagogy to practice
\"Community-Based Research, or CBR, is a mix of innovative, participatory approaches that put the community at the heart of the research process. Learning and Teaching Community-Based Research shows that CBR can also operate as an innovative pedagogical practice, engaging community members, research experts, and students.
Book
Insulin receptor endocytosis in the pathophysiology of insulin resistance
Insulin signaling controls cell growth and metabolic homeostasis. Dysregulation of this pathway causes metabolic diseases such as diabetes. Insulin signaling pathways have been extensively studied. Upon insulin binding, the insulin receptor (IR) triggers downstream signaling cascades. The active IR is then internalized by clathrin-mediated endocytosis. Despite decades of studies, the mechanism and regulation of clathrin-mediated endocytosis of IR remain incompletely understood. Recent studies have revealed feedback regulation of IR endocytosis through Src homology phosphatase 2 (SHP2) and the mitogen-activated protein kinase (MAPK) pathway. Here we review the molecular mechanism of IR endocytosis and its impact on the pathophysiology of insulin resistance, and discuss the potential of SHP2 as a therapeutic target for type 2 diabetes.Insulin: Keeping the receptors signalingA potential cancer treatment also shows promise for treatment of type 2 diabetes. When insulin receptors (IRs) on cell surfaces bind to insulin, they send out signals that trigger glucose uptake, lowering blood sugar. The duration of IR signaling is crucial for metabolic health, but its regulation is poorly understood. Eunhee Choi, Columbia University, New York, and Hongtao Yu, Westlake University, Hangzhou, and a coworker have reviewed how IR signaling is controlled. They report that inhibiting the protein SHP2 may prolong IR signaling and improve how the body responds to insulin. Because SHP2 is also implicated in cancer, inhibitors have already been developed and could be tested for treatment of metabolic diseases. These results illuminate the fundamentals of a key metabolic pathway, and may help in treatment of type 2 diabetes.
Journal Article
Long COVID: mechanisms, risk factors and recovery
New Findings What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies. Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post‐viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post‐viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID‐related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro‐clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.
Journal Article