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"Hall, Derek"
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Life sciences
Presents the biographies and discoveries of notables in the life sciences field. Includes time lines.
Book
STAT3 promotes IFNγ/TNFα‐induced muscle wasting in an NF‐κB‐dependent and IL‐6‐independent manner
Cachexia is a debilitating syndrome characterized by involuntary muscle wasting that is triggered at the late stage of many cancers. While the multifactorial nature of this syndrome and the implication of cytokines such as IL‐6, IFNγ, and TNFα is well established, we still do not know how various effector pathways collaborate together to trigger muscle atrophy. Here, we show that IFNγ/TNFα promotes the phosphorylation of STAT3 on Y705 residue in the cytoplasm of muscle fibers by activating JAK kinases. Unexpectedly, this effect occurs both
in vitro
and
in vivo
independently of IL‐6, which is considered as one of the main triggers of STAT3‐mediated muscle wasting. pY‐STAT3 forms a complex with NF‐κB that is rapidly imported to the nucleus where it is recruited to the promoter of the
iNos
gene to activate the iNOS/NO pathway, a well‐known downstream effector of IFNγ/TNFα‐induced muscle loss. Together, these findings show that STAT3 and NF‐κB respond to the same upstream signal and cooperate to promote the expression of pro‐cachectic genes, the identification of which could provide effective targets to combat this deadly syndrome.
Synopsis
Proinflammatory cytokines such as IFNγ and TNFα are known to be key mediators of cancer cachexia‐induced muscle loss. Here, they are shown to promote muscle atrophy by directly activating the transcription factor STAT3.
IFNγ/TNFα activate the JAKs/STAT3 signaling pathway in an IL‐6‐independent manner in skeletal muscle fibers.
IFNγ/TNFα trigger the formation of an NF‐κB/STAT3 complex.
NF‐κB is required for the translocation of STAT3 to the nucleus.
STAT3 mediates the expression of iNOS to promote IFNγ/TNFα‐induced muscle atrophy.
Graphical Abstract
Proinflammatory cytokines such as IFNγ and TNFα are known to be key mediators of cancer cachexia‐induced muscle loss. Here, they are shown to promote muscle atrophy by directly activating the transcription factor STAT3.
Journal Article
Chemistry, Earth, and space sciences
Presents the biographies and discoveries of scientists in the chemistry, Earth, and space fields. Includes time lines.
Book
Primitive Accumulation, Accumulation by Dispossession and the Global Land Grab
Critical scholars have made extensive use of the concepts of primitive accumulation and accumulation by dispossession to analyse the global land grab. These concepts have been crucial to efforts to understand the land grab in terms of the creation, expansion and reproduction of capitalist social relations, of accumulation by extra-economic means, and of dispossessory responses to capitalist crises. This paper provides an overview of these approaches. It also argues that there are substantial challenges involved in the use of primitive accumulation and accumulation by dispossession, including tensions and ambiguities over what the concepts mean, the assumptions embedded within them and problems of fit with other conceptualisations of the land grab. The paper also highlights resources for engaging with these challenges in the land grab literature.
Journal Article
Physical sciences
Presents the biographies and discoveries of scientists in the physical sciences field. Includes time lines.
Book
A Review of Potential Electrochemical Applications in Buildings for Energy Capture and Storage
The integration of distributed renewable energy technologies (such as building-integrated photovoltaics (BIPV)) into buildings, especially in space-constrained urban areas, offers sustainable energy and helps offset fossil-fuel-related carbon emissions. However, the intermittent nature of these distributed renewable energy sources can negatively impact the larger power grids. Efficient onsite energy storage solutions capable of providing energy continuously can address this challenge. Traditional large-scale energy storage methods like pumped hydro and compressed air energy have limitations due to geography and the need for significant space to be economically viable. In contrast, electrochemical storage methods like batteries offer more space-efficient options, making them well suited for urban contexts. This literature review aims to explore potential substitutes for batteries in the context of solar energy. This review article presents insights and case studies on the integration of electrochemical energy harvesting and storage into buildings. The seamless integration can provide a space-efficient source of renewable energy for new buildings or existing structures that often have limited physical space for retrofitting. This work offers a comprehensive examination of existing research by reviewing the strengths and drawbacks of various technologies for electrochemical energy harvesting and storage, identifying those with the potential to integrate into building skins, and highlighting areas for future research and development.
Journal Article
Brexit and tourism : process, impacts and non-policy
\"This book offers a multidisciplinary, holistic appraisal of the implications of the UK's withdrawal from the European Union (EU) for tourism and related mobilities. It attempts to look beyond the short- to medium-term consequences of these processes for both the UK and the EU\"-- Provided by publisher.
Book
The AMPK agonist 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation‐associated cachectic muscle wasting
Activation of AMPK has been associated with pro‐atrophic signaling in muscle. However, AMPK also has anti‐inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory‐driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα‐induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A‐769662, a specific AMPK activator. AICAR and A‐769662 co‐treatment was found to be synergistic, suggesting that the anti‐cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation‐driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.
Synopsis
Cachexia is a co‐morbidity characterized by the loss of skeletal muscle that arises in patients with pro‐inflammatory diseases, like cancer. Activators of AMPK were found to protect against inflammation‐induced muscle atrophy, demonstrating the potential of targeting AMPK for therapy in cachexia.
The AMPK activator AICAR, but not metformin, protected C2C12 myotubes from IFNγ/TNFα‐driven atrophy.
The differential effects of AICAR and metformin were associated with the ability to restore or inhibit mitochondrial function during inflammation, suggesting that the mechanism of AMPK activation affects the outcome of treatment.
The anti‐cachectic properties of AICAR were impaired by treatment with the AMPK inhibitor Compound C and were synergistic with the AMPK activator A‐769662, suggesting that the effects of AICAR were mediated by AMPK activation.
AICAR, but not metformin, was effective at preventing muscle mass loss in mice in both the C26 model of cancer cachexia and an endotoxin model of sepsis.
Collectively, this study suggests that treatment with AMPK activators during the early stages of cachexia could be a novel avenue for the development of therapies.
Graphical Abstract
Cachexia is a co‐morbidity characterized by the loss of skeletal muscle that arises in patients with pro‐inflammatory diseases, like cancer. Activators of AMPK were found to protect against inflammation‐induced muscle atrophy, demonstrating the potential of targeting AMPK for therapy in cachexia.
Journal Article
The modern world
Describes the advances made in rocket technology, space exploration, telephones, computers and medical science.
Book
Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy
The master posttranscriptional regulator HuR promotes muscle fiber formation in cultured muscle cells. However, its impact on muscle physiology and function in vivo is still unclear. Here, we show that muscle-specific HuR knockout (muHuR-KO) mice have high exercise endurance that is associated with enhanced oxygen consumption and carbon dioxide production. muHuR-KO mice exhibit a significant increase in the proportion of oxidative type I fibers in several skeletal muscles. HuR mediates these effects by collaborating with the mRNA decay factor KSRP to destabilize the
PGC-1α
mRNA. The type I fiber-enriched phenotype of muHuR-KO mice protects against cancer cachexia-induced muscle loss. Therefore, our study uncovers that under normal conditions HuR modulates muscle fiber type specification by promoting the formation of glycolytic type II fibers. We also provide a proof-of-principle that HuR expression can be targeted therapeutically in skeletal muscles to combat cancer-induced muscle wasting.
HuR is an RNA-binding protein that regulates myotube differentiation in vitro. Here, the authors show that the muscle-specific ablation of HuR in mice leads to enhanced endurance capacity and an increase in oxidative fibres by destabilising PGC1α-mRNA, and show that the mice are protected against cancer cachexia
Journal Article