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"Lyons, C."
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Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter
AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics which coordinates metabolism by phosphorylating a plethora of substrates throughout the cell. But how AMPK activity is regulated at different subcellular locations for precise spatiotemporal control over metabolism is unclear. Here we present a sensitive, single-fluorophore AMPK activity reporter (ExRai AMPKAR), which reveals distinct kinetic profiles of AMPK activity at the mitochondria, lysosome, and cytoplasm. Genetic deletion of the canonical upstream kinase liver kinase B1 (LKB1) results in slower AMPK activity at lysosomes but does not affect the response amplitude at lysosomes or mitochondria, in sharp contrast to the necessity of LKB1 for maximal cytoplasmic AMPK activity. We further identify a mechanism for AMPK activity in the nucleus, which results from cytoplasmic to nuclear shuttling of AMPK. Thus, ExRai AMPKAR enables illumination of the complex subcellular regulation of AMPK signaling.
AMP activated protein kinase (AMPK) is a master regulator of cellular metabolism, but how AMPK activity is spatiotemporally regulated remains unclear. Here, Schmitt et al develop a sensitive biosensor for AMPK, which they use to uncover mechanisms for AMPK activity in the lysosome and nucleus.
Journal Article
Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation
Sleep deprivation has far-reaching consequences on the brain and behavior, impacting memory, attention, and metabolism. Previous research has focused on gene expression changes in individual brain regions, such as the hippocampus or cortex. Therefore, it is unclear how uniformly or heterogeneously sleep loss affects the brain. Here, we use spatial transcriptomics to define the impact of a brief period of sleep deprivation across the brain in male mice. We find that sleep deprivation induced pronounced differences in gene expression across the brain, with the greatest changes in the hippocampus, neocortex, hypothalamus, and thalamus. Both the differentially expressed genes and the direction of regulation differed markedly across regions. Importantly, we developed bioinformatic tools to register tissue sections and gene expression data into a common anatomical space, allowing a brain-wide comparison of gene expression patterns between samples. Our results suggest that distinct molecular mechanisms acting in discrete brain regions underlie the biological effects of sleep deprivation.
Sleep deprivation impacts molecular changes across brain regions. Here, the authors utilize a spatial. transcriptomics approach to elucidate acute sleep deprivation-induced gene expression signature. across regions and subregions of the brain.
Journal Article
Tales from 1,001 nights : Aladdin, Ali Baba and other favourite tales
A collection of tales from the classic work, including the stories of Ali Baba, Aladdin, and Sindbad.
Book
Rewilding of Fukushima’s human evacuation zone
There is substantial interest in understanding the ecological impacts of the nuclear accidents at the Chernobyl and Fukushima Daiichi nuclear power plants. However, population-level data for large mammals have been limited, and there remains much speculation regarding the status of wildlife species in these areas. Using a network of remote cameras placed along a gradient of radiological contamination and human presence, we collected data on population-level impacts to wildlife (that is, abundance and occupancy patterns) following the 2011 Fukushima Daiichi nuclear accident. We found no evidence of population-level impacts in mid-to large-sized mammals or gallinaceous birds, and show several species were most abundant in human-evacuated areas, despite the presence of radiological contamination. These data provide unique evidence of the natural rewilding of the Fukushima landscape following human abandonment, and suggest that if any effects of radiological exposure in mid-to large-sized mammals in the Fukushima Exclusion Zone exist, they occur at individual or molecular scales, and do not appear to manifest in population-level responses.
Journal Article
The man of wiles in popular Arabic literature : a study of a medieval Arab hero
The Man of Wiles (otherwise known as the Master Thief, the Trickster or the Fool) appears in every hero cycle within classical Arabic literature - proof of this figure's popularity with the audiences of Arab story-tellers. He embodies views acceptable to an otherwise inarticulate part of the population, allowing Islam to be treated in a paradoxical and sometimes humorous light in contrast to conventional piety. And he shares with Odysseus not only his wiles but his function as 'the sacker of cities', redressing the idea that classical Arabic literature is unrelated to anything outside its own borders. The study of this popular form sets out in detail the recorded lives of these Men of Wiles for those to whom the original texts are not available. -- Jacket.
Book
The Law of Nations in the Diplomacy of the American Revolution
Historians have long known that leaders of the American Revolution looked to the law of nations for insight into the rights and obligations of independent states. In so doing, Americans relied largely on the writings of European legal theorists, such as Hugo Grotius and Emerich de Vattel, whose treatises on the law of nations are regarded today as having laid the foundations of international law. As this article demonstrates, however, early modern statesmen did not base their conduct on such treatises, but on a customary law of nations that they derived from precedent and the text of earlier treaties. This article elucidates the distinction between the customary and theoretical branches of the law of nations. It then goes on to examine the law of nations’ impact on revolutionary-era diplomacy, drawing particular attention to a series of wartime negotiations over rights to the Mississippi River. As the article shows, most American emissaries lacked experience with the customary laws of diplomacy and struggled to use that law effectively in their negotiations. The most serious consequences were averted due in part to French legal advice, and because one American, John Jay, acquired enough competence in customary law to guide his colleagues toward an effective negotiation of peace.
Journal Article
Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
Fibrin has been used clinically for wound coverings, surgical glues, and cell delivery because of its affordability, cytocompatibility, and ability to modulate angiogenesis and inflammation. However, its rapid degradation rate has limited its usefulness as a scaffold for 3D cell culture and tissue engineering. Previous studies have sought to slow the degradation rate of fibrin with the addition of proteolysis inhibitors or synthetic crosslinkers that require multiple functionalization or polymerization steps. These strategies are difficult to implement in vivo and introduce increased complexity, both of which hinder the use of fibrin in research and medicine. Previously, we demonstrated that additional crosslinking of fibrin gels using bifunctionalized poly(ethylene glycol)-n-hydroxysuccinimide (PEG-NHS) slows the degradation rate of fibrin. In this study, we aimed to further improve the longevity of these PEG-fibrin gels such that they could be used for tissue engineering in vitro or in situ without the need for proteolysis inhibitors. It is well documented that increasing the salinity of fibrin precursor solutions affects the resulting gel morphology. Here, we investigated whether this altered morphology influences the fibrin degradation rate. Increasing the final sodium chloride (NaCl) concentration from 145 mM (physiologic level) to 250 mM resulted in fine, transparent high-salt (HS) fibrin gels that degrade 2–3 times slower than coarse, opaque physiologic-salt (PS) fibrin gels both in vitro (when treated with proteases and when seeded with amniotic fluid stem cells) and in vivo (when injected subcutaneously into mice). Increased salt concentrations did not affect the viability of encapsulated cells, the ability of encapsulated endothelial cells to form rudimentary capillary networks, or the ability of the gels to maintain induced pluripotent stem cells. Finally, when implanted subcutaneously, PS gels degraded completely within one week while HS gels remained stable and maintained viability of seeded dermal fibroblasts. To our knowledge, this is the simplest method reported for the fabrication of fibrin gels with tunable degradation properties and will be useful for implementing fibrin gels in a wide range of research and clinical applications.
Journal Article