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result(s) for
"DAVIS, Michael"
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Conditioning-induced expression of novel glucose transporters in canine skeletal muscle homogenate
2023
Athletic conditioning can increase the capacity for insulin-stimulated skeletal muscle glucose uptake through increased sarcolemmal expression of GLUT4 and potentially additional novel glucose transporters. We used a canine model that has previously demonstrated conditioning-induced increases in basal, insulin- and contraction-stimulated glucose uptake to identify whether expression of glucose transporters other than GLUT4 was upregulated by athletic conditioning. Skeletal muscle biopsies were obtained from 12 adult Alaskan Husky racing sled dogs before and after a full season of conditioning and racing, and homogenates from those biopsies were assayed for expression of GLUT1, GLUT3, GLUT4, GLUT6, GLUT8, and GLUT12 using western blots. Athletic conditioning resulted in a 1.31 ± 0.70 fold increase in GLUT1 (p <0.0001), 1.80 ± 1.99 fold increase in GLUT4 (p = 0.005), and 2.46 ± 2.39 fold increase in GLUT12 (p = 0.002). The increased expression of GLUT1 helps explain the previous findings of conditioning-induced increases in basal glucose clearance in this model, and the increase in GLUT12 provides an alternative mechanism for insulin- and contraction-mediated glucose uptake and likely contributes to the substantial conditioning-induced increases in insulin sensitivity in highly trained athletic dogs. Furthermore, these results suggest that athletic dogs can serve as a valuable resource for the study of alternative glucose transport mechanisms in higher mammals.
Journal Article
Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes
by
Goldberg, Joanna B
,
Potter-Bynoe, Gail
,
Kishony, Roy
in
631/208/2489/144
,
631/208/514/1948
,
631/326/41/2531
2011
Roy Kishony and colleagues sequenced the genomes of 112
Burkholderia dolosa
isolates recovered from 14 individuals with cystic fibrosis as part of a retrospective study from a hospital epidemic monitored over the course of 16 years. They tracked recurrent mutations occurring in the bacterial isolates and found that 17 genes showed evidence of parallel adaptive evolution.
Bacterial pathogens evolve during the infection of their human host
1
,
2
,
3
,
4
,
5
,
6
,
7
,
8
, but separating adaptive and neutral mutations remains challenging
9
,
10
,
11
. Here we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple individuals. We conducted a retrospective study of a
Burkholderia dolosa
outbreak among subjects with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired nonsynonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes affect important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition and implicate oxygen-dependent regulation as paramount in lung infections. Several genes have not previously been implicated in pathogenesis and may represent new therapeutic targets. The identification of parallel molecular evolution as a pathogen spreads among multiple individuals points to the key selection forces it experiences within human hosts.
Journal Article
Gilbert Simondon's Psychic and collective individuation : a critical introduction and guide
A critical commentary on Simondon's Psychic and collective individuation. This book clarifies Simondon's complex terminology and structure through chapter by chapter commentary. It also invites a dialogue with other thinkers/philosophers and places the work in its historical context. It includes a discussion about Simondon's relevance to current ideas about biopolitics and post-Nietzschean ethics.
Hong Kong: How Beijing Perfected Repression
2022
China's move to impose on Hong Kong a new National Security Law (NSL) in 2020 and accompanying \"electoral reforms\" in 2021 represent a complete hollowing out and abandonment of the city's liberal-democratic constitutional model that Beijing had promised to let stand. These policies turned Hong Kong's vaunted legal system into the chief instrument of repression, challenging the independence of the city's courts, law enforcement, and legislative process. This article traces the mass arrests made under the NSL and other challenges posed to basic freedoms across all sectors of the city's society. Does this hollowing out of constitutional guarantees represent the oft-discussed PRC alternative to Western liberal democracy?
Journal Article
The secret body : how the new science of the human body is changing the way we live
Traversing six key frontiers of human biology, Daniel Davis shows how these radical possibilities have been made real - thanks to the ingenious, decades-long work of scientists whose breakthrough discoveries are transforming our understanding of how the body works, what it is capable of and how we might manipulate it. By bringing together the latest understanding of the immune system, the brain, the microbiome, the interaction of cells and the development of the foetus, including developments such as optogenetics, super-resolution microscopy, the human cell atlas and systems biology, we arrive at a vision of the human body of dizzying complexity, wonder and possibility.
Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage
2024
Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes
1
–
17
, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in
Prox1-GFP
lymphatic reporter mice
18
, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.
The nasopharyngeal lymphatic plexus is a major hub for cerebrospinal fluid outflow to deep cervical lymph nodes.
Journal Article