ORCID Profile
0000-0001-9091-214X
Current Organisations
University of Sydney
,
The University of Texas at Austin
,
Westmead Institute for Medical Research
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Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2022
DOI: 10.1101/2022.07.22.501201
Abstract: Diabetes is a global public health burden and is characterized clinically by a relative or absolute insulin deficiency. Therapeutic agents that stimulate and improve insulin secretion and insulin sensitivity are in high demand as diabetic treatment. CD47 is a cell surface glycoprotein implicated in multiple cellular functions, including recognition of self, angiogenesis, and nitric oxide signaling, however its role in the regulation of insulin secretion remains unknown. For the first time we demonstrate that CD47 receptor signaling inhibits insulin release from β-cells and that it can be pharmacologically exploited to boost insulin secretion. CD47 depletion stimulates insulin granule exocytosis via activation of the Rho GTPase Cdc42. CD47 deficiency improved glucose clearance and insulin sensitivity in mice. CD47 blockade enhanced islet transplantation efficiency and improved outcomes. Further, anti-CD47 antibody treatment delayed the onset of diabetes in non-obese diabetic mice and protected them from overt diabetes. Our findings identify CD47 as a previously unrecognized regulator of insulin secretion and its manipulation in β-cells offers a novel therapeutic opportunity for diabetes and islet transplantation by correcting insulin deficiency. CD47 limits insulin secretion and islet transplant outcomes
Publisher: Psychology Press
Date: 31-07-2013
Publisher: Psychology Press
Date: 15-03-2011
Publisher: Wiley
Date: 12-2008
Publisher: Psychology Press
Date: 15-02-2013
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-07-2007
Abstract: Women are generally assumed to be more talkative than men. Data were analyzed from 396 participants who wore a voice recorder that s led ambient sounds for several days. Participants' daily word use was extrapolated from the number of recorded words. Women and men both spoke about 16,000 words per day.
Publisher: Informa UK Limited
Date: 09-08-2011
DOI: 10.1080/10410236.2011.571759
Abstract: Web-based methodologies may provide a new and unique insight into public response to an infectious disease outbreak. This naturalistic study investigates the effectiveness of new web-based methodologies in assessing anxiety and information seeking in response to the 2009 H1N1 outbreak by examining language use in weblogs ("blogs"), newspaper articles, and web-based information seeking. Language use in blogs and newspaper articles was assessed using Linguistic Inquiry and Word Count, and information seeking was examined using the number of daily visits to H1N1-relevant Wikipedia articles. The results show that blogs mentioning "swine flu" used significantly higher levels of anxiety, health, and death words and lower levels of positive emotion words than control blogs. Change in language use on blogs was strongly related to change in language use in newspaper coverage for the same day. Both the measure of anxiety in blogs mentioning "swine flu" and the number of Wikipedia visits followed similar trajectories, peaking shortly after the announcement of H1N1 and then declining rapidly. Anxiety measured in blogs preceded information seeking on Wikipedia. These results show that the public reaction to H1N1 was rapid and short-lived. This research suggests that analysis of web behavior can provide a source of naturalistic data on the level and changing pattern of public anxiety and information seeking following the outbreak of a public health emergency.
Publisher: Wiley
Date: 31-08-2019
Publisher: Springer Science and Business Media LLC
Date: 15-12-2020
DOI: 10.1038/S41598-020-78936-5
Abstract: Acute kidney injury (AKI) is a major health problem affecting millions of patients globally. There is no effective treatment for AKI and new therapies are urgently needed. Novel drug development, testing and progression to clinical trials is overwhelmingly expensive. Drug repurposing is a more cost-effective measure. We identified 2 commonly used drugs (colchicine and metformin) that alter inflammatory cell function and signalling pathways characteristic of AKI, and tested them in models of acute and chronic kidney injury to assess therapeutic benefit. We assessed the renoprotective effects of colchicine or metformin in C57BL/6 mice challenged with renal ischemia reperfusion injury (IRI), treated before or after injury. All animals underwent analysis of renal function and biomolecular phenotyping at 24 h, 48 h and 4 weeks after injury. Murine renal tubular epithelial cells were studied in response to in vitro mimics of IRI. Pre-emptive treatment with colchicine or metformin protected against AKI, with lower serum creatinine, improved histological changes and decreased TUNEL staining. Pro-inflammatory cytokine profile and multiple markers of oxidative stress were not substantially different between groups. Metformin augmented expression of multiple autophagic proteins which was reversed by the addition of hydroxychloroquine. Colchicine led to an increase in inflammatory cells within the renal parenchyma. Chronic exposure after acute injury to either therapeutic agent in the context of reduced renal mass did not mitigate the development of fibrosis, with colchicine significantly worsening an ischemic phenotype. These data indicate that colchicine and metformin affect acute and chronic kidney injury differently. This has significant implications for potential drug repurposing, as baseline renal disease must be considered when selecting medication.
Location: United States of America
Location: No location found
No related grants have been discovered for James Pennebaker.