69 research outputs found
Systematic analysis of funding awarded for antimicrobial resistance research to institutions in the UK, 1997-2010
Objectives: To assess the level of research funding awarded to UK institutions specifically for antimicrobial resistance-related research and how closely the topics funded relate to the clinical and public health burden of resistance.Methods: Databases and web sites were systematically searched for information on how infectious disease research studies were funded for the period 1997–2010. Studies specifically related to antimicrobial resistance, including bacteriology, virology, mycology and parasitology research, were identified and categorized in terms of funding by pathogen and disease and by a research and development value chain describing the type of science.Results: The overall dataset included 6165 studies receiving a total investment of £2.6 billion, of which £102 million was directed towards antimicrobial resistance research (5.5% of total studies, 3.9% of total spend). Of 337 resistance-related projects, 175 studies focused on bacteriology (40.2% of total resistance-related spending), 42 focused on antiviral resistance (17.2% of funding) and 51 focused on parasitology (27.4% of funding). Mean annual funding ranged from £1.9 million in 1997 to £22.1 million in 2009.Conclusions: Despite the fact that the emergence of antimicrobial resistance threatens our future ability to treat many infections, the proportion of the UK infection-research spend targeting this important area is small. There are encouraging signs of increased investment in this area, but it is important that this is sustained and targeted at areas of projected greatest burden. Two areas of particular concern requiring more investment are tuberculosis and multidrug-resistant Gram-negative bacteria.<br/
Inhibition of protein phosphatases-1 and -2A with acanthifolicin Comparison with diarrhetic shellfish toxins and identification of a region on okadaic acid important for phosphatase inhibition
AbstractAcanthifolicin (9,10-epithio-okadaic acid from Pandoras acanthifolium) inhibited protein phosphatase-1 (PP1) similarly to okadaic acid (IC50 = 20 nM and 19 nM, respectively) but was slightly less active against protein phosphatase-2A (PP2A) (IC50 1 nM and 0.2 nM, respectively). Methyl esterification of acanthifolicin sharply reduced its activity. PP2A was inhibited with an IC50 = 5.0 μM, whilst PP1 was inhibited < 10% at 250 μM toxin. Okadaic acid methyl ester was similarly inactive whereas dinophysistoxin-1 (35-methyl okadaic acid) inhibited PP1/2A almost as potently as okadaic acid. Pure acanthifolicin/okadaic acid methyl ester may be useful as specific inhibitors of PP2A at 1–10 μM concentrations in vitro and perhaps in vivo. The data also indicate that a region on these toxins important for PP1/2A inhibition comprises the single carboxyl group
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BrGDGT temperature reconstruction from interior Alaska: Assessing 14,000 years of deglacial to Holocene temperature variability and potential effects on early human settlement
Aeolian deposits in the middle Tanana Valley of central Alaska offer a well-preserved record of paleoenvironmental change since the deglacial period (c. 16,000–11,000 cal yr BP). These deposits also contain some of North America's oldest archaeological occupations (c. 14,000–13,000 cal yr BP), making this region critically important for understanding human migration into the high latitudes and the Americas. Major research questions involve assessing the magnitude of deglacial climatic change and the influence of climate on early human groups. This study uses branched glycerol dialkyl glycerol tetraethers (brGDGTs) from six loess-paleosol sequences to develop a quantitative paleotemperature record within terrestrial locations in the Tanana basin that are close to archaeological sites. BrGDGT-derived temperatures demonstrate a lack of cooler temperatures associated with deglacial conditions, making this region relatively “warm” compared to other parts of the globe. Additionally, our brGDGT record shows little coherent temperature change associated with deglacial climate variability (e.g., Bølling-Allerød, Younger Dryas), and Holocene temperatures are relatively stable as well, indicating that temperature fluctuation was not the main driver of environmental or archaeological change over time. We recommend averaging data across multiple terrestrial exposures to produce regional temperature reconstrutions. © 2023Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
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