396 research outputs found
Real-Time Measurement of F-Actin Remodelling during Exocytosis Using Lifeact-EGFP Transgenic Animals
F-actin remodelling is essential for a wide variety of cell processes. It is important in exocytosis, where F-actin coats fusing exocytic granules. The purpose of these F-actin coats is unknown. They may be important in stabilizing the fused granules, they may play a contractile role and promote expulsion of granule content and finally may be important in endocytosis. To elucidate these functions of F-actin remodelling requires a reliable method to visualize F-actin dynamics in living cells. The recent development of Lifeact-EGFP transgenic animals offers such an opportunity. Here, we studied the characteristics of exocytosis in pancreatic acinar cells obtained from the Lifeact-EGFP transgenic mice. We show that the time-course of agonist-evoked exocytic events and the kinetics of each single exocytic event are the same for wild type and Lifeact-EGFP transgenic animals. We conclude that Lifeact-EGFP animals are a good model to study of exocytosis and reveal that F-actin coating is dependent on the de novo synthesis of F-actin and that development of actin polymerization occurs simultaneously in all regions of the granule. Our insights using the Lifeact-EGFP mice demonstrate that F-actin coating occurs after granule fusion and is a granule-wide event
Electron excitation and energy transfer rates for H2O in the upper atmosphere
Recent measurements of the cross sections for electronic state excitations in
H2O have made it possible to calculate rates applicable to these excitation
processes. We thus present here calculations of electron energy transfer rates
for electronic and vibrational state excitations in H2O, as well as rates for
excitation of some of these states by atmospheric thermal and auroral secondary
electrons. The calculation of these latter rates is an important first step
towards our aim of including water into a statistical equilibrium model of the
atmosphere under auroral conditions.Comment: 15 pages, 8 figure
Estimating retention benchmarks for salvage logging to protect biodiversity
S.T. was supported by the Humboldt-Foundation and by the MOST (Ministry of Science
and Technology) Taiwan Research Fellowship to work with A.C. at National Tsing Hua
University, Taiwan. S.T. received funds from the Gregor Louisoder Environmental
Foundation. A.B.L. received funds from the Humboldt-Foundation.Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a
widespread management practice conducted predominantly to recover economic capital,
produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed
forests are among the most threatened habitats in the world, with consequences for their
associated biodiversity. However, there are no evidence-based benchmarks for the proportion
of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity.
We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset
from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find
that 75 Âą 7% (mean Âą SD) of a naturally disturbed area of a forest needs to be left unlogged
to maintain 90% richness of its unique species, whereas retaining 50% of a naturally disturbed
forest unlogged maintains 73 Âą 12% of its unique species richness. These values do
not change with the time elapsed since disturbance but vary considerably among taxonomic
groups.Open Access funding enabled and organized by Projekt DEA
Daily life stress and the cortisol awakening response : testing the anticipation hypothesis
Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD
Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines
The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers
Two-loop Yang-Mills diagrams from superstring amplitudes
Starting from the superstring amplitude describing interactions among
D-branes with a constant world-volume field strength, we present a detailed
analysis of how the open string degeneration limits reproduce the corresponding
field theory Feynman diagrams. A key ingredient in the string construction is
represented by the twisted (Prym) super differentials, as their periods encode
the information about the background field. We provide an efficient method to
calculate perturbatively the determinant of the twisted period matrix in terms
of sets of super-moduli appropriate to the degeneration limits. Using this
result we show that there is a precise one-to-one correspondence between the
degeneration of different factors in the superstring amplitudes and
one-particle irreducible Feynman diagrams capturing the gauge theory effective
action at the two-loop level.Comment: 42 pages plus appendices, 10 figure
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Order recall in verbal short-term memory: The role of semantic networks
In their recent article, Acheson, MacDonald, and Postle (Journal of Experimental Psychology: Learning, Memory, and Cognition 37:44-59, 2011) made an important but controversial suggestion: They hypothesized that (a) semantic information has an effect on order information in short-term memory (STM) and (b) order recall in STM is based on the level of activation of items within the relevant lexico-semantic long-term memory (LTM) network. However, verbal STM research has typically led to the conclusion that factors such as semantic category have a large effect on the number of correctly recalled items, but little or no impact on order recall (Poirier & Saint-Aubin, Quarterly Journal of Experimental Psychology 48A:384-404, 1995; Saint-Aubin, Ouellette, & Poirier, Psychonomic Bulletin & Review 12:171-177, 2005; Tse, Memory 17:874-891, 2009). Moreover, most formal models of short-term order memory currently suggest a separate mechanism for order coding-that is, one that is separate from item representation and not associated with LTM lexico-semantic networks. Both of the experiments reported here tested the predictions that we derived from Acheson et al. The findings show that, as predicted, manipulations aiming to affect the activation of item representations significantly impacted order memory
How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRRâs Rehabilitation Engineering Research Centers
Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a âtotal approach to rehabilitationâ, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970âs, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program
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