7,912 research outputs found
Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure
The control of meal size is the best studied aspect of the control of energy balance, and manipulation of this system constitutes a promising target to treat obesity. A major part of this control system is based on gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1) or amylin, which are released in response to a meal and which limit the size of an ongoing meal. Both amylin and GLP-1 have also been shown to increase energy expenditure in experimental rodents, but mechanistically we know much less how this effect may be mediated, which brain sites may be involved, and what the physiological relevance of these findings may be. Most studies indicate that the effect of peripheral amylin is centrally mediated via the area postrema, but other brain areas, such as the ventral tegmental area, may also be involved. GLP-1's effect on eating seems to be mainly mediated by vagal afferents projecting to the caudal hindbrain. Chronic exposure to amylin, GLP-1 or their analogs decrease food intake and body weight gain. Next to the induction of satiation, amylin may also constitute an adiposity signal and in fact interact with the adiposity signal leptin. Amylin analogs are under clinical consideration for their effect to reduce food intake and body weight in humans, and similar to rodents, amylin analogs seem to be particularly active when combined with leptin analogs
Creating the amylin story
This paper is based on a presentation given at the Annual Meeting of the Society for the Study of Ingestive Behavior in July 2021 and provides a personal view on some of the milestones in the discovery of amylin as a constituent of pancreatic islet amyloid deposits, as a pancreatic beta-cell hormone, and on its role in physiology and pathophysiology. Only selected effects of amylin are discussed here because we recently published extensive reviews on the physiology and pathophysiology of amylin. Amylin was discovered as the main constituent of islet amyloid that is predominantly found in pancreatic islets in type 2 diabetics. These deposits, and in particular small oligomer aggregates of amylin seem to contribute to the progressive beta-cell damage seen in type 2 diabetics. Amylin is also a physiologically relevant circulating hormone with diverse metabolic functions, e.g. inhibition of eating, of pancreatic glucagon secretion and of gastric emptying. Knowledge of these types of functions and amylin's mechanisms of action lead to the development of amylin analogues that are now among the most promising anti-obesity targets in clinical testing. With this review, I want to give a short overview of 35 exciting years of amylin research
Cooperative behavior between oscillatory and excitable units: the peculiar role of positive coupling-frequency correlations
We study the collective dynamics of noise-driven excitable elements,
so-called active rotators. Crucially here, the natural frequencies and the
individual coupling strengths are drawn from some joint probability
distribution. Combining a mean-field treatment with a Gaussian approximation
allows us to find examples where the infinite-dimensional system is reduced to
a few ordinary differential equations. Our focus lies in the cooperative
behavior in a population consisting of two parts, where one is composed of
excitable elements, while the other one contains only self-oscillatory units.
Surprisingly, excitable behavior in the whole system sets in only if the
excitable elements have a smaller coupling strength than the self-oscillating
units. In this way positive local correlations between natural frequencies and
couplings shape the global behavior of mixed populations of excitable and
oscillatory elements.Comment: 10 pages, 6 figures, published in Eur. Phys. J.
Effects of BPA in snails : Oehlmann et al. respond
We welcome critical appraisals that help to provide balance; however, Dietrich et al. gave an unjustified reproach. We feel that Dietrich’s position is severely compromised because he serves as an expert for the bisphenol A (BPA) Industry Group (Brussels, Belgium). We would like to respond to the issues raised by Dietrich et al., as well as to their oversights and inappropriate interpretations of our findings..
Bisphenol A induces superfeminization in the Ramshorn snail Marisa cornuarietis (Gastropoda: Prosobranchia) at environmentally relevant concentrations
Previous investigations have shown that bisphenol A (BPA) induces a superfeminization syndrome in the freshwater snail Marisa cornuarietis at concentrations as low as 1 μg/L. Superfemales are characterized by the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production, resulting in increased female mortality. However, these studies were challenged on the basis of incomplete experimentation. Therefore, the objective of the current approach was to bridge several gaps in knowledge by conducting additional experiments. In an initial series of experiments, study results from the reproductive phase of the snails were evaluated in the sub-micrograms per liter range. Before and after the spawning season, superfemale responses were observed [NOEC (no observed effect concentration) 7.9 ng/L, EC10 (effective concentration at 10%) 13.9 ng/L], which were absent during the spawning season. A further experiment investigated the temperature dependence of BPA responses by exposing snails at two temperatures in parallel. The adverse effect of BPA was at least partially masked at 27°C (EC10 998 ng/L) when compared with 20°C (EC10 14.8 ng/L). In M. cornuarietis, BPA acts as an estrogen receptor (ER) agonist, because effects were completely antagonized by a co-exposure to tamoxifen and Faslodex. Antiandrogenic effects of BPA, such as a significant decrease in penis length at 20°C, were also observed. Competitive receptor displacement experiments indicate the presence of androgen- and estrogen-specific binding sites. The affinity for BPA of the estrogen binding sites in M. cornuarietis is higher than that of the ER in aquatic vertebrates. The results emphasize that prosobranchs are affected by BPA at lower concentrations than are other wildlife groups, and the findings also highlight the importance of exposure conditions
A controlled experiment for the empirical evaluation of safety analysis techniques for safety-critical software
Context: Today's safety critical systems are increasingly reliant on
software. Software becomes responsible for most of the critical functions of
systems. Many different safety analysis techniques have been developed to
identify hazards of systems. FTA and FMEA are most commonly used by safety
analysts. Recently, STPA has been proposed with the goal to better cope with
complex systems including software. Objective: This research aimed at comparing
quantitatively these three safety analysis techniques with regard to their
effectiveness, applicability, understandability, ease of use and efficiency in
identifying software safety requirements at the system level. Method: We
conducted a controlled experiment with 21 master and bachelor students applying
these three techniques to three safety-critical systems: train door control,
anti-lock braking and traffic collision and avoidance. Results: The results
showed that there is no statistically significant difference between these
techniques in terms of applicability, understandability and ease of use, but a
significant difference in terms of effectiveness and efficiency is obtained.
Conclusion: We conclude that STPA seems to be an effective method to identify
software safety requirements at the system level. In particular, STPA addresses
more different software safety requirements than the traditional techniques FTA
and FMEA, but STPA needs more time to carry out by safety analysts with little
or no prior experience.Comment: 10 pages, 1 figure in Proceedings of the 19th International
Conference on Evaluation and Assessment in Software Engineering (EASE '15).
ACM, 201
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