Sleeve Gastrectomy Leads to Weight Loss in the Magel2 Knockout Mouse

Background Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia, obesity, cardiopulmonary diseases, and increased mortality. Although successful weight loss improves health in PWS, few treatments cause sustained weight loss in obese patients let alone obese individuals with PWS. Objectives The present study uses the Magel2 knockout (KO) mouse, an animal model of PWS, to conduct a preclinical study on the efficacy of sleeve gastrectomy(SG) in PWS. Setting Academic research laboratory, United States. Methods We performed sham or SG surgeries in 24- to 28-week-old male Magel2 KO and wild-type littermate control mice (WT) who had been maintained on a high-fat diet for 10 weeks. We monitored weight, food intake, and fat and lean mass pre- and postoperatively. Fasting glucose, glucose tolerance, and counter-regulation were measured postoperatively. Results Magel2 KO animals had similar recovery and mortality rates compared with WT. SG resulted in similar weight loss, specifically loss of fat but not lean mass, in both Magel2 KO and WT mice. SG also resulted in significantly lower fasting glucose levels and a reduction in fat intake in both Magel2 KO and WT mice. We also found that Magel2 KO mice failed to increase their food intake in response to the glucoprivic agent 2-deoxy-D-glucose, suggesting impaired glucose counter-regulation, but this occurred regardless of surgical status. All results were considered significant when P\u3c .05. Conclusion We find in this mouse model of PWS, SG is a well-tolerated, effective strategy for weight and fat loss

Metabolic Effects of Bariatric Surgery in Mouse Models of Circadian Disruption

Background/Objectives: Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity. Subjects/Methods: Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption. Results: VSG led to a reduction in body weight and fat mass in both ClockΔ19 mutant and constant-light mouse models (PP\u3e0.05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (P\u3c0.05). Conclusions: Together these data demonstrate that VSG is an effective treatment for the obesity associated with circadian disruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, as the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption

A new absolute arrival time data set for Europe

The main aim of this study is to create a data set of accurate absolute arrival times for stations in Europe which do not report to the International Seismological Centre (ISC). Waveforms were obtained from data centres and temporary experiments and a semi-automatic picking method was applied to determine absolute arrival times for P and S phases. 85 000 arrival times were picked whose distribution of residuals shows generally low standard deviations on the order of 0.5-0.7 s. Furthermore, mean teleseismic station residuals reflect the properties of the underlying crust and uppermost mantle. Comparison to ISC data for matching event-station-phase combinations also confirms the good quality of the new absolute arrival time picks. Most importantly, this data set complements the ISC data as it fills regional data coverage gaps in Europ

Interaction energy functional for lattice density functional theory: Applications to one-, two- and three-dimensional Hubbard models

The Hubbard model is investigated in the framework of lattice density functional theory (LDFT). The single-particle density matrix $\gamma_{ij}$ with respect the lattice sites is considered as the basic variable of the many-body problem. A new approximation to the interaction-energy functional $W[\gamma]$ is proposed which is based on its scaling properties and which recovers exactly the limit of strong electron correlations at half-band filling. In this way, a more accurate description of $W$ is obtained throughout the domain of representability of $\gamma_{ij}$, including the crossover from weak to strong correlations. As examples of applications results are given for the ground-state energy, charge-excitation gap, and charge susceptibility of the Hubbard model in one-, two-, and three-dimensional lattices. The performance of the method is demonstrated by comparison with available exact solutions, with numerical calculations, and with LDFT using a simpler dimer ansatz for $W$. Goals and limitations of the different approximations are discussed.Comment: 25 pages and 8 figures, submitted to Phys. Rev.

The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism

The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. Interestingly, exposure to lighting conditions that disrupt circadian rhythms improve their glucose tolerance. This improvement occurs through an increase in glucose clearance by skeletal muscle and is food intake and body weight independent. Restoring Mc4r expression to the paraventricular nucleus prevents the improvement in glucose tolerance, supporting a role for the paraventricular nucleus in the integration of circadian light cues and metabolism. Altogether these data suggest that Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system

On the inertia of heat

Does heat have inertia? This question is at the core of a long-standing controversy on Eckart's dissipative relativistic hydrodynamics. Here I show that the troublesome inertial term in Eckart's heat flux arises only if one insists on defining thermal diffusivity as a spacetime constant. I argue that this is the most natural definition, and that all confusion disappears if one considers instead the space-dependent comoving diffusivity, in line with the fact that, in the presence of gravity, space is an inhomogeneous medium.Comment: 3 page

Does bariatric surgery improve adipose tissue function?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134250/1/obr12429_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134250/2/obr12429.pd

A dynamic optimization framework for integration of design, control and scheduling of multi-product chemical processes under disturbance and uncertainty

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.compchemeng.2017.05.007 © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/A novel dynamic optimization framework is presented for integration of design, control, and scheduling for multi-product processes in the presence of disturbances and parameter uncertainty. This framework proposes an iterative algorithm that decomposes the overall problem into flexibility and feasibility analyses. The flexibility problem is solved under a critical (worst-case) set of disturbance and uncertainty realizations, whereas the feasibility problem evaluates the dynamic feasibility of each realization, and updates the critical set accordingly. The algorithm terminates when a robust solution is found, which is feasible under all identified scenarios. To account for the importance of grade transitions in multiproduct processes, the proposed framework integrates scheduling into the dynamic model by the use of flexible finite elements. This framework is applied to a multi-product continuous stirred-tank reactor (CSTR) system subject to disturbance and parameter uncertainty. The proposed method is shown to return robust solutions that are of higher quality than the traditional sequential method. The results indicate that scheduling decisions are affected by design and control decisions, thus motivating the need for integration of these three aspects.Natural Sciences & Engineering Council of Canada (NSERC)Ontario Graduate Scholarship (OGS

Genera of phytopathogenic fungi: GOPHY 3

This paper represents the third contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions, information about the pathology, distribution, hosts and disease symptoms for the treated genera, as well as primary and secondary DNA barcodes for the currently accepted species included in these. This third paper in the GOPHY series treats 21 genera of phytopathogenic fungi and their relatives including: Allophoma, Alternaria, Brunneosphaerella, Elsinoe, Exserohilum, Neosetophoma, Neostagonospora, Nothophoma, Parastagonospora, Phaeosphaeriopsis, Pleiocarpon, Pyrenophora, Ramichloridium, Seifertia, Seiridium, Septoriella, Setophoma, Stagonosporopsis, Stemphylium, Tubakia and Zasmidium. This study includes three new genera, 42 new species, 23 new combinations, four new names, and three typifications of older names