Firesides

This year we again continued the tradition of firesides. A fireside is when a professor invites into his home eight to fifteen students for dinner and conversation, usually on a Sunday evening. These firesides allow the students to become better acquainted with the professors, meet their families, and provides the opportunity to socialize with the other students while enjoying a special meal

Environmental Contaminant Exposure and Effects on Bats: Studies in Sichuan Province, China and Colorado, U.S.A.

As the world’s only flying mammals, bats fill an important ecological role in most ecosystems, acting as agents of seed dispersal, pollination, fertilization, and insect control. The human-mediated release of environmental contaminants has been implicated in the decline of many bat populations over the past few decades. Given bats’ ecological significance, I studied how bat presence and activity related to contaminated food and water sources in two global regions: 1) in and around the growing urban city of Chengdu, the capital of Sichuan Province, China, and 2) along the eastern slope of the Rocky Mountains in Colorado, U.S.A., which has been subject to 150 years of mining. In China (Chapter II), I tested mercury concentrations in fur and organochlorine concentrations in guano to assess their relationships to land use type and bat species, relative age, body condition, and phonic type. Because the Japanese pipistrelle (Pipistrellus abramus) had the highest fur mercury concentrations of bats sampled, in Chapter III I examined genetic identity and gene flow to confirm that all bats sampled were indeed P. abramus and to better understand local movements and potential implications of the contaminant concentrations. Finally, in Colorado (Chapter IV), I tested whether bat activity and feeding attempts differed locally above streams of high versus low metal contamination at high-elevation sites (\u3e2,900 m). In China (Chapter II), total mercury concentrations were significantly higher in adult P. abramus than in adult Chinese noctules (Nyctalus plancyi) (P \u3c 0.001), and significantly higher in adult N. plancyi relative to juveniles (P \u3c 0.001). There was no significant difference in concentrations by land use type (urban versus suburban), but 57% of adult pipistrelles had fur mercury concentrations above the threshold for reduced homeostatic control, with the maximum (33 ppm) from an adult female in an agricultural area. There was no relationship between fur mercury concentration and bat body condition for either species. Hexachlorobenzene, alpha-chlordane, p,p’-DDE, o,p’-DDD, and p,p’-DDD were detected in guano but at levels well below those associated with harm. More bat phonic types were detected at a forested mountain site than agricultural or urban areas, though this could not be related to contaminant concentrations. In Chapter III, mitochondrial (cyt b) and nuclear studies confirmed that all individuals assumed to be P. abramus matched the species genetically and that there was weak population structure in Chengdu. This corroborated high gene flow in the area and a likely home range size o

Leon County Surface Water Management Activities

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Decision Modeling in Markovian Multi-Agent Systems

In this paper, we model a decision-making process involving a set of interacting agents. We use Markovian opinion dynamics, where each agent switches between decisions according to a continuous time Markov chain. Existing opinion dynamics models are extended by introducing attractive and repulsive forces that act within and between groups of agents, respectively. Such an extension enables the resemblance of behaviours emerging in networks where agents make decisions that depend both on their own preferences and the decisions of specific groups of surrounding agents. The considered modeling problem and the contributions in this paper are inspired by the interaction among road users (RUs) at traffic junctions, where each RU has to decide whether to go or to yield

Collective Decision Making using Attractive and Repulsive Forces in Markovian Opinion Dynamics

In this paper, we model a decision-making process involving a set of interacting agents. We use Markovian opinion dynamics, where each agent switches between decisions according to a continuous time Markov chain. Existing opinion dynamics models are extended by introducing attractive and repulsive forces that act within and between groups of agents, respectively. Such an extension enables the resemblance of behaviours emerging in networks where agents make decisions that depend both on their own preferences and the decisions of specific groups of surrounding agents. The considered modeling problem and the contributions in this paper are inspired by the interaction among road users (RUs) at traffic junctions, where each RU has to decide whether to go or to yield

Decision Modeling in Markovian Multi-Agent Systems

In this paper, we model a decision-making process involving a set of interacting agents. We use Markovian opinion dynamics, where each agent switches between decisions according to a continuous time Markov chain. Existing opinion dynamics models are extended by introducing attractive and repulsive forces that act within and between groups of agents, respectively. Such an extension enables the resemblance of behaviours emerging in networks where agents make decisions that depend both on their own preferences and the decisions of specific groups of surrounding agents. The considered modeling problem and the contributions in this paper are inspired by the interaction among road users (RUs) at traffic junctions, where each RU has to decide whether to go or to yield

A unique serpin P1′ glutamate and a conserved β-sheet C arginine are key residues for activity, protease recognition and stability of serpinA12 (vaspin)

SerpinA12 (vaspin) is thought to be mainly expressed in adipose tissue and has multiple beneficial effects on metabolic, inflammatory and atherogenic processes related to obesity. KLK7 (kallikrein 7) is the only known protease target of vaspin to date and is inhibited with a moderate inhibition rate. In the crystal structure, the cleavage site (P1-P1′) of the vaspin reactive centre loop is fairly rigid compared with the flexible residues before P2, possibly supported by an ionic interaction of P1′ glutamate (Glu379) with an arginine residue (Arg302) of the β-sheet C. A P1′ glutamate seems highly unusual and unfavourable for the protease KLK7. We characterized vaspin mutants to investigate the roles of these two residues in protease inhibition and recognition by vaspin. Reactive centre loop mutations changing the P1′ residue or altering the reactive centre loop conformation significantly increased inhibition parameters, whereas removal of the positive charge within β-sheet C impeded the serpin–protease interaction. Arg302 is a crucial contact to enable vaspin recognition by KLK7 and it supports moderate inhibition of the serpin despite the presence of the detrimental P1′ Glu379, which clearly represents a major limiting factor for vaspin-inhibitory activity. We also show that the vaspin-inhibition rate for KLK7 can be modestly increased by heparin and demonstrate that vaspin is a heparin-binding serpin. Noteworthily, we observed vaspin as a remarkably thermostable serpin and found that Glu379 and Arg302 influence heat-induced polymerization. These structural and functional results reveal the mechanistic basis of how reactive centre loop sequence and exosite interaction in vaspin enable KLK7 recognition and regulate protease inhibition as well as stability of this adipose tissue-derived serpin

Reduced expression of chemerin in visceral adipose tissue associates with hepatic steatosis in patients with obesity

Objective: This study aimed to evaluate whether circulating levels and/or visceral adipose tissue (VAT) expression of recently described adipokines associate with histopathological severity of nonalcoholic fatty liver disease (NAFLD), independent of obesity and insulin resistance. Methods: Serum levels of adiponectin, omentin, chemerin, monocyte chemoattractant protein-1, and secreted frizzled-related protein 4 were measured using enzyme-linked immunosorbent assay in 81 patients with obesity and NAFLD and 18 lean control subjects. Expression in VAT was measured using real-time PCR and histopathological grading was scored using the NAFLD activity score (NAS). Results: When NAFLD patients were subdivided into groups with simple steatosis, borderline nonalcoholic steatohepatitis (NASH), and NASH, adiponectin serum levels and omentin expression were lower in NASH versus simple steatosis patients. Serum adiponectin was generally lower with higher histopathological grading. Chemerin VAT expression was negatively associated with NAS (r = -0.331, P = 0.022) and steatosis score (r = -0.335, P = 0.020), independent of age, BMI, and HOMA-IR. In addition, adjusting for chemerin VAT expression in a multivariate model explained part of the association between NAS and HOMA-IR. Conclusions: These findings suggest that lower VAT expression of chemerin in patients with obesity may be involved in the pathophysiology of hepatic steatosis, potentially by modulating the link between insulin resistance and NAFLD

Vaspin inhibits kallikrein 7 by serpin mechanism

The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-013-1258-8) contains supplementary material, which is available to authorized users

Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue

Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss