Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function.

Background/objectiveYouth with obesity have an altered high-density lipoprotein (HDL) subspecies profile characterized by depletion of large apoE-rich HDL particles and an enrichment of small HDL particles. The goal of this study was to test the hypothesis that this atherogenic HDL profile is reversible and that HDL function would improve with metabolic surgery.MethodsSerum samples from adolescent males with severe obesity mean±s.d. age of 17.4±1.6 years were studied at baseline and 1 year following vertical sleeve gastrectomy (VSG). HDL subspecies and HDL function were evaluated pre and post VSG using paired t-tests. A lean group of adolescents was included as a reference group.ResultsAfter VSG, body mass index decreased by 32% and insulin resistance as estimated by homeostatic model assessment of insulin resistance decreased by 75% (both P<0.01). Large apoE-rich HDL subspecies increased following VSG (P<0.01) and approached that of lean adolescents despite participants with considerable residual obesity. In addition, HDL function improved compared with baseline (cholesterol efflux capacity increased by 12%, HDL lipid peroxidation potential decreased by 30% and HDL anti-oxidative capacity improved by 25%, all P<0.01).ConclusionsMetabolic surgery results in a significant improvement in the quantity of large HDL subspecies and HDL function. Our data suggest metabolic surgery may improve cardiovascular risk in adolescents and young adults

Diffusion on random site percolation clusters. Theory and NMR microscopy experiments with model objects

Quasi two-dimensional random site percolation model objects were fabricate based on computer generated templates. Samples consisting of two compartments, a reservoir of H$_2$O gel attached to a percolation model object which was initially filled with D$_2$O, were examined with NMR (nuclear magnetic resonance) microscopy for rendering proton spin density maps. The propagating proton/deuteron inter-diffusion profiles were recorded and evaluated with respect to anomalous diffusion parameters. The deviation of the concentration profiles from those expected for unobstructed diffusion directly reflects the anomaly of the propagator for diffusion on a percolation cluster. The fractal dimension of the random walk, $d_w$, evaluated from the diffusion measurements on the one hand and the fractal dimension, $d_f$, deduced from the spin density map of the percolation object on the other permits one to experimentally compare dynamical and static exponents. Approximate calculations of the propagator are given on the basis of the fractional diffusion equation. Furthermore, the ordinary diffusion equation was solved numerically for the corresponding initial and boundary conditions for comparison. The anomalous diffusion constant was evaluated and is compared to the Brownian case. Some ad hoc correction of the propagator is shown to pay tribute to the finiteness of the system. In this way, anomalous solutions of the fractional diffusion equation could experimentally be verified for the first time.Comment: REVTeX, 12 figures in GIF forma

Groundwater resources of the Pataskala area, Southwest Licking County, Ohio

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Determining Cleavage Site Sequences to Characterize the Active Site of BACE1 Aspartic Protease

University of Minnesota M.S. thesis. April 2015. Major: Chemistry. Advisor: Joseph Johnson. 1 computer file (PDF); xi, 89 pages.Proteases play key roles in physiology and disease development due to their active role in the regulation of other proteins. Understanding and characterizing the active site of relevant proteases provides information vital to the production of inhibitors and elucidates potential native substrates that may be affected by inhibitors. Once the preferred sequence of the active site of a target protease, such as β-secretase (BACE1), has been defined, protease inhibitors can be created to treat or manage diseases such as Alzheimer's disease (AD). BACE1 is an aspartic protease that is overexpressed in the AD brain and is believed to initiate the AD disease pathway. As such, it is a strong candidate for drug design. However, chronic administration of BACE1 inhibitors could result in undesirable side effects due to the impairment of its ability to hydrolyze native substrates; therefore, the amino acid peptide sequence preferentially cleaved by BACE1 needs to be characterized. Not only will this indicate potential substrates that may be affected by BACE1 inhibition, it will also aid in the synthesis of viable inhibitors. Recently, a novel method for determing the cleavage sequence of proteases was reported. Proteomic identification of cleavage sites (PICS) is a method designed to accurately identify cleavage sequence preferences and neighbor interactions in the cleavage site that influence protease cleavage. This method gives additional information with less bias than previous methods used to characterize protease active sites. Multiple controls were used to confirm the validity of the procedure. These controls demonstrated our ability to successfully identify the amino acid sequence preferences for well characterized proteases. We were thus able to confidently use PICS to obtain the sequence of amino acids preferentially cleaved by BACE. BACE1A has two noticeable characteristics for the amino acid sequence cleaved: aromatic amino acids are preferred in the P1 site and leucine is strongly preferred in P2'. Other preferred amino acids are observed in the sequence, but not to the extent of P1 and P2'. Neighbor interactions were also investigated. Positive cooperativity resulted with leucine or valine in P3 and with phenylalanine or tyrosine in P1. There were strong interactions between valine in P3 and phenylalanine in P1 and between tyrosine in P1 and valine in P2'. Sequence preferences were also investigated for BACE2A, which exhibited both similarities and differences between BACE1A and BACE2A. The next step in this research will be to use knowledge of the preferred cleavage sites to determine physiological substrates of BACE1A. This will reveal more information about the natural function of BACE1A and identify potential side effects of its inhibition

Regulation of proteasome assembly and activity in health and disease

The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.</p

Different arguments, same conclusions: how is action against invasive alien species justified in the context of European policy?

The prevention and management of invasive alien species (IAS) has become a high priority in European environmental policy. At the same time, ways of evaluating IAS continue to be a topic of lively debate. In particular, it is far from clear how directly policy makers’ value judgements are linked to the European (EU) policy against IAS. We examine the arguments used to support value judgements of both alien species and invasive alien species as well as the relation between these value judgements and the policy against IAS being developed at European level. Our study is based on 17 semi-structured interviews with experts from EU policy making and from the EU member states Austria, Belgium, Germany and Hungary. We found that our interviewees conceived of IAS in very different ways, expressed a variety of visions of biodiversity and ecosystem services, and adhered to widely different values expressed in their perceptions of IAS and the impacts of IAS. However, only some of these conceptualizations and value judgements are actually addressed in the rationale given in the preamble to the European IAS Regulation. Although value judgements about IAS differed, there was considerable agreement regarding the kind of action to be taken against them. © 2016 Springer Science+Business Media Dordrech

Managing science-policy interfaces for impact : Interactions within the environmental governance meshwork

Science-policy interface organizations and initiatives (SPIORG) are a key component of environmental governance designed to make links between science and society. However, the science­policy interface literature lacks a structured approach to explaining the impacts of context on and by these initiatives. To better understand these impacts on and interactions with governance, this paper uses the concept of the governance ‘meshwork’ to explore how dynamic processes – encompassing prior, current and anticipated interactions – co­produce knowledge and impact via processes, negotiation and networking activities at multiple governance levels. To illustrate the interactions between SPIORGs and governance meshwork we use five cases representing archetypal SPIORGs. These cases demonstrate how all initiatives and organizations link to their contexts in complex and unique ways, yet also identifies ten important aspects that connect the governance meshwork to SPIORGs. These aspects of the meshwork, together with the typology of organizations, provide a comprehensive framework that can help make sense how the SPIORGs are embedded in the surrounding governance contexts. We highlight that SPIORGs must purposively consider and engage with their contexts to increase their potential impact on knowledge co-­production and policy making.Peer reviewe