Determination of Stent Frame Displacement After Endovascular Aneurysm Sealing

Purpose: To describe and validate a new methodology for visualizing and quantifying 3-dimensional (3D) displacement of the stent frames of the Nellix endosystem after endovascular aneurysm sealing (EVAS). Methods: The 3D positions of the stent frames were registered to 5 fixed anatomical landmarks on the post-EVAS computed tomography (CT) scans, facilitating comparison of the position and shape of the stent frames between consecutive follow-up scans. Displacement of the proximal and distal ends of the stent frames, the entire stent frame trajectories, as well as changes in distance between the stent frames were determined for 6 patients with >5-mm displacement and 6 patients with 5-mm displacement on the 1-year CT as determined by the new methodology, 2 went on to develop a type Ia endoleak in longer follow-up, and displacement progressed to >15 mm for 2 other patients. No endoleak or progressive displacement was appreciated for the patients with 5 mm on the 1-year CT scans reconstructed with the new methodology may forecast impaired sealing and anchoring of the Nellix endosystem

Acupuncture on GB34 activates the precentral gyrus and prefrontal cortex in Parkinson’s disease

Background: Acupuncture is increasingly used as an additional treatment for patients with Parkinson’s disease (PD). Methods: In this functional magnetic resonance imaging study, brain activation in response to acupuncture in a group of 12 patients with PD was compared with a group of 12 healthy participants. Acupuncture was conducted on a specific acupoint, the right GB 34 (Yanglingquan), which is a frequently used acupoint for motor function treatment in the oriental medical field. Results: Acupuncture stimulation on this acupoint activates the prefrontal cortex, precentral gyrus, and putamen in patients with PD; areas that are known to be impaired in patients with PD. Compared with healthy participants, patients with PD showed significantly higher brain activity in the prefrontal cortex and precentral gyrus, especially visible in the left hemisphere. Conclusions: The neuroimaging results of our study suggest that in future acupuncture research; the prefrontal cortex as well as the precentral gyrus should be treated for symptoms of Parkinson’s disease and that GB 34 seems to be a suitable acupoint. Moreover, acupuncture evoked different brain activations in patients with Parkinson’s disease than in healthy participants in our study, stressing the importance of conducting acupuncture studies on both healthy participants as well as patients within the same study, in order to detect acupuncture efficacy. Trial registration KCT0001122 at cris.nih.go.kr (registration date: 20140530) Electronic supplementary material The online version of this article (doi:10.1186/1472-6882-14-336) contains supplementary material, which is available to authorized users

Sustainability of Individual EndoAnchor Implants in Therapeutic Use to Treat Type Ia Endoleak After Endovascular Aneurysm Repair

Purpose: To investigate changes in penetration depths and angles of EndoAnchor implants with initially good penetration after therapeutic use in endovascular aneurysm repair. Materials and Methods: Patients were selected from the Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR; ClinicalTrials.gov identifier NCT01534819). Inclusion criteria were (1) EndoAnchor implantation to treat intraoperative or late type Ia endoleak and (2) at least 2 postoperative computed tomography angiography (CTA) scans. Exclusion criteria were the use of adjunct procedures. Based on these criteria, 54 patients (44 men) with 360 EndoAnchor implants were eligible for this analysis. Penetration depth of each EndoAnchor implant into the aortic wall was judged as (1) good (2-mm penetration), (2) borderline (</p

Functional characterization of Schistosoma mansoni fucosyltransferases in Nicotiana benthamiana plants

Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses. Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host–parasite interface. As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids. Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized. To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants. All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs. This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions. The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation. Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines

Synthesis of Stable NAD+ Mimics as Inhibitors for the Legionella pneumophila Phosphoribosyl Ubiquitylating Enzyme SdeC

Stable NAD+ analogues carrying single atom substitutions in either the furanose ring or the nicotinamide part have proven their value as inhibitors for NAD+‐consuming enzymes. To investigate the potential of such compounds to inhibit the adenosine diphosphate ribosyl (ADPr) transferase activity of the Legionella SdeC enzyme, we prepared three NAD+ analogues, namely carbanicotinamide adenosine dinucleotide (c‐NAD+), thionicotinamide adenosine dinucleotide (S‐NAD+) and benzamide adenosine dinucleotide (BAD). We optimized the chemical synthesis of thionicotinamide riboside and for the first time used an enzymatic approach to convert all three ribosides into the corresponding NAD+ mimics. We thus expanded the known scope of substrates for the NRK1/NMNAT1 enzyme combination by turning all three modified ribosides into NAD+ analogues in a scalable manner. We then compared the three NAD+ mimics side‐by‐side in a single assay for enzyme inhibition on Legionella effector enzyme SdeC. The class of SidE enzymes to which SdeC belongs was recently identified to be important in bacterial virulence, and we found SdeC to be inhibited by S‐NAD+ and BAD with IC50 values of 28 and 39 μM, respectively.Bio-organic Synthesi

Information content based model for the topological properties of the gene regulatory network of Escherichia coli

Gene regulatory networks (GRN) are being studied with increasingly precise quantitative tools and can provide a testing ground for ideas regarding the emergence and evolution of complex biological networks. We analyze the global statistical properties of the transcriptional regulatory network of the prokaryote Escherichia coli, identifying each operon with a node of the network. We propose a null model for this network using the content-based approach applied earlier to the eukaryote Saccharomyces cerevisiae. (Balcan et al., 2007) Random sequences that represent promoter regions and binding sequences are associated with the nodes. The length distributions of these sequences are extracted from the relevant databases. The network is constructed by testing for the occurrence of binding sequences within the promoter regions. The ensemble of emergent networks yields an exponentially decaying in-degree distribution and a putative power law dependence for the out-degree distribution with a flat tail, in agreement with the data. The clustering coefficient, degree-degree correlation, rich club coefficient and k-core visualization all agree qualitatively with the empirical network to an extent not yet achieved by any other computational model, to our knowledge. The significant statistical differences can point the way to further research into non-adaptive and adaptive processes in the evolution of the E. coli GRN.Comment: 58 pages, 3 tables, 22 figures. In press, Journal of Theoretical Biology (2009)

Neutron-encoded diubiquitins to profile linkage selectivity of deubiquitinating enzymes

Deubiquitinating enzymes are key regulators in the ubiquitin system and an emerging class of drug targets. These proteases disassemble polyubiquitin chains and many deubiquitinases show selectivity for specific polyubiquitin linkages. However, most biochemical insights originate from studies of single diubiquitin linkages in isolation, whereas in cells all linkages coexist. To better mimick this diubiquitin substrate competition, we develop a multiplexed mass spectrometry-based deubiquitinase assay that can probe all ubiquitin linkage types simultaneously to quantify deubiquitinase activity in the presence of all potential diubiquitin substrates. For this, all eight native diubiquitins are generated and each linkage type is designed with a distinct molecular weight by incorporating neutron-encoded amino acids. Overall, 22 deubiquitinases are profiled, providing a three-dimensional overview of deubiquitinase linkage selectivity over time and enzyme concentration.</p