Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

Projection of the sexually dimorphic area of the gerbil hypothalamus to the retrorubral field is essential for male sexual behavior: Role of A8 and other cells.

To determine if the sexually dimorphic area (SDA) of the gerbil hypothalamus affects male sexual behavior through its projections to the retrorubral field (RRF) or ventrolateral periaqueductal gray (PAGvl), these pathways were lesioned asymmetrically. Unilateral radio frequency lesions of the lateral SDA (LSDA), the major source of the pathways, impaired mating when combined with contralateral RRF, but not PAGvl, lesions. N-methyl-{d}-aspartate (NMDA) lesions of the medial SDA, LSDA, and the area between them (the total pathway source) eliminated mating when combined with contralateral, but not ipsilateral, NMDA lesions of the RRF. To determine if A8 cells contributed to these effects, males received NMDA in the SDA and NMDA or 6-hydroxydopamine in the contralateral RRF. When combined with large SDA lesions, A8 lesions impaired but did not eliminate mating. Thus the SDA–RRF pathway, but not an SDA-A8 pathway, is essential for sexual behavior in male gerbils. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isotherm analyses for single component and multi-component metal sorption onto lignite

The adsorption of the three metal ions, copper, cadmium and zinc in single component and multi-component mixtures in aqueous solutions by lignite is reported. A comparison is made between the single component saturation uptake and the multi-component uptakes. The isotherms indicate a competitive uptake with copper being preferentially absorbed by the lignite in multi-component solutions. The isotherms are plotted to obtain the Langmuir constants, the Freundlich constants and the Redlich–Peterson constants. Lignite is shown to possess an affinity for the metal ions which make its use as an adsorbent a possible alternative to the use of more expensive activated carbons.     

Display of functional alphabeta single-chain T-cell receptor molecules on the surface of bacteriophage

The ability to display functional T-cell receptors (TCR) on the surface of bacteriophage could have numerous applications. For instance, TCR phage-display could be used to develop new strategies for isolating TCRs with unique specificity or it could be used to carry out mutagenesis studies on TCR molecules for analyzing their structure-function. We initially selected a TCR from the murine T-cell hybridoma, DO11.10, as our model system, and genetically engineered a three domain single-chain TCR (scTCR) linked to the gene p8 protein of the Escherichia coli bacteriophage fd. Immunoblotting studies revealed that (1) E. coli produced a soluble scTCR/p8 fusion protein and (2) the fusion protein was packaged by the phage. Cellular competition assays were performed to evaluate the functionality of the TCR and showed the DO11.10 TCR-bearing phage could significantly inhibit stimulation of DO11.10 T hybridoma cells by competing for binding to immobilized MHC/peptide IA(d)/OVA(323-339). Flow cytometric analysis was carried out to evaluate direct binding of DO11.10 TCR-bearing phage onto the surface of cells displaying either IAd containing irrelevant peptide or OVA peptide. The results revealed binding of DO11.10 TCR-bearing phage only on cells expressing IA(d) loaded with OVA peptide showing TCR fine specificity for peptide. To illustrate the generality of TCR phage-display, we also cloned and displayed on phage a second TCR which recognizes a peptide fragment from human tumor suppressor protein p53 restricted by HLA-A2. These findings demonstrate functional TCR can be displayed on bacteriophage potentially leading to the development of novel applications involving TCR phage-display.     

Development of materials specifications and emplacement procedures for backfilling nuclear fuel waste vaults

Atomic Energy of Canada Limited and Ontario Hydro are conducting a research program to assess the environmental impact and safety of the concept of disposal of nuclear fuel waste in an underground vault in plutonic rock of the Canadian Shield. The Vault Sealing Program, one of the components of the Nuclear Fuel Waste Management Program, is concerned with the development of materials specifications and emplacement procedures for backfilling the vault. Backfilling materials would surround the nuclear waste containers and fill all vault openings to minimize leaching and movement of radionuclides. This paper presents the procedure followed to select candidate backfill materials, the integration of mathematical modelling studies and physical testing for the definition of materials specifications, and the principal elements of the recommended handling and emplacement systems.     

Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1^r/rα2^s/s mouse failed to do so in the α1^s/sα2^s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.     

Adaptive output-feedback stabilization of non-local hyperbolic PDEs

We address the problem of adaptive output-feedback stabilization of general first-order hyperbolic partial integro-differential equations (PIDE). Such systems are also referred to as PDEs with non-local (in space) terms. We apply control at one boundary, take measurements on the other boundary, and allow the system’s functional coefficients to be unknown. To deal with the absence of both full-state measurement and parameter knowledge, we introduce a pre-transformation (which happens to be based on backstepping) of the system into an observer canonical form. In that form, the problem of adaptive observer design becomes tractable. Both the parameter estimator and the control law employ only the input and output signals (and their histories over one unit of time). Prior to presenting the adaptive design, we present the non-adaptive/baseline controller, which is novel in its own right and facilitates the understanding of the more complex, adaptive system. The parameter estimator is of the gradient type, based on a parametric model in the form of an integral equation relating delayed values of the input and output. For the closed-loop system we establish boundedness of all signals, pointwise in space and time, and convergence of the PDE state to zero pointwise in space. We illustrate our result with a simulation.     

Sex pheromone specificity as a reproductive isolating mechanism among the sibling speciesArchips argyrospilus andA. mortuanus and other sympatric tortricine moths (Lepidoptera: Tortricidae)

MaleArchips argyrospilus (Walker) were maximally attracted to a 60404200 admixture of (Z)-11-tetradecenyl, (E)-11-tetradecenyl, (Z)-9-tetradecenyl and dodecyl acetates. The identification of (Z)-9-tetradecenyl acetate, in addition to the other 3 components reported previously, is the first report of a 4-component pheromone system in moths.Archips mortuanus Kearfoot, a sibling species, was maximally attracted to a blend of the same components, but in a 90101 mix of the tetradecenyl acetates. Among a number of tortricine moths that co-occur on apples and other hosts in New York, British Columbia, and elsewhere, differences in diel rhythms of attraction and seasonal distribution are insufficient to maintain reproductive isolation. Although the attractant systems of these species often possess components in common, males are maximally attracted to a speciesspecific blend. In tortricine moths attraction specificity appears to be a paramount mechanism for species partitioning.