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.     

Expression of type 2 11beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in early human fetal life

In adult life, the type 2 isozyme of 11beta-hydroxysteroid dehydrogenase (11betaHSD2) protects the mineralocorticoid receptor (MR) from glucocorticoid by inactivating cortisol to cortisone. 11betaHSD2 activity has been reported in human fetal tissues, where glucocorticoids may impair fetal growth yet are also required for normal fetal development. Using digoxigenin-labeled complementary ribonucleic acid (RNA) probes and an in-house 11betaHSD2 antiserum, we have analyzed the expression of 11betaHSD2, MR, and glucocorticoid receptor (GR) in human fetal tissues of gestational age 6-17 weeks (n=15). 11BetaHSD2 expression was absent at gestational age 6+ weeks, but was expressed in abundance in many fetal tissues between 8-12 weeks. At this time, 11betaHSD2 colocalized with GR messenger RNA (mRNA) expression in metanephros, gut, muscle, spinal cord and dorsal root ganglia, periderm, sex chords of testis, and adrenal. In particular within fetal kidney, intense expression of 11betaHSD2 and GR mRNA was observed over Bowman's capsule and the vascular tufts of developing glomeruli as they migrated from the surface of the kidney to the inner cortex. Only lung and adrenal medullary rests demonstrated high levels of GR mRNA but low levels of 11betaHSD2. 11BetaHSD2 mRNA and immunoreactivity staining patterns were similar, with the exception of the fetal adrenal, where mRNA was localized to the outer definitive zone but immunoreactivity was localized to the inner fetal zone. Colocalization of 11betaHSD2 (and GR mRNA) with MR mRNA was observed principally within epithelial cells of collecting ducts, particularly after 16 weeks gestation when the pattern of distribution of 11betaHSD2 became more adult in nature. High levels of MR mRNA were observed within developing bone. The data indicate that 11betaHSD2 in fetal life principally modulates ligand access to the GR in most fetal tissues, notably glomeruli and tubules in the developing kidney, testis, and periderm, and this may be have ramifications for fetal sodium homeostasis and differentiation. The development of tissues previously shown to have a critical requirement for glucocorticoids, such as lung and adrenal medulla, is facilitated by the expression of GR mRNA, but not 11betaHSD2. The expression of MR mRNA in high abundance in bone suggests a role for corticosteroids in human bone development, and the low/absent expression of 11betaHSD2 at this site suggests that it is functionally acting as a GR.     

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.     

Examining cognitive function across the lifespan using a mobile application

Many studies conducted in a laboratory or university setting are limited by funding, personnel, space, and time constraints. In the present study, we introduce a method of data collection using a mobile application that circumvents these typical experiment administration issues. Using the application, we examined cross-sectional age differences in cognitive function. We obtained data from more than 15,000 participants and replicated specific patterns of age-related differences in cognition. Using a subset of these participants, we also examined the processing speed account of age-related cognitive differences, and the association of exercise and leisure activity with cognitive function across the lifespan. We discuss the relative advantages and disadvantages of data collection with a mobile application, and provide recommendations for the use of this method in research.     

Samuel Bourne of Nottingham

Abstract

Samuel Bourne was one of the great pioneers of travel photography, and the photographs which he took in India during the 1860s have become familiar to a wide audience through their inclusion in exhibitions, their use as book illustrations and also through television coverage. Although acknowledging the merit of that aspect of his work, this paper discusses the hitherto comparatively little-known role which he played in the arena of photography during the period immediately before he went to India, and also his activities in the latter part of the 19th and early 20th centuries.     

Improved thin film stability of differently formulated,printed, and crosslinked polymer layers against successive solvent printing

Interface control remains a top challenge of solution-processed organic light emitting diodes (OLED) stacks since the device performance heavily relies on it. Film stability of an inkjet deposited and crosslinked layer against subsequent exposure to a suitable inkjet printed solvent has been investigated. Impact of processing solvent (solvent used to prepare the polymer layer) on solution-cast thin film properties has already been shown for polymer films. To our knowledge, this study is the first one analyzing thin films stability against solvent exposure using technology relevant materials processed via inkjet printing (IJP). The outcome of this research showed that the stability of the crosslinked films is affected by the solvent used for ink formulation. These findings are of great interest for multilayered semiconductors devices, such as OLEDs, field-effect transistors and dye-sensitized solar cells. Differential scanning calorimetry (DSC) was used to quantify the efficiency of the polymer crosslinking reaction in pure powder and in thin films, as processed from different solvents. Crosslinking efficiency measured by DSC correlated well with the deformation induced by the solvent and observed on layer surfaces. The interaction in solution between polymer and solvent has also been evaluated to explain its impact on thin film stability against successive solvent printing. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48895.