Isolation and composition analysis of bioactive glycosaminoglycans from whelk

Glycosaminoglycans (GAGs) are found covalently attached to proteins, which create conjugates known as proteoglycans. GAGs have remarkable biological activity as co-receptors for a variety of growth factors, cytokines, and chemokines. The present study identifies the key compositional differences between the GAGs isolated from whelk and mammalian GAGs. This polysaccharide represents a new, previously undescribed GAG with cytotoxic activity on cancer cells. Disaccharides were obtained by sample digestion with heparinases I, II, and III and chondroitinase ABC. The resistant oligosaccharides from whelk GAGs treated with heparinase I, II, and III and chondroitinase ABC were retained by the filter due to their larger size. Disaccharide analysis was performed using Glycan Reduction Isotope Labeling (GRIL LCQ-MS). The amounts of filter-retained fragments, as assessed by monosaccharides analysis, suggested that a proportion of the whelk GAG chains remained resistant to the enzymes used in the disaccharide analysis. Thus, the proportions of individual disaccharide produced in this analysis may not truly represent the overall proportions of disaccharide types within the intact whelk GAGs chain. However, they do serve as important descriptors for the classification and make-up of the anti-cancer GAGs chains. Furthermore, these data represent clear evidence of the compositional differences between whelk GAGs and commercial mammalian GAGs

Thermoelectric effects in a rectangular Aharonov-Bohm geometry

The thermoelectric transport properties of a rectangular Aharonov-Bohm ring at low temperature are investigated using a theoretical approach based on Green's functions. The oscillations in the transmission coefficient as the field is varied can be used to tune the thermoelectric response of the ring. Large magnitude thermopowers are obtainable which, in conjunction with low conductance, can result in a high thermoelectric figure of merit. The effects of single site impurities and more general Anderson disorder are considered explicitly in the context of evaluating their effect on the Fano-type resonances in the transmission coefficient. Importantly, it is shown that even for moderate levels of disorder the thermoelectric figure of merit can remain significant, increasing the appeal of such structures from the perspective of specialist thermoelectric applications

The young active star SAO 51891 (V383 Lac)

Our aim is investigating surface inhomogeneities of the young late-type star SAO51891, from photosphere to upper chromosphere, analyzing contemporaneous high-resolution spectra and broad-band photometry. The FOCES@CAHA spectral range is used to determine spectral classification and derive vsini and Vrad. The Li abundance is measured to estimate the age. The BVRIJHKs bands are used to construct the SED. The variations of our BV fluxes and Teff are used to infer the presence of photospheric spots and observe their behavior over time. The chromospheric activity is studied applying the spectral subtraction technique to Halpha, CaII H&K, Heps, and CaII IRT lines. We find SAO51891 to be a young K0-1V star with Li abundance close to the Pleiades upper envelope, confirming its youth (~100 Myr), also inferred from its kinematical membership to the Local Association. We detect no IR excess from SED analysis, and rotational modulation of luminosity, Teff, CaII, and Heps total fluxes. A spot model with two active regions, ~240 K cooler than the surrounding photosphere, fits our light/Teff curves, and reproduces the small-amplitude Vrad variations. The anti-correlation of light curves and chromospheric diagnostics indicates plages spatially associated with spots. The large amplitude observed in the Heps-flux curve suggests that this line is very sensitive to the plage presence. Finally, SAO51891 is a young active star, lacking significant amounts of circumstellar dust or any evidence for low mass companions. The spots turn out to be larger and warmer than those in less active MS stars. The Vrad variation produced by spots has an amplitude comparable with those induced by Jupiter-mass planets orbiting close to the star. SAO51891 is a good example of star where the detection of planets may be hampered by the high activity level.Comment: 16 pages, 12 figures, 7 tables, accepted by Astronomy and Astrophysics; abstract here was shortene

Classification of beach response to extreme storms

publisher: Elsevier articletitle: Classification of beach response to extreme storms journaltitle: Geomorphology articlelink: http://dx.doi.org/10.1016/j.geomorph.2017.07.022 content_type: article copyright: Crown Copyright © 2017 Published by Elsevier B.V

Scale-dependent perspectives on the geomorphology and evolution of beachdune systems

Despite widespread recognition that landforms are complex Earth systems with process-response linkages that span temporal scales from seconds to millennia and spatial scales from sand grains to landscapes, research that integrates knowledge across these scales is fairly uncommon. As a result, understanding of geomorphic systems is often scale-constrained due to a host of methodological, logistical, and theoretical factors that limit the scope of how Earth scientists study landforms and broader landscapes. This paper reviews recent advances in understanding of the geomorphology of beach-dune systems derived from over a decade of collaborative research from Prince Edward Island (PEI), Canada. A comprehensive summary of key findings is provided from short-term experiments embedded within a decade-long monitoring program and a multi-decadal reconstruction of coastal landscape change. Specific attention is paid to the challenges of scale integration and the contextual limitations research at specific spatial and/or temporal scales imposes. A conceptual framework is presented that integrates across key scales of investigation in geomorphology and is grounded in classic ideas in Earth surface sciences on the effectiveness of formative events at different scales. The paper uses this framework to organize the review of this body of research in a 'scale aware' way and, thereby, identifies many new advances in knowledge on the form and function of subaerial beach-dune systems. Finally, the paper offers a synopsis of how greater understanding of the complexities at different scales can be used to inform the development of predictive models, especially those at a temporal scale of decades to centuries, which are most relevant to coastal management issues. Models at this (landform) scale require an understanding of controls that exist at both ‘landscape’ and ‘plot’ scales. Landscape scale controls such as sea level change, regional climate, and the underlying geologic framework essentially provide bounding conditions for independent variables such as winds, waves, water levels, and littoral sediment supply. Similarly, an holistic understanding of the range of processes, feedbacks, and linkages at the finer plot scale is required to inform and verify the assumptions that underly the physical modelling of beach-dune interaction at the landform scale

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Heparan sulphate synthetic and editing enzymes in ovarian cancer

Several angiogenic growth factors including fibroblast growth factors 1 and 2 (FGF1 and FGF2) depend on heparan sulphate (HS) for biological activity. We previously showed that all cellular elements in ovarian tumour tissue synthesised HS but biologically active HS (i.e. HS capable of binding FGF2 and its receptor) was confined to ovarian tumour endothelium. In this study, we have sought to explain this observation. Heparan sulphate sulphotransferases 1 and 2 (HS6ST1 and HS6ST2) attach sulphate groups to C-6 of glucosamine residues in HS that are critical for FGF2 activation. These enzymes were strongly expressed by tumour cells, but only HS6ST1 was found in endothelial cells. Immunostaining with the 3G10 antibody of tissue sections pretreated with heparinases indicated that HS proteoglycans were produced by tumour and endothelial cells. These results indicated that, in contrast to the endothelium, HS produced by tumour cells may be modified by cell-surface heparanase (HPA1) or endosulphatase (SULF). Protein and RNA analysis revealed that HPA1 was strongly expressed by ovarian tumour cells in eight of ten specimens examined. HSULF-1, which removes specific 6-O-sulphate groups from HS, was abundant in tumour cells but weakly expressed in the endothelium. If this enzyme was responsible for the lack of biologically active HS on the tumour cell surface, we would expect exogenous FGF2 binding to be preserved; we showed previously that this was indeed the case although FGF2 binding was reduced compared to the endothelium and stroma. Thus, the combined effects of heparanase and HSULF could account for the lack of biologically active HS in tumour cells rather than deficiencies in the biosynthetic enzymes

China’s Pledge to Civilise “All Under Heaven”

With China's global rise, both its state leadership and key academics have engaged in developing a civilisational discourse for the twenty-first century partly based on ancient cosmological concepts. This article explores the meanings of and intentions behind this discourse, including its promise of a Chinese-led world order, and discusses its intended audience and international appeal. In the backdrop of theoretical debates on empires and their missions, the article claims that without a corresponding cultural appeal, China's rising economic power and geostrategic clout are insufficient conditions to realise an empire in the classical sense. Growing inconsistencies mar the country's imperial ambitions, such as those between a global civilising outreach and a toughening domestic embrace. Instead, imperial rhetoric is cautiously integrated in the party-state's restoration of a Chinese "empire within," indicating self-centredness and a lurking re-traditionalising of Chinese state power

ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX-Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics