Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications.

Published versio

A common periodic representation of interaural time differences in mammalian cortex

Binaural hearing, the ability to detect small differences in the timing and level of sounds at the two ears, underpins the ability to localize sound sources along the horizontal plane, and is important for decoding complex spatial listening environments into separate objects - a critical factor in 'cocktail-party listening'. For human listeners, the most important spatial cue is the interaural time difference (ITD). Despite many decades of neurophysiological investigations of ITD sensitivity in small mammals, and computational models aimed at accounting for human perception, a lack of concordance between these studies has hampered our understanding of how the human brain represents and processes ITDs. Further, neural coding of spatial cues might depend on factors such as head-size or hearing range, which differ considerably between humans and commonly used experimental animals. Here, using magnetoencephalography (MEG) in human listeners, and electro-corticography (ECoG) recordings in guinea pig-a small mammal representative of a range of animals in which ITD coding has been assessed at the level of single-neuron recordings-we tested whether processing of ITDs in human auditory cortex accords with a frequency-dependent periodic code of ITD reported in small mammals, or whether alternative or additional processing stages implemented in psychoacoustic models of human binaural hearing must be assumed. Our data were well accounted for by a model consisting of periodically tuned ITD-detectors, and were highly consistent across the two species. The results suggest that the representation of ITD in human auditory cortex is similar to that found in other mammalian species, a representation in which neural responses to ITD are determined by phase differences relative to sound frequency rather than, for instance, the range of ITDs permitted by head size or the absolute magnitude or direction of ITD

A surface oxidised Fe-S catalyst for the liquid phase hydrogenation of CO₂

Rapidly increasing anthropogenic carbon dioxide (CO_{2}) emissions, coupled with irreversible climate change and depleting fossil fuel reserves, have significantly increased the drive for CO_{2} utilisation. Iron sulfide as a catalyst for the hydrogenation of CO_{2} has been discussed in the literature for decades, especially in an origin-of-life context, but little experimental evidence exists in the literature for its feasibility. Here we report the catalytic properties of pyrrhotite (Fe_{1−x}S) for the hydrogenation of CO_{2} into formate. Advanced material characterisation methods in combination with computational studies have allowed us to identify surface S–Fe–O moieties as active sites for the reaction

The role of surface oxidation and Fe-Ni synergy in Fe-Ni-S catalysts for CO2 hydrogenation.

Increasing carbon dioxide (CO2) emissions, resulting in climate change, have driven the motivation to achieve the effective and sustainable conversion of CO2 into useful chemicals and fuels. Taking inspiration from biological processes, synthetic iron-nickel-sulfides have been proposed as suitable catalysts for the hydrogenation of CO2. In order to experimentally validate this hypothesis, here we report violarite (Fe,Ni)3S4 as a cheap and economically viable catalyst for the hydrogenation of CO2 into formate under mild, alkaline conditions at 125 °C and 20 bar (CO2 : H2 = 1 : 1). Calcination of violarite at 200 °C resulted in excellent catalytic activity, far superior to that of Fe-only and Ni-only sulfides. We further report first principles simulations of the CO2 conversion on the partially oxidised (001) and (111) surfaces of stoichiometric violarite (FeNi2S4) and polydymite (Ni3S4) to rationalise the experimentally observed trends. We have obtained the thermodynamic and kinetic profiles for the reaction of carbon dioxide (CO2) and water (H2O) on the catalyst surfaces via substitution and dissociation mechanisms. We report that the partially oxidised (111) surface of FeNi2S4 is the best catalyst in the series and that the dissociation mechanism is the most favourable. Our study reveals that the partial oxidation of the FeNi2S4 surface, as well as the synergy of the Fe and Ni ions, are important in the catalytic activity of the material for the effective hydrogenation of CO2 to formate

Thermal Properties and Segregation Behavior of Pt Nanowires Modified with Au, Ag, and Pd Atoms: A Classical Molecular Dynamics Study

Platinum nanowires (NWs) have been reported to be catalytically active toward the oxygen reduction reaction (ORR). The edge modification of Pt NWs with metals M (M = Au, Ag, or Pd) may have a positive impact on the overall ORR activity by facilitating diffusion of adsorbed oxygen, Oads, and hydroxyl groups, OHads, between the {001} and {111} terraces. In the present study, we have employed classical molecular dynamics simulations to investigate the segregation behavior of Au, Ag, and Pd decorating the edges of Pt NWs. We observe that, under vacuum conditions, Pd prefers to diffuse toward the core rather than stay on the NW surface. Ag and Au atoms are mobile at temperatures as low as 900 K; they remain on the surface but do not appear to be preferentially more stable at edge sites. To effect segregation of Au and Ag atoms toward the edge, we propose annealing in the presence of different reactive gas environments. Overall, our study suggests potential experimental steps required for the synthesis of Pt nanowires and nanoparticles with improved Oads and OHads interfacet diffusion rates and consequently an improved ORR activity

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

CD26/dipeptidyl peptidase IV (DPPIV) is a surface antigen with multiple functions, including a role in T-cell activation and the development of certain human cancers. We previously demonstrated that CD26/DPPIV enhanced sensitivity of Jurkat cells to doxorubicin. We now show that expression of CD26/DPPIV enhanced sensitivity of CD26 Jurkat transfectants to G2–M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G2–M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34cdc2 kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposide-induced G2–M arrest was also observed in serum-free media, suggesting an effect of CD26 on cell-derived processes rather than serum-derived factors. Importantly, our work elucidated a potential mechanism for the enhanced susceptibility of CD26-expressing Jurkat cells to the topoisomerase II inhibitors by demonstrating that CD26/DPPIV surface expression was associated with increased topoisomerase II α levels and enhanced enzyme activity. Besides being the first to show a functional association between the multifaceted molecule CD26 and the key cellular protein topoisomerase II α, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies

Multi-component assessment of chronic obstructive pulmonary disease: an evaluation of the ADO and DOSE indices and the global obstructive lung disease categories in international primary care data sets

Acknowledgements We thank Sian Williams of the International Primary Care Respiratory Group for her help and encouragement with the project. The OPCRD database was made available courtesy of the Respiratory Effectiveness Group and RIRL and the data were kindly prepared for analysis by Julie von Ziegenweidt. Funding The International Primary Care Respiratory Group (IPCRG) provided funding for this research project as an UNLOCK group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. The latter funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Database access for the OPCRD was provided by the Respiratory Effectiveness Group (REG) and Research in Real Life; the OPCRD statistical analysis was funded by REG. The Bocholtz Study was funded by PICASSO for COPD, an initiative of Boehringer Ingelheim, Pfizer and the Caphri Research Institute, Maastricht University, The Netherlands.Peer reviewedPublisher PD

Surface Oxidized Fe-S catalyst for the Liquid Phase Hydrogenation of CO2

Rapidly increasing anthropogenic carbon dioxide (CO2) emissions, coupled with irreversible climate change and depleting fossil fuels reserves, has significantly increased the drive for CO2 utilization. Iron sulfide as a catalyst for the hydrogenation of CO2 has been discussed in the literature for decades, especially in an origin-of-life context, however little experimental evidence exists in the literature for its feasibility. Here we report the catalytic properties of pyrrhotite (Fe1-xS) for the hydrogenation of CO2 into formate under mild, alkaline conditions at 125 oC and 20 bar (CO2:H2, 1:1). Controlled surface oxidation of pyrrhotite, via high temperature calcination, increased the surface oxygen species that in turn resulted in an increased catalytic activity, with the optimum calcination temperature being 200 oC. X-ray based characterisation methods in combination with computational studies, allowed us to identify surface S-Fe-O moieties as active sites for the reaction

MJA Practice Essentials - 2: Recent advances in therapy of diabetes - Endocrinology

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.As suboptimal blood glucose control has a lasting harmful effect even if control improves later, intensive insulin therapy to minimise hyperglycaemia is now recommended for all patients with type 1 diabetes. The new rapid- and long-acting insulin analogues offer more physiological insulin profiles than traditional insulin preparations. Continuous insulin infusion (“pump therapy”) may provide a solution for some patients with frequent hypoglycaemia or hypoglycaemic unawareness. Continuous blood glucose monitoring reveals postprandial hyperglycaemia and asymptomatic nocturnal hypoglycaemia and may be especially useful for programming overnight basal insulin rates for pump therapy. In type 2 diabetes, management should change with disease progression; introduction of insulin should not be delayed if metabolic control becomes suboptimal. More individualised and physiological therapy is now possible.Jennifer J Couper and Johannes B Prin