Modeling of enzyme–substrate complexes for the metalloproteases MMP-3, ADAM-9 and ADAM-10

The matrix metalloproteases (MMPs) and the ADAMs (A Disintegrin And Metalloprotease domain) are proteolytic enzyme families containing a catalytic zinc ion, that are implicated in a variety of normal and pathological processes involving tissue remodeling and cancer. Synthetic MMP inhibitors have been designed for applications in pathological situations. However, a greater understanding of substrate binding and the catalytic mechanism is required so that more effective and selective inhibitors may be developed for both experimental and clinical purposes. By modeling a natural substrate spanning P4-P4‘ in complex with the catalytic domains, we aim to compare substrate-specificities between Stromelysin-1 (MMP-3), ADAM-9 and ADAM–10, with the aid of molecular dynamics simulations. Our results show that the substrate retains a favourable antiparallel beta-sheet conformation on the P-side in addition to the well-known orientation of the P'-region of the scissile bond, and that the primary substrate selectivity is dominated by the sidechains in the S1' pocket and the S2/S3 region. ADAM-9 has a hydrophobic residue as the central determinant in the S1' pocket, while ADAM-10 has an amphiphilic residue, which suggests a different primary specificity. The S2/S3 pocket is largely hydrophobic in all three enzymes. Inspired by our molecular dynamics calculations and supported by a large body of literature, we propose a novel, hypothetical, catalytic mechanism where the Zn-ion polarizes the oxygens from the catalytic glutamate to form a nucleophile, leading to a tetrahedral oxyanion anhydride transition state.

Frederick McCoy and his contributions to stratigraphical palaeontology

Sir Frederick McCoy made a significant contribution to the foundation of stratigraphical palaeontology. He carried out extensive taxonomic work sorting, naming and describing the Palaeozoic fossils of Ireland and Britain, and also played a decisive role in the debate between Adam Sedgwick and Roderick Murchison on where to draw the boundary between the Cambrian and Silurian systems. On his arrival in the Colony of Victoria in December 1854 he found that, contrary to the expectations of most European scientists, much of the stratigraphy and palaeontology paralleled that in the Northern Hemisphere. Hence McCoy was the first to confirm that the geological column was a global phenomenon.

Social media conflict: platforms for racial vilification, or acts of provocation and citizenship?

Although racism remains an issue for social media sites such as YouTube, this focus often overshadows the site’s productive capacity to generate ‘agonistic publics’ from which expressions of cultural citizenship and solidarity might emerge. This paper examines these issues through two case studies: the recent proliferation of mobile phone video recordings of racist rants on public transport, and racist interactions surrounding the performance of a Maori ‘flash mob’ haka in New Zealand that was recorded and uploaded to YouTube. We contrast these incidents as they are played out primarily through social media, with the case of Australian Football League player Adam Goodes and the broadcast media reaction to a racial slur aimed against him by a crowd member during the AFL’s Indigenous Round. We discuss the prevalence of vitriolic exchange and racial bigotry, but also, and more importantly, the productive and equally aggressive defence of more inclusive and tolerant forms of cultural identification that play out across these different media forms. Drawing on theories of cultural citizenship along with the political theory of Chantal Mouffe, we point to the capacities of YouTube as ‘platform’, and to social media practices, in facilitating ground-up antiracism and generating dynamic, contested and confronting micropublics.

Where did we go wrong? An examination of students treatment of experimental error in engineering mechanics laboratories

The ability of engineers and applied scientists to undertake experimental measurements is a fundamental requirement of the profession. However, it is not simply good enough to be able to perform experiments if we are not able to interpret the results. In this study, reports prepared by mechanical engineering students were examined to determine how students dealt with the disparity between experimental measurements and theoretical results in their Engineering Mechanics laboratories. Analysis of the reports, and discussions with students in their laboratory classes, revealed a superficial understanding or regard for experimental error. This superficial treatment of experimental error is, most likely, due to a number of factors that are discussed. Some possible strategies for addressing the issue are also examined.

The silence of the 7th floor

This thesis explored the conundrum of the trauma narrative requiring a suspension of disbelief from the reader, whilst simultaneously being acknowledged as bona fide truth. This paradox was examined via the identification of common themes and writerly techniques used in both trauma testimony and trauma novels.

Water-binding capacity and viscosity of Australian sweet lupin kernel fibre under in vitro conditions simulating the human upper gastrointestinal tract

There is currently little understanding of the physicochemical properties in the human gastrointestinal tract of Australian sweet lupin (Lupinus angustifolius) kernel fibre (LKF), a novel food ingredient with potential for the fibre enrichment of foods such as baked goods. Since physicochemical properties of dietary fibres have been related to beneficial physiological effects in vitro, this study compared water-binding capacity and viscosity of LKF with that of other fibres currently used for fibre-enrichment of baked goods, under in vitro conditions simulating the human upper gastrointestinal tract. At between 8.47 and 11.07g water/g dry solids, LKF exhibited water-binding capacities that were significantly higher (P<0.05) than soy fibre, pea hull fibre, cellulose and wheat fibre at all of the simulated gastrointestinal stages examined. Similarly, viscosity of LKF was significantly higher (P<0.05) than that of the other fibres at all simulated gastrointestinal stages. The relatively high water-binding capacity and viscosity of LKF identified in this study suggests that this novel fibre ingredient may elicit different and possibly more beneficial physiological effects in the upper human gastrointestinal tract than the conventional fibre ingredients currently used in fibre-enriched baked goods manufacture. We are now performing human studies to investigate the effect of LKF in the diet on health-related gastrointestinal events.

Contribution of fungi to primary biogenic aerosols in the atmosphere: wet and dry discharged spores, carbohydrates, and inorganic ions

Biogenic aerosols play important roles in atmospheric chemistry physics, the biosphere, climate, and public health. Here, we show that fungi which actively discharge their spores with liquids into the air, in particular actively wet spore discharging Ascomycota (AAM) and actively wet spore discharging Basidiomycota (ABM), are a major source of primary biogenic aerosol particles and components. We present the first estimates for the global average emission rates of fungal spores.

Measurement results and budget calculations based on investigations in Amazonia (Balbina, Brazil, July 2001) indicate that the spores of AAM and ABM may account for a large proportion of coarse particulate matter in tropical rainforest regions during the wet season (0.7–2.3 μg m⁻³). For the particle diameter range of 1–10 μm, the estimated proportions are ~25% during day-time, ~45% at night, and ~35% on average. For the sugar alcohol mannitol, the budget calculations indicate that it is suitable for use as a molecular tracer for actively wet discharged basidiospores (ABS). ABM emissions seem to account for most of the atmospheric abundance of mannitol (10–68 ng m⁻³), and can explain the observed diurnal cycle (higher abundance at night). ABM emissions of hexose carbohydrates might also account for a significant proportion of glucose and fructose in air particulate matter (7–49 ng m⁻³), but the literature-derived ratios are not consistent with the observed diurnal cycle (lower abundance at night). AAM emissions appear to account for a large proportion of potassium in air particulate matter over tropical rainforest regions during the wet season (17–43 ng m⁻³), and they can also explain the observed diurnal cycle (higher abundance at night). The results of our investigations and budget calculations for tropical rainforest aerosols are consistent with measurements performed at other locations.

Based on the average abundance of mannitol reported for extratropical continental boundary layer air (~25 ng m⁻³), we have also calculated a value of ~17 Tg yr⁻¹ as a first estimate for the global average emission rate of ABS over land surfaces, which is consistent with the typically observed concentrations of ABS (~10³–10⁴ m⁻³; ~0.1^–1 μg m⁻³). The global average atmospheric abundance and emission rate of total fungal spores, including wet and dry discharged species, are estimated to be higher by a factor of about three, i.e. 1 μg m⁻³ and ~50 Tg yr⁻¹. Comparisons with estimated rates of emission and formation of other major types of organic aerosol (~47 Tg yr⁻¹ of anthropogenic primary organic aerosol; 12–70 Tg yr⁻¹ of secondary organic aerosol) indicate that emissions from fungi should be taken into account as a significant global source of organic aerosol. The effects of fungal spores and related chemical components might be particularly important in tropical regions, where both physicochemical processes in the atmosphere and biological activity at the Earth's surface are particularly intense, and where the abundance of fungal spores and related chemical compounds are typically higher than in extratropical regions.

Dystopian visions of global capitalism : Philip Reeve's Mortal Engines and M. T. Anderson's Feed

This article examines Philip Reeve’s novel for children, Mortal Engines, and M.T. Anderson’s young adult novel, Feed, by assessing these dystopias as prototypical texts of what Ulrich Beck calls risk society. Through their visions of a fictional future, the two narratives explore the hazards created by contemporary techno-economic progress, predatory global politics and capitalist excesses of consumption. They implicitly pose the question: “In the absence of a happy ending for western civilisation, what kind of children can survive in dystopia?”

Effect of glycerol-induced hyperhydration on thermoregulation and metabolism during exercise in the heat

This study examined the effect of glycerol ingestion on fluid homeostasis, thermoregulation, and metabolism during rest and exercise. Six endurance-trained men ingested either 1 g glycerol in 20 ml H₂O.kg^-1 body weight (bw) (GLY) or 20 ml H₂O.kg^-1bw (CON) in a randomized double-blind fashion, 120 min prior to undertaking 90 min of steady state cycle exercise (SS) at 98 % of lactate threshold in dry heat (35 degrees C, 30 % RH), with ingestion of CHO-electrolyte beverage (6 % CHO) at 15-min intervals. A 15-min cycle, where performance was quantified in kJ, followed (PC). Pre-exercise urine volume was lower in GLY than CON (1119 ± 97 vs. 1503 ± 146 ml· 120 min^-1; p < .05). Heart rate was lower (p < .05) throughout SS in GLY, while forearm blood flow was higher (17.1 ± 1.5 vs. 13.7 ± 3.0 ml.100 g tissue·min^-1; p < .05) and rectal  temperature lower (38.7 ± 0.1 vs. 39.1 ± 0.1 ° C; p < .05) in GLY late in SS. Despite these changes, skin and muscle temperatures and circulating catecholamines were not different between trials. Accordingly, no differences were observed in muscle glycogenolysis, lactate accumulation, adenine nucleotide, and phosphocreatine degradation or inosine 5'-monophosphate accumulation when comparing GLY with CON. Of note, the work performed during PC was 5 % greater in GLY (252 ± 10 vs. 240 ± 9 kJ; p < .05). These results demonstrate that glycerol, when ingested with a bolus of water 2 hours prior to exercise, results in fluid retention, which is capable of reducing cardiovascular strain and enhancing thermoregulation. Furthermore, this practice increases exercise performance in the heat by mechanisms other than alterations in muscle metabolism.

Dry your eyes princess : an analysis of gender and 'other' based discources in police organisations

This paper examines the literature relevant to an analysis of gender and discourse in police organisations with a view to testing it through research. Much of the literature on policing can be divided into four key topic areas: the features and construction of police culture; women’s integration into policing; organisational structures and styles of police leadership; and debates about the nature of police work. An examination of the literature has revealed a deficiency of research in discourses within policing and in particular, the impact of discourses on gender and police training. Assumptions underpinning the research project and supported by literature include: formal and informal structures and practices within organisations produce and reproduce gender relations; power, gender relations and masculinity are characteristics of police culture; discourses are products and resources of interactions which establish particular truths; and police organisations have been slow to respond to anti-discrimination legislation and to integrate women into police services. Critical to any analysis of culture, power, gender, discourses, difference, and subjectification is the dynamic and complex nature of culture. Applying Shearing’s and Ericson’s definition of culture as ‘figurative logic’ has resonance in police organisations where symbols, rhetoric and metaphors function as vehicles for discourses.