EP: Styling Knowledge

Discussion forming part of the MA General Theory Forum 2014, convened by Stephen Wilson

Can BCAT1 Expression Level Help Predict Disease Progression in Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common blood cancer in the UK, with an incidence of >3500 newly diagnosed cases per year resulting in >1000 deaths. Disease prevalence increases with age, where the majority of patients are >65 years old [1]. CLL is a largely indolent disease and is routinely staged according to the Binet system as follows; stage A (involving 0-2 lymphoid sites), stage B (involving 2-5 lymphoid cites) and stage C (platelets < 1x1011/L or haemoglobin <10g/dL), the latter stage reflecting loss of bone marrow function [2]. Whilst for some stage A patients, the disease may remain stable for many decades (median life expectancy of 13 years), for others the disease progresses more rapidly [3]. This observation likely reflects the genetic and molecular heterogeneity of CLL. As such there are several prognostic risk factors used to stratify newly diagnosed patients, which include; trisomy-12, 13q/17p/11q23 deletion, advanced stage, males>females, unmutated VH Ig genes, raised lactate dehydrogenase activity and expression of Zap70 and CD38 [4]. CLL is traditionally treated with a combination of chemotherapeutic reagents, namely, Fludarabine/ Cyclophosphamide/Rituximab (FCR), however treatment remains challenging within the elderly population [1]. Lately the Brutan’s tyrosine kinase inhibitor, Ibrutinib, has shown great promise for the treatment of CLL [5]. However, exceptions are identified as well as treatment resistance prompting further research into CLL treatment strategies [6]

Can BCAT1 expression level help predict disease progression in chronic lymphocytic leukaemia

Can BCAT1 expression level help predict disease progression in chronic lymphocytic leukaemi

Sheared turbulent flows and wake dynamics of an idled floating tidal turbine

Ocean energy extraction is on the rise. While tides are the most predictable amongst marine renewable resources, turbulent and complex flows still challenge reliable tidal stream energy extraction and there is also uncertainty in how devices change the natural environment. To ensure the long-term integrity of emergent floating tidal turbine technologies, advances in field measurements are required to capture multiscale, real-world flow interactions. Here we use aerial drones and acoustic profiling transects to quantify the site- and scale-dependent complexities of actual turbulent flows around an idled, utility-scale floating tidal turbine (20 m rotor diameter, D). The combined spatial resolution of our baseline measurements is sufficiently high to quantify sheared, turbulent inflow conditions (reversed shear profiles, turbulence intensity \u3e20%, and turbulence length scales \u3e 0.4D). We also detect downstream velocity deficits (approaching 20% at 4D) and trace the far-wake propagation using acoustic backscattering techniques in excess of 30D. Addressing the energy-environment nexus, our oceanographic lens on flow characterisation will help to validate multiscale flow physics around offshore energy platforms that have thus far only been simulated

Seagrass communities of the Great Barrier Reef and their desired state: applications for spatial planning and management

The research program reported here evolved from an interest in developing ecologically relevant target criteria that, if met, correspond to desired ecological outcomes (e.g. desired state) for the Great Barrier Reef World Heritage Area (GBRWHA) and to achieving the overarching objective of the Great Barrier Reef Marine Park Authority’s Long-term Sustainability Plan. The objective of the original National Environment Science Program (NESP) Tropical Water Quality Hub (TWQ) Project 3.2.1 Deriving ecologically relevant load targets to meet desired ecosystem condition for the Great Barrier Reef: a case study for seagrass meadows in the Burdekin region was to examine relationships between catchment inputs of sediment and seagrass desired state, and to compare these against the 2018 Water Quality Improvement Plan’s ecological targets. This objective was met using a case study in Cleveland Bay based on sediment loads from the Burdekin River and other smaller catchments that discharge into the bay (Collier et al., 2020). The techniques developed in the Cleveland Bay case study are used in the present report at the scale of the whole GBRWHA for NESP TWQ Hub Project 5.4. To achieve this we followed three steps: (1) a consolidation and verification of seagrass data at the GBRWHA scale, (2) an analysis of the distribution of GBRWHA seagrass habitat and communities, and (3) an estimation of a desired state target for communities with sufficient data. To achieve step 1, we compiled and standardised 35 years of seagrass survey data in a spatial database, including 81,387 georeferenced data points. Twelve seagrass species were recorded, the deepest of which (Halophila spinulosa) was found at 76 m. This database is a valuable resource that provides coastal managers, researchers and the global marine community with a long-term spatial resource describing seagrass populations from the mid1980s against which to benchmark change. For step 2, we identified 88,331 km2 of potential seagrass habitat within the GBRWHA; 1,111 km2 in estuaries, 16,276 km2 in coastal areas, and 70,934 km2 in reef areas. Thirty-six seagrass community types were defined by species assemblages. The environmental conditions that structure the location and extent of these communities included depth, tidal exposure, latitude, current speed, benthic light, proportion of mud, water type, water temperature, salinity, and wind speed. Environmental parameters interact with the topography of the reef and changes in the coastal plain, its watersheds, and its development with latitude. We describe seagrass distributions and communities that are shaped by multiple combinations of these environmental complexities and how that may influence marine spatial planning and environmental protection initiatives (Chapter 3). For step 3, we used more than 20 years of historical data (1995-2018) on seagrass biomass for the diverse seagrass communities of the GBRWHA to develop desired state benchmarks. Of the 36 seagrass communities, desired state was identified for 25 of them, with the remainder having insufficient data. Desired state varied by more than one order of magnitude between community types, and was influenced by the mix of species in the communities and the range of environmental conditions that define community boundaries. We identified a historical, decadal-scale cycle of decline and recovery. Recovery to desired state has occurred for coastal intertidal communities following the most recent declines in 2008 - 2012. A number of the estuarine and coastal subtidal communities have not recovered to desired state biomass in recent years (Chapter 4). This body of work provides a huge step forward in our understanding of the complexities of GBRWHA seagrass communities. We discuss the relevance of these research outputs to future marine spatial planning and management. This includes zoning in “representative areas”, hierarchical monitoring design (e.g. RIMReP), and the setting of ecologically relevant sediment load targets for desired state (e.g. Lambert et al., 2019). The updated seagrass data, seagrass distribution, community classification and desired state targets provides important new information for incorporation into marine spatial planning and management that is discussed in Chapter 5. These applications include: • Future assessments of non-reef habitats within the GBRWHA and GBRMP. • Assessing how risk and spatial protection intersect with seagrass communities and the role they play in protecting seagrass, e.g. Queensland State and Commonwealth marine parks, Fish Habitat Areas, Dugong Protected Areas, Port Exclusion Zones. • Expanding our spatial analysis to areas ecologically connected but outside of the GBRWHA such as Torres Strait, the Gulf of Carpentaria, and Fraser Island coast, where we already have seagrass data. • Designing a hierarchical seagrass monitoring design with coarse scales (intertidal, subtidal, estuary, coast, reef) and fine scales (36 communities). We have identified significant knowledge gaps that should guide future monitoring efforts (e.g. RIMReP and Queensland Land and Sea Ranger Program), including a lack of consistent and recent data for reef seagrass communities. • We identified communities where data is deficient, such as in estuaries where important seagrass communities have potential exposure to multiple threats for which more consistent environmental data would be valuable. • Identifying potential restoration sites. Our work has highlighted the critical role of historical data in understanding spatial complexity and for making informed management decisions on the current state of seagrass in the GBRWHA. Our approach can be adapted for monitoring, management and assessment of pressures at other relevant scales and jurisdictions. Our results guide conservation planning through prioritisation of at-risk communities that are continuing to fail to attain desired state

Blood Pressure in Normotensive Young Adults Is Not Influenced by Resistance Training Rest Interval Duration

Introduction: We aimed to examine the effect of resistance training rest interval length on chronic changes of systolic (SBP) and diastolic blood pressure (DBP). Methods: 27 normotensive young adults were randomly assigned to one of three rest interval length groups: 30-sec, 90-sec, or 150-sec. Baseline and post-training SBP and DBP measurements were obtained. Participants trained and logged their sessions in a smartphone application three times per week for 8 weeks. They also measured their blood pressure weekly with a home kit. Changes in SBP and DBP between the three groups were tested using a mixed model 3 x 2 ANOVA with follow-up post-hocs as necessary. Results: There was no significant interaction between rest interval group and time for SBP or DBP. For SBP, there was a significant main effect for time, p\u3c0.001 (pre: 115 mmHg vs. post: 108 mmHg). Conclusions: SBP and DBP were not significantly influenced by rest interval length over time. The resistance-training program had no effect on DBP but significantly decreased SBP regardless of rest interval. These results indicate that young normotensive adults may use short, moderate, or long duration rest intervals to elicit reductions in SBP

An unexplored role for Peroxiredoxin in exercise-induced redox signalling?

Peroxiredoxin (PRDX) is a ubiquitous oxidoreductase protein with a conserved ionised thiol that permits catalysis of hydrogen peroxide (H2O2) up to a million times faster than any thiol-containing signalling protein. The increased production of H2O2 within active tissues during exercise is thought to oxidise conserved cysteine thiols, which may in turn facilitate a wide variety of physiological adaptations. The precise mechanisms linking H2O2 with the oxidation of signalling thiol proteins (phosphates, kinases and transcription factors) are unclear due to these proteins' low reactivity with H2O2 relative to abundant thiol peroxidases such as PRDX. Recent work has shown that following exposure to H2O2 in vitro, the sulfenic acid of the PRDX cysteine can form mixed disulphides with transcription factors associated with cell survival. This implicates PRDX as an ‘active’ redox relay in transmitting the oxidising equivalent of H2O2 to downstream proteins. Furthermore, under oxidative stress, PRDX can form stable oxidised dimers that can be secreted into the extracellular space, potentially acting as an extracellular ‘stress’ signal. There is extensive literature assessing non-specific markers of oxidative stress in response to exercise, however the PRDX catalytic cycle may offer a more robust approach for measuring changes in redox balance following exercise. This review discusses studies assessing PRDX-mediated cellular signalling and integrates the recent advances in redox biology with investigations that have examined the role of PRDX during exercise in humans and animals. Future studies should explore the role of PRDX as a key regulator of peroxide mediated-signal transduction during exercise in humans

Room-temperature exciton-polaritons with two-dimensional WS2

Two-dimensional transition metal dichalcogenides exhibit strong optical transitions with significant potential for optoelectronic devices. In particular they are suited for cavity quantum electrodynamics in which strong coupling leads to polariton formation as a root to realisation of inversionless lasing, polariton condensationand superfluidity. Demonstrations of such strongly correlated phenomena to date have often relied on cryogenic temperatures, high excitation densities and were frequently impaired by strong material disorder. At room-temperature, experiments approaching the strong coupling regime with transition metal dichalcogenides have been reported, but well resolved exciton-polaritons have yet to be achieved. Here we report a study of monolayer WS$_2$ coupled to an open Fabry-Perot cavity at room-temperature, in which polariton eigenstates are unambiguously displayed. In-situ tunability of the cavity length results in a maximal Rabi splitting of $\hbar \Omega_{\rm{Rabi}} = 70$ meV, exceeding the exciton linewidth. Our data are well described by a transfer matrix model appropriate for the large linewidth regime. This work provides a platform towards observing strongly correlated polariton phenomena in compact photonic devices for ambient temperature applications.Comment: 12 pages, 6 figure

Community-specific "desired" states for seagrasses through cycles of loss and recovery

Seagrass habitats provide critical ecosystem services, yet there is ongoing concern over mounting pressures and continuing degradation. Defining a desired state for these habitats is a key step in implementing appropriate management but is often difficult given the challenges of available data and an evaluation of where to set benchmarks. We use more than 20 years of historical seagrass biomass data (1995–2018) for the diverse seagrass communities of Australia's Great Barrier Reef World Heritage Area (GBRWHA) to develop desired state benchmarks. Desired state for seagrass biomass was estimated for 25 of 36 previously defined seagrass communities with the remainder having insufficient data. Desired state varied by more than one order of magnitude between community types and was influenced by the mix of species in the communities and the range of environmental conditions. We identify a historical, decadal-scale cycle of decline with recovery to desired state in coastal intertidal communities. In contrast a number of the estuary and coastal subtidal communities have not recovered to desired state biomass. Understanding a historical context is critically important for setting benchmarks and making informed management decisions on the present state of seagrass in the GBRWHA. The approach we have developed is scalable for monitoring, management and assessment of pressures for other management areas and for other jurisdictions. Our results guide conservation planning through prioritization of the at-risk seagrass communities that are continuing to fall below their desired state

High intensity interval exercise increases the frequency of peripheral PD-1+ CD8+ central memory T-cells and soluble PD-L1 in humans

Exercise can exert anti-inflammatory effects in an intensity-dependent manner; however, the mechanisms mediating these effects are continually being established. Programme Death Receptor-1 (PD-1) is a membrane bound receptor that maintains immune tolerance by dampening immune cell interactions, such as those mediated by cytotoxic T-cell lymphocytes (CD8+). The aim of this study was to characterise sub-populations of CD8+ T-cells with regards to their expression of PD-1 before and immediately after exercise. Interleukin (IL)-6, soluble PD-1 (sPD-1) and its ligand (sPD-L1) were also quantified in plasma. Eight individuals (mean ± SD: age 29 ± 5 years; BMI 24.2 ± 3.4 kg.m2; O2max 44.5 ± 6.4 ml·kg-1·min-1) undertook two time and energy-matched cycling bouts in a counterbalanced study design: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE). Both MOD and HIIE increased the number, but not the proportion of circulating CD8+ PD-1+ cells, with no differences between trials. Within the CD8+ PD-1+ pool, the expression of PD-1 increased on central memory cells following HIIE only (fold change: MOD 1.0 vs HIIE +1.4), as well the concentration of CD8+PD-1+ memory cells within the circulation (cells/uL: MOD -0.4 vs HIIE +5.8). This response composed a very small part of the exercise-induced CD8+ lymphocytosis (Pre-Ex: 0.38% to Post-Ex: 0.69%; p>.05). sPD-L1 and IL-6 concentration increased in tandem following MOD and HIIE (r=0.57; P=0.021), with a reciprocal decline in sPD-1 observed. The current data demonstrate that PD-1+ CD8+ lymphocytes were mobilised following both MOD and HIIE. Both the number of central memory CD8+ T-cells expressing PD-1 and the expression level on these cells were increased following HIIE only. This intensity-dependent phenotypic response, in conjunction with increased circulatory sPD-L1 may represent an aspect of the anti-inflammatory response to exercise and warrants further investigation