PAK4 phosphorylates p53 at serine 215 to promote liver cancer metastasis

PAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of our studies. By stably overexpressing or silencing PAK4 in HCC cells we showed that it was critical for their migration. Mechanistic investigations in this setting revealed that PAK4 directly phosphorylated p53 at S215, which not only attenuated transcriptional transactivation activity but also inhibited p53-mediated suppression of HCC cell invasion. Taken together, our results showed how PAK4 overexpression in HCC promotes metastatic invasion by regulating p53 phosphorylation.postprin

Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures

Novel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. Recombinant viruses of A/Shanghai/2/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E + Q591K and PB2-K627E + D701N were generated by plasmid-based reverse genetics. PB2-E627K was essential for efficient replication of rgH7N9 in ex vivo cultures of human and swine respiratory tracts. Mutant rgPB2-K627E + D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus. The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PMϕ) at 37 °C while the compensatory mutant rgPB2-K627E + Q591K and rgPB2-K627E + D701N had partly restored replication competence in PMϕ. Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts.published_or_final_versio

Quantitative estimation of muscle shear elastic modulus of the upper trapezius with supersonic shear imaging during arm positioning

2012-2013 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

An empirical study of the impact of intellectual capital performance on business performance

This study attempts to shed light on intellectual capital (IC) performance of Hong Kong companies and its possible associations with business performance. Audited accounting data were collected from the constituent companies of Hang Seng Index in Hong Kong Stock Exchange between 2005 – 2008. In order to compute a set of IC efficiency indexes based on VAIC™. Value Added Intellectual Coefficient (VAIC™) is a quantitative IC measurement method which was pioneered by Pulic (2000) of the Austrian IC Research Centre. Four accounting ratios: market-to-book value (MB), return on assets (ROA), asset turnover (ATO) and return on equity (ROE) were used as proxies for measuring business performance. VAIC™ and its associated indexes, and the accounting ratios of sample companies are submitted to regression analysis for the detection of their associations. No conclusive evidence was found to support the associations between VAIC™ and the four financial indicators. However, components of VAIC™ were found to be able to predict a substantial variance in business performance. For example, Capital Employed Efficiency (CEE) has been found to be the key factor in predicting business financial performance. In addition, Structural Capital Efficiency (SCE) has an effect on market valuation as measured by MB as well as profitability as measured by ROE. Interestingly, negative correlations were observed between Human Capital Efficiency (HCE) and the financial indicators which, perhaps, were due to the existence of a gap between the traditional accounting perspective and value creation perspective which is central to the VAIC™ methodology in measuring IC. It is believed that the empirical results of this research have provided some new insights to the stakeholders of Hong Kong companies in utilizing IC, particularly the noted impact of structural capital. While physical and financial assets, still, appears to be taking on an important role as the key resources in delivering business success, IC, or to be exact, structural capital may be silently making headway into the fabric of Hong Kong’s economy as illustrated by its impact in delivering return on equity (ROE).postprintThe 7th International Conference on Intellectual Capital, Knowledge Management & Organisational Learning (ICICKM 2010), Hong Kong, China, 11-12 November 2010. In Proceedings of the 7th ICICKM, 2010, p. 70-7

Kondo physics in carbon nanotubes

The connection of electrical leads to wire-like molecules is a logical step in the development of molecular electronics, but also allows studies of fundamental physics. For example, metallic carbon nanotubes are quantum wires that have been found to act as one-dimensional quantum dots, Luttinger-liquids, proximity-induced superconductors and ballistic and diffusive one-dimensional metals. Here we report that electrically-contacted single-wall nanotubes can serve as powerful probes of Kondo physics, demonstrating the universality of the Kondo effect. Arising in the prototypical case from the interaction between a localized impurity magnetic moment and delocalized electrons in a metallic host, the Kondo effect has been used to explain enhanced low-temperature scattering from magnetic impurities in metals, and also occurs in transport through semiconductor quantum dots. The far higher tunability of dots (in our case, nanotubes) compared with atomic impurities renders new classes of Kondo-like effects accessible. Our nanotube devices differ from previous systems in which Kondo effects have been observed, in that they are one-dimensional quantum dots with three-dimensional metal (gold) reservoirs. This allows us to observe Kondo resonances for very large electron number (N) in the dot, and approaching the unitary limit (where the transmission reaches its maximum possible value). Moreover, we detect a previously unobserved Kondo effect, occurring for even values of N in a magnetic field.Comment: 7 pages, pdf onl

Synergies for Improving Oil Palm Production and Forest Conservation in Floodplain Landscapes

Lowland tropical forests are increasingly threatened with conversion to oil palm as global demand and high profit drives crop expansion throughout the world’s tropical regions. Yet, landscapes are not homogeneous and regional constraints dictate land suitability for this crop. We conducted a regional study to investigate spatial and economic components of forest conversion to oil palm within a tropical floodplain in the Lower Kinabatangan, Sabah, Malaysian Borneo. The Kinabatangan ecosystem harbours significant biodiversity with globally threatened species but has suffered forest loss and fragmentation. We mapped the oil palm and forested landscapes (using object-based-image analysis, classification and regression tree analysis and on-screen digitising of high-resolution imagery) and undertook economic modelling. Within the study region (520,269 ha), 250,617 ha is cultivated with oil palm with 77% having high Net-Present-Value (NPV) estimates ($413/ha?yr–$637/ha?yr); but 20.5% is under-producing. In fact 6.3% (15,810 ha) of oil palm is commercially redundant (with negative NPV of $-299/ha?yr-$-65/ha?yr) due to palm mortality from flood inundation. These areas would have been important riparian or flooded forest types. Moreover, 30,173 ha of unprotected forest remain and despite its value for connectivity and biodiversity 64% is allocated for future oil palm. However, we estimate that at minimum 54% of these forests are unsuitable for this crop due to inundation events. If conversion to oil palm occurs, we predict a further 16,207 ha will become commercially redundant. This means that over 32,000 ha of forest within the floodplain would have been converted for little or no financial gain yet with significant cost to the ecosystem. Our findings have globally relevant implications for similar floodplain landscapes undergoing forest transformation to agriculture such as oil palm. Understanding landscape level constraints to this crop, and transferring these into policy and practice, may provide conservation and economic opportunities within these seemingly high opportunity cost landscapes

Multi-decadal trends in large-bodied fish populations in the New South Wales Murray-Darling Basin, Australia

Context: Native fish populations in Australia's Murray-Darling Basin (MDB) have experienced severe declines since European settlement. Information on their status is needed to guide management and recovery. Aims: To quantify trends in MDB fish populations in New South Wales (NSW) from 1994 to 2022. Methods: Relative abundance, biomass, and size structure were examined using generalised additive mixed models at NSW MDB and river catchment (valley) scales for five native species (Murray cod, Maccullochella peelii, golden perch, Macquaria ambigua, silver perch, Bidyanus bidyanus, Macquarie perch, Macquaria australasica, freshwater catfish, Tandanus tandanus) and one alien species (common carp, Cyprinus carpio). Key results: There was strong inter-annual variation in relative abundance, biomass and population structure for all species. At the Basin scale, relative abundance of Murray cod, golden perch and common carp increased across the time series, with no clear trends for silver perch, Macquarie perch or freshwater catfish. Patterns in relative abundance, biomass, and population structure were variable among valleys for most species. Conclusions and implications: Although native fish populations in the MDB remain degraded and face escalating threats, recent increases in the abundance of some native species are an encouraging sign that integrated restoration efforts can improve the outlook for native fish

Interior pathways of the North Atlantic meridional overturning circulation

To understand how our global climate will change in response to natural and anthropogenic forcing, it is essential to determine how quickly and by what pathways climate change signals are transported throughout the global ocean, a vast reservoir for heat and carbon dioxide. Labrador Sea Water (LSW), formed by open ocean convection in the subpolar North Atlantic, is a particularly sensitive indicator of climate change on interannual to decadal timescales. Hydrographic observations made anywhere along the western boundary of the North Atlantic reveal a core of LSW at intermediate depths advected southward within the Deep Western Boundary Current (DWBC). These observations have led to the widely held view that the DWBC is the dominant pathway for the export of LSW from its formation site in the northern North Atlantic towards the Equator. Here we show that most of the recently ventilated LSW entering the subtropics follows interior, not DWBC, pathways. The interior pathways are revealed by trajectories of subsurface RAFOS floats released during the period 2003-2005 that recorded once-daily temperature, pressure and acoustically determined position for two years, and by model-simulated 'e-floats' released in the subpolar DWBC. The evidence points to a few specific locations around the Grand Banks where LSW is most often injected into the interior. These results have implications for deep ocean ventilation and suggest that the interior subtropical gyre should not be ignored when considering the Atlantic meridional overturning circulation.Dissertatio

The association between blood glucose and oxidized lipoprotein(a) in healthy young women

<p>Abstract</p> <p>Background</p> <p>Oxidized lipoproteins play important roles in the atherosclerotic processes. Oxidized lipoprotein(a) (oxLp(a)) may be more potent in atherosclerotic pathophysiology than native Lp(a), a cardiovascular disease-relevant lipoprotein. Increased blood glucose concentrations can induce oxidative modification of lipoproteins. The aim of this study was to investigate the association between circulating oxLp(a) and cardiometabolic variables including blood glucose in healthy volunteers within the normal range of blood glucose.</p> <p>Methods</p> <p>Several cardiometabolic variables and serum oxLp(a) (using an ELISA system) were measured among 70 healthy females (mean age, 22 years).</p> <p>Results</p> <p>Lp(a) and glucose were significantly and positively correlated with oxLp(a) in simple correlation test. Furthermore, a multiple linear regression analysis showed oxLp(a) to have a weakly, but significantly positive and independent correlation with only blood glucose (<it>β </it>= 0.269, <it>P </it>< 0.05).</p> <p>Conclusions</p> <p>These results suggest that increased glucose may enhance the oxidization of Lp(a) even at normal glucose levels.</p