Breast cancer cells stimulate osteoprotegerin (OPG) production by endothelial cells through direct cell contact

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the sprouting of capillaries from existing blood vessels, is central to tumour growth and progression, however the molecular regulation of this process remains to be fully elucidated. The secreted glycoprotein osteoprotegerin (OPG) is one potential pro-angiogenic factor, and clinical studies have demonstrated endothelial cells within a number of tumour types to express high levels of OPG compared to those in normal tissue. Additionally, OPG can increase endothelial cell survival, proliferation and migration, as well as induce endothelial cell tube formation <it>in vitro</it>. This study aims to elucidate the processes involved in the pro-angiogenic effects of OPG <it>in vitro</it>, and also how OPG levels may be regulated within the tumour microenvironment.</p> <p>Results</p> <p>It has previously been demonstrated that OPG can induce tube formation on growth factor reduced matrigel. In this study, we demonstrate that OPG enhances the pro-angiogenic effects of VEGF and that OPG does not stimulate endothelial cell tube formation through activation of the VEGFR2 receptor. We also show that cell contact between HuDMECs and the T47D breast cancer cell line increases endothelial cell OPG mRNA and protein secretion levels in <it>in vitro </it>co-cultures. These increases in endothelial cell OPG secretion were dependent on α_νβ₃ligation and NFκB activation. In contrast, the pro-angiogenic factors VEGF, bFGF and TGFβ had no effect on HuDMEC OPG levels.</p> <p>Conclusion</p> <p>These findings suggest that the VEGF signalling pathway is not involved in mediating the pro-angiogenic effects of OPG on endothelial cells <it>in vitro</it>. Additionally, we show that breast cancer cells cause increased levels of OPG expression by endothelial cells, and that direct contact between endothelial cells and tumour cells is required in order to increase endothelial OPG expression and secretion. Stimulation of OPG secretion was shown to involve α_νβ₃ligation and NFκB activation.</p

Accelerometer-measured physical activity in mid-age Australian adults

BACKGROUND: Raw data from accelerometers can provide valuable insights into specific attributes of physical activity, such as time spent in intensity-specific activity. The aim of this study was to describe physical activity assessed with raw data from triaxial wrist-worn accelerometers in mid-age Australian adults. METHODS: Data were from 700 mid-age adults living in Brisbane, Australia (mean age: 60.4; SD:7.1 years). Data from a non-dominant wrist worn triaxial accelerometer (Actigraph wGT3X-BT), expressed as acceleration in gravitational equivalent units (1 mg = 0.001 g), were used to estimate time spent in moderate-vigorous intensity physical activity (MVPA; >100 mg) using different bout criteria (non-bouted, 1-, 5-, and 10-min bouts), and the proportion of participants who spent an average of at least one minute per day in vigorous physical activity. RESULTS: Mean acceleration was 23.2 mg (SD: 7.5) and did not vary by gender (men: 22.4; women: 23.7; p-value: 0.073) or education (p-value: 0.375). On average, mean acceleration was 10% (2.5 mg) lower per decade of age from age 55y. The median durations in non-bouted, 1-min, 5-min and 10-min MVPA bouts were, respectively, 68 (25th -75th : 45–99), 26 (25th -75th : 12–46), 10 (25th -75th : 3–24) and 8 (25th -75th : 0–19) min/day. Around one third of the sample did at least one minute per day in vigorous intensity activities. CONCLUSION: This population-based cohort provided a detailed description of physical activity based on raw data from accelerometers in mid-age adults in Australia. Such data can be used to investigate how different patterns and intensities of physical activity vary across the day/week and influence health outcomes

The association between sedentary leisure and physical activity in middle-aged adults

Aim The aim of this study was to examine the association between time spent in sedentary leisure and physical activity level in mid-aged men and women

Two-Phase and Vapor Phase PvTx Propertiesof the Difluoromethane + cis-1,3,3,3-Tetrafluoroprop-1-ene Binary System

This paper provides 84 two-phase and 66 vapor phase PvTx measurements for binary blends comprising difluoromethane (R32) and cis-1,3,3,3-tetrafluoroprop-1-ene (R1234ze(Z)). The data are for seven i..

Cep63 and Cep152 Cooperate to Ensure Centriole Duplication

Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation

Exploring the limits of the self consistent Born approximation for inelastic electronic transport

The non equilibrium Green function formalism is today the standard computational method for describing elastic transport in molecular devices. This can be extended to include inelastic scattering by the so called self-consistent Born approximation (SCBA), where the interaction of the electrons with the vibrations of the molecule is assumed to be weak and it is treated perturbatively. The validity of such an assumption and therefore of the SCBA is difficult to establish with certainty. In this work we explore the limitations of the SCBA by using a simple tight-binding model with the electron-phonon coupling strength $\rm{\alpha}$ chosen as a free parameter. As model devices we consider Au mono-atomic chains and a $\rm{H_2}$ molecule sandwiched between Pt electrodes. In both cases our self-consistent calculations demonstrate a breakdown of the SCBA for large $\rm{\alpha}$ and we identify a weak and strong coupling regime. For weak coupling our SCBA results compare closely with those obtained with exact scattering theory. However in the strong coupling regime large deviations are found. In particular we demonstrate that there is a critical coupling strength, characteristic of the materials system, beyond which multiple self-consistent solutions can be found depending on the initial conditions in the simulation. We attribute these features to the breakdown of the perturbative expansion leading to the SCBA.Comment: 12 pages, 16 figures, 1 Tabl

Palladium(II)-Catalysed Aminocarbonylation of Terminal Alkynes for the Synthesis of 2-Ynamides: Addressing the Challenges of Solvents and Gas Mixtures

2‐Ynamides can be synthesised through Pd(II) catalysed oxidative carbonylation, utilising low catalyst loadings. A variety of alkynes and amines can be used to afford 2‐ynamides in high yields, whilst overcoming the drawbacks associated with previous oxidative methods, which rely on dangerous solvents and gas mixtures. The use of [NBu(4)]I allows the utilisation of the industrially recommended solvent ethyl acetate. O(2) can be used as the terminal oxidant, and the catalyst can operate under safer conditions with low O(2) concentrations

Biodiversity of nematode assemblages from the region of the Clarion-Clipperton Fracture Zone, an area of commercial mining interest

BACKGROUND: The possibility for commercial mining of deep-sea manganese nodules is currently under exploration in the abyssal Clarion-Clipperton Fracture Zone. Nematodes have potential for biomonitoring of the impact of commercial activity but the natural biodiversity is unknown. We investigate the feasibility of nematodes as biomonitoring organisms and give information about their natural biodiversity. RESULTS: The taxonomic composition (at family to genus level) of the nematode fauna in the abyssal Pacific is similar, but not identical to, the North Atlantic. Given the immature state of marine nematode taxonomy, it is not possible to comment on the commonality or otherwise of species between oceans. The between basin differences do not appear to be directly linked to current ecological factors. The abyssal Pacific region (including the Fracture Zone) could be divided into two biodiversity subregions that conform to variations in the linked factors of flux to the benthos and of sedimentary characteristics. Richer biodiversity is associated with areas of known phytodetritus input and higher organic-carbon flux. Despite high reported sample diversity, estimated regional diversity is less than 400 species. CONCLUSION: The estimated regional diversity of the CCFZ is a tractable figure for biomonitoring of commercial activities in this region using marine nematodes, despite the immature taxonomy (i.e. most marine species have not been described) of the group. However, nematode ecology is in dire need of further study

Chiral Symmetry and light resonances in hot and dense matter

We present a study of the $\pi\pi$ scattering amplitude in the $\sigma$ and $\rho$ channels at finite temperature and nuclear density within a chiral unitary framework. Meson resonances are dynamically generated in our approach, which allows us to analyze the behavior of their associated scattering poles when the system is driven towards chiral symmetry restoration. Medium effects are incorporated in three ways: (a) by thermal corrections of the unitarized scattering amplitudes, (b) by finite nuclear density effects associated to a renormalization of the pion decay constant, and complementarily (c) by extending our calculation of the scalar-isoscalar channel to account for finite nuclear density and temperature effects in a microscopic many-body implementation of pion dynamics. Our results are discussed in connection with several phenomenological aspects relevant for nuclear matter and Heavy-Ion Collision experiments, such as $\rho$ mass scaling vs broadening from dilepton spectra and chiral restoration signals in the $\sigma$ channel. We also elaborate on the molecular nature of $\pi\pi$ resonances.Comment: 14 pages, 14 figures. Contribution to Hard Probes 2008, Illa de A Toxa, Spain, June 8th-14th 200