Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases

Vascular endothelial growth factor (VEGF) is the predominant pro-angiogenic cytokine in human malignancy, and its expression correlates with disease recurrence and poor outcomes in patients with colorectal cancer. Recently, expression of vascular endothelial growth factor receptors (VEGFRs) has been observed on tumours of epithelial origin, including those arising in the colon, but the molecular mechanisms governing potential VEGF-driven biologic functioning in these tumours are not well characterised. In this report, we investigated the role of Src family kinases (SFKs) in VEGF-mediated signalling in human colorectal carcinoma (CRC) cell lines. Vascular endothelial growth factor specifically activated SFKs in HT29 and KM12L4 CRC cell lines. Further, VEGF stimulation resulted in enhanced cellular migration, which was effectively blocked by pharmacologic inhibition of VEGFR-1 or Src kinase. Correspondingly, migration studies using siRNA clones with reduced Src expression confirmed the requirement for Src in VEGF-induced migration in these cells. Furthermore, VEGF treatment enhanced VEGFR-1/SFK complex formation and increased tyrosine phosphorylation of focal adhesion kinase, p130 cas and paxillin. Finally, we demonstrate that VEGF-induced migration is not due, at least in part, to VEGF acting as a mitogen. These results suggest that VEGFR-1 promotes migration of tumour cells through a Src-dependent pathway linked to activation of focal adhesion components that regulate this process

The Effect of Carbon Credits on Savanna Land Management and Priorities for Biodiversity Conservation

Carbon finance offers the potential to change land management and conservation planning priorities. We develop a novel approach to planning for improved land management to conserve biodiversity while utilizing potential revenue from carbon biosequestration. We apply our approach in northern Australia's tropical savanna, a region of global significance for biodiversity and carbon storage, both of which are threatened by current fire and grazing regimes. Our approach aims to identify priority locations for protecting species and vegetation communities by retaining existing vegetation and managing fire and grazing regimes at a minimum cost. We explore the impact of accounting for potential carbon revenue (using a carbon price of US$14 per tonne of carbon dioxide equivalent) on priority areas for conservation and the impact of explicitly protecting carbon stocks in addition to biodiversity. Our results show that improved management can potentially raise approximately US$5 per hectare per year in carbon revenue and prevent the release of 1–2 billion tonnes of carbon dioxide equivalent over approximately 90 years. This revenue could be used to reduce the costs of improved land management by three quarters or double the number of biodiversity targets achieved and meet carbon storage targets for the same cost. These results are based on generalised cost and carbon data; more comprehensive applications will rely on fine scale, site-specific data and a supportive policy environment. Our research illustrates that the duel objective of conserving biodiversity and reducing the release of greenhouse gases offers important opportunities for cost-effective land management investments

Guiding principles for rewilding

There has been much recent interest in the concept of rewilding as a tool for nature conservation, but also confusion over the idea, which has limited its utility. We developed a unifying definition and 10 guiding principles for rewilding through a survey of 59 rewilding experts, a summary of key organizations’ rewilding visions, and workshops involving over 100 participants from around the world. The guiding principles convey that rewilding exits on a continuum of scale, connectivity, and level of human influence and aims to restore ecosystem structure and functions to achieve a self-sustaining autonomous nature. These principles clarify the concept of rewilding and improve its effectiveness as a tool to achieve global conservation targets, including those of the UN Decade on Ecosystem Restoration and post-2020 Global Biodiversity Framework. Finally, we suggest differences in rewilding perspectives lie largely in the extent to which it is seen as achievable and in specific interventions. An understanding of the context of rewilding projects is the key to success, and careful site-specific interpretations will help achieve the aims of rewilding

Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and anti-invasive effects in vitro, and inhibited metastasis in a murine model of bladder cancer. Antiproliferative activity of AZD0530 in vitro varied between cell lines (IC50 0.2 –> 10 μM). AZD0530 inhibited tumor growth in 4/10 xenograft models tested and dynamically inhibited in vivo phosphorylation of Src substrates paxillin and FAK in both growth-inhibition-resistant and -sensitive xenografts. The activity of AZD0530 in NBT-II bladder cancer cells in vitro was consistent with inhibition of cell migration and stabilization of cell–cell adhesion. These data suggest a dominant anti-invasive pharmacology for AZD0530 that may limit tumor progression in a range of cancers. AZD0530 is currently in Phase II clinical trials

Technical Feasibility of a Combined Noncontrast Magnetic Resonance Protocol for Preoperative Transcatheter Aortic Valve Replacement Evaluation.

The aim of this study was to prospectively evaluate the technical feasibility of a noncontrast magnetic resonance angiography (MRA) protocol using investigational prototype self-navigated 3D (SN3D) radial whole-heart and quiescent-interval single-shot (QISS) pulse sequences regarding their potential in planning transcatheter aortic valve replacement (TAVR). Five patients (76±7 y) with severe aortic valve stenosis and prior computed tomographic angiography (CTA) for TAVR planning and 10 healthy volunteers (28±6 y) underwent noncontrast MRA on a 1.5 T system. A SN3D whole-heart acquisition was used to assess the aortic root anatomy. Evaluation of the aortoiliac access route was performed with both SN3D and QISS. Measurements were compared among SN3D, QISS, and CTA using a paired t test or 1-way analysis of variance. Image quality ratings and contrast-to-noise ratios (CNR) were analyzed using Mann-Whitney U tests. Interobserver agreement was evaluated using Cohen's κ. The combined SN3D and QISS protocol provided a 10.1±1.6-minute acquisition time. TAVR-relevant evaluation was technically feasible in healthy volunteers. All measurements showed good agreement with CTA in patients (all P>0.098). SN3D and QISS produced similar image quality both in volunteers and in patients (all P>0.122). There was no difference in qualitative ratings between MRA and CTA (all P>0.119). Interobserver agreement was good for MRA (κ=0.71 to 0.76) and excellent for CTA (κ=0.82 to 0.84). Thoracic SN3D provided a similar CNR compared with CTA (P=0.117). CTA yielded higher CNR in the abdominopelvic region compared with QISS (P=0.006). A noncontrast MRA protocol combining SN3D and QISS acquisitions for the assessment of cardiac and vascular access route anatomy has technical feasibility for TAVR planning

Quantum well infrared photodetector for the SWIR range

An InGaAs/InAlAs superlattice infrared photodetector is developed to reach the forbidden gap in the SWIR range for arsenides, between 1.7 and 2.5 μm, appropriate for surveillance imaging. The figures of merit of the device are determined to be 120 K for the BLIP temperature and 2.1 mA/W and 3 × 106 Jones for the best responsivity and detectivity, respectively, obtained at 120 K under +4 V bias. Possible approaches to improve the device performance are addressed152363370International conference of research applied to defense and securit

Quantitative inversion time prescription for myocardial late gadolinium enhancement using T1-mapping-based synthetic inversion recovery imaging: reducing subjectivity in the estimation of inversion time

Cardiovascular Aspects of Radiolog

Progress in symmetric and asymmetric superlattice quantum well infrared photodetectors

Herein, two challenges are addressed, which quantum well infrared photodetectors (QWIPs), based on III-V semiconductors, face, namely: photodetection within the so-called "forbidden gap", between 1.7 and 2.5 microns, and room temperature operation using thermal sources. First, to reach this forbidden wavelength range, a QWIP which consists of a superlattice structure with a central quantum well (QW) with a different thickness is presented. The different QW in the symmetric structure, which plays the role of a defect in the otherwise periodic structure, gives rise to localized states in the continuum. The proposed InGaAs/InAlAs superlattice QWIP detects radiation around 2.1 microns, beyond the materials bandoffset. Additionally, the wavefunction parity anomaly is explored to increase the oscillator strength of the optical transitions involving higher order states. Second, with the purpose of achieving room temperature operation, an asymmetric InGaAs/InAlAs superlattice, in which the QW with a different thickness is not in the center, is used to detect infrared radiation around 4 microns at 300 K. This structure operates in the photovoltaic mode because it gives rise to states in the continuum which are localized in one direction and extended in the other, leading to a preferential direction for current flow531634th International Conference on the Physics of Semiconductors (ICPS)FAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeir