Survival outcome and EMT suppression mediated by a lectin domain interaction of Endo180 and CD147

Epithelial cell-cell contacts maintain normal glandular tissue homeostasis, and their breakage can trigger epithelial-to-mesenchymal transition (EMT), a fundamental step in the development of metastatic cancer. Despite the ability of C-type lectin domains (CTLD) to modulate cell-cell adhesion, it is not known if they modulate epithelial adhesion in EMT and tumor progression. Here, the multi-CTLD mannose receptor, Endo180 (MRC2/uPARAP), was shown using the Kaplan-Meier analysis to be predictive of survival outcome in men with early prostate cancer. A proteomic screen of novel interaction partners with the fourth CTLD (CTLD4) in Endo180 revealed that its complex with CD147 is indispensable for the stability of three-dimensional acini formed by nontransformed prostate epithelial cells (PEC). Mechanistic study using knockdown of Endo180 or CD147, and treatment with an Endo180 mAb targeting CTLD4 (clone 39.10), or a dominant-negative GST-CTLD4 chimeric protein, induced scattering of PECs associated with internalization of Endo180 into endosomes, loss of E-cadherin (CDH1/ECAD), and unzipping of cell-cell junctions. These findings are the first to demonstrate that a CTLD acts as a suppressor and regulatory switch for EMT; thus, positing that stabilization of Endo180-CD147 complex is a viable therapeutic strategy to improve rates of prostate cancer survival

A new era of wide-field submillimetre imaging: on-sky performance of SCUBA-2

SCUBA-2 is the largest submillimetre wide-field bolometric camera ever built. This 43 square arc-minute field-of-view instrument operates at two wavelengths (850 and 450 microns) and has been installed on the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. SCUBA-2 has been successfully commissioned and operational for general science since October 2011. This paper presents an overview of the on-sky performance of the instrument during and since commissioning in mid-2011. The on-sky noise characteristics and NEPs of the 450 and 850 micron arrays, with average yields of approximately 3400 bolometers at each wavelength, will be shown. The observing modes of the instrument and the on-sky calibration techniques are described. The culmination of these efforts has resulted in a scientifically powerful mapping camera with sensitivities that allow a square degree of sky to be mapped to 10 mJy/beam rms at 850 micron in 2 hours and 60 mJy/beam rms at 450 micron in 5 hours in the best weather.Comment: 18 pages, 15 figures.SPIE Conference series 8452, Millimetre, Submillimetre and Far-infrared Detectors and Instrumentation for Astronomy VI 201

Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2 signalling in prostate cancer cells

Background: Androgens drive the onset and progression of prostate cancer (PCa) via androgen receptor (AR) signalling. The principal treatment for PCa is androgen deprivation therapy, although the majority of patients eventually develop a lethal castrate-resistant form of the disease, where despite low serum testosterone levels AR signalling persists. Advanced PCa often has hyper-activated RAS/ERK1/2 signalling thought to be due to loss of function of key negative regulators of the pathway, the details of which are not fully understood.<p></p> Methods: We recently carried out a genome-wide study and identified a subset of 226 novel androgen-regulated genes (PLOS ONE 6:e29088, 2011). In this study we have meta-analysed this dataset with genes and pathways frequently mutated in PCa to identify androgen-responsive regulators of the RAS/ERK1/2 pathway.<p></p> Results: We find the PTGER4 and TSPYL2 genes are up-regulated by androgen stimulation and the ADCY1, OPKR1, TRIB1, SPRY1 and PTPRR are down-regulated by androgens. Further characterisation of PTPRR protein in LNCaP cells revealed it is an early and direct target of the androgen receptor which negatively regulates the RAS/ERK1/2 pathway and reduces cell proliferation in response to androgens.<p></p> Conclusion: Our data suggest that loss of PTPRR in clinical PCa is one factor that might contribute to activation of the RAS/ERK1/2 pathway

AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C-type lectin-like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin-based contractility [myosin-light chain-2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE-modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180ΔEx2–6/ΔEx2–6 mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour in non-transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors

Faunal Remains: Results by Species

https://orcid.org/0000-0001-7487-2635This book is distributed under the terms of the Creative Commons Attribution + Noncommercial 4.0 license. Copyright is retained by the author(s). The attached file is the published version of the article

Archaeological bone lipids as palaeodietary markers

Rationale Stable isotope analysis of archaeological and fossil bone samples can provide important insights into past environments, ecologies and diets. Previous studies have focused on stable carbon and nitrogen isotopes in bone collagen, or carbon isotopes in bone mineral (bioapatite). Carbon isotope analysis of lipids from archaeological bone has received much less attention, partly due to the lack of suitable methodologies allowing sufficient recovery of compounds for structural and isotopic characterisation. Here we show that lipids can be easily and reliably recovered from archaeological bone using a modified protocol, and that these provide complementary dietary information to other bone components. Methods Human and animal bones were obtained from a variety of archaeological contexts. Lipids were sequentially extracted using solvent extraction (dichloromethane/methanol), followed by acidified methanol extraction (methanol/H2SO4). The lipids were then analysed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Results Appreciable amounts of endogenous lipid were recovered from archaeological bone. Importantly, a comparison between compound-specific and bulk collagen isotopic data shows that archaeological bone lipids reflect dietary input and can be used to distinguish between marine and terrestrial consumers, as well as between C3 and C4 plant consumers. Furthermore, the presence of essential fatty acids directly incorporated from diet to bone may provide additional palaeodietary information. Conclusions Our findings suggest that archaeological bone lipids are a hitherto untapped resource of dietary information that offer additional insights to those gained from other isotopic analyses of bone

Low leakage-current InAsSb nanowire photodetectors on silicon

Axially doped p–i–n InAs0.93Sb0.07 nanowire arrays have been grown on Si substrates and fabricated into photodetectors for shortwave infrared detection. The devices exhibit a leakage current density around 2 mA/cm2 and a 20% cutoff of 2.3 μm at 300 K. This record low leakage current density for InAsSb based devices demonstrates the suitability of nanowires for the integration of III–V semiconductors with silicon technology

Flinders Island spotted fever rickettsioses caused by "marmionii" strain of rickettsia honei, Eastern Australia

Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus, Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a rickettsiosis with an acute onset and symptoms of fever (100%), headache (71%), arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%), nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases were most prevalent in autumn and from eastern Australia, including Queensland, Tasmania, and South Australia. One patient had a history of tick bite (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and 100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes, respectively, of Rickettsia honei. This Australian rickettsiosis has similar symptoms to Flinders Island spotted fever, and the strain is genetically related to R. honei. It has been designated the "marmionii" strain of R. honei, in honor of Australian physician and scientist Barrie Marmion

Blue light and UV radiation accelerate spring and autumn leaf phenology in temperate tree species

Non peer reviewe

Robustness of hierarchical spatial critical infrastructure networks

PhD ThesisThe economic state and wellbeing of a nation is dependent upon the critical infrastructure networks that deliver resources, goods and services. However, these are increasingly exposed to a number of hazards, both natural and man-made, which threaten to disrupt their ability to function. It is essential that in order to develop long-term strategic plans of infrastructure provision we are able to understand their current robustness to such hazards. The robustness of critical infrastructure networks has typically been investigated from a topological perspective as a means of simplifying the complexities associated with their analysis. Such work has led to many studies suggesting critical infrastructures exhibit a topological structure, from random to exponential degree distributions. However, often such analysis ignores the explicit spatial characteristics of the node and edge assets. Furthermore, the very nature of topological analysis means that flows/movements that take place over such networks cannot be considered. This work addresses these weaknesses by extending traditional topological analysis to consider emergent properties critical infrastructure networks exhibit when considering higher-order connectivity and flows. An analysis of a suite of synthetic networks with a spectrum of topologies alongside real infrastructure spatial networks, in terms of their basic topology and high-order connectivity, shows that a number of critical infrastructure networks seem to be better characterised as hierarchical networks. Subsequent failure modelling reveals that such hierarchical networks responded in a dramatically different manner to perturbations; complete failure occurring approximately 19 and 34 percent sooner for random and targeted failures compared to random networks. Such poor robustness is further exacerbated when flow simulation modelling over the resulting hierarchical networks is undertaken, revealing particular sensitivity to cascading failures from spatial hazards. In light of these results, it is suggested that it is essential to improve the robustness of critical infrastructure networks that exhibit a hierarchical spatial organisation.School of Civil Engineering and Geosciences, Newcastle University