Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with 68Ga-PSMA-HBED-CC has been shown to ...detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate.
In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis.
A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value.
A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy.
Assessing the environmental impact of salmon farms on benthic systems is traditionally undertaken using biotic indices derived from microscopic analyses of macrobenthic infaunal (MI) communities. In ...this study, we tested the applicability of using foraminiferal-specific high-throughput sequencing (HTS) metabarcoding for monitoring these habitats. Sediment samples and physico-chemical data were collected along an enrichment gradient radiating out from three Chinook salmon (Oncorhynchus tshawytscha) farms in New Zealand. HTS of environmental DNA and RNA (eDNA/eRNA) resulted in 1,875,300 sequences that clustered into 349 Operational Taxonomic Units. Strong correlations were observed among various biotic indices calculated from MI data and normalized fourth-root transformed HTS data. Correlations were stronger using eRNA compared to eDNA data. Quantile regression spline analyses identified 12 key foraminiferal taxa that have potential to be used as bioindicator species. This study demonstrates the huge potential for using this method for biomonitoring of fish-farming and other marine industrial activities.
•Foraminiferal metabarcoding is a cost-effective tool for monitoring environmental impacts of fish farming.•Metabarcoding data correlate strongly with traditional biotic indices derived from macrobenthic infaunal community data.•Correlations are stronger using eRNA compared to eDNA data.•Quantile regression spline analysis identifies 12 key foraminiferal taxa that have potential to be used as bioindicator species.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Swift J0243.6+6124 is a newly discovered Galactic Be/X-ray binary, revealed in late 2017 September in a giant outburst with a peak luminosity of 2 × 1039(d/7 kpc)2 erg s−1 (0.1-10 keV), with no ...formerly reported activity. At this luminosity, Swift J0243.6+6124 is the first known galactic ultraluminous X-ray pulsar. We describe Neutron star Interior Composition Explorer (NICER) and Fermi Gamma-ray Burst Monitor (GBM) timing and spectral analyses for this source. A new orbital ephemeris is obtained for the binary system using spin frequencies measured with GBM and 15-50 keV fluxes measured with the Neil Gehrels Swift Observatory Burst Alert Telescope to model the system's intrinsic spin-up. Power spectra measured with NICER show considerable evolution with luminosity, including a quasi-periodic oscillation near 50 mHz that is omnipresent at low luminosity and has an evolving central frequency. Pulse profiles measured over the combined 0.2-100 keV range show complex evolution that is both luminosity and energy dependent. Near the critical luminosity of L ∼ 1038 erg s−1, the pulse profiles transition from single peaked to double peaked, the pulsed fraction reaches a minimum in all energy bands, and the hardness ratios in both NICER and GBM show a turnover to softening as the intensity increases. This behavior repeats as the outburst rises and fades, indicating two distinct accretion regimes. These two regimes are suggestive of the accretion structure on the neutron star surface transitioning from a Coulomb collisional stopping mechanism at lower luminosities to a radiation-dominated stopping mechanism at higher luminosities. This is the highest observed (to date) value of the critical luminosity, suggesting a magnetic field of B ∼ 1013 G.
The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for ...photoperiodic synchronization in plants. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that long photoperiods induce the circadian transcription factor BMAL2, in the pars tuberalis of the pituitary, and triggers summer biology through the eyes absent/thyrotrophin (EYA3/TSH) pathway. Conversely, long-duration melatonin signals on short photoperiods induce circadian repressors including DEC1, suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock-pituitary epigenetic pathway interactions form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates.
•Climate change may challenge urban forests’ capacity to provide ecosystem services (ES).•Shifting canopy composition to climate-tolerant species could impact ES provisioning.•We model ES ...provisioning resulting from alternative canopy compositions.•More functionally diverse canopies provide greater ES provisioning.•Stratified replanting based on tree functional groups can mitigate multiple threats.
Cities are home to an increasing number of people who depend on urban forests to provide ecosystem services such as temperature regulation, air quality improvement and storm water abatement. Climate change may challenge the capacity of urban forests to provide these services. Intensification of heat waves, droughts and strengthening storms could lead to tree die-offs. In Quebec City, work has suggested that the urban canopy is vulnerable to future projected climates, i.e. hotter and drier summers. Compounding this threat, the exotic emerald ash borer is expected to kill 11 % of municipal trees over the next decade. Together these pressures could lead to a significant loss of canopy cover and ecosystem service provisioning in the near-term.
We test whether replanting strategies for lost ash, which shift the forest community towards a more climate-tolerant canopy using a functional trait-based approach, can help to mitigate or improve ecosystem service provisioning in the near-term. Using a municipal database of urban trees, we simulate canopy growth and replacement over 20-years for three different replanting scenarios: i) ‘business-as-usual’, ii) ‘stratified’ or iii) ‘conifer-focused’ replanting strategy, and compare their delivery of ecosystem services.
Results from the simulations find clear trade-offs in ecosystem service provisioning within and between replanting approaches. The ‘conifer-focused’ scenario provides the highest level of air quality improvement, storm water abatement and reduced energy demands in winter, however there are limitations on where coniferous trees can be planted in cities. In contrast, the ‘business-as-usual’ scenario achieved greater canopy cover, carbon sequestration, and high summertime cooling, but remains vulnerable to climate change. Stratifying replanting across tree functional groups results in the greatest increase to canopy diversity, intermediate levels of ecosystem service provisioning and important reduction in vulnerability to future pests . We suggest that a replanting approach focused on increasing the functional trait diversity of the urban canopy will likely confer the greatest ecosystem service benefits to the urban population and improve the resilience of the urban canopy to pests and climate pressures in the future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Freshwater cyanobacterial blooms have increased worldwide, channeling organic carbon into these systems, and threatening animal health through the production of cyanotoxins. Both toxic and nontoxic ...Microcoleus proliferations usually occur when there are moderate concentrations of dissolved inorganic nitrogen, but when phosphorus is scarce. In order to understand how Microcoleus establishes thick biofilms (or mats) on riverbeds under phosphorus-limiting conditions, we collected Microcoleus-dominated biofilms over a 19-day proliferation event for proteogenomics. A single pair of nitrogen-dependent Microcoleus species were consistently present in relatively high abundance, although each followed a unique metabolic trajectory. Neither possessed anatoxin gene clusters, and only very low concentrations of anatoxins (~2 µg kg
) were detected, likely originating from rarer Microcoleus species also present. Proteome allocations were dominated by photosynthesizing cyanobacteria and diatoms, and data indicate biomass was actively recycled by Bacteroidetes and Myxococcales. Microcoleus likely acquired nutrients throughout the proliferation event by uptake of nitrate, urea, and inorganic and organic phosphorus. Both species also harbored genes that could be used for inorganic phosphate solubilization with pyrroloquinoline quinone cofactors produced by cohabiting Proteobacteria. Results indicate that Microcoleus are equipped with diverse mechanisms for nitrogen and phosphorus acquisition, enabling them to proliferate and out-compete others in low-phosphorus waters.
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NUK, SBMB, SBNM, UL, UM, UPUK
The role of extracellular vesicles (EVs) as vehicles for cell-to-cell communication between a tumour and its environment is a relatively new concept. The hypothesis that EVs may be critical in ...co-opting tissues by tumours to generate distant metastatic niches is particularly pertinent to prostate cancer (PCa), where metastatic-tropism to bone predominates over other tissue types. The potential role of EVs as a means of communication between PCa cells and cells of the bone stroma such as osteoblasts, is yet to be fully explored. In this study, we demonstrate that PCa cell EVs both enhance osteoblast viability and produce a significantly more supportive growth environment for PCa cells when grown in co-culture with EV-treated osteoblasts (p < 0.005). Characterisation of the RNA cargo of EVs produced by the bone-metastatic PCa cell line PC3, highlights the EV-RNA cargo is significantly enriched in genes relating to cell surface signalling, cell-cell interaction, and protein translation (p < 0.01). Using novel techniques to track RNA, we demonstrate the delivery of a set of PCa-RNAs to osteoblast via PCa-EVs and show the effect on osteoblast endogenous transcript abundance. Taken together, by using proof-of-concept studies we demonstrate for the first time the contribution of the RNA element of the PCa EV cargo, providing evidence to support PCa EV communication via RNA molecules as a potential novel route to mediate bone metastasis. We propose targeting PCa EVs could offer a potentially important preventative therapy for men at risk of metastatic PCa.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mars Water-Ice Clouds and Precipitation Whiteway, J.A; Komguem, L; Dickinson, C ...
Science (American Association for the Advancement of Science),
07/2009, Volume:
325, Issue:
5936
Journal Article
Peer reviewed
The light detection and ranging instrument on the Phoenix mission observed water-ice clouds in the atmosphere of Mars that were similar to cirrus clouds on Earth. Fall streaks in the cloud structure ...traced the precipitation of ice crystals toward the ground. Measurements of atmospheric dust indicated that the planetary boundary layer (PBL) on Mars was well mixed, up to heights of around 4 kilometers, by the summer daytime turbulence and convection. The water-ice clouds were detected at the top of the PBL and near the ground each night in late summer after the air temperature started decreasing. The interpretation is that water vapor mixed upward by daytime turbulence and convection forms ice crystal clouds at night that precipitate back toward the surface.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Incom Inc. Large Area Picosecond Photodetector (LAPPD) 38 has been tested at Jefferson Lab to identify single-photoelectron signals to assess the potential of this type of device for future ...applications in Cherenkov light detection. Single-photoelectron signals were clearly detected if a tight masking of photons impinging on the photocathode was used compared to the pixelation of the charge collection signal board.
Liver‐derived small extracellular vesicles (sEVs), prepared from small sets of banked serum samples using a novel two‐step protocol, were deployed as liquid biopsy to study the induction of ...cytochromes P450 (CYP3A4, CYP3A5, and CYP2D6) and organic anion transporting polypeptides (OATP1B1 and OATP1B3) during pregnancy (nonpregnant (T0), first, second, and third (T3) trimester women; N = 3 each) and after administration of rifampicin (RIF) to healthy male subjects. Proteomic analysis revealed induction (mean fold‐increase, 90% confidence interval) of sEV CYP3A4 after RIF 300 mg × 7 days (3.5, 95% CI = 2.5–4.5, N = 4, P = 0.029) and 600 mg × 14 days (3.7, 95% CI = 2.1–6.0, N = 5, P = 0.018) consistent with the mean oral midazolam area under the plasma concentration time curve (AUC) ratio in the same subjects (0.28, 95% CI = 0.22–0.34, P < 0.0001; and 0.17, 95% CI = 0.13–0.22, P < 0.0001). Compared with CYP3A4, liver sEV CYP3A5 protein (subjects genotyped CYP3A5*1/*3) was weakly induced (≤ 1.5‐fold). It was also possible to measure liver sEV‐catalyzed dextromethorphan (DEX) O‐demethylation to dextrorphan (DXO), correlated with sEV CYP2D6 expression (r = 0.917, P = 0.0001; N = 10) and 3‐hour plasma DXO‐to‐DEX concentration ratio (r = 0.843, P = 0.002, N = 10), and show that CYP2D6 was not induced by RIF. Nonparametric analysis of liver sEV revealed significantly higher CYP3A4 (3.2‐fold, P = 0.003) and CYP2D6 (3.7‐fold, P = 0.03) protein expression in T3 vs. T0 women. In contrast, expression of both OATPs in liver sEV was unaltered by RIF administration and pregnancy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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