Novel detection of provenance in the illegal wildlife trade using elemental data

© 2018, The Author(s). Despite being the fourth largest criminal market in the world, no forensic tools have been sufficiently developed to accurately determine the legal status of seized animals and their parts. Although legal trading is permissible for farmed or captive-bred animals, many animals are illegally removed from the wild and laundered by masquerading them as captive bred. Here we present high-resolution x-ray fluorescence (XRF) as a non-invasive and cost-effective tool for forensic classification. We tested the efficacy of this technique by using machine learning on a training set of zoo specimens and wild-caught individuals of short-beaked echidnas (Tachyglossus aculeatus), a small insectivorous monotreme in Australia. XRF outperformed stable isotope analysis (δ13C, δ15N), reducing overall classification error below 4%. XRF has the added advantage of providing samples every 200 μm on a single quill, enabling 100% classification accuracy by taking the consensus of votes per quill. This accurate and cost-effective forensic technique could provide a much needed in situ solution for combating the illegal laundering of wildlife, and conversely, assist with certification of legally bred animals

Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain

Tc1 mouse model of Down syndrome (DS) is functionally trisomic for ∼120 human chromosome 21 (HSA21) classical protein-coding genes. Tc1 mice display features relevant to the DS phenotype, including abnormalities in learning and memory and synaptic plasticity. To determine the molecular basis for the phenotypic features, the levels of 90 phosphorylation-specific and phosphorylation-independent proteins were measured by Reverse Phase Protein Arrays in hippocampus and cortex, and 64 in cerebellum, of Tc1 mice and littermate controls. Abnormal levels of proteins involved in MAP kinase, mTOR, GSK3B and neuregulin signaling were identified in trisomic mice. In addition, altered correlations among the levels of N-methyl-D-aspartate (NMDA) receptor subunits and the HSA21 proteins amyloid beta (A4) precursor protein (APP) and TIAM1, and between immediate early gene (IEG) proteins and the HSA21 protein superoxide dismutase-1 (SOD1) were found in the hippocampus of Tc1 mice, suggesting altered stoichiometry among these sets of functionally interacting proteins. Protein abnormalities in Tc1 mice were compared with the results of a similar analysis of Ts65Dn mice, a DS mouse model that is trisomic for orthologs of 50 genes trisomic in the Tc1 plus an additional 38 HSA21 orthologs. While there are similarities, abnormalities unique to the Tc1 include increased levels of the S100B calcium-binding protein, mTOR proteins RAPTOR and P70S6, the AMP-kinase catalytic subunit AMPKA, the IEG proteins FBJ murine osteosarcoma viral oncogene homolog (CFOS) and activity-regulated cytoskeleton-associated protein (ARC), and the neuregulin 1 receptor ERBB4. These data identify novel perturbations, relevant to neurological function and to some seen in Alzheimer's disease, that may occur in the DS brain, potentially contributing to phenotypic features and influencing drug responses

Reducing unscheduled hospital care for adults with diabetes following a hypoglycaemic event: which community-based interventions are most effective? A systematic review

AIM: To determine which community-based interventions are most effective at reducing unscheduled hospital care for hypoglycaemic events in adults with diabetes. METHODS: Medline Ovid, CINAHL Plus and ProQuest Health and Medical Collection were searched using both key search terms and medical subject heading terms (MeSH) to identify potentially relevant studies. Eligible studies were those that involved a community-based intervention to reduce unscheduled admissions in adults with diabetes. Papers were initially screened by the primary researcher and then a secondary reviewer. Relevant data were then extracted from papers that met the inclusion criteria. RESULTS: The search produced 2226 results, with 1360 duplicates. Of the remaining 866 papers, 198 were deemed appropriate based on titles, 90 were excluded following abstract review. A total of 108 full papers were screened with 19 full papers included in the review. The sample size of the 19 papers ranged from n = 25 to n = 104,000. The average ages within the studies ranged from 41 to 74 years with females comprising 57% of the participants. The following community-based interventions were identified that explored reducing unscheduled hospital care in people with diabetes; telemedicine, education, integrated care pathways, enhanced primary care and care management teams. CONCLUSIONS: This systematic review shows that a range of community-based interventions, requiring different levels of infrastructure, are effective in reducing unscheduled hospital care for hypoglycaemia in people with diabetes. Investment in effective community-based interventions such as integrated care and patient education must be a priority to shift the balance of care from secondary to primary care, thereby reducing hospital admissions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00817-z

PGF2α-F-prostanoid receptor signalling via ADAMTS1 modulates epithelial cell invasion and endothelial cell function in endometrial cancer

<p>Abstract</p> <p>Background</p> <p>An increase in cancer cell invasion and microvascular density is associated with a poorer prognosis for patients with endometrial cancer. In endometrial adenocarcinoma F-prostanoid (FP) receptor expression is elevated, along with its ligand prostaglandin (PG)F_2α, where it regulates expression and secretion of a host of growth factors and chemokines involved in tumorigenesis. This study investigates the expression, regulation and role of a disintegrin and metalloproteinase with thrombospondin repeat 1 (ADAMTS1) in endometrial adenocarcinoma cells by PGF_2αvia the FP receptor.</p> <p>Methods</p> <p>Human endometrium and adenocarcinoma tissues were obtained in accordance with Lothian Research Ethics Committee guidance with informed patient consent. Expression of ADAMTS1 mRNA and protein in tissues was determined by quantitative RT-PCR analysis and immunohistochemistry. Signal transduction pathways regulating ADAMTS1 expression in Ishikawa cells stably expressing the FP receptor to levels seen in endometrial cancer (FPS cells) were determined by quantitative RT-PCR analysis. In vitro invasion and proliferation assays were performed with FPS cells and human umbilical vein endothelial cells (HUVECs) using conditioned medium (CM) from PGF_2α-treated FPS cells from which ADAMTS1 was immunoneutralised and/or recombinant ADAMTS1. The role of endothelial ADAMTS1 in endothelial cell proliferation was confirmed with RNA interference. The data in this study were analysed by T-test or ANOVA.</p> <p>Results</p> <p>ADAMTS1 mRNA and protein expression is elevated in endometrial adenocarcinoma tissues compared with normal proliferative phase endometrium and is localised to the glandular and vascular cells. Using FPS cells, we show that PGF2α-FP signalling upregulates ADAMTS1 expression via a calmodulin-NFAT-dependent pathway and this promotes epithelial cell invasion through ECM and inhibits endothelial cell proliferation. Furthermore, we show that CM from FPS cells regulates endothelial cell ADAMTS1 expression in a rapid biphasic manner. Using RNA interference we show that endothelial cell ADAMTS1 also negatively regulates cellular proliferation.</p> <p>Conclusions</p> <p>These data demonstrate elevated ADAMTS1 expression in endometrial adenocarcinoma. Furthermore we have highlighted a mechanism whereby FP receptor signalling regulates epithelial cell invasion and endothelial cell function via the PGF_2α-FP receptor mediated induction of ADAMTS1.</p

Hypoxia and Prostaglandin E Receptor 4 Signalling Pathways Synergise to Promote Endometrial Adenocarcinoma Cell Proliferation and Tumour Growth

The prostaglandin endoperoxide synthase (PTGS) pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG) E2. PTGS2 expression and PGE2 biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE2 regulate endometrial tumour growth is unknown. Here we investigated (a) the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3) and PGE receptors (PTGER1–4) in endometrial adenocarcinomas compared with normal endometrium and (b) the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells) xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE2 and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE2 and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells

Electron quantum metamaterials in van der Waals heterostructures

In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

A UMLS-based spell checker for natural language processing in vaccine safety

BACKGROUND: The Institute of Medicine has identified patient safety as a key goal for health care in the United States. Detecting vaccine adverse events is an important public health activity that contributes to patient safety. Reports about adverse events following immunization (AEFI) from surveillance systems contain free-text components that can be analyzed using natural language processing. To extract Unified Medical Language System (UMLS) concepts from free text and classify AEFI reports based on concepts they contain, we first needed to clean the text by expanding abbreviations and shortcuts and correcting spelling errors. Our objective in this paper was to create a UMLS-based spelling error correction tool as a first step in the natural language processing (NLP) pipeline for AEFI reports. METHODS: We developed spell checking algorithms using open source tools. We used de-identified AEFI surveillance reports to create free-text data sets for analysis. After expansion of abbreviated clinical terms and shortcuts, we performed spelling correction in four steps: (1) error detection, (2) word list generation, (3) word list disambiguation and (4) error correction. We then measured the performance of the resulting spell checker by comparing it to manual correction. RESULTS: We used 12,056 words to train the spell checker and tested its performance on 8,131 words. During testing, sensitivity, specificity, and positive predictive value (PPV) for the spell checker were 74% (95% CI: 74–75), 100% (95% CI: 100–100), and 47% (95% CI: 46%–48%), respectively. CONCLUSION: We created a prototype spell checker that can be used to process AEFI reports. We used the UMLS Specialist Lexicon as the primary source of dictionary terms and the WordNet lexicon as a secondary source. We used the UMLS as a domain-specific source of dictionary terms to compare potentially misspelled words in the corpus. The prototype sensitivity was comparable to currently available tools, but the specificity was much superior. The slow processing speed may be improved by trimming it down to the most useful component algorithms. Other investigators may find the methods we developed useful for cleaning text using lexicons specific to their area of interest