Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics

Introduction: The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry. Studies using advanced mass spectrometry (MS) have resulted in new insights into cell biology and the aetiology of diseases as well as its use in clinical applications. Areas Covered: This review will discuss recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It will also discuss the issues around translating the research findings to the clinic and provide an outline of where the field is moving. Expert Opinion: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics

Improved early detection of ovarian cancer using longitudinal multimarker models

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Background: Ovarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer. Methods: This case–control study nested within UKCTOCS used 490 serial serum samples from 49 women later diagnosed with ovarian cancer and 31 control women who were cancer-free. Proteomics-based biomarker discovery was carried out using pooled samples and selected candidates, including those from the literature, assayed in all serial samples. Multimarker longitudinal models were derived and tested against CA125 for early detection of ovarian cancer. Results: The best performing models, incorporating CA125, HE4, CHI3L1, PEBP4 and/or AGR2, provided 85.7% sensitivity at 95.4% specificity up to 1 year before diagnosis, significantly improving on CA125 alone. For Type II cases (mostly high-grade serous), models achieved 95.5% sensitivity at 95.4% specificity. Predictive values were elevated earlier than CA125, showing the potential of models to improve lead time. Conclusions: We have identified candidate biomarkers and tested longitudinal multimarker models that significantly improve on CA125 for early detection of ovarian cancer. These models now warrant independent validation.Peer reviewe

Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling.

The aim of this discovery study was the identification of peptide serum biomarkers for detecting biliary tract cancer (BTC) using samples from healthy volunteers and benign cases of biliary disease as control groups. This work was based on the hypothesis that cancer-specific exopeptidase activities in serum can generate cancer-predictive peptide fragments from circulating proteins during coagulation

The complete plasmid sequences of Salmonella enterica serovar Typhimurium U288.

Salmonella enterica Serovar Typhimurium U288 is an emerging pathogen of pigs. The strain contains three plasmids of diverse origin that encode traits that are of concern for food security and safety, these include antibiotic resistant determinants, an array of functions that can modify cell physiology and permit genetic mobility. At 148,711 bp, pSTU288-1 appears to be a hybrid plasmid containing a conglomerate of genes found in pSLT of S. Typhimurium LT2, coupled with a mosaic of horizontally-acquired elements. Class I integron containing gene cassettes conferring resistance against clinically important antibiotics and compounds are present in pSTU288-1. A curious feature of the plasmid involves the deletion of two genes encoded in the Salmonella plasmid virulence operon (spvR and spvA) following the insertion of a tnpA IS26-like element coupled to a blaTEM gene. The spv operon is considered to be a major plasmid-encoded Salmonella virulence factor that is essential for the intracellular lifecycle. The loss of the positive regulator SpvR may impact on the pathogenesis of S. Typhimurium U288. A second 11,067 bp plasmid designated pSTU288-2 contains further antibiotic resistance determinants, as well as replication and mobilization genes. Finally, a small 4675 bp plasmid pSTU288-3 was identified containing mobilization genes and a pleD-like G-G-D/E-E-F conserved domain protein that modulate intracellular levels of cyclic di-GMP, and are associated with motile to sessile transitions in growth

A Cognitive Model of an Epistemic Community: Mapping the Dynamics of Shallow Lake Ecosystems

We used fuzzy cognitive mapping (FCM) to develop a generic shallow lake ecosystem model by augmenting the individual cognitive maps drawn by 8 scientists working in the area of shallow lake ecology. We calculated graph theoretical indices of the individual cognitive maps and the collective cognitive map produced by augmentation. The graph theoretical indices revealed internal cycles showing non-linear dynamics in the shallow lake ecosystem. The ecological processes were organized democratically without a top-down hierarchical structure. The steady state condition of the generic model was a characteristic turbid shallow lake ecosystem since there were no dynamic environmental changes that could cause shifts between a turbid and a clearwater state, and the generic model indicated that only a dynamic disturbance regime could maintain the clearwater state. The model developed herein captured the empirical behavior of shallow lakes, and contained the basic model of the Alternative Stable States Theory. In addition, our model expanded the basic model by quantifying the relative effects of connections and by extending it. In our expanded model we ran 4 simulations: harvesting submerged plants, nutrient reduction, fish removal without nutrient reduction, and biomanipulation. Only biomanipulation, which included fish removal and nutrient reduction, had the potential to shift the turbid state into clearwater state. The structure and relationships in the generic model as well as the outcomes of the management simulations were supported by actual field studies in shallow lake ecosystems. Thus, fuzzy cognitive mapping methodology enabled us to understand the complex structure of shallow lake ecosystems as a whole and obtain a valid generic model based on tacit knowledge of experts in the field.Comment: 24 pages, 5 Figure

Service provision and barriers to care for homeless people with mental health problems across 14 European capital cities

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Evidence for a lineage of virulent bacteriophages that target Campylobacter.

BACKGROUND: Our understanding of the dynamics of genome stability versus gene flux within bacteriophage lineages is limited. Recently, there has been a renewed interest in the use of bacteriophages as 'therapeutic' agents; a prerequisite for their use in such therapies is a thorough understanding of their genetic complement, genome stability and their ecology to avoid the dissemination or mobilisation of phage or bacterial virulence and toxin genes. Campylobacter, a food-borne pathogen, is one of the organisms for which the use of bacteriophage is being considered to reduce human exposure to this organism. RESULTS: Sequencing and genome analysis was performed for two Campylobacter bacteriophages. The genomes were extremely similar at the nucleotide level (> or = 96%) with most differences accounted for by novel insertion sequences, DNA methylases and an approximately 10 kb contiguous region of metabolic genes that were dissimilar at the sequence level but similar in gene function between the two phages. Both bacteriophages contained a large number of radical S-adenosylmethionine (SAM) genes, presumably involved in boosting host metabolism during infection, as well as evidence that many genes had been acquired from a wide range of bacterial species. Further bacteriophages, from the UK Campylobacter typing set, were screened for the presence of bacteriophage structural genes, DNA methylases, mobile genetic elements and regulatory genes identified from the genome sequences. The results indicate that many of these bacteriophages are related, with 10 out of 15 showing some relationship to the sequenced genomes. CONCLUSIONS: Two large virulent Campylobacter bacteriophages were found to show very high levels of sequence conservation despite separation in time and place of isolation. The bacteriophages show adaptations to their host and possess genes that may enhance Campylobacter metabolism, potentially advantaging both the bacteriophage and its host. Genetic conservation has been shown to extend to other Campylobacter bacteriophages, forming a highly conserved lineage of bacteriophages that predate upon campylobacters and indicating that highly adapted bacteriophage genomes can be stable over prolonged periods of time

Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

Anthropogenic heat flux: advisable spatial resolutions when input data are scarce

Anthropogenic heat flux (QF) may be significant in cities, especially under low solar irradiance and at night. It is of interest to many practitioners including meteorologists, city planners and climatologists. QF estimates at fine temporal and spatial resolution can be derived from models that use varying amounts of empirical data. This study compares simple and detailed models in a European megacity (London) at 500 m spatial resolution. The simple model (LQF) uses spatially resolved population data and national energy statistics. The detailed model (GQF) additionally uses local energy, road network and workday population data. The Fractions Skill Score (FSS) and bias are used to rate the skill with which the simple model reproduces the spatial patterns and magnitudes of QF, and its sub-components, from the detailed model. LQF skill was consistently good across 90% of the city, away from the centre and major roads. The remaining 10% contained elevated emissions and B hot spots ^ representing 30 – 40% of the total city-wide energy. This structure was lost because it requires workday population, spatially resolved building energy consumption and/or road network data. Daily total building and traffic energy consumption estimates from national data were within ± 40% of local values. Progressively coarser spatial resolutions to 5 km improved skill for total Q F , but important features (hot spots, transport network) were lost at all resolutions when residential population controlled spatial variations. The results demonstrate that simple QF models should be applied with conservative spatial resolution in cities that, like London, exhibit time-varying energy use patterns