Quantifying mucosal hemodynamics in a murine model of Ulcerative Colitis with diffuse reflectance spectroscopy

Ulcerative colitis (UC) is a gastrointestinal, autoimmune disease that causes ulceration and inflammation of the colon with an incidence 10 out of every 100,000 people in North America and Western Europe. Though the exact etiology is uncertain, a number of studies have shown that inflammatory cells along with environmental factors, genetics, and lifestyle habits can contribute to the sustained inflammatory response. In order to determine the cellular mechanism behind relapse and remission of UC, researchers have frequently employed immunohistochemistry, western blotting and gene sequencing, but these destructive analysis methods require the removal of a sample, necessarily limiting these methods to non-living tissues. There is an emerging interest in using non-invasive techniques to study the in vivo, longitudinal effects of UC on the mucosa in the colon. Here we have developed a mouse model of UC using dextran sulfate sodium and a non-invasive spectroscopy monitoring modality to study the changes in the tissue hemodynamics during active UC

MicroRNA and other non-coding RNAs in Epstein–Barr virus-associated cancers

Simple Summary Epstein-Barr virus (EBV) is associated with a variety of malignancies. In this review, we discuss EBV-encoded microRNAs and ncRNAs and consider how their detection could aid in the diagnosis, prognostication, and monitoring of treatment in patients with EBV-associated malignancies, including classical Hodgkin's lymphoma (cHL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), nasopharyngeal carcinoma (NPC), and gastric carcinoma (GC). EBV is a direct causative agent in around 1.5% of all cancers. The oncogenic properties of EBV are related to its ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. The EBV latency program is required for the immortalization of infected B cells and involves the expression of non-coding RNAs (ncRNAs), including viral microRNAs. These ncRNAs have different functions that contribute to virus persistence in the asymptomatic host and to the development of EBV-associated cancers. In this review, we discuss the function and potential clinical utility of EBV microRNAs and other ncRNAs in EBV-associated malignancies. This review is not intended to be comprehensive, but rather to provide examples of the importance of ncRNAs

Reversal of economic fortunes: institutions and the changing ascendancy of Barcelona and Madrid as economic hubs

This paper looks at the divergent economic trajectories of Barcelona and Madrid since Spain's transition to democracy. It highlights how Barcelona, the city that was better positioned four decades ago to emerge as the main Spanish economic hub, has lost out to Madrid. We argue that the contrasting trajectories of the two cities have less to do with the pull of Madrid as the capital of Spain, with the development of new infrastructure in the country, or with agglomeration economies, and more with institutional factors. A growing societal divide in Barcelona along economic, social, and identity lines has led to a greater breakdown of trust and to the development of strong groups with limited capacity to bridge with one another than in Madrid. This has entailed the emergence of negative externalities that have limited the economic potential for growth in Barcelona and facilitated the rise of Madrid as the main economic hub within Spain

Scientific merits and analytical challenges of tree-ring densitometry

R.W. was supported by NERC grant NE/K003097/1.X-ray microdensitometry on annually-resolved tree-ring samples has gained an exceptional position in last-millennium paleoclimatology through the maximum latewood density parameter (MXD), but also increasingly through other density parameters. For fifty years, X-ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light-based techniques are becoming increasingly popular and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree-ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh ?long-standing wisdom?, but also provide new insights. Key outcomes include; i) a demonstration of the need for mass/volume based re-calibration to accurately estimate average ring density; ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density datasets for climate reconstructions; and iii) insights into the relevance of analytical measurement resolution in signals derived from tree-ring density data. Finally, we provide recommendations expected to facilitate future inter-comparability and interpretations for global change research.Publisher PDFPeer reviewe

Effects of Anti-VEGF on Predicted Antibody Biodistribution: Roles of Vascular Volume, Interstitial Volume, and Blood Flow

BACKGROUND: The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. METHODOLOGY/PRINCIPAL FINDINGS: Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. CONCLUSIONS/SIGNIFICANCE: These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF

Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.

While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clones with EBV, but surprisingly not transduction with individual BL-associated latent viral genes, restored protection from apoptosis. Expression profiling and functional analysis of apoptosis-related proteins and transcripts in BL cells revealed that EBV inhibits the upregulation of the proapoptotic BH3-only proteins, BIM and PUMA. We conclude that latent EBV genes cooperatively enhance the survival of BL cells by suppression of the intrinsic apoptosis pathway signalling via inhibition of the potent apoptosis initiators, BIM and PUMA.Cell Death and Differentiation advance online publication, 29 September 2017; doi:10.1038/cdd.2017.150

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Plant Reactome: a knowledgebase and resource for comparative pathway analysis

Plant Reactome (https://plantreactome.gramene.org) is an open-source, comparative plant pathway knowledgebase of the Gramene project. It uses Oryza sativa (rice) as a reference species for manual curation of pathways and extends pathway knowledge to another 82 plant species via gene-orthology projection using the Reactome data model and framework. It currently hosts 298 reference pathways, including metabolic and transport pathways, transcriptional networks, hormone signaling pathways, and plant developmental processes. In addition to browsing plant pathways, users can upload and analyze their omics data, such as the gene-expression data, and overlay curated or experimental gene-gene interaction data to extend pathway knowledge. The curation team actively engages researchers and students on gene and pathway curation by offering workshops and online tutorials. The Plant Reactome supports, implements and collaborates with the wider community to make data and tools related to genes, genomes, and pathways Findable, Accessible, Interoperable and Re-usable (FAIR)

Advances in quantum metrology

The statistical error in any estimation can be reduced by repeating the measurement and averaging the results. The central limit theorem implies that the reduction is proportional to the square root of the number of repetitions. Quantum metrology is the use of quantum techniques such as entanglement to yield higher statistical precision than purely classical approaches. In this Review, we analyse some of the most promising recent developments of this research field and point out some of the new experiments. We then look at one of the major new trends of the field: analyses of the effects of noise and experimental imperfections