Effect of microplastic on the gills of the Shore Crab Carcinus maenas

This is a “Just Accepted” manuscript. "Just Accepted manuscripts" have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.Microscopic plastic debris (microplastics, <5mm in diameter) is ubiquitous in the marine environment. Previous work has shown that microplastics may be ingested and inhaled by the shore crab Carcinus maenas although the biological consequences are unknown. Here, we show that acute aqueous exposure to polystyrene microspheres (8μm) with different surface coatings had significant but transient effects on branchial function. Microspheres inhaled into the gill chamber had a small but significant dose dependent effect on oxygen consumption after 1 hour of exposure, returning to normal levels after 16 h. Ion exchange was also affected, with a small but significant decrease in hemolymph sodium ions and an increase in calcium ions after 24 h post exposure. To further asses the effects on osmoregulation, crabs were challenged with reduced salinity after microplastic exposure. Neither microspheres nor natural sediments altered the crab’s response to osmotic stress, regardless of plastic concentration added. Carboxylated (COOH) and aminated (NH2) polystyrene microspheres were distributed differently across the gill surface, although neither had a significant adverse impact on gill function. These results illustrate the extent of the physiological effects of microplastics, compared to the physiological resilience of shore crabs in maintaining osmoregulatory and respiratory function after acute exposure to both anthropogenic plastics and natural particles.W, CL and TG acknowledge funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 308370. The contents of this publication are the responsibility of the CleanSea project and can in no way be taken to reflect the views of the European Union. TG and CL acknowledge additional support from NERC NE/L007010/1

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in 'Molecular pharmaceutics', copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/mp500527xThere are very few drug delivery systems that target key organs via the oral route, as oral delivery advances normally address gastrointestinal drug dissolution, permeation, and stability. Here we introduce a nanomedicine in which nanoparticles, while also protecting the drug from gastric degradation, are taken up by the gastrointestinal epithelia and transported to the lung, liver, and spleen, thus selectively enhancing drug bioavailability in these target organs and diminishing kidney exposure (relevant to nephrotoxic drugs). Our work demonstrates, for the first time, that oral particle uptake and translocation to specific organs may be used to achieve a beneficial therapeutic response. We have illustrated this using amphotericin B, a nephrotoxic drug encapsulated within N-palmitoyl-N-methyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycol chitosan (GCPQ) nanoparticles, and have evidenced our approach in three separate disease states (visceral leishmaniasis, candidiasis, and aspergillosis) using industry standard models of the disease in small animals. The oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral liposomal AmB (AmBisome). Our work thus paves the way for others to use nanoparticles to achieve a specific targeted delivery of drug to key organs via the oral route. This is especially important for drugs with a narrow therapeutic index

Metabolic profiling of live cancer tissues using NAD(P)H fluorescence lifetime imaging

Altered metabolism is a hallmark of cancer, both resulting from and driving oncogenesis. The NAD and NADP redox couples play a key role in a large number of the metabolic pathways involved. In their reduced forms, NADH and NADPH, these molecules are intrinsically fluorescent. As the average time for fluorescence to be emitted following excitation by a laser pulse, the fluorescence lifetime, is exquisitely sensitive to changes in the local environment of the fluorophore, imaging the fluorescence lifetime of NADH and NADPH offers the potential for label-free monitoring of metabolic changes inside living tumors. Here, we describe the biological, photophysical, and methodological considerations required to establish fluorescence lifetime imaging (FLIM) of NAD(P)H as a routine method for profiling the metabolism of living cancer cells and tissues