Microplastic ingestion decreases energy reserves in marine worms

The indiscriminate disposal of plastic to the environment is of concern. Microscopic plastic litter (<5 mm diameter; 'microplastic') is increasing in abundance in the marine environment, originating from the fragmentation of plastic items and from industry and personal-care products [1]. On highly impacted beaches, microplastic concentrations (<1mm) can reach 3% by weight, presenting a global conservation issue [2]. Microplastics are a novel substrate for the adherence of hydrophobic contaminants [1], deposition of eggs [3], and colonization by unique bacterial assemblages [4]. Ingestion by indiscriminate deposit-feeders has been reported, yet physical impacts remain understudied [1]. Here, we show that deposit-feeding marine worms maintained in sediments spiked with microscopic unplasticised polyvinylchloride (UPVC) at concentrations overlapping those in the environment had significantly depleted energy reserves by up to 50% (Figure 1). Our results suggest that depleted energy reserves arise from a combination of reduced feeding activity, longer gut residence times of ingested material and inflammation.This work was funded by the Department for Environment, Food & Rural Affairs; 1-SW-P-N21-000-031-DN-A1-05102. We thank Peter Splatt for SEM imaging assistance, Professor Stuart Bearhop for invaluable comments on the manuscript and Dr. Adil Bakir for UPVC chemistry analyses

'I found myself a despicable being!':Medical students face disturbing moral dilemmas

CONTEXT: The psychological realm of medical students` moral experiences is explored tangentially in medical education literature, often in the context of ethics or professionalism education. This study deepens our understanding by (1) investigating the nature of moral dilemmas experienced at the onset of clinical practice, (2) exploring students` emotional response to these dilemmas, and (3) examining how students perceive the influence of these dilemmas on their professional development. METHODS: This is a cross-sectional qualitative study carried out in 2017 that applied Thematic Template Analysis to individual interviews performed with last-year medical students. The interviews followed the drawing of a Rich Picture representing moral dilemmas experienced by medical students at the onset of clinical practice. RESULTS: Moral dilemmas have four intertwined dimensions. The first relates to students` struggle to prioritize, balance and apply conflicting moral values; the second comprises the clash between students` inner motivation and the external constraints that limit the moral action; the third refers to the conflict between students' current attitudes with the desired/idealized attitudes of the doctor they intend to become; the forth corresponds to weighting conflicting ethical principles during the moral decision. Students` emotional responses are intense, long-lasting, and with a remarkable residue effect, particularly when the moral decision does not align with their moral beliefs. Moral dilemmas are impactful experiences that affect the professional development of medical students and can culminate in both detachment or growth in moral courage. CONCLUSION: Moral dilemmas are memorable, complex, and emotionally intense experiences that impact the professional development of medical students. Understanding students` moral dilemmas can help educators to devise pedagogical activities to anticipate and reflect on these experiences. These activities should happen under the guidance of a non-judgmental facilitator, capable of listening and legitimating students' thoughts and feelings while providing insights to nurture their professional development

Developmental delay and progressive seizures in 2-month-old child with diffuse MRI abnormalities

2 month-old infant presented with seizures, radiological findings of diffuse elevated T2 signal with frontal lobe sparing and extensive symmetrical post contrast enhancement. At autopsy, the brain stem was pale and atrophic, with areas of cystic degeneration. Medullary sections showed perivascular Rosenthal fibre deposition

Are we underestimating microplastic abundance in the marine environment? A comparison of microplastic capture with nets of different mesh-size

Microplastic debris is ubiquitous and yet sampling, classifying and enumerating this prolific pollutant in marine waters has proven challenging. Typically, waterborne microplastic sampling is undertaken using nets with a 333 μm mesh, which cannot account for smaller debris. In this study, we provide an estimate of the extent to which microplastic concentrations are underestimated with traditional sampling. Our efforts focus on coastal waters, where microplastics are predicted to have the greatest influence on marine life, on both sides of the North Atlantic Ocean. Microplastic debris was collected via surface trawls using 100, 333 and 500 μm nets. Our findings show that sampling using nets with a 100 μm mesh resulted in the collection of 2.5-fold and 10-fold greater microplastic concentrations compared with using 333 and 500 μm meshes respectively (P < 0.01). Based on the relationship between microplastic concentrations identified and extrapolation of our data using a power law, we estimate that microplastic concentrations could exceed 3700 microplastics m−3 if a net with a 1 μm mesh size is used. We further identified that use of finer nets resulted in the collection of significantly thinner and shorter microplastic fibres (P < 0.05). These results elucidate that estimates of marine microplastic concentrations could currently be underestimated

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS

Ebookness

Since the mid-2000s, the ebook has stabilized into an ontologically distinct form, separate from PDFs and other representations of the book on the screen. The current article delineates the ebook from other emerging digital genres with recourse to the methodologies of platform studies and book history. The ebook is modelled as three concentric circles representing its technological, textual and service infrastructure innovations. This analysis reveals two distinct properties of the ebook: a simulation of the services of the book trade and an emphasis on user textual manipulation. The proposed model is tested with reference to comparative studies of several ebooks published since 2007 and defended against common claims of ebookness about other digital textual genres

Cell migration leads to spatially distinct but clonally related airway cancer precursors

Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree

Prostaglandin E2 Regulates AMPA Receptor Phosphorylation and Promotes Membrane Insertion in Preoptic Area Neurons and Glia during Sexual Differentiation

Sexual differentiation of the rodent brain is dependent upon the organizing actions of the steroid hormone, estradiol. In the preoptic area, a brain region critical for the expression of adult reproductive behavior, there are twice as many dendritic spine synapses per unit length on newborn male neurons compared to female neurons and this sex difference correlates with the expression of adult male copulatory behavior. The sex difference in the POA is achieved via estradiol's upregulation of the membrane-derived lipid signaling molecule prostaglandin E2 (PGE2); PGE2 is necessary and sufficient to masculinize both dendritic spine density and adult sexual behavior in rats. We have previously shown that PGE2 activates EP2 and EP4 receptors which increases protein kinase A (PKA) activity and that masculinized dendritic spine density and sex behavior are both dependent upon PKA as well as activation of AMPA type glutamate receptors. In the current experiments, we build upon this signaling cascade by determining that PGE2 induces phosphorylation of the AMPA receptor subunit, GluR1, which leads to increased AMPA receptor insertion at the membrane. Treating female pups on the day of birth with PGE2 induced the phosphorylation of GluR1 at the PKA-sensitive site within 2 hours of treatment, an effect that was blocked by co-administration of the PKA/AKAP inhibitor, HT31 with PGE2. Brief treatment of mixed neuronal/glial POA cultures with PGE2 or the cAMP/PKA stimulator, forskolin, increased membrane associated GluR1 in both neurons and glia. We speculate that PGE2 induced increases in AMPA receptor associated with the membrane underlies our previously observed increase in dendritic spine density and is a critical component in the masculinization of rodent sex behavior

Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency