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

Partially Saturated Bicyclic Heteroaromatics as an sp³-Enriched Fragment Collection.

Fragment-based lead generation has proven to be an effective means of identifying high-quality lead compounds for drug discovery programs. However, the fragment screening sets often used are principally comprised of sp²-rich aromatic compounds, which limits the structural (and hence biological) diversity of the library. Herein, we describe strategies for the synthesis of a series of partially saturated bicyclic heteroaromatic scaffolds with enhanced sp³ character. Subsequent derivatization led to a fragment collection featuring regio- and stereo-controlled introduction of substituents on the saturated ring system, often with formation of new stereocenters.EPSRC BBSRC MRC Wellcome Trust D.G.T. thanks AstraZeneca for funding. S.L.M. thanks BASF for funding.

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

Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signaling Loop

Rationale: In the endothelium, insulin stimulates endothelial NO synthase (eNOS) to generate the antiatherosclerotic signaling radical NO. Insulin-resistant type 2 diabetes mellitus is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. Objective: To answer this question, we generated a mouse with endothelial cell (EC)–specific overexpression of the human insulin receptor (hIRECO) using the Tie2 promoter–enhancer. Methods and Results: hIRECO demonstrated significant endothelial dysfunction measured by blunted endothelium-dependent vasorelaxation to acetylcholine, which was normalized by a specific Nox2 NADPH oxidase inhibitor. Insulin-stimulated phosphorylation of protein kinase B was increased in hIRECO EC as was Nox2 NADPH oxidase–dependent generation of superoxide, whereas insulin-stimulated and shear stress–stimulated eNOS activations were blunted. Phosphorylation at the inhibitory residue Y657 of eNOS and expression of proline-rich tyrosine kinase 2 that phosphorylates this residue were significantly higher in hIRECO EC. Inhibition of proline-rich tyrosine kinase 2 improved insulin-induced and shear stress–induced eNOS activation in hIRECO EC. Conclusions: Enhancing insulin sensitivity specifically in EC leads to a paradoxical decline in endothelial function, mediated by increased tyrosine phosphorylation of eNOS and excess Nox2-derived superoxide. Increased EC insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide. Inhibition of proline-rich tyrosine kinase 2 restores insulin-induced and shear stress–induced NO production. This study demonstrates for the first time that increased endothelial insulin sensitivity leads to a proatherosclerotic imbalance between NO and superoxide

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

Transgenerational Effects of Stress Exposure on Offspring Phenotypes in Apomictic Dandelion

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects

Restoring Akt1 activity in outgrowth endothelial cells from south asian men rescues vascular reparative potential

Recent data suggest reduced indices of vascular repair in South Asian men, a group at increased risk of cardiovascular events. Outgrowth endothelial cells (OEC) represent an attractive tool to study vascular repair in humans and may offer potential in cell-based repair therapies. We aimed to define and manipulate potential mechanisms of impaired vascular repair in South Asian (SA) men. In vitro and in vivo assays of vascular repair and angiogenesis were performed using OEC derived from SA men and matched European controls, prior defining potentially causal molecular mechanisms. SA OEC exhibited impaired colony formation, migration, and in vitro angiogenesis, associated with decreased expression of the proangiogenic molecules Akt1 and endothelial nitric oxide synthase (eNOS). Transfusion of European OEC into immunodeficient mice after wire-induced femoral artery injury augmented reendothelialization, in contrast with SA OEC and vehicle; SA OEC also failed to promote angiogenesis after induction of hind limb ischemia. Expression of constitutively active Akt1 (E17KAkt), but not green fluorescent protein control, in SA OEC increased in vitro angiogenesis, which was abrogated by a NOS antagonist. Moreover, E17KAkt expressing SA OEC promoted re-endothelialization of wire-injured femoral arteries, and perfusion recovery of ischemic limbs, to a magnitude comparable with nonmanipulated European OEC. Silencing Akt1 in European OEC recapitulated the functional deficits noted in SA OEC. Reduced signaling via the Akt/eNOS axis is causally linked with impaired OEC-mediated vascular repair in South Asian men. These data prove the principle of rescuing marked reparative dysfunction in OEC derived from these men.This work was supported by the British Heart Foundation, London, UK, and the Diabetes Research and Wellness Foundation, Portsmouth, UK

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Repeatability of short-duration transient visual evoked potentials in normal subjects

To evaluate the within-session and inter-session repeatability of a new, short-duration transient visual evoked potential (SD-tVEP) device on normal individuals, we tested 30 normal subjects (20/20 visual acuity, normal 24-2 SITA Standard VF) with SD-tVEP. Ten of these subjects had their tests repeated within 1–2 months from the initial visit. Synchronized single-channel EEG was recorded using a modified Diopsys Enfant™ System (Diopsys, Inc., Pine Brook, New Jersey, USA). A checkerboard stimulus was modulated at two reversals per second. Two different contrasts of checkerboard reversal patterns were used: 85% Michelson contrast with a mean luminance of 66.25 cd/m2 and 10% Michelson contrast with a mean luminance of 112 cd/m2. Each test lasted 20 s. Both eyes, independently and together, were tested 10 times (5 times at each contrast level). The following information was identified from the filtered N75-P100-N135 complex: N75 amplitude, N75 latency, P100 amplitude, P100 latency, and Delta Amplitude (N75-P100). The median values for each eye’s five SD-tVEP parameters were calculated and grouped into two data sets based on contrast level. Mean age was 27.3 ± 5.2 years. For OD only, the median (95% confidence intervals) of Delta Amplitude (N75-P100) amplitudes at 10% and 85% contrast were 4.6 uV (4.1–5.9) and 7.1 uV (5.15–9.31). The median P100 latencies were 115.2 ms (112.0–117.7) and 104.0 ms (99.9–106.0). There was little within-session variability for any of these parameters. Intraclass correlation coefficients ranged between 0.64 and 0.98, and within subject coefficients of variation were 3–5% (P100 latency) and 15–30% (Delta Amplitude (N75-P100) amplitude). Bland–Altman plots showed good agreement between the first and fifth test sessions (85% contrast Delta Amplitude (N75-P100) delta amplitude, mean difference, 0.48 mV, 95% CI, −0.18–1.12; 85% contrast P100 latency delay, −0.82 ms, 95% CI, −3.12–1.46; 10% contrast Delta Amplitude (N75-P100) amplitude, 0.58 mV, 95% CI, −0.27–1.45; 10% contrast P100 latency delay, −2.05 mV, 95% CI, −5.12–1.01). The inter-eye correlation and agreement were significant for both SD-tVEP amplitude and P100 latency measurements. For the subset of eyes in which the inter-session repeatability was tested, the intraclass correlation coefficients ranged between 0.71 and 0.86 with good agreement shown on Bland–Altman plots. Short-duration transient VEP technology showed good within-session, inter-session repeatability, and good inter-eye correlation and agreement

Preventing childhood obesity: what works?

Rates of overweight in North American children and adolescents have increased dramatically since the 1970s. Childhood obesity has reached epidemic proportions and calls for prevention and treatment programs to reverse this trend have been made. However, the evidence base needed for effective action is still incomplete, especially for childhood obesity prevention programs. This paper focuses on primary prevention of childhood obesity and has three aims: (1) to briefly describe current primary prevention approaches for childhood obesity and the evidence for their impact; (2) to elucidate promising, but untested intervention strategies using an ecological framework and evidence from experimental and epidemiological research on factors influencing children\u27s eating and weight status; and (3) to introduce a multiphase strategy for screening intervention components and building and evaluating potent interventions for childhood obesity. Most childhood obesity prevention programs have focused on school-aged children and have had little success. We suggest that, given these findings, prevention efforts should be expanded to explore other contexts in which children live as possible settings for intervention efforts, including the family and childcare settings. Given that 25% of preschool children are already overweight, intervening with children before school entry should be a priority. A review of experimental research on the developing controls of food intake in infancy and childhood suggests possible intervention strategies, focusing on parenting and aspects of the feeding environment. Epidemiological findings point to even earlier modifiable risk factors, including gestational weight gain, maternal prepregnancy weight, and formula feeding. However, the potential impact of altering these risk factors remains to be evaluated. In response to this problem, we suggest a new, multiphase method for accomplishing this, including screening intervention components, refining intervention designs and confirming component efficacy to build and evaluate potent, optimized interventions