Climatic impacts of stratospheric geoengineering with sulfate, black carbon and titania injection

In this paper, we examine the potential climatic effects of geoengineering by sulfate, black carbon and titania injection against a baseline RCP8.5 scenario. We use the HadGEM2-CCS model to simulate scenarios in which the top-of-the-atmosphere radiative imbalance due to rising greenhouse gas concentrations is offset by sufficient aerosol injection throughout the 2020–2100 period. We find that the global-mean temperature is effectively maintained at historical levels for the entirety of the period for all 3 aerosol-injection scenarios, though there are a wide range of side-effects which are discussed in detail. The most prominent conclusion is that although the BC injection rate necessary to produce an equivalent global mean temperature-response is much lower, the severity of stratospheric temperature changes (> +70 °C) and precipitation impacts effectively exclude BC from being a viable option for geoengineering. Additionally, while it has been suggested that titania would be an effective particle because of its high scattering efficiency, it also efficiently absorbs solar ultraviolet radiation producing a significant stratospheric warming (> +20 °C). As injection rates for titania are close to those for sulfate, there appears little benefit of using titania when compared to injection of sulfur dioxide, which has the added benefit of being well modelled through extensive research that has been carried out on naturally occurring explosive volcanic eruptions.The authors would like to thank Valentina Aquila for supplying AVHRR and SAGE data, and to Peter Cox, Angus Ferraro, David Keith and Alan Robock for helpful discussions. A. C. Jones was supported by a Met Office/NERC CASE (ref. 580 009 183) PhD studentship; J. M. Haywood and A. Jones were supported by the Joint UK DECC/Defra Met Office Hadley Centre Climate Programme (GA01101)

Ferritin and Iron Studies in Anaemia and Chronic Disease

Anaemia is a condition in which the number of red cells necessary to meet the body's physiological requirements is insufficient. Iron deficiency anaemia (IDA) and the anaemia of chronic disease (ACD) are the two most common causes of anaemia worldwide; iron homeostasis plays a pivotal role in the pathogenesis of both diseases. An understanding of how iron studies can be used to distinguish between these diseases is therefore essential, not only for diagnosis but also in guiding management. This review will primarily focus on IDA and ACD; however iron overload in anaemia will also be briefly discussed

The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p

Microalbuminuria could improve risk stratification in patients with TIA and minor stroke.

Published onlineJournal ArticleThis is the final version of the article. Available from Wiley Open Access via the DOI in this record.OBJECTIVE: Transient ischemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes. Current stroke risk prediction scores such as ABCD2, although widely used, lack optimal sensitivity and specificity. Elevated urinary albumin excretion predicts cardiovascular disease, stroke, and mortality. We explored the role of microalbuminuria (using albumin creatinine ratio (ACR)) in predicting recurrence risk in patients with TIA and minor stroke. METHODS: Urinary ACR was measured on a spot sample in 150 patients attending a daily stroke clinic with TIA or minor stroke. Patients were followed up at day 7, 30, and 90 to determine recurrent stroke, cardiovascular events, or death. Eligible patients had a carotid ultrasound Doppler investigation. High-risk patients were defined as those who had an event within 90 days or had >50% internal carotid artery (ICA) stenosis. RESULTS: Fourteen (9.8%) recurrent events were reported by day 90 including two deaths. Fifteen patients had severe ICA stenosis. In total, 26 patients were identified as high risk. These patients had a higher frequency of previous stroke or hypercholesterolemia compared to low-risk patients (P = 0.04). ACR was higher in high-risk patients (3.4 [95% CI 2.2-5.2] vs. 1.7 [1.5-2.1] mg/mmol, P = 0.004), independent of age, sex, blood pressure, diabetes, and previous stroke. An ACR greater than 1.5 mg/mmol predicted high-risk patients (Cox proportional hazard ratio 3.5 (95% CI 1.3-9.5, P = 0.01). INTERPRETATION: After TIA or minor stroke, a higher ACR predicted recurrent events and significant ICA stenosis. Incorporation of urinary ACR from a spot sample in the acute setting could improve risk stratification in patients with TIA and minor stroke.This article presents independent research supported by the NIHR Exeter Clinical Research Facility and the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR Exeter Clinical Research Facility, the NHS, the NIHR or the Department of Health in England. We also acknowledge and thank the South West Stroke Research Network for their help with patient recruitment and follow-up, and Mrs. Audrey Peters and Mr. Frank Summers for performing the carotid Doppler scans

Metal-based imaging agents: progress towards interrogating neurodegenerative disease.

Central nervous system (CNS) neurodegeneration is defined by a complex series of pathological processes that ultimately lead to death. The precise etiology of these disorders remains unknown. Recent efforts show that a mechanistic understanding of the malfunctions underpinning disease progression will prove requisite in developing new treatments and cures. Transition metals and lanthanide ions display unique characteristics (i.e., magnetism, radioactivity, and luminescence), often with biological relevance, allowing for direct application in CNS focused imaging modalities. These techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and luminescent-based imaging (LumI). In this Tutorial Review, we have aimed to highlight the various metal-based imaging techniques developed in the effort to understand the pathophysiological processes associated with neurodegeneration. Each section has been divided so as to include an introduction to the particular imaging technique in question. This is then followed by a summary of key demonstrations that have enabled visualization of a specific neuropathological biomarker. These strategies have either exploited the high binding affinity of a receptor for its corresponding biomarker or a specific molecular transformation caused by a target species, all of which produce a concomitant change in diagnostic signal. Advantages and disadvantages of each method with perspectives on the utility of molecular imaging agents for understanding the complexities of neurodegenerative disease are discussed

Street-view greenspace exposure and objective sleep characteristics among children

Greenspace may benefit sleep by enhancing physical activity, reducing stress or air pollution exposure. Studies on greenspace and children's sleep are limited, and most use satellite-derived measures that do not capture ground-level exposures that may be important for sleep. We examined associations of street view imagery (SVI)-based greenspace with sleep in Project Viva, a Massachusetts pre-birth cohort. We used deep learning algorithms to derive novel metrics of greenspace (e.g., %trees, %grass) from SVI within 250m of participant residential addresses during 2007–2010 (mid-childhood, mean age 7.9 years) and 2012–2016 (early adolescence, 13.2y) (N = 533). In early adolescence, participants completed >5 days of wrist actigraphy. Sleep duration, efficiency, and time awake after sleep onset (WASO) were derived from actigraph data. We used linear regression to examine cross-sectional and prospective associations of mid-childhood and early adolescence greenspace exposure with early adolescence sleep, adjusting for confounders. We compared associations with satellite-based greenspace (Normalized Difference Vegetation Index, NDVI). In unadjusted models, mid-childhood SVI-based total greenspace and %trees (per interquartile range) were associated with longer sleep duration at early adolescence (9.4 min/day; 95%CI:3.2,15.7; 8.1; 95%CI:1.7,14.6 respectively). However, in fully adjusted models, only the association between %grass at mid-childhood and WASO was observed (4.1; 95%CI:0.2,7.9). No associations were observed between greenspace and sleep efficiency, nor in cross-sectional early adolescence models. The association between greenspace and sleep differed by racial and socioeconomic subgroups. For example, among Black participants, higher NDVI was associated with better sleep, in neighborhoods with low socio-economic status (SES), higher %grass was associated with worse sleep, and in neighborhoods with high SES, higher total greenspace and %grass were associated with better sleep time. SVI metrics may have the potential to identify specific features of greenspace that affect sleep

Structure of a single-chain Fv bound to the 17 N-terminal residues of huntingtin provides insights into pathogenic amyloid formation and suppression.

Huntington's disease is triggered by misfolding of fragments of mutant forms of the huntingtin protein (mHTT) with aberrant polyglutamine expansions. The C4 single-chain Fv antibody (scFv) binds to the first 17 residues of huntingtin [HTT(1-17)] and generates substantial protection against multiple phenotypic pathologies in situ and in vivo. We show in this paper that C4 scFv inhibits amyloid formation by exon1 fragments of huntingtin in vitro and elucidate the structural basis for this inhibition and protection by determining the crystal structure of the complex of C4 scFv and HTT(1-17). The peptide binds with residues 3-11 forming an amphipathic helix that makes contact with the antibody fragment in such a way that the hydrophobic face of this helix is shielded from the solvent. Residues 12-17 of the peptide are in an extended conformation and interact with the same region of another C4 scFv:HTT(1-17) complex in the asymmetric unit, resulting in a β-sheet interface within a dimeric C4 scFv:HTT(1-17) complex. The nature of this scFv-peptide complex was further explored in solution by high-resolution NMR and physicochemical analysis of species in solution. The results provide insights into the manner in which C4 scFv inhibits the aggregation of HTT, and hence into its therapeutic potential, and suggests a structural basis for the initial interactions that underlie the formation of disease-associated amyloid fibrils by HTT.E.D.G. and C.M.D. are grateful for support by the Medical Research Council (G1002272). We also thank the Hereditary Disease Foundation (A.M.). D.Y.C. is supported by the Crystallographic X-ray Facility at the Department of Biochemistry, University of Cambridge. We would like to acknowledge Dr. Katherine Stott at the Biophysics Facility at the Department of Biochemistry, University of Cambridge, for her help with the ultracentrifugation experiments and Prof. Weiss and Dr. Desplancq at the Ecole Supérieure de Biotechnologie de Strasbourg for the kind gift of the gankyrin-specific scFv, scFvR19 as a control for our in vitro aggregation experiments.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S002228361500217X#