Gordon Valentine Manley and his contribution to the study of climate change: a review of his life and work

British climatologist and geographer, Gordon Manley (1902–1980), is perhaps best known for his pioneering work on climate variability in the UK, for establishing the Central England Temperature series and, for his pivotal role in demonstrating the powerful relationship between climate, weather, and culture in post-World War II Britain. Yet Manley made many contributions, both professional and popular, to climate change debates in the twentieth century, where climate change is broadly understood to be changes over a range of temporal and spatial scales rather than anthropogenic warming per se. This review first establishes how Manley's work, including that on snow and ice, was influenced by key figures in debates over climatic amelioration around the North Atlantic between 1920s and 1950s. His research exploring historical climate variability in the UK using documentary sources is then discussed. His perspectives on the relationship between climate changes and cultural history are reviewed, paying particular attention to his interpretation of this relationship as it played out in the UK. Throughout, the review aims to show Manley to be a fieldworker and an empiricist and reveals how he remained committed to rigorous scientific investigation despite changing trends within his academic discipline

Transition-Metal-Free Homopolymerization of Pyrrolo[2,3-d:5,4-d′]bisthiazoles via Nucleophilic Aromatic Substitution

Novel methods to synthesize electron-deficient π-conjugated polymers utilizing transition-metal-free coupling reactions for the use of nonfunctionalized monomers are attractive due to their improved atom economy and environmental prospective. Herein we describe the use of iPrMgCl·LiCl complex to afford thiazole-based conjugated polymers in the absence of any transition metal catalyst, that enables access to well-defined polymers with good molecular weights. The mechanistically distinct polymerizations proceeded via nucleophilic aromatic substitution (SNAr) reaction supported by density functional theory (DFT) calculations. This work demonstrates the first example of fully conjugated thiazole-based aromatic homopolymers without the need of any transition metal catalyst

Percentiles of fasting serum insulin, glucose, HbA1c and HOMA-IR in pre-pubertal normal weight European children from the IDEFICS cohort

OBJECTIVES: The aim of this study is to present age-and sex-specific reference values of insulin, glucose, glycosylated haemoglobin (HbA1c) and the homeostasis model assessment to quantify insulin resistance (HOMA-IR) for pre-pubertal children. METHODS: The reference population consists of 7074 normal weight 3- to 10.9-year-old pre-pubertal children from eight European countries who participated in at least one wave of the IDEFICS ('identification and prevention of dietary-and lifestyle-induced health effects in children and infants') surveys (2007-2010) and for whom standardised laboratory measurements were obtained. Percentile curves of insulin (measured by an electrochemiluminescence immunoassay), glucose, HbA1c and HOMA-IR were calculated as a function of age stratified by sex using the general additive model for location scale and shape (GAMLSS) method. RESULTS: Levels of insulin, fasting glucose and HOMA-IR continuously show an increasing trend with age, whereas HbA1c shows an upward trend only beyond the age of 8 years. Insulin and HOMA-IR values are higher in girls of all age groups, whereas glucose values are slightly higher in boys. Median serum levels of insulin range from 17.4 and 13.2 pmol l(-1) in 3-< 3.5-year-old girls and boys, respectively, to 53.5 and 43.0 pmol l(-1) in 10.5-< 11-year-old girls and boys. Median values of glucose are 4.3 and 4.5 mmol l(-1) in the youngest age group and 49.3 and 50.6 mmol l(-1) in the oldest girls and boys. For HOMA-IR, median values range from 0.5 and 0.4 in 3-< 3.5-year-old girls and boys to 1.7 and 1.4 in 10.5-< 11-year-old girls and boys, respectively. CONCLUSIONS: Our study provides the first standardised reference values for an international European children's population and provides the, up to now, largest data set of healthy pre-pubertal children to model reference percentiles for markers of insulin resistance. Our cohort shows higher values of Hb1Ac as compared with a single Swedish study while our percentiles for the other glucose metabolic markers are in good accordance with previous studies

The instantaneous helical axis of the subtalar and talocrural joints: a non-invasive in vivo dynamic study

<p>Abstract</p> <p>Background</p> <p>An understanding of rear-foot (talocrural and subtalar joints) kinematics is critical for diagnosing foot pathologies, designing total ankle implants, treating rear-foot injuries and quantifying gait abnormalities. The majority of kinematic data available have been acquired through static cadaver work or passive <it>in vivo </it>studies. The applicability of these data to dynamic <it>in vivo </it>situations remains unknown. Thus, the purpose of this study was to fully quantify subtalar, talocrural and calcaneal-tibial <it>in vivo </it>kinematics in terms of the instantaneous helical axis (IHA) in twenty-five healthy ankles during a volitional activity that simulated single-leg toe-raises with partial-weight support, requiring active muscle control.</p> <p>Methods</p> <p>Subjects were each placed supine in a 1.5 T MRI and asked to repeat this simulated toe-raise while a full sagittal-cine-phase contrast (dynamic) MRI dataset was acquired. From the cine-phase contrast velocity a full kinematic description for each joint was derived.</p> <p>Results</p> <p>Nearly all motion quantified at the calcaneal-tibial joint was attributable to the talocrural joint. The subtalar IHA orientation and position were highly variable; whereas, the talocrural IHA orientation and position were extremely consistent.</p> <p>Conclusion</p> <p>The talocrural was well described by the IHA and could be modeled as a fixed-hinge joint, whereas the subtalar could not be.</p

A comparative study on the efficacy of 10% hypertonic saline and equal volume of 20% mannitol in the treatment of experimentally induced cerebral edema in adult rats

<p>Abstract</p> <p>Background</p> <p>Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP) at present. In this connection, 10% hypertonic saline (HS) alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol.</p> <p>Results</p> <p>Adult male Sprague-Dawley (SD) rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO) and treated with a continuous intravenous infusion of 10% HS, 20% mannitol or D-[1-³H(N)]-mannitol. Brain water content (BWC) as analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats decreased more significantly after 10% HS treatment compared with 20% mannitol. Concentration of serum Na⁺and plasma crystal osmotic pressure of the 10% HS group at 2, 6, 12 and 18 h following permanent MCAO increased significantly when compared with 20% mannitol treated group. Moreover, there was negative correlation between the BWC of the ipsilateral ischemic hemisphere and concentration of serum Na⁺, plasma crystal osmotic pressure and difference value of concentration of serum Na⁺and concentration of brain Na⁺in ipsilateral ischemic hemisphere in the 10% HS group at the various time points after MCAO. A remarkable finding was the progressive accumulation of mannitol in the ischemic brain tissue.</p> <p>Conclusions</p> <p>We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.</p

Crystal Structures of the FAK Kinase in Complex with TAE226 and Related Bis-Anilino Pyrimidine Inhibitors Reveal a Helical DFG Conformation

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase required for cell migration, proliferation and survival. FAK overexpression has been documented in diverse human cancers and is associated with a poor clinical outcome. Recently, a novel bis-anilino pyrimidine inhibitor, TAE226, was reported to efficiently inhibit FAK signaling, arrest tumor growth and invasion and prolong the life of mice with glioma or ovarian tumor implants. Here we describe the crystal structures of the FAK kinase bound to TAE226 and three related bis-anilino pyrimidine compounds. TAE226 induces a conformation of the N-terminal portion of the kinase activation loop that is only observed in FAK, but is distinct from the conformation in both the active and inactive states of the kinase. This conformation appears to require a glycine immediately N-terminal to the “DFG motif”, which adopts a helical conformation stabilized by interactions with TAE226. The presence of a glycine residue in this position contributes to the specificity of TAE226 and related compounds for FAK. Our work highlights the fact that kinases can access conformational space that is not necessarily utilized for their native catalytic regulation, and that such conformations can explain and be exploited for inhibitor specificity

Optimization of Cell Morphology Measurement via Single-Molecule Tracking PALM

In neurons, the shape of dendritic spines relates to synapse function, which is rapidly altered during experience-dependent neural plasticity. The small size of spines makes detailed measurement of their morphology in living cells best suited to super-resolution imaging techniques. The distribution of molecular positions mapped via live-cell Photoactivated Localization Microscopy (PALM) is a powerful approach, but molecular motion complicates this analysis and can degrade overall resolution of the morphological reconstruction. Nevertheless, the motion is of additional interest because tracking single molecules provides diffusion coefficients, bound fraction, and other key functional parameters. We used Monte Carlo simulations to examine features of single-molecule tracking of practical utility for the simultaneous determination of cell morphology. We find that the accuracy of determining both distance and angle of motion depend heavily on the precision with which molecules are localized. Strikingly, diffusion within a bounded region resulted in an inward bias of localizations away from the edges, inaccurately reflecting the region structure. This inward bias additionally resulted in a counterintuitive reduction of measured diffusion coefficient for fast-moving molecules; this effect was accentuated by the long camera exposures typically used in single-molecule tracking. Thus, accurate determination of cell morphology from rapidly moving molecules requires the use of short integration times within each image to minimize artifacts caused by motion during image acquisition. Sequential imaging of neuronal processes using excitation pulses of either 2 ms or 10 ms within imaging frames confirmed this: processes appeared erroneously thinner when imaged using the longer excitation pulse. Using this pulsed excitation approach, we show that PALM can be used to image spine and spine neck morphology in living neurons. These results clarify a number of issues involved in interpretation of single-molecule data in living cells and provide a method to minimize artifacts in single-molecule experiments

Reconstructing 800 years of summer temperatures in Scotland from tree rings

We thank The Carnegie Trust for the Universities of Scotland for providing funding for Miloš Rydval’s PhD. The Scottish pine network expansion has been an ongoing task since 2007 and funding must be acknowledged to the following projects: EU project ‘Millennium’ (017008-2), Leverhulme Trust project ‘RELiC: Reconstructing 8000 years of Environmental and Landscape change in the Cairngorms (F/00 268/BG)’ and the NERC project ‘SCOT2K: Reconstructing 2000 years of Scottish climate from tree rings (NE/K003097/1)’.This study presents a summer temperature reconstruction using Scots pine tree-ring chronologies for Scotland allowing the placement of current regional temperature changes in a longer-term context. ‘Living-tree’ chronologies were extended using ’subfossil’ samples extracted from nearshore lake sediments resulting in a composite chronology > 800 years in length. The North Cairngorms (NCAIRN) reconstruction was developed from a set of composite blue intensity high-pass and ring-width low-pass chronologies with a range of detrending and disturbance correction procedures. Calibration against July-August mean temperature explains 56.4% of the instrumental data variance over 1866-2009 and is well verified. Spatial correlations reveal strong coherence with temperatures over the British Isles, parts of western Europe, southern Scandinavia and northern parts of the Iberian Peninsula. NCAIRN suggests that the recent summer-time warming in Scotland is likely not unique when compared to multi-decadal warm periods observed in the 1300s, 1500s, and 1730s, although trends before the mid-16th century should be interpreted with some caution due to greater uncertainty. Prominent cold periods were identified from the 16th century until the early 1800s – agreeing with the so-called Little Ice Age observed in other tree-ring reconstructions from Europe - with the 1690s identified as the coldest decade in the record. The reconstruction shows a significant cooling response one year following volcanic eruptions although this result is sensitive to the datasets used to identify such events. In fact, the extreme cold (and warm) years observed in NCAIRN appear more related to internal forcing of the summer North Atlantic Oscillation.Publisher PDFPeer reviewe