Book Reviews

Anchor of the Soul (a documentary video about black life in Maine) produced by Shoshana Hoose and Karen Odlin; Headstrong: The Biography of Amy Morris Bradley, 1823-1904, A Life of Nobel Usefulness by Diane Cobb Cashman; Fifty year of Fortitude: The Maritime Career of Captain Jotham Blaisdell of Kennebunk, Maine 1820-1860 by Kendrick Price Daggett; The Civil War Letters of Capt. John Franklin Godfrey edited by Candace Sawyer and Laura Orcut; Dearest Father: The Civil War Letters of Lt. Frank Dickerson, A Son of Belfast, Maine edited by Draper Hunt; Dear Friend Anna: The Civil War Letters of a Common Soldier from Maine edited by Beverly Hayes Kallgren and James L. Crouthamel; William E. Barry\u27s Sketch of an Old River: Shipbuilding on the Kennebunk edited by Joyce Butler; Maine Politics and Government by Kenneth T. Palmer, G. Thomas Taylor and Marcus A. Librizzi

Infrared spectroscopy reveals multi-step multi-timescale photoactivation in the photoconvertible protein archetype dronpa

Photochromic fluorescent proteins play key roles in super-resolution microscopy and optogenetics. The light-driven structural changes that modulate the fluorescence involve both trans-to-cis isomerization and proton transfer. The mechanism, timescale and relative contribution of chromophore and protein dynamics are currently not well understood. Here, the mechanism of off-to-on-state switching in dronpa is studied using femtosecond-to-millisecond time-resolved infrared spectroscopy and isotope labelling. Chromophore and protein dynamics are shown to occur on multiple timescales, from picoseconds to hundreds of microseconds. Following excitation of the trans chromophore, a ground-state primary product is formed within picoseconds. Surprisingly, the characteristic vibrational spectrum of the neutral cis isomer appears only after several tens of nanoseconds. Further fluctuations in protein structure around the neutral cis chromophore are required to form a new intermediate, which promotes the final proton-transfer reaction. These data illustrate the interplay between chromophore dynamics and the protein environment underlying fluorescent protein photochromism

A review of research into business coaching supervision

A systematic search of the coaching literature for original peer-reviewed studies into business coaching supervision yielded seven research reports. Evaluation of these studies showed them to be low in the reporting of methodological rigour. However, as an emerging area of research with great importance for the development of the profession of business coaching these studies provide valuable insights into the functions of supervision and its benefits. Gaps in knowledge and directions for future research are identified. There is a need for future research to be more rigorous in its reporting of methods and analytic procedures, small scale qualitative research that can provide insight into the issues and challenges of coaching supervision in specific contexts, and large scale quantitative research which can provide broader and generalizable understandings into the uses and benefits of supervision

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Replication timing maintains the global epigenetic state in human cells

ACKNOWLEDGMENTS We thank R. Didier and B. Alexander of the FSU Flow Cytometry and Confocal Microscopy Facilities for their help with flow cytometry and fluorescence-activated cell sorting for this project. Thanks to A. Brown of the FSU Biological Science Core Labs and to Y. Yang and C. Vied of the FSU Translational Labs. Thanks to S. R. Westermann of SCIGRAPHIX for generating the model figure. Thanks to B. van Steensel, J. Phillips-Cremins, and P. Fraser for critical reading of the manuscript. Funding: This work was supported by NIH grant GM083337 to D.M.G., GM035463 to V.G.C., and GM085354 to D.M.G., S.D., and V.G.C. D.L. is supported by the Hong Kong Research Grant Council (ECS 26104216). T.B. is supported by the William C. and Joyce C. O’Neil Charitable Trust, Memorial Sloan Kettering Single Cell Sequencing InitiativePeer reviewedPostprin

Separation of DNA Replication from the Assembly of Break-Competent Meiotic Chromosomes

The meiotic cell division reduces the chromosome number from diploid to haploid to form gametes for sexual reproduction. Although much progress has been made in understanding meiotic recombination and the two meiotic divisions, the processes leading up to recombination, including the prolonged pre-meiotic S phase (meiS) and the assembly of meiotic chromosome axes, remain poorly defined. We have used genome-wide approaches in Saccharomyces cerevisiae to measure the kinetics of pre-meiotic DNA replication and to investigate the interdependencies between replication and axis formation. We found that replication initiation was delayed for a large number of origins in meiS compared to mitosis and that meiotic cells were far more sensitive to replication inhibition, most likely due to the starvation conditions required for meiotic induction. Moreover, replication initiation was delayed even in the absence of chromosome axes, indicating replication timing is independent of the process of axis assembly. Finally, we found that cells were able to install axis components and initiate recombination on unreplicated DNA. Thus, although pre-meiotic DNA replication and meiotic chromosome axis formation occur concurrently, they are not strictly coupled. The functional separation of these processes reveals a modular method of building meiotic chromosomes and predicts that any crosstalk between these modules must occur through superimposed regulatory mechanisms

Synthesis and in vitro and in vivo characterization of highly β1-Selective β-Adrenoceptor partial agonists

β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-selective molecules exist. To address this clinical need, we re-evaluated LK 204-545 (1),1 a selective β1-adrenoceptor antagonist, and discovered it possessed significant partial agonism. Removal of 1’s aromatic nitrile afforded 19, a ligand with similar β1-adrenoceptor selectivity and partial agonism (log KD of −7.75 and −5.15 as an antagonist of functional β1- and β2-mediated responses, respectively, and 34% of the maximal response of isoprenaline (β1)). In vitro β-adrenoceptor selectivity and partial agonism of 19 were mirrored in vivo. We designed analogues of 19 to improve affinity, selectivity, and partial agonism. Although partial agonism could not be fully attenuated, SAR suggests that an extended alkoxyalkoxy side chain, alongside substituents at the meta- or para-positions of the phenylurea, increases ligand affinity and β1- selectivity

Curation of complex, context-dependent immunological data

BACKGROUND: The Immune Epitope Database and Analysis Resource (IEDB) is dedicated to capturing, housing and analyzing complex immune epitope related data . DESCRIPTION: To identify and extract relevant data from the scientific literature in an efficient and accurate manner, novel processes were developed for manual and semi-automated annotation. CONCLUSION: Formalized curation strategies enable the processing of a large volume of context-dependent data, which are now available to the scientific community in an accessible and transparent format. The experiences described herein are applicable to other databases housing complex biological data and requiring a high level of curation expertise

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy