Synaptotagmin-1 membrane binding is driven by the C2B domain and assisted cooperatively by the C2A domain

Synaptotagmin interaction with anionic lipid (phosphatidylserine/phosphatidylinositol) containing membranes, both in the absence and presence of calcium ions (Ca2+), is critical to its central role in orchestrating neurotransmitter release. The molecular surfaces involved, namely the conserved polylysine motif in the C2B domain and Ca2+-binding aliphatic loops on both C2A and C2B domains, are known. Here we use surface force apparatus combined with systematic mutational analysis of the functional surfaces to directly measure Syt1-membrane interaction and fully map the site-binding energetics of Syt1 both in the absence and presence of Ca2+. By correlating energetics data with the molecular rearrangements measured during confinement, we find that both C2 domains cooperate in membrane binding, with the C2B domain functioning as the main energetic driver, and the C2A domain acting as a facilitator.Fil: Gruget, Clémence. Ecole Normale Supérieure; FranciaFil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Coleman, Jeff. University of Yale. School of Medicine; Estados UnidosFil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados UnidosFil: Perez, Eric. Ecole Normale Supérieure; FranciaFil: Rothman, James E.. University of Yale. School of Medicine; Estados UnidosFil: Pincet, Frederic. Ecole Normale Supérieure; Francia. University of Yale. School of Medicine; Estados UnidosFil: Donaldson, Stephen H.. Ecole Normale Supérieure; Franci

Framework for E‐Learning Assessment in Dental Education: A Global Model for the Future

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153544/1/jddj002203372013775tb05504x.pd

Stakeholder Theory and Marketing: Moving from a Firm-Centric to a Societal Perspective

This essay is inspired by the ideas and research examined in the special section on “Stakeholder Marketing” of the Journal of Public Policy & Marketing in 2010. The authors argue that stakeholder marketing is slowly coalescing with the broader thinking that has occurred in the stakeholder management and ethics literature streams during the past quarter century. However, the predominant view of stakeholders that many marketers advocate is still primarily pragmatic and company centric. The position advanced herein is that stronger forms of stakeholder marketing that reflect more normative, macro/societal, and network-focused orientations are necessary. The authors briefly explain and justify these characteristics in the context of the growing “prosociety” and “proenvironment” perspectives—orientations that are also in keeping with the public policy focus of this journal. Under the “hard form” of stakeholder theory, which the authors endorse, marketing managers must realize that serving stakeholders sometimes requires sacrificing maximum profits to mitigate outcomes that would inflict major damage on other stakeholders, especially society

Leadership in Compassionate Care: Final Report 2012

This report reflects the initiation, planning, running and the important outcomes emerging from the Leadership in Compassionate Care Programme. The team worked in close partnership across the School of Nursing, Midwifery and Social Care, Edinburgh Napier University and NHS Lothian. This report also shares the highlights, challenges and solutions to embed compassionate care education and nursing practice.Additional co-authors: Fiona Smith, Stephen DM Smith, Ria Tocher, and Anne Waug

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

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

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