Calmodulin and PI(3,4,5)P3 cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production

Precise regulation of the kinetics and magnitude of Ca2+ signaling enables this signal to mediate diverse responses, such as cell migration, differentiation, vesicular trafficking, and cell death. Here, we showed that the Ca2+-binding protein calmodulin (CaM) acted in a positive feedback loop to potentiate Ca2+ signaling downstream of the Tec kinase family member Itk. Using NMR (nuclear magnetic resonance), we mapped CaM binding to two loops adjacent to the lipid-binding pocket within the Itk pleckstrin homology (PH) domain. The Itk PH domain bound synergistically to Ca2+/CaM and the lipid phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3], such that binding to Ca2+/CaM enhanced the binding to PI(3,4,5)P3 and vice versa. Disruption of CaM binding attenuated Itk recruitment to the membrane and diminished release of Ca2+ from the endoplasmic reticulum. Moreover, disruption of this feedback loop abrogated Itk-dependent production of the proinflammatory cytokine IL-17A (interleukin-17A) by CD4+ T cells. Additionally, we found that CaM associated with PH domains from other proteins, indicating that CaM may regulate other PH domain–containing proteins

Communication and marketing as tools to cultivate the public's health: a proposed "people and places" framework

<p>Abstract</p> <p>Background</p> <p>Communication and marketing are rapidly becoming recognized as core functions, or core competencies, in the field of public health. Although these disciplines have fostered considerable academic inquiry, a coherent sense of precisely how these disciplines can inform the practice of public health has been slower to emerge.</p> <p>Discussion</p> <p>In this article we propose a framework – based on contemporary ecological models of health – to explain how communication and marketing can be used to advance public health objectives. The framework identifies the attributes of people (as individuals, as social networks, and as communities or populations) and places that influence health behaviors and health. Communication, i.e., the provision of information, can be used in a variety of ways to foster beneficial change among both people (e.g., activating social support for smoking cessation among peers) and places (e.g., convincing city officials to ban smoking in public venues). Similarly, marketing, i.e., the development, distribution and promotion of products and services, can be used to foster beneficial change among both people (e.g., by making nicotine replacement therapy more accessible and affordable) and places (e.g., by providing city officials with model anti-tobacco legislation that can be adapted for use in their jurisdiction).</p> <p>Summary</p> <p>Public health agencies that use their communication and marketing resources effectively to support people in making healthful decisions and to foster health-promoting environments have considerable opportunity to advance the public's health, even within the constraints of their current resource base.</p

Crime script analysis for adult image-based sexual abuse: a study of crime intervention points for retribution-style offenders

ObjectiveThis research uses crime scripts to understand adult retribution-style image-based sexual abuse (RS-IBSA) offender decision-making and offending in offline and online environments. We explain the crime-commission process of adult RS-IBSA and identify crime intervention points at eight crime script stages.MethodsPublicly released court transcripts of adult RS-IBSA prosecution cases (n = 18) in New Zealand from 2015 to 2018 were utilised to examine the crime-commission process of adult RS-IBSA. We analysed the court transcripts thematically at offence-level prior to constructing the crime scripts.FindingsThe study identified four types of adult RS-IBSA acts including the non-consensual dissemination of a victim’s intimate images, violent cyber sextortion, covert intimate photography, and unauthorised access of a victim’s phone/media. From our analysis, we identified three script tracks and constructed three distinct crime scripts: (1) threats, sextortion and dissemination; (2) unauthorised access of a victim’s mobile device and dissemination; and (3) covert intimate filming. We highlight areas for potential intervention for law enforcement agencies and policy makers to increase deterrence and personal security in online and offline spaces.ConclusionAdult RS-IBSA occurs in a range of dating and domestic contexts. This study develops crime scripts for adult RS-IBSA and advances our understanding of how the Internet/smartphones/digital media translates into virtual crime scenes with opportunities for maximum harm infliction. We offer several policy implications including revising current RS-IBSA legislation and supporting law enforcement agencies with policing online and offline intimate relationship spaces through situational prevention

Calmodulin and PI(3,4,5)P3 cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production

Precise regulation of the kinetics and magnitude of Ca2+ signaling enables this signal to mediate diverse responses, such as cell migration, differentiation, vesicular trafficking, and cell death. Here, we showed that the Ca2+-binding protein calmodulin (CaM) acted in a positive feedback loop to potentiate Ca2+ signaling downstream of the Tec kinase family member Itk. Using NMR (nuclear magnetic resonance), we mapped CaM binding to two loops adjacent to the lipid-binding pocket within the Itk pleckstrin homology (PH) domain. The Itk PH domain bound synergistically to Ca2+/CaM and the lipid phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3], such that binding to Ca2+/CaM enhanced the binding to PI(3,4,5)P3 and vice versa. Disruption of CaM binding attenuated Itk recruitment to the membrane and diminished release of Ca2+ from the endoplasmic reticulum. Moreover, disruption of this feedback loop abrogated Itk-dependent production of the proinflammatory cytokine IL-17A (interleukin-17A) by CD4+ T cells. Additionally, we found that CaM associated with PH domains from other proteins, indicating that CaM may regulate other PH domain–containing proteins.This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Signaling on vol. 7 (2014), DOI: 10.1126/scisignal.2005147. </p