A Sense of Duty: Retiring the Special Relationship Rule and Holding Gun Manufacturers Liable for Negligently Distributing Guns

In response to recent litigation brought against the gun industry on behalf of individuals and municipalities victimized as a result of the negligent marketing, design, and distribution of guns, the gun industry has argued that they cannot be held responsible for the victims\u27 injuries because they have no special relationship with the victims. Without a special relationship, gun manufacturers claim to have no duty whatsoever to design, market, or distribute guns in a reasonable fashion. This article examines the fallacies inherent in the gun industry\u27s special relationship argument and discusses the factual, legal and policy grounds that support holding the gun industry responsible for its role in facilitating the misuse of guns

Cellular eIF2B subunit localisation: implications for the integrated stress response and its control by small molecule drugs

eIF2 is a G protein critical for translation. It is tightly regulated in the integrated stress response (ISR) via phosphorylation of eIF2α and the subsequent control of eIF2B, a multisubunit guanine nucleotide exchange factor (GEF). Through studying the localisation of eIF2B subunits we identified cytoplasmic eIF2B bodies in mammalian cells. We highlight a relationship between body size and the eIF2B subunits localising to them; larger bodies contain all subunits and smaller bodies contain predominantly catalytic subunits. eIF2 localises to eIF2B bodies and shuttles within these bodies in a manner which correlates with eIF2B activity. Upon stress eIF2α-P localises predominately to larger bodies and results in a decreased shuttling of eIF2. Interestingly drugs which inhibit the ISR can rescue eIF2 shuttling in a manner correlating to levels of eIF2α-P. In contrast, smaller bodies show increased eIF2 shuttling in response to stress, which is accompanied by the localisation of eIF2Bδ to these bodies, suggesting the formation of a novel trimeric complex of eIF2B. This response is mimicked by ISR inhibiting drugs, providing insight into their potential mechanism of action. This study provides evidence that the composition and function of mammalian eIF2B bodies is regulated by the ISR and drugs which control it

OncoLog Volume 50, Number 01, January 2005

New Perspectives on Brain Metastasis Out of the Darkroom Equity and Health House Call: Blood and Platelet Donors Give Life DiaLog: Cancer Pain Control in the New Millennium, by Allen W. Burton, MD, Section Chief, Cancer Pain Management Department of Anesthesiology and Pain Medicinehttps://openworks.mdanderson.org/oncolog/1142/thumbnail.jp

A rapid review examining purchasing changes resulting from fiscal measures targeted at high sugar food and non-alcoholic drinks

To aim of the review was to examine the most recent (2010 onwards) research evidence on the health and behavioural impacts, in adults and children, of fiscal strategies that target high sugar foods and sugar-sweetened drinks (SSDs). A pragmatic rapid review was undertaken using a systematic search strategy. The review was part of a programme of work to support policy development in relation to high sugar food and SSDs. A total of 11 primary research publications were included, describing evidence from France (n = 1), the Netherlands (n = 3), and the United States of America (n = 7), assessed through a variety of study designs, with the majority in adult populations (n = 10). The evidence reviewed focused on consumer behaviour outcomes and suggested that fiscal strategies can influence purchases of high sugar products. Although the majority of studies (n = 10), including three field studies, demonstrated that an increase in the price of high sugar foods and SSDs resulted in a decrease in purchases, eight studies were conducted in a laboratory or virtual setting which may not reflect real-life situations. Findings from this review support evidence from the broader literature that suggests that fiscal measures can be effective in influencing the purchasing of high sugar foods and SSDs

Pharmacy Staff Perspectives on Alcohol and Medication Interaction Prevention Among Older Rural Adults

Older adults are at high risk for alcohol and medication interactions (AMI). Pharmacies have the potential to act as ideal locations for AMI education, as pharmacy staff play an important role in the community. This study examined the perspectives of pharmacy staff on AMI prevention programming messaging, potential barriers to and facilitators of older adult participation in such programming, and dissemination methods for AMI prevention information. Flyers, telephone calls, and site visits were used to recruit 31 pharmacy staff members who participated in semistructured interviews. A content analysis of interview transcriptions was conducted to identify major themes, categories, and subcategories. The main categories identified for AMI prevention messaging were Informational, Health Significance, and Recommendations. Within barriers to participation, the main categories identified were Health Illiteracy, Personal Attitudes, and Feasibility. The main categories identified for program facilitators were Understanding, Beneficial Consequences, and Practicality. Multimethod dissemination strategies were commonly suggested. This study found positive pharmacy staff perspectives for the planning and implementation of AMI prevention programming, and future development and feasibility testing of such programming in the pharmacy setting is warranted

Pharmacy Staff Perspectives on Alcohol and Medication Interaction Prevention Among Older Rural Adults

Older adults are at high risk for alcohol and medication interactions (AMI). Pharmacies have the potential to act as ideal locations for AMI education, as pharmacy staff play an important role in the community. This study examined the perspectives of pharmacy staff on AMI prevention programming messaging, potential barriers to and facilitators of older adult participation in such programming, and dissemination methods for AMI prevention information. Flyers, telephone calls, and site visits were used to recruit 31 pharmacy staff members who participated in semistructured interviews. A content analysis of interview transcriptions was conducted to identify major themes, categories, and subcategories. The main categories identified for AMI prevention messaging were Informational, Health Significance, and Recommendations. Within barriers to participation, the main categories identified were Health Illiteracy, Personal Attitudes, and Feasibility. The main categories identified for program facilitators were Understanding, Beneficial Consequences, and Practicality. Multimethod dissemination strategies were commonly suggested. This study found positive pharmacy staff perspectives for the planning and implementation of AMI prevention programming, and future development and feasibility testing of such programming in the pharmacy setting is warranted

Modelling Immunological Systems using PEPA: a preliminary report

We present preliminary work on modelling aspects of the immune system using process algebra. The problem addressed is how T-helper cell populations respond to co-infections with parasites making conflicting immunological demands. Our goal is to build PEPA models of alternative hypotheses around T-helper cell behaviour and to evaluate those with respect to experimental data

A Link between Dimerization and Autophosphorylation of the Response Regulator PhoB

Response regulator proteins within two-component signal transduction systems are activated by phosphorylation and can catalyze their own covalent phosphorylation using small molecule phosphodonors. To date, comprehensive kinetic characterization of response regulator autophosphorylation is limited to CheY, which follows a simple model of phosphodonor binding followed by phosphorylation. We characterized autophosphorylation of the response regulator PhoB, known to dimerize upon phosphorylation. In contrast to CheY, PhoB time traces exhibited an initial lag phase and gave apparent pseudo-first order rate constants that increased with protein concentration. Furthermore, plots of the apparent autophosphorylation rate constant versus phosphodonor concentration were sigmoidal, as were PhoB binding isotherms for the phosphoryl group analog BeF3−. Successful mathematical modeling of the kinetic data necessitated inclusion of the formation of a PhoB heterodimer (one phosphorylated and one unphosphorylated monomer) with an enhanced rate of phosphorylation. Specifically, dimerization constants for the PhoB heterodimer and homodimer (two phosphorylated monomers) were similar, but the rate constant for heterodimer phosphorylation was ∼10-fold higher than for the monomer. In a test of the model, disruption of the known PhoBN dimerization interface by mutation led to markedly slower and noncooperative autophosphorylation kinetics. Furthermore, phosphotransfer from the sensor kinase PhoR was enhanced by dimer formation. Phosphorylation-mediated dimerization allows many response regulators to bind to tandem DNA-binding sites and regulate transcription. Our data challenge the notion that response regulator dimers primarily form between two phosphorylated monomers and raise the possibility that response regulator heterodimers containing one phosphoryl group may participate in gene regulation

Designer diatom episomes delivered by bacterial conjugation.

Eukaryotic microalgae hold great promise for the bioproduction of fuels and higher value chemicals. However, compared with model genetic organisms such as Escherichia coli and Saccharomyces cerevisiae, characterization of the complex biology and biochemistry of algae and strain improvement has been hampered by the inefficient genetic tools. To date, many algal species are transformable only via particle bombardment, and the introduced DNA is integrated randomly into the nuclear genome. Here we describe the first nuclear episomal vector for diatoms and a plasmid delivery method via conjugation from Escherichia coli to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. We identify a yeast-derived sequence that enables stable episome replication in these diatoms even in the absence of antibiotic selection and show that episomes are maintained as closed circles at copy number equivalent to native chromosomes. This highly efficient genetic system facilitates high-throughput functional characterization of algal genes and accelerates molecular phytoplankton research