A Tobacco Homolog of DCN1 is Involved in Cellular Reprogramming and in Developmental Transitions

Plant proteomes show remarkable plasticity in reaction to environmental challenges and during developmental transitions. Some of this adaptability comes from ubiquitin-mediated protein destruction regulated by cullin-RING E3 ubiquitin ligases (CRLs). CRLs are activated through modification of the cullin subunit with the ubiquitin-like protein RUB/NEDD8 by an E3 ligase called defective in cullin neddylation 1 (DCN1). Here we show that tobacco DCN1 binds ubiquitin and RUB/NEDD8, and associates with cullin. When knocked down by RNAi, tobacco pollen formation stopped and zygotic embryogenesis was blocked around the globular stage. Additionally, we found that RNAi of DCN1 inhibited the stress-triggered reprogramming of cultured microspores from their intrinsic gametophytic mode of development to an embryogenic state. This stress-induced developmental switch is a known feature in many important crops and leads ultimately to the formation of haploid embryos and plants. Compensating the RNAi effect by re-transformation with a promoter-silencing construct restored pollen development and zygotic embryogenesis, as well as the ability for stress-induced formation of embryogenic microspores. Overexpression of DCN1, however, accelerated pollen tube growth and increased the potential for microspore reprogramming. These results demonstrate that the biochemical function of DCN1 is conserved in plants and that its activity is specifically required for transitions during pollen development and embryogenesis, and for pollen tube tip growth

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

Enhanced Platelet-activating Factor synthesis facilitates acute and delayed effects of ethanol intoxicated thermal burn injury

Thermal burn injuries in patients alcohol intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator Platelet-activating factor (PAF) in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic PAF generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury, were suppressed in mice lacking PAF receptors. Together, these studies provide a potential mechanism and novel treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator PAF

FSP1 is a glutathione-independent ferroptosis suppressor

Ferroptosis is an iron-dependent form of necrotic cell death marked by oxidative damage to phospholipids1,2. To date, ferroptosis has been believed to be controlled only by the phospholipid hydroperoxide-reducing enzyme glutathione peroxidase 4 (GPX4)3,4 and radical-trapping antioxidants5,6. However, elucidation of the factors that underlie the sensitivity of a given cell type to ferroptosis7 is critical to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatment of cancer. Although metabolic constraints8 and phospholipid composition9,10 contribute to ferroptosis sensitivity, no cell-autonomous mechanisms have been identified that account for the resistance of cells to ferroptosis. Here we used an expression cloning approach to identify genes in human cancer cells that are able to complement the loss of GPX4. We found that the flavoprotein apoptosis-inducing factor mitochondria-associated 2 (AIFM2) is a previously unrecognized anti-ferroptotic gene. AIFM2, which we renamed ferroptosis suppressor protein 1 (FSP1) and which was initially described as a pro-apoptotic gene11, confers protection against ferroptosis elicited by GPX4 deletion. We further demonstrate that the suppression of ferroptosis by FSP1 is mediated by ubiquinone (also known as coenzyme Q10 (CoQ10)): the reduced form, ubiquinol, traps lipid peroxyl radicals that mediate lipid peroxidation, whereas FSP1 catalyses the regeneration of CoQ10 using NAD(P)H. Pharmacological targeting of FSP1 strongly synergizes with GPX4 inhibitors to trigger ferroptosis in a number of cancer entities. In conclusion, the FSP1–CoQ10–NAD(P)H pathway exists as a stand-alone parallel system, which co-operates with GPX4 and glutathione to suppress phospholipid peroxidation and ferroptosis

Attributions of responsibility for addiction: the effects of gender and type of substance.

In 1997, 248 urban university students in central Massachusetts rated responsibility for addiction using the Attributions of Responsibility for Addiction Scale (ARAS), developed for this study with university-based financial support. The vignette-based factorial design varied sex of drug user and type of addictive substance. Factor analysis yielded two subscales: internal and external responsibility attributions; the dependent variable was the internal-to-external attribution ratio. Analysis of variance indicated main effects for substance type and drug abuse experience and showed interaction effects for participant\u27s sex by user\u27s sex and user\u27s sex by substance type. Authors discuss implications, study limitations, and future research

Emergency department utilization among recently released prisoners: a retrospective cohort study.

BACKGROUND: The population of ex-prisoners returning to their communities is large. Morbidity and mortality is increased during the period following release. Understanding utilization of emergency services by this population may inform interventions to reduce adverse outcomes. We examined Emergency Department utilization among a cohort of recently released prisoners. METHODS: We linked Rhode Island Department of Corrections records with electronic health record data from a large hospital system from 2007 to 2009 to analyze emergency department utilization for mental health disorders, substance use disorders and ambulatory care sensitive conditions by ex-prisoners in the year after release from prison in comparison to the general population, controlling for patient- and community-level factors. RESULTS: There were 333,369 total ED visits with 5,145 visits by a cohort of 1,434 ex-prisoners. In this group, 455 ex-prisoners had 3 or more visits within 1 year of release and 354 had a first ED visit within 1 month of release. ED visits by ex-prisoners were more likely to be made by men (85% vs. 48%, p \u3c 0.001) and by blacks (26% vs. 16%, p \u3c 0.001) compared to the Rhode Island general population. Ex-prisoners were more likely to have an ED visit for a mental health disorder (6% vs. 4%, p \u3c 0.001) or substance use disorder (16%vs. 4%, p \u3c 0.001). After controlling for patient- and community-level factors, ex-prisoner visits were significantly more likely to be for mental health disorders (OR 1.43; 95% CI 1.27-1.61), substance use disorders (OR 1.93; 95% CI 1.77-2.11) and ambulatory care sensitive conditions (OR 1.09; 95% CI 1.00-1.18). CONCLUSIONS: ED visits by ex-prisoners were significantly more likely due to three conditions optimally managed in outpatient settings. Future work should determine whether greater access to outpatient services after release from prison reduces ex-prisoners\u27 utilization of emergency services

Three brief alcohol screens for detecting hazardous drinking in incarcerated women.

OBJECTIVE: Screening methods for hazardous drinking have not been evaluated in a population of incarcerated women. This study examines abbreviated versions of the Alcohol Use Disorders Identification Test (AUDIT) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) heavy episodic drinking criterion in a sample of female detainees. METHOD: A total of 2,079 women at the Adult Correctional Institute in Rhode Island were approached for screening between February 2004 and June 2007. The AUDIT-consumption (AUDIT-C), AUDIT-3, and the NIAAA heavy episodic drinking criterion (four or more drinks on one occasion for women) were compared with the full AUDIT at different cut points. RESULTS: More than 55% of the sample endorsed an AUDIT score of 4 or greater--the NIAAA recommended threshold for detecting hazardous drinking. The three-item AUDIT-C with a cut score of 3 yielded a classification most consistent with the AUDIT score of 4 or more; sensitivity and specificity exceeded .9, and 91.5% of participants were correctly classified. The AUDIT-3 and NIAAA episodic drinking criteria were less sensitive measures. We found no evidence of interactions between the screening instruments and age or ethnicity. CONCLUSIONS: The three-item AUDIT-C has robust test characteristics for detecting hazardous drinking in female inmates. Universal screening for hazardous drinking is recommended for incarcerated women, given their high rates of alcohol misuse