Investigating nucleo-cytoplasmic shuttling of the human DEAD-box helicase DDX3.

The human DEAD-box helicase DDX3 is a multi-functional protein involved in the regulation of gene expression and additional non-conventional roles as signalling adaptor molecule that are independent of its enzymatic RNA remodeling activity. It is a nucleo-cytoplasmic shuttling protein and it has previously been suggested that dysregulation of its subcellular localization could contribute to tumourigenesis. Indeed, both tumour suppressor and oncogenic functions have been attributed to DDX3. In this study, we investigated the regulation of DDX3's nucleocytoplasmic shuttling. We confirmed that an N-terminal conserved Nuclear Export Signal (NES) is required for export of human DDX3 from the nucleus, and identified three regions within DDX3 that can independently facilitate its nuclear import. We also aimed to identify conditions that alter DDX3's subcellular localisation. Viral infection, cytokine treatment and DNA damage only induced minor changes in DDX3's subcellular distribution as determined by High Content Analysis. However, DDX3's nuclear localization increased in early mitotic cells (during prophase) concomitant with an increase in DDX3 expression levels. Our results are likely to have implications for the proposed use of (nuclear) DDX3 as a prognostic biomarker in cancer.

Marine litter from beach-based sources: Case study of an Eastern Mediterranean coastal town.

Marine litter has been a serious and growing problem for some decades now. Yet, there is still much speculation among researchers, policy makers and planners about how to tackle marine litter from land-based sources. This paper provides insights into approaches for managing marine litter by reporting and analyzing survey results of litter dispersal and makeup from three areas along an Arab-Israeli coastal town in view of other recent studies conducted around the Mediterranean Sea. Based on our results and analysis, we posit that bathing beach activities should be a high priority for waste managers as a point of intervention and beach-goers must be encouraged to take a more active role in keeping beaches clean. Further, plastic fragments on the beach should be targeted as a first priority for prevention (and cleanup) of marine litter with plastic bottle caps being a high priority to be targeted among plastics. More survey research is needed on non-plastic litter composition for which amounts and geographic dispersal in the region vary greatly from place to place along Mediterranean shores. In general, findings of this study lead us to recommend exploring persuasive beach trash can design coupled with greater enforcement for short term waste management intervention while considering the local socio-economic and institutional context further for long-term efforts.

Situating Arab-Israeli artisanal fishermen's perceptions of marine litter in a socio-institutional and socio-cultural context.

Understanding the mental constructs underlying people's social responses, decisions and behaviors is crucial to defining the governance challenges faced in dealing with marine anthropogenic litter. Using interactive governance theory, this study provides qualitative insights into how a small group of Arab-Israeli artisanal fishermen perceive marine litter and its impact (system to be governed) in the context of the socio-institutional structures (governing system) which manage waste and aim to protect the surrounding environment. It demonstrates that, until the relationships between local people and the various governing institutions are transformed, there is little hope for citizen cooperation in reducing marine litter long-term in the case-study site. More generally, underlying narratives and politics playing out at a local level need to be understood in order to identify which interventions are likely to be effective and which are not. An intervention checklist to assess the potential effectiveness of a marine litter intervention is proposed.

The 'yips' in golf: a continuum between a focal dystonia and choking.

The definition of the 'yips' has evolved over time. It is defined as a motor phenomenon of involuntary movements affecting golfers. In this paper, we have extended the definition to encompass a continuum from the neurologic disorder of dystonia to the psychologic disorder of choking. In many golfers, the pathophysiology of the 'yips' is believed to be an acquired deterioration in the function of motor pathways (e.g. those involving the basal ganglia) which are exacerbated when a threshold of high stress and physiologic arousal is exceeded. In other golfers, the 'yips' seems to result from severe performance anxiety. Physically, the 'yips' is manifested by symptoms of jerks, tremors or freezing in the hands and forearms. These symptoms can result in: (i) a poor quality of golf performance (adds 4.9 strokes per 18 holes); (ii) prompt use of alcohol and beta-blockers; and (iii) contribute to attrition in golf. Golfers with the 'yips' average 75 rounds per year, although many 'yips'-affected golfers decrease their playing time or quit to avoid exposure to this embarrassing problem. While more investigation is needed to determine the cause of the 'yips', this review article summarises and organises the available research. A small study included in this paper describes the 'yips' phenomenon from the subjective experience of 'yips'-affected golfers. The subjective experience (n = 72) provides preliminary support for the hypothesis suggesting that the 'yips' is on a continuum. Based on the subjective definitions of 72 'yips'-affected golfers, the 'yips' was differentiated into type I (dystonia) and type II (choking). A theoretical model provides a guide for future research on golfers with either type I or type II 'yips'.

Human DEAD box helicase 3 couples IκB kinase ε to interferon regulatory factor 3 activation.

The human DEAD box protein 3 (DDX3) has been implicated in different processes contributing to gene expression. Interestingly, DDX3 is required as an essential host factor for the replication of HIV and hepatitis C virus (HCV) and is therefore considered a potential drug target. On the other hand, DDX3 interacts with IκB kinase ε (IKKε) and TANK-binding kinase 1 (TBK1) and contributes to the induction of antiviral type I interferons (IFNs). However, the molecular mechanism by which DDX3 contributes to IFN induction remains unclear. Here we show that DDX3 mediates phosphorylation of interferon regulatory factor 3 (IRF3) by the kinase IKKε. DDX3 directly interacts with IKKε and enhances its autophosphorylation and activation. IKKε then phosphorylates several serine residues in the N terminus of DDX3. Phosphorylation of DDX3 at serine 102 (S102) is required for recruitment of IRF3 to DDX3, facilitating its phosphorylation by IKKε. Mutation of S102 to alanine disrupted the interaction between DDX3 and IRF3 but not that between DDX3 and IKKε. The S102A mutation failed to enhance ifnb promoter activation, suggesting that the DDX3-IRF3 interaction is crucial for this effect. Our data implicates DDX3 as a scaffolding adaptor that directly facilitates phosphorylation of IRF3 by IKKε. DDX3 might thus be involved in pathway-specific activation of IRF3.