Biodegradative mechanism of the brown rot basidiomycete Gloeophyllum trabeum: evidence for an extracellular hydroquinone-driven fenton reaction

AbstractWe have identified key components of the extracellular oxidative system that the brown rot fungus Gloeophyllum trabeum uses to degrade a recalcitrant polymer, polyethylene glycol, via hydrogen abstraction reactions. G. trabeum produced an extracellular metabolite, 2,5-dimethoxy-1,4-benzoquinone, and reduced it to 2,5-dimethoxyhydroquinone. In the presence of 2,5-dimethoxy-1,4-benzoquinone, the fungus also reduced extracellular Fe3+ to Fe2+ and produced extracellular H2O2. Fe3+ reduction and H2O2 formation both resulted from a direct, non-enzymatic reaction between 2,5-dimethoxyhydroquinone and Fe3+. polyethylene glycol depolymerization by G. trabeum required both 2,5-dimethoxy-1,4-benzoquinone and Fe3+ and was completely inhibited by catalase. These results provide evidence that G. trabeum uses a hydroquinone-driven Fenton reaction to cleave polyethylene glycol. We propose that similar reactions account for the ability of G. trabeum to attack lignocellulose

Nicotine replacement therapy for agitation and delirium management in the intensive care unit: a systematic review of the literature.

BACKGROUND: Active smokers are prevalent within the intensive care setting and place a significant burden on healthcare systems. Nicotine withdrawal due to forced abstinence on admission may contribute to increased agitation and delirium in this patient group. The aim of this systematic review was to determine whether management of nicotine withdrawal, with nicotine replacement therapy (NRT), reduces agitation and delirium in critically ill patients admitted to the intensive care unit (ICU). METHODS: The following sources were used in this review: MEDLINE, EMBASE, and CINAHL Plus databases. Included studies reported delirium or agitation outcomes in current smokers, where NRT was used as management of nicotine withdrawal, in the intensive care setting. Studies were included regardless of design or number of participants. Data were extracted on ICU classification; study design; population baseline characteristics; allocation and dose of NRT; agitation and delirium assessment methods; and the frequency of agitation, delirium, and psychotropic medication use. RESULTS: Six studies were included. NRT was mostly prescribed for smokers with heavier smoking histories. Three studies reported an association between increased agitation or delirium and NRT use; one study could not find any significant benefit or harm from NRT use; and two described a reduction of symptomatic nicotine withdrawal. A lack of consistent and validated assessment measures, combined with limitations in the quality of reported data, contribute to conflicting results. CONCLUSIONS: Current evidence for the use of NRT in agitation and delirium management in the ICU is inconclusive. An evaluation of risk versus benefit on an individual patient basis should be considered when prescribing NRT. Further studies that consider prognostic balance, adjust for confounders, and employ validated assessment tools are urgently needed

Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca2+ Homeostasis

Triadin (Tdn) and Junctin (Jct) are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum (jSR). However, the specific contribution of each protein to the jSR architecture and to excitation-contraction (e-c) coupling has not been fully established. Here, using mouse models lacking either Tdn (Tdn-null), Jct (Jct-null) or both (Tdn/Jct-null), we identify Tdn as the main component of periodically located anchors connecting CASQ to the RyR-bearing jSR membrane. Both proteins proved to be important for the structural organization of jSR cisternae and retention of CASQ within them, but with different degrees of impact. Our results also suggest that the presence of CASQ is responsible for the wide lumen of the jSR cisternae. Using Ca2+ imaging and Ca2+ selective microelectrodes we found that changes in e-c coupling, SR Ca2+content and resting [Ca2+] in Jct, Tdn and Tdn/Jct-null muscles are directly correlated to the effect of each deletion on CASQ content and its organization within the jSR. These data suggest that in skeletal muscle the disruption of Tdn/CASQ link has a more profound effect on jSR architecture and myoplasmic Ca2+ regulation than Jct/CASQ association

Perspective-Taking and Willingness to Engage in Intergroup Contact

The current research explored whether perspective-taking increases willingness to engage in contact with stereotyped outgroup members. Across three studies, we find that perspective-taking increases willingness to engage in contact with negatively-stereotyped targets. In Study 1, perspective-takers sat closer to, whereas stereotype suppressors sat further from, a hooligan compared to control participants. In Study 2, individual differences in perspective-taking tendencies predicted individuals' willingness to engage in contact with a hooligan, having effects above and beyond those of empathic concern. Finally, Study 3 demonstrated that perspective-taking's effects on intergroup contact extend to the target's group (i.e., another homeless man), but not to other outgroups (i.e., a man of African descent). Consistent with other perspective-taking research, our findings show that perspective-taking facilitates the creation of social bonds by increasing contact with stereotyped outgroup members

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference