Multi-omic Analyses of Extensively Decayed Pinus contorta Reveal Expression of a Diverse Array of Lignocellulose-Degrading Enzymes.

Fungi play a key role cycling nutrients in forest ecosystems, but the mechanisms remain uncertain. To clarify the enzymatic processes involved in wood decomposition, the metatranscriptomics and metaproteomics of extensively decayed lodgepole pine were examined by RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. Following de novo metatranscriptome assembly, 52,011 contigs were searched for functional domains and homology to database entries. Contigs similar to basidiomycete transcripts dominated, and many of these were most closely related to ligninolytic white rot fungi or cellulolytic brown rot fungi. A diverse array of carbohydrate-active enzymes (CAZymes) representing a total of 132 families or subfamilies were identified. Among these were 672 glycoside hydrolases, including highly expressed cellulases or hemicellulases. The CAZymes also included 162 predicted redox enzymes classified within auxiliary activity (AA) families. Eighteen of these were manganese peroxidases, which are key components of ligninolytic white rot fungi. The expression of other redox enzymes supported the working of hydroquinone reduction cycles capable of generating reactive hydroxyl radicals. These have been implicated as diffusible oxidants responsible for cellulose depolymerization by brown rot fungi. Thus, enzyme diversity and the coexistence of brown and white rot fungi suggest complex interactions of fungal species and degradative strategies during the decay of lodgepole pine.IMPORTANCE The deconstruction of recalcitrant woody substrates is a central component of carbon cycling and forest health. Laboratory investigations have contributed substantially toward understanding the mechanisms employed by model wood decay fungi, but few studies have examined the physiological processes in natural environments. Herein, we identify the functional genes present in field samples of extensively decayed lodgepole pine (Pinus contorta), a major species distributed throughout the North American Rocky Mountains. The classified transcripts and proteins revealed a diverse array of oxidative and hydrolytic enzymes involved in the degradation of lignocellulose. The evidence also strongly supports simultaneous attack by fungal species employing different enzymatic strategies

Hydromorphone for neuropathic pain in adults

BACKGROUND Opioid drugs, including hydromorphone, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for hydromorphone, at any dose, and by any route of administration. Other opioids are considered in separate reviews.This review is part of an update of a previous review, Hydromorphone for acute and chronic pain that was withdrawn in 2013 because it needed updating and splitting to be more specific for different pain conditions. This review focuses only on neuropathic pain. OBJECTIVES To assess the analgesic efficacy of hydromorphone for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), via the CRSO; MEDLINE via Ovid; and EMBASE via Ovid from inception to 17 November 2015, together with reference lists of retrieved papers and reviews, and two online study registries. SELECTION CRITERIA We included randomised, double-blind studies of two weeks' duration or longer, comparing hydromorphone (at any dose, by any route of administration, or in any formulation) with placebo or another active treatment in chronic neuropathic pain. DATA COLLECTION AND ANALYSIS Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS Searches identified seven publications relating to four studies. We excluded three studies. One post hoc (secondary) analysis of a study published in four reports assessed the efficacy of hydromorphone in neuropathic pain, satisfied our inclusion criteria, and was included in the review. The single included study had an enriched enrolment, randomised withdrawal design with 94 participants who were successfully switched from oral morphine to oral hydromorphone extended release (about 60% of those enrolled). These participants were then randomised to continuing hydromorphone for 12 weeks or tapering down the hydromorphone dose to placebo. The methodological quality of the study was generally good, but we judged the risk of bias for incomplete outcome data as unclear, and for study size as high.Since we identified only one study for inclusion, we were unable to carry out any analyses. The included study did not report any of our prespecified primary outcomes, which relate to the number of participants achieving moderate or substantial levels of pain relief. It did report a slightly larger increase in average pain intensity for placebo in the randomised withdrawal phase than for continuing with hydromorphone. It also reported the number of participants who withdrew due to lack of efficacy in the randomised withdrawal phase, which may be an indicator of efficacy. However, in addition to using an enriched enrolment, randomised withdrawal study design, there was an unusual choice of imputation methods for withdrawals (about 50% of participants); the evidence was of very low quality and inadequate to make a judgement on efficacy. Adverse events occurred in about half of participants with hydromorphone, the most common being constipation and nausea. A similar proportion of participants experienced adverse events with placebo, the most common being opioid withdrawal syndrome (very low quality evidence). Most adverse events were mild or moderate in intensity. One in eight participants withdrew while taking hydromorphone during the conversion and titration phase, despite participants being opioid-tolerant (very low quality evidence).We downgraded the quality of the evidence to very low because there was only one study with few participants, it did not report clinically useful efficacy outcomes, and it was a post hoc analysis. AUTHORS' CONCLUSIONS There was insufficient evidence to support or refute the suggestion that hydromorphone has any efficacy in any neuropathic pain condition

Pressed for Space: The Effects of Justification and the Printing Process on Fifteenth-Century Orthography

There is a long-held belief that, prior to the standardisation of written English, printers altered spellings to justify their type. I investigate this claim through an analysis of spelling changes in William Caxton’s two editions of the Canterbury Tales—by examining text within one book, written by one author, and set by one compositor, the only difference between the sections of verse and the sections of prose should be the requirement for justification within the latter. Were the compositors altering spellings to justify their type, we would expect to see a greater number of altered spellings in the prose sections of text. This is not what the results of this study show—instead there is no statistically significant difference between the frequency of spelling changes in justified and non-justified text. However, there is a significantly higher number of abbreviations introduced into the justified text. These results suggest that the compositor of Caxton’s second edition Canterbury Tales did not change spellings to justify his type

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Ophthalmic features of HIV associated cryptococcal meningitis in Malawian Adults: an observational study

Background: Cryptococcal meningitis (CM) is the commonest neurological complication in patients with advanced HIV. Visual disturbance is a frequent presenting symptom. Papilloedema is commonly reported but other ophthalmic findings are not well described. Methods: We performed an observational study comparing severely immunocompromised HIV-infected patients with and without CM to determine the nature and prevalence of retinal pathology attributable to CM. 70 adult patients were enrolled in Blantyre Malawi, 35 with CM and 35 HIV-infected patients without CM. Results: 79% (19/24) of CM patients examined on day one had evidence of retinal abnormalities compared to 17% (6/35) of HIV-infected controls (p <0.001). In the CM group, retinal whitening was the commonest abnormality (50%), followed by optic disc swelling (29%), haemorrhage (25%) and vascular abnormalities (7%). Retinal whitening was the only abnormality observed in the comparator group (17%). In CM, there was no significant difference between those with and without retinal abnormalities in fungal burden (13,550 cfu/ml vs. 9,150 cfu/ml; p = 0.65), CD4 count (28 cells/µl vs. 76 cells/µl; p = 0.79) or CSF opening pressure (21cm H20 vs. 27cm H20; p = 0.5).  There was no association between presence/absence of retinal abnormalities and death (40% 10-week mortality vs. 26%; p = 0.6). Conclusions: Whether the presence of CM retinopathy could be used as a marker of disease severity warrants further investigation. The observed ophthalmic findings provide a descriptive framework for CM retinopathy to be utilised in future CM studies. Trial registration: ISRCTN ( ISRCTN45035509 ) 19/06/2012

Qualitative Impact Assessment of Land Management Interventions on Ecosystem Services (“QEIA”). Report-1: Executive Summary: QEIA Evidence Review & Integrated Assessment

The focus of this project was to provide an expert-led, rapid qualitative assessment of land management interventions on Ecosystem Services (ES) proposed for inclusion in Environmental Land Management (ELM) schemes. This involved a review of the current evidence base for 741 land management actions on 33 Ecosystem Services and 53 Ecosystem Service indicators by ten teams involving 45 experts drawn from the independent research community in a consistent series of Evidence Reviews covering the broad topics of: • Air quality • Greenhouse gas emissions • Soils • Water management • Biodiversity: croplands • Biodiversity: improved grassland • Biodiversity: semi-natural habitats • Biodiversity: integrated systems-based actions • Carbon sequestration • Cultural services (including recreation, geodiversity and regulatory services). It should be noted that this piece of work is just one element of the wider underpinning work Defra has commissioned to support the development of the ELM schemes