RNA-binding proteins: modular design for efficient function

Many RNA-binding proteins have modular structures and are composed of multiple repeats of just a few basic domains that are arranged in various ways to satisfy their diverse functional requirements. Recent studies have investigated how different modules cooperate in regulating the RNA-binding specificity and the biological activity of these proteins. They have also investigated how multiple modules cooperate with enzymatic domains to regulate the catalytic activity of enzymes that act on RNA. These studies have shown how, for many RNA-binding proteins, multiple modules define the fundamental structural unit that is responsible for biological function.     

Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis

Mycophenolate mofetil (MMF) is an immunosuppressant drug being used for induction and maintenance of remission of lupus nephritis in systemic lupus erythematosus. Evidence about its use was sought from full publications and abstracts of randomised trials and cohort studies by using a variety of search strategies. Efficacy and adverse event outcomes were sought. Five randomised trials enrolled patients with World Health Organization (WHO) class III, IV, or V (mostly IV) lupus nephritis, predominantly comparing MMF (1 to 3 g daily) with cyclophosphamide and steroid. Complete response and complete or partial response was significantly more frequent with MMF than with cyclophosphamide, with numbers needed to treat of 8 (95% confidence interval 4.3 to 60) to induce one additional complete or partial response, with wide confidence intervals. Death was reported less frequently with MMF (0.7%, 1 death in 152 patients) than with cyclophosphamide (7.8%, 12 deaths in 154 patients), with a number needed to treat to prevent (NNTp) one death of 14 (8 to 48). Hospital admission was also lower with MMF (1.7% versus 15%; NNTp 7.4 [4.8 to 16]). Serious infections, leucopaenia, amenorrhoea, and hair loss were all significantly less frequent with MMF than with cyclophosphamide, but diarrhoea was significantly more common with MMF. Ten of 18 cohort studies enrolled only patients with lupus nephritis (author-defined or WHO class III to V). Seven of these 10 reported that complete or partial response with MMF (mostly 1 or 2 g daily) with steroid occurred in 121/151 (80%) and that treatment failure or no response occurred in 30/151 (20%). Adverse events were generally similar in cohort studies with and without only patients with lupus nephritis. In all 18 cohorts, gastrointestinal adverse events (diarrhoea, nausea, vomiting) occurred in 30%, infection in 23%, and serious infection in 4.3%. Adverse event discontinuations occurred in 14% and lack of efficacy occurred in 10%. There was a single death with MMF, a mortality rate over the course of 1 year of approximately 0.2%. The results form a basis on which to plan future studies and provide a guide for the use of MMF in lupus nephritis until results of larger studies are available. At least one such study is under way.     

Evaluation of the Patient Acceptable Symptom State in a pooled analysis of two multicentre, randomised, double-blind, placebo-controlled studies evaluating lumiracoxib and celecoxib in patients with osteoarthritis

Patient Acceptable Symptom State (PASS) is an absolute threshold proposed for symptomatic variables in osteoarthritis (OA) to determine the point beyond which patients consider themselves well and, as such, are satisfied with treatment. Two large previously reported studies of knee OA have shown that both lumiracoxib and celecoxib were superior to placebo in terms of conventional outcome measures. To assess the clinical relevance of these results from the patient's perspective, the same data pooled from these two studies were analysed with respect to the PASS. In total, 3,235 patients were included in two multicentre, randomised, double-blind studies of identical design. Patients were randomly assigned to receive lumiracoxib 100 mg once daily (n = 811), lumiracoxib 100 mg once daily with an initial dose of lumiracoxib 200 mg once daily for the first 2 weeks (100 mg once daily with initial dose [n = 805]), celecoxib 200 mg once daily (n = 813), or placebo (n = 806) for 13 weeks. Treatments were compared with respect to the PASS criteria (for OA pain, patient's global assessment of disease activity, and the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 [WOMAC LK 3.1] Function [difficulty in performing daily activities] subscale score). At week 13, 43.3%, 45.3%, and 42.2% of patients in the lumiracoxib 100 mg once daily, lumiracoxib 100 mg once daily with initial dose, and the celecoxib 200 mg once daily groups, respectively, considered their current states as satisfactory versus 35.5% in the placebo group. Similar results were observed for patient's global assessment of disease activity and WOMAC LK 3.1 Function subscale score. This post hoc analysis suggests that the statistical significance of the results observed with lumiracoxib or celecoxib compared with placebo using conventional outcome variables is complemented by clinical relevance to the patient. Trial registration numbers: NCT00366938 and NCT00367315.     

Litter Decomposition in Temperate Peatland Ecosystems: The Effect of Substrate and Site

Abstract The large accumulation of organic matter in peatlands is primarily caused by slow rates of litter decomposition. We determined rates of decomposition of major peat-forming litters of vascular plants and mosses at five sites: a poor fen in New Hampshire and a bog hummock, a poor fen, a beaver pond margin and a beaver pond in Ontario. We used the litterbag technique, retrieving triplicate litterbags six or seven times over 3–5 years, and found that simple exponential decay and continuous-quality non-linear regression models could adequately characterize the decomposition in most cases. Within each site, the rate of decomposition at the surface was generally Typha latifolia leaves = Chamaedaphne calyculata leaves = Carex leaves > Chamaedaphne calyculata stems > hummock Sphagnum = lawn/hollow Sphagnum, with exponential decay constant (k) values generally ranging from 0.05 to 0.37 and continuous-quality model initial quality (q ₀ ) values ranging from 1.0 (arbitrarily set for Typha leaves) to 0.7 (Sphagnum). In general, surface decay rates were slowest at the bog hummock site, which had the lowest water table, and in the beaver pond, which was inundated, and fastest at the fens. The continuous-quality model site decomposition parameter (u ₀ ) ranged from 0.80 to 0.17. Analysis of original litter samples for carbon, nitrogen and proximate fractions revealed a relatively poor explanation of decomposition rates, as defined by k and q ₀ , compared to most well-drained ecosystems. Three litters, roots of sedge and a shrub and Typha leaves, were placed at depths of 10, 30 and 60 cm at the sites. Decomposition rates decreased with depth at each site, with k means of 0.15, 0.08 and 0.05 y⁻¹ at 10, 30 and 60 cm, respectively, and u ₀ of 0.25, 0.13 and 0.07. These differences are primarily related to the position of the water table at each site and to a lesser extent the cooler temperatures in the lower layers of the peat. The distinction between bog and fen was less important than the position of the water table. These results show that we can characterize decomposition rates of surface litter in northern peatlands, but given the large primary productivity below-ground in these ecosystems, and the differential rates of decomposition with depth, subsurface input and decomposition of organic matter is an important and relatively uncertain attribute.     

Preface: to the special issue: photochemistry and electrochemistry of natural and artificial photosynthesis

Photosynthesis Research -     

Abundant Trimethylornithine Lipids and Specific Gene Sequences Are Indicative of Planctomycete Importance at the Oxic/Anoxic Interface in Sphagnum-Dominated Northern Wetlands

Northern wetlands make up a substantial terrestrial carbon sink and are often dominated by decay-resistant Sphagnum mosses. Recent studies have shown that planctomycetes appear to be involved in degradation of Sphagnum-derived debris. Novel trimethylornithine (TMO) lipids have recently been characterized as abundant lipids in various Sphagnum wetland planctomycete isolates, but their occurrence in the environment has not yet been confirmed. We applied a combined intact polar lipid (IPL) and molecular analysis of peat cores collected from two northern wetlands (Saxnäs Mosse [Sweden] and Obukhovskoye [Russia]) in order to investigate the preferred niche and abundance of TMO-producing planctomycetes. TMOs were present throughout the profiles of Sphagnum bogs, but their concentration peaked at the oxic/anoxic interface, which coincided with a maximum abundance of planctomycete-specific 16S rRNA gene sequences. The sequences detected at the oxic/anoxic interface were affiliated with the Isosphaera group, while sequences present in the anoxic peat layers were related to an uncultured planctomycete group. Pyrosequencing-based analysis identified Planctomycetes as the major bacterial group at the oxic/anoxic interface at the Obukhovskoye peat (54% of total 16S rRNA gene sequence reads), followed by Acidobacteria (19% reads), while in the Saxnäs Mosse peat, Acidobacteria were dominant (46%), and Planctomycetes contributed to 6% of the total reads. The detection of abundant TMO lipids in planctomycetes isolated from peat bogs and the lack of TMO production by cultures of acidobacteria suggest that planctomycetes are the producers of TMOs in peat bogs. The higher accumulation of TMOs at the oxic/anoxic interface and the change in the planctomycete community with depth suggest that these IPLs could be synthesized as a response to changing redox conditions at the oxic/anoxic interface.     

白蚁生物多样性及其对生态环境变化的指示作用

白蚁是热带和亚热带生态系统最主要的无脊椎动物分解者,具有十分重要的生态作用,但因长期缺乏标准化取样方法,白蚁生物多样性研究及其在生态管理中的应用受到限制。本文回顾了白蚁生物多样性及其对环境变化响应的研究进展,概述了白蚁功能分类的现状,介绍了白蚁多样性取样方法的发展,分析了白蚁多样性对生态环境的差异、人为干扰的响应及其生态指示作用,以期为白蚁生物多样性的深入研究及其在生态管理中的应用提供思路与方向。