Highly Selective Hydroformylation of the Cinchona Alkaloids

The four naturally occurring cinchona alkaloids were subjected to hydroformylation to create an extra functional group that allows immobilization. Cinchonidine, quinine, and quinidine, could be hydroformylated with virtually complete terminal selectivity, using a rhodium/tetraphosphite catalyst. The cinchonidine aldehyde was reduced to the alcohol and subjected to reductive amination with benzylamine.

Matrices, Moments and Quadrature: Applications to Time- Dependent Partial Differential Equations

The numerical solution of a time-dependent PDE generally involves the solution of a stiff system of ODEs arising from spatial discretization of the PDE. There are many methods in the literature for solving such systems, such as exponential propagation iterative (EPI) methods, that rely on Krylov projection to compute matrix function-vector products. Unfortunately, as spatial resolution increases, these products require an increasing number of Krylov projection steps, thus drastically increasing computational expense

How specialised must natural enemies be to facilitate coexistence among plants?

The Janzen‐Connell hypothesis proposes that plant interactions with host‐specific antagonists can impair the fitness of locally abundant species and thereby facilitate coexistence. However, insects and pathogens that associate with multiple hosts may mediate exclusion rather than coexistence. We employ a simulation model to examine the effect of enemy host breadth on plant species richness and defence community structure, and to assess expected diversity maintenance in example systems. Only models in which plant enemy similarity declines rapidly with defence similarity support greater species richness than models of neutral drift. In contrast, a wide range of enemy host breadths result in spatial dispersion of defence traits, at both landscape and local scales, indicating that enemy‐mediated competition may increase defence‐trait diversity without enhancing species richness. Nevertheless, insect and pathogen host associations in Panama and Papua New Guinea demonstrate a potential to enhance plant species richness and defence‐trait diversity comparable to strictly specialised enemies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99082/1/ele12130.pd

Hydroxychloroquine Suppresses Interferon-inducible Genes and B Cell Activating Factor in Patients With Incomplete and New-onset Systemic Lupus Erythematosus

OBJECTIVE: Hydroxychloroquine (HCQ) is commonly used as first-line treatment for systemic lupus erythematosus (SLE). Interferon (IFN)-inducible gene expression, IFN-γ-induced protein 10 (IP-10) and B cell activating factor (BAFF) are early mediators in SLE. The purpose of this study was to analyze the effects of HCQ on these factors. METHODS: Patients with incomplete SLE (iSLE; antinuclear antibody titer ≥ 1:80, symptoms < 5 years, ≥ 1 objectified clinical American College of Rheumatology or SLE International Collaborating Clinics criteria), or new-onset, mild SLE were included when HCQ treatment was started for clinical reasons. Blood samples were taken at start and after 16 weeks. Three SLE-related IFN-inducible genes were measured in whole blood by real-time PCR, and an IFN score was calculated. Serum levels of IP-10 and BAFF were measured using ELISA. RESULTS: In total, 9 patients were included: 7 with iSLE and 2 with new-onset SLE. The median SLE Disease Activity Index (SLEDAI) was 4. After 16 weeks of treatment with HCQ, the expression of IFN-inducible genes decreased in 8 of 9 patients, and the IFN-3 score decreased significantly (P = 0.012). There was a trend towards lower IP-10 levels (P = 0.055), and a significant decrease in BAFF levels (P = 0.023). CONCLUSION: HCQ suppresses IFN score and BAFF levels in patients with iSLE or new-onset SLE, and there is a trend towards lowering IP-10 levels. As these biomarkers are early mediators in SLE, this might support the hypothesis that HCQ could influence disease progression. However, prospective research with a larger sample size and longer follow-up is needed

From incomplete to complete systemic lupus erythematosus; A review of the predictive serological immune markers

Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease. A main challenge faced by clinicians is early identification of SLE, frequently resulting in diagnostic delay. Timely treatment, however, is important to limit disease progression, and prevent organ damage and mortality. Often, patients present with clinical symptoms and immunologic abnormalities suggestive of SLE, while not meeting classification criteria yet. This is referred to as incomplete SLE (iSLE). However, not all these patients will develop SLE. Therefore, there is need for predictive biomarkers that can distinguish patients at high risk of developing SLE, in order to allow early treatment. This article reviews the current literature on immunological changes in patients with stages preceding SLE, focusing on autoantibodies, type-I and -II interferons, and the complement system. We also provide an overview of possible predictive markers for progression to SLE that are applicable in daily clinical practice

High nutrient-use efficiency during early seedling growth in diverse Grevillea species (Proteaceae)

Several hypotheses have been proposed to explain the rich floristic diversity in regions characterised by nutrient-impoverished soils; however, none of these hypotheses have been able to explain the rapid diversification over a relatively short evolutionary time period of Grevillea, an Australian plant genus with 452 recognised species/subspecies and only 11 million years of evolutionary history. Here, we hypothesise that the apparent evolutionary success of Grevillea might have been triggered by the highly efficient use of key nutrients. The nutrient content in the seeds and nutrient-use efficiency during early seedling growth of 12 species of Grevillea were compared with those of 24 species of Hakea, a closely related genus. Compared with Hakea, the Grevillea species achieved similar growth rates (root and shoot length) during the early stages of seedling growth but contained only approximately half of the seed nutrient content. We conclude that the high nutrient-use efficiency observed in Grevillea might have provided a selective advantage in nutrient-poor ecosystems during evolution and that this property likely contributed to the evolutionary success in Grevillea

Cell-free Embryonic Stem Cell Extract-mediated Derivation of Multi-potent Stem Cells from NIH3T3 Fibroblasts for Functional and Anatomical Ischemic Tissue Repair

The oocyte-independent generation of multipotent stem cells is one of the goals in regenerative medicine. We report that upon exposure to mouse ES cell (ESC) extracts, reversibly permeabilized NIH3T3 cells undergo de-differentiation followed by stimulus-induced re-differentiation into multiple lineage cell types. Genome-wide expression profiling revealed significant differences between NIH3T3 and ESC-extract treated NIH3T3 cells including re-activation of ESC specific transcripts. Epigenetically, ESC extracts induced CpG de-methylation of Oct4 promoter, hyper-acetylation of histones 3 and 4 and decreased lysine 9 (K-9) dimethylation of histone 3. In mouse models of surgically-induced hind limb ischemia (HLI) or acute myocardial infarction (AMI) transplantation of reprogrammed NIH3T3 cells significantly improved post-injury physiological functions and showed antomical evidence of engraftment and trans-differentiation into skeletal muscle, endothelial cell and cardiomyocytes. These data provide evidence for the generation of functional multi-potent stem like cells from terminally differentiated somatic cells without the introduction of trans-genes or ESC fusion

Incomplete Systemic Lupus Erythematosus:What Remains After Application of American College of Rheumatology and Systemic Lupus International Collaborating Clinics criteria?

Incomplete systemic lupus (iSLE) is an acknowledged condition of patients with clinical signs of lupus who do not fulfill classification criteria for SLE. Some patients with iSLE have persistent mild disease, but others have serious organ involvement, and up to 55% progress to established SLE. Research on this subject could reveal predictive or diagnostic biomarkers for SLE. Ideally, it would become possible to discern those patients with critical organ involvement or a high risk for progression to SLE. This high-risk group might benefit from early treatment, which would preferably be confirmed in randomized controlled trials. This process would, however, require agreement on a definition of iSLE. The Systemic Lupus International Collaborating Clinics (SLICC) classification criteria was composed in order to diagnose SLE earlier. The present review outlines the clinical characteristics of iSLE after introduction of SLICC criteria and furthermore proposes a definition of iSLE with the aim of discriminating the high-risk group from those with a lower risk

Altered leaf elemental composition with climate change is linked to reductions in photosynthesis, growth and survival in a semi‐arid shrubland

1. Climate change will increase heat and drought stress in many dryland areas, which could reduce soil nutrient availability for plants and aggravate nutrient limitation of primary productivity. Any negative impacts of climate change on foliar nutrient contents would be expected to negatively affect the photosynthetic capacity, water use efficiency and overall fitness of dryland vegetation. 2. We conducted a 4‐year manipulative experiment using open top chambers and rainout shelters to assess the impacts of warming (~2°C, W), rainfall reduction (~30%, RR) and their combination (W + RR) on the nutrient status and ecophysiological performance of six native shrub species of contrasting phylogeny in a semi‐arid ecosystem. Leaf nutrient status and gas exchange were assessed yearly, whereas biomass production and survival were measured at the end of the study. 3. Warming (W and W + RR) advanced shoot growth phenology and reduced foliar macro‐ (N, P, K) and micronutrient (Cu, Fe, Zn) concentrations (by 8%–18% and 14%–56% respectively), net photosynthetic rate (32%), above‐ground biomass production (28%–39%) and survival (23%–46%). Decreased photosynthesis and growth in W and W + RR plants were primarily linked to enhanced nutritional constraints on carbon fixation. Poor leaf nutrient status in W and W + RR plants partly decoupled carbon assimilation from water flux and led to drastic reductions in water use efficiency (WUEi; ~41%) across species. The RR treatment moderately decreased foliar macro‐ and micronutrients (6%–17%, except for Zn) and biomass production (22%). The interactive impacts of warming and rainfall reduction (W + RR treatment) on plant performance were generally smaller than expected from additive single‐factor effects. 4. Synthesis. Large decreases in plant nutrient pool size and productivity combined with increased mortality during hotter droughts will reduce vegetation cover and nutrient retention capacity, thereby disrupting biogeochemical processes and accelerating dryland degradation with impending climate change. Increased macro‐ and micronutrient co‐limitation of photosynthesis with forecasted climate change conditions may offset any gains in WUEi and productivity derived from anthropogenic CO2 elevation, thereby increasing dryland vegetation vulnerability to drought stress in a warmer and drier climate. The generalized reduction in leaf nutrient contents with warming compromises plant nutritional quality for herbivores, with potential cascading negative effects across trophic levels.This study was supported by the Spanish Ministerio de Economía y Competitividad (projects CGL2010‐21064, CGL2013‐48753‐R and CGL2013‐44661‐R co‐funded by European Union FEDER funds), Fundación Séneca (19477/PI/14) and the European Research Council (ERC Grant agreements 242658 [BIOCOM] and 647038 [BIODESERT]). L.L.‐S. and I.P. acknowledge support from the JAE‐CSIC and Juan de la Cierva Programs (FPDI‐2013‐16221) respectively

Phosphorus-acquisition strategies of canola, wheat and barley in soil amended with sewage sludges

Crops have different strategies to acquire poorly-available soil phosphorus (P) which are dependent on their architectural, morphological, and physiological root traits, but their capacity to enhance P acquisition varies with the type of fertilizer applied. The objective of this study was to examine how P-acquisition strategies of three main crops are affected by the application of sewage sludges, compared with a mineral P fertilizer. We carried out a 3-months greenhouse pot experiment and compared the response of P-acquisition traits among wheat, barley and canola in a soil amended with three sludges or a mineral P fertilizer. Results showed that the P-acquisition strategy differed among crops. Compared with canola, wheat and barley had a higher specific root length and a greater root carboxylate release and they acquired as much P from sludge as from mineral P. By contrast, canola shoot P content was greater with sludge than with mineral P. This was attributed to a higher rootreleased acid phosphatase activity which promoted the mineralization of sludge-derived P-organic. This study showed that contrasted P-acquisition strategies of crops allows increased use of renewable P resources by optimizing combinations of crop and the type of P fertilizer applied within the cropping system