Prenylated arylbenzofuran derivatives from Morus mesozygia with antioxidant activity

Five prenylated arylbenzofurans, moracins Q-U, were isolated from Morus mesozygia (Moraceae). Their structures were elucidated on the basis of spectroscopic evidence. Along with these compounds, 3β-acetoxyurs-12-en-11-one, marsformoxide, moracin C, moracin M, moracin K, artocarpesin, cycloartocarpesin, morachalcone A were also isolated. Four of the five compounds, (moracins R-U) displayed potent antioxidant activity.     

Circadian rhythms lit up in Chlamydomonas

Recent work on the circadian clock of the unicellular green alga Chlamydomonas reinhardtii strengthens its standing as a convenient model system for circadian study. It was shown to be amenable to molecular engineering using a luciferase-based real-time reporter for circadian rhythms. Together with the completed draft genomic sequence, the new system opens the door for genome-scale forward and reverse genetic analysis.     

Coexpression and interaction of CXCL10 and CD26 in mesenchymal cells by synergising inflammatory cytokines: CXCL8 and CXCL10 are discriminative markers for autoimmune arthropathies

Leukocyte infiltration during acute and chronic inflammation is regulated by exogenous and endogenous factors, including cytokines, chemokines and proteases. Stimulation of fibroblasts and human microvascular endothelial cells with the inflammatory cytokines interleukin-1beta (IL-1beta) or tumour necrosis factor alpha (TNF-alpha) combined with either interferon-alpha (IFN-alpha), IFN-beta or IFN-gamma resulted in a synergistic induction of the CXC chemokine CXCL10, but not of the neutrophil chemoattractant CXCL8. In contrast, simultaneous stimulation with different IFN types did not result in a synergistic CXCL10 protein induction. Purification of natural CXCL10 from the conditioned medium of fibroblasts led to the isolation of CD26/dipeptidyl peptidase IV-processed CXCL10 missing two NH2-terminal residues. In contrast to intact CXCL10, NH2-terminally truncated CXCL10(3-77) did not induce extracellular signal-regulated kinase 1/2 or Akt/protein kinase B phosphorylation in CXC chemokine receptor 3-transfected cells. Together with the expression of CXCL10, the expression of membrane-bound CD26/dipeptidyl peptidase IV was also upregulated in fibroblasts by IFN-gamma, by IFN-gamma plus IL-1beta or by IFN-gamma plus TNF-alpha. This provides a negative feedback for CXCL10-dependent chemotaxis of activated T cells and natural killer cells. Since TNF-alpha and IL-1beta are implicated in arthritis, synovial concentrations of CXCL8 and CXCL10 were compared in patients suffering from crystal arthritis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. All three groups of autoimmune arthritis patients (ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis) had significantly increased synovial CXCL10 levels compared with crystal arthritis patients. In contrast, compared with crystal arthritis, only rheumatoid arthritis patients, and not ankylosing spondylitis or psoriatic arthritis patients, had significantly higher synovial CXCL8 concentrations. Synovial concentrations of the neutrophil chemoattractant CXCL8 may therefore be useful to discriminate between autoimmune arthritis types.     

High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase

The circadian clock underlies daily rhythms of diverse physiological processes, and alterations in clock function have been linked to numerous pathologies. To apply chemical biology methods to modulate and dissect the clock mechanism with new chemical probes, we performed a circadian screen of ～120,000 uncharacterized compounds on human cells containing a circadian reporter. The analysis identified a small molecule that potently lengthens the circadian period in a dose-dependent manner. Subsequent analysis showed that the compound also lengthened the period in a variety of cells from different tissues including the mouse suprachiasmatic nucleus, the central clock controlling behavioral rhythms. Based on the prominent period lengthening effect, we named the compound longdaysin. Longdaysin was amenable for chemical modification to perform affinity chromatography coupled with mass spectrometry analysis to identify target proteins. Combined with siRNA-mediated gene knockdown, we identified the protein kinases CKIδ, CKIα, and ERK2 as targets of longdaysin responsible for the observed effect on circadian period. Although individual knockdown of CKIδ, CKIα, and ERK2 had small period effects, their combinatorial knockdown dramatically lengthened the period similar to longdaysin treatment. We characterized the role of CKIα in the clock mechanism and found that CKIα-mediated phosphorylation stimulated degradation of a clock protein PER1, similar to the function of CKIδ. Longdaysin treatment inhibited PER1 degradation, providing insight into the mechanism of longdaysin-dependent period lengthening. Using larval zebrafish, we further demonstrated that longdaysin drastically lengthened circadian period in vivo. Taken together, the chemical biology approach not only revealed CKIα as a clock regulatory kinase but also identified a multiple kinase network conferring robustness to the clock. Longdaysin provides novel possibilities in manipulating clock function due to its ability to simultaneously inhibit several key components of this conserved network across species.     

Environmental correlates of avian diversity in lowland Panama rain forests

Aim The composition of communities is known to be influenced by biogeographical history, but also by local environmental conditions. Yet few studies have evaluated the relative importance of the direct and indirect effects of multiple factors on species diversity in rich Neotropical forests. Our study aims to assess drivers of change in local bird species richness in lowland tropical rain forests. Location Thirty‐two physiographic subregions along the corridor of the Panama Canal, Panama. Methods We mapped the distributions of all forest‐dwelling bird species and quantified the environmental characteristics of all subregions, including mean annual rainfall, topographic complexity, elevational variability, forest age and forest area. Plant species richness, believed to be correlated with structural complexity, was estimated by interpolation through kriging for subregions where data were unavailable. Results The study region has a strong rainfall gradient across a short distance (65 km), which is also accompanied by steep gradients in plant and bird species diversity. Path analysis showed that precipitation strongly affected plant species diversity, which in turn affected avian diversity. Forest age and topography affected bird diversity independently of plant diversity. Forest area and its proportion occurring in the largest two fragments of each subregion (habitat configuration) were also positive correlates of bird species richness. Main conclusions Our results suggest that plant species richness, known to be influenced in part by biogeographical history and geology, also affects bird species assemblages locally. We provide support for the hypothesis that bird species richness increases with structural complexity of the habitat. Our analysis of the distributions of the region's most disturbance‐sensitive bird species showed that subregions with more rainfall, more complex topography and older forests harboured not only richer communities but also more sensitive species; while subregions with the opposite characteristics usually lacked large fractions of the regional forest bird community and hosted only common, widely distributed species. Results also emphasize the importance of preserving forest diversity from habitat loss and fragmentation, and confirm that larger, continuous forest tracts are necessary to maintain the rich avian diversity in the region.     

Implications of productivity and nutrient requirements on greenhouse gas balance of annual and perennial bioenergy crops

Biomass from dedicated crops is expected to contribute significantly to the replacement of fossil resources. However, sustainable bioenergy cropping systems must provide high biomass production and low environmental impacts. This study aimed at quantifying biomass production, nutrient removal, expected ethanol production, and greenhouse gas (GHG) balance of six bioenergy crops: Miscanthus × giganteus, switchgrass, fescue, alfalfa, triticale, and fiber sorghum. Biomass production and N, P, K balances (input‐output) were measured during 4 years in a long‐term experiment, which included two nitrogen fertilization treatments. These results were used to calculate a posteriori ‘optimized’ fertilization practices, which would ensure a sustainable production with a nil balance of nutrients. A modified version of the cost/benefit approach proposed by Crutzen et al. (2008), comparing the GHG emissions resulting from N‐P‐K fertilization of bioenergy crops and the GHG emissions saved by replacing fossil fuel, was applied to these ‘optimized’ situations. Biomass production varied among crops between 10.0 (fescue) and 26.9 t DM ha^?1 yr^?1 (miscanthus harvested early) and the expected ethanol production between 1.3 (alfalfa) and 6.1 t ha^?1 yr^?1 (miscanthus harvested early). The cost/benefit ratio ranged from 0.10 (miscanthus harvested late) to 0.71 (fescue); it was closely correlated with the N/C ratio of the harvested biomass, except for alfalfa. The amount of saved CO₂ emissions varied from 1.0 (fescue) to 8.6 t CO₂eq ha^?1 yr^?1 (miscanthus harvested early or late). Due to its high biomass production, miscanthus was able to combine a high production of ethanol and a large saving of CO₂ emissions. Miscanthus and switchgrass harvested late gave the best compromise between low N‐P‐K requirements, high GHG saving per unit of biomass, and high productivity per hectare.