Organic dust augments nucleotide-binding oligomerization domain expression via an NF-{kappa}B pathway to negatively regulate inflammatory responses

Nucleotide-binding oligomerization domain 2 (NOD2) is involved in innate immune responses to peptidoglycan degradation products. Peptidoglycans are important mediators of organic dust-induced airway diseases in exposed agriculture workers; however, the role of NOD2 in response to complex organic dust is unknown. Monocytes/macrophages were exposed to swine facility organic dust extract (ODE), whereupon NOD2 expression was evaluated by real-time PCR and Western blot. ODE induced significant NOD2 mRNA and protein expression at 24 and 48 h, respectively, which was mediated via a NF-κB signaling pathway as opposed to a TNF-α autocrine/paracrine mechanism. Specifically, NF-κB translocation increased rapidly following ODE stimulation as demonstrated by EMSA, and inhibition of the NF-κB pathway significantly reduced ODE-induced NOD2 expression. However, there was no significant reduction in ODE-induced NOD2 gene expression when TNF-α was inhibited or absent. Next, it was determined whether NOD2 regulated ODE-induced inflammatory cytokine production. Knockdown of NOD2 expression by small interfering RNA resulted in increased CXCL8 and IL-6, but not TNF-α production in response to ODE. Similarly, primary lung macrophages from NOD2 knockout mice demonstrated increased IL-6, CXCL1, and CXCL1, but not TNF-α, expression. Lastly, a higher degree of airway inflammation occurred in the absence of NOD2 following acute (single) and repetitive (3 wk) ODE exposure in an established in vivo murine model. In summary, ODE-induced NOD2 expression is directly dependent on NF-κB signaling, and NOD2 is a negative regulator of complex, organic dust-induced inflammatory cytokine/chemokine production in mononuclear phagocytes.     

Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials

Introduction  

The efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS.     

Perthamide C Inhibits eNOS and iNOS Expression and Has Immunomodulating Activity In Vivo

Here we have characterized perthamide C, a cyclopeptide from a Solomon Lithistid sponge Theonella swinhoei, which displays an anti-inflammatory/immunomodulatory activity. The study has been performed using the carragenan-induced mouse paw edema that displays an early (0–6 h) and a late phase (24–96 h). Perthamide C significantly inhibits neutrophils infiltration in tissue both in the early and late phases. This effect was coupled to a reduced expression of the endothelial nitric oxide synthase (eNOS) in the early phase while cyclooxygenase-1 and 2 (COX-1, COX-2), and inducible NOS (iNOS) expression were unaffected. In the late phase perthamide C reduced expression of both NOS isoforms without affecting COXs expression. This peculiar selectivity toward the two enzymes deputed to produce NO lead us to investigate on a possible action of perthamide C on lymphocytes infiltration and activation. We found that perthamide C inhibited the proliferation of peripheral lymphocytes, and that this effect was secondary to its metabolic activation in vivo. Indeed, in vitro perthamide C did not inhibit proliferation as opposite to its metabolite perthamide H.In conclusion, perthamide C selectively interferes with NO generation triggered by either eNOS or iNOS without affecting either COX-1 or COX-2. This in turn leads to modulation of the inflammatory response through a reduction of vascular permeability, neutrophil infiltration as well as lymphocyte proliferation.     

Hastifolins A–G,antifeedant neo-clerodane diterpenoids from Scutellaria hastifolia

From the aerial parts of Scutellaria hastifolia, family Lamiaceae (Labiatae), seven neo-clerodane diterpenoids (hastifolins A–G) were isolated. The products are similar to the known scuteparvin and are characterized by being trans-cinnamoyl derivatives. Structures and stereochemistry were determined by intensive NMR investigation. Six of the products form three pairs of epimers at C-13. Hastifolins A–C showed significant antifeedant activity.     

Increasing picocyanobacteria success in shelf waters contributes to long‐term food web degradation

Continental margins are disproportionally important for global primary production, fisheries and CO₂ uptake. However, across the Northeast Atlantic shelves, there has been an ongoing summertime decline of key biota—large diatoms, dinoflagellates and copepods—that traditionally fuel higher tropic levels such as fish, sea birds and marine mammals. Here, we combine multiple time series with in situ process studies to link these declines to summer nutrient stress and increasing proportions of picophytoplankton that can comprise up to 90% of the combined pico‐ and nanophytoplankton biomass in coastal areas. Among the pico‐fraction, it is the cyanobacterium Synechococcus that flourishes when iron and nitrogen resupply to surface waters are diminished. Our field data show how traits beyond small size give Synechococcus a competitive edge over pico‐ and nanoeukaryotes. Key is their ability to grow at low irradiances near the nutricline, which is aided by their superior light‐harvesting system and high affinity to iron. However, minute size and lack of essential biomolecules (e.g. omega‐3 polyunsaturated fatty acids and sterols) render Synechococcus poor primary producers to sustain shelf sea food webs efficiently. The combination of earlier spring blooms and lower summer food quantity and quality creates an increasing period of suboptimal feeding conditions for zooplankton at a time of year when their metabolic demand is highest. We suggest that this nutrition‐related mismatch has contributed to the widespread, ~50% decline in summer copepod abundance we observe over the last 60 years. With Synechococcus clades being prominent from the tropics to the Arctic and their abundances increasing worldwide, our study informs projections of future food web dynamics in coastal and shelf areas where droughts and stratification lead to increasing nutrient starvation of surface waters.     

Anaerobic microbial communities and their potential for bioenergy production in heavily biodegraded petroleum reservoirs

Most of the oil in low temperature, non-uplifted reservoirs is biodegraded due to millions of years of microbial activity, including via methanogenesis from crude oil. To evaluate stimulating additional methanogenesis in already heavily biodegraded oil reservoirs, oil sands samples were amended with nutrients and electron acceptors, but oil sands bitumen was the only organic substrate. Methane production was monitored for over 3000 days. Methanogenesis was observed in duplicate microcosms that were unamended, amended with sulfate or that were initially oxic, however methanogenesis was not observed in nitrate-amended controls. The highest rate of methane production was 0.15 μmol CH₄ g⁻¹ oil d⁻¹, orders of magnitude lower than other reports of methanogenesis from lighter crude oils. Methanogenic Archaea and several potential syntrophic bacterial partners were detected following the incubations. GC–MS and FTICR–MS revealed no significant bitumen alteration for any specific compound or compound class, suggesting that the very slow methanogenesis observed was coupled to bitumen biodegradation in an unspecific manner. After 3000 days, methanogenic communities were amended with benzoate resulting in methanogenesis rates that were 110-fold greater. This suggests that oil-to-methane conversion is limited by the recalcitrant nature of oil sands bitumen, not the microbial communities resident in heavy oil reservoirs.