No Evidence That Soluble TACI Induces Signalling via Membrane-Expressed BAFF and APRIL in Myeloid Cells

Myeloid cells express the TNF family ligands BAFF/BLyS and APRIL, which exert their effects on B cells at different stages of differentiation via the receptors BAFFR, TACI (Transmembrane Activator and CAML-Interactor) and/or BCMA (B Cell Maturation Antigen). BAFF and APRIL are proteins expressed at the cell membrane, with both extracellular and intracellular domains. Therefore, receptor/ligand engagement may also result in signals in ligand-expressing cells via so-called “reverse signalling”. In order to understand how TACI-Fc (atacicept) technically may mediate immune stimulation instead of suppression, we investigated its potential to activate reverse signalling through BAFF and APRIL. BAFFR-Fc and TACI-Fc, but not Fn14-Fc, reproducibly stimulated the ERK and other signalling pathways in bone marrow-derived mouse macrophages. However, these effects were independent of BAFF or APRIL since the same activation profile was observed with BAFF- or APRIL-deficient cells. Instead, cell activation correlated with the presence of high molecular mass forms of BAFFR-Fc and TACI-Fc and was strongly impaired in macrophages deficient for Fc receptor gamma chain. Moreover, a TACI-Fc defective for Fc receptor binding elicited no detectable signal. Although these results do not formally rule out the existence of BAFF or APRIL reverse signalling (via pathways not tested in this study), they provide no evidence in support of reverse signalling and point to the importance of using appropriate specificity controls when working with Fc receptor-expressing myeloid cells.     

Key Features of Intertidal Food Webs That Support Migratory Shorebirds

The migratory shorebirds of the East Atlantic flyway land in huge numbers during a migratory stopover or wintering on the French Atlantic coast. The Brouage bare mudflat (Marennes-Oléron Bay, NE Atlantic) is one of the major stopover sites in France. The particular structure and function of a food web affects the efficiency of carbon transfer. The structure and functioning of the Brouage food web is crucial for the conservation of species landing within this area because it provides sufficient food, which allows shorebirds to reach the north of Europe where they nest. The aim of this study was to describe and understand which food web characteristics support nutritional needs of birds. Two food-web models were constructed, based on in situ measurements that were made in February 2008 (the presence of birds) and July 2008 (absence of birds). To complete the models, allometric relationships and additional data from the literature were used. The missing flow values of the food web models were estimated by Monte Carlo Markov Chain – Linear Inverse Modelling. The flow solutions obtained were used to calculate the ecological network analysis indices, which estimate the emergent properties of the functioning of a food-web.The total activities of the Brouage ecosystem in February and July are significantly different. The specialisation of the trophic links within the ecosystem does not appear to differ between the two models. In spite of a large export of carbon from the primary producer and detritus in winter, the higher recycling leads to a similar retention of carbon for the two seasons. It can be concluded that in February, the higher activity of the ecosystem coupled with a higher cycling and a mean internal organization, ensure the sufficient feeding of the migratory shorebirds.     

Potential Impact of Influenza A/H1N1 Pandemic and Hand-Gels on Acute Diarrhea Epidemic in France

Background

The 2009 A/H1N1 influenza pandemic has received a great deal of attention from public health authorities. Our study examines whether this pandemic and the resulting public health measures could have impacted acute diarrhea, a prevalent, highly transmissible and historically monitored disease.

Methods

Using augmentation procedures of national data for the previous five years (2004–2009), we estimated the expected timing and incidence of acute diarrhea in France in 2009–2010 and evaluated differences with the observed. We also reviewed national hand gels for the same period.

Findings

Number of episodes of acute diarrhea in France in 2009–2010 was significantly lower than expected until the third week of December (−24%, 95% CI [−36%; −9%]), then significantly higher (+40%, 95% CI [22%; 62%]), leading to a surplus of 574,440 episodes. The epidemic was delayed by 5 weeks with a peak 1.3 times higher than expected. Hand-gels sales inversely correlated with incidence of both influenza-like illness and acute diarrheal disease. Among individuals >65 yo, no excess cases of influenza and no excess rebound in acute diarrhea were observed, despite similar delay in the onset of the seasonal diarrheal epidemic.

Interpretation

Our results suggest that at least one endemic disease had an unexpected behavior in 2009–2010. Acute diarrhea seems to have been controlled during the beginning of the pandemic in all age groups, but later peaked higher than expected in the younger population. The all-age delay in seasonal onset seems partly attributable to hand-gels use, while the differential magnitude of the seasonal epidemic between young and old, concurrent for both influenza and acute diarrhea, is compatible with disease interaction.     

De novo indol-3-ylmethyl glucosinolate biosynthesis,and not long-distance transport,contributes to defence of Arabidopsis against powdery mildew

Powdery mildew is a fungal disease that affects a wide range of plants and reduces crop yield worldwide. As obligate biotrophs, powdery mildew fungi manipulate living host cells to suppress defence responses and to obtain nutrients. Members of the plant order Brassicales produce indole glucosinolates that effectively protect them from attack by non-adapted fungi. Indol-3-ylmethyl glucosinolate is constitutively produced in the phloem and transported to epidermal cells for storage. Upon attack, indol-3-ylmethyl glucosinolate is activated by CYP81F2 to provide broad-spectrum defence against fungi. How de novo biosynthesis and transport contribute to defence of powdery mildew-attacked epidermal cells is unknown. Bioassays and glucosinolate analysis demonstrate that GTR glucosinolate transporters are not involved in antifungal defence. Using quantitative live-cell imaging of fluorophore-tagged markers, we show that accumulation of the glucosinolate biosynthetic enzymes CYP83B1 and SUR1 is induced in epidermal cells attacked by the non-adapted barley powdery mildew Blumeria graminis f.sp. hordei. By contrast, glucosinolate biosynthesis is attenuated during interaction with the virulent powdery mildew Golovinomyces orontii. Interestingly, SUR1 induction is delayed during the Golovinomyces orontii interaction. We conclude that epidermal de novo synthesis of indol-3-ylmethyl glucosinolate contributes to CYP81F2-mediated broad-spectrum antifungal resistance and that adapted powdery mildews may target this process.     

Chemical preservation of tail feathers from Anchiornis huxleyi,a theropod dinosaur from the Tiaojishan Formation (Upper Jurassic,China)

A panel of geochemical techniques is used here to investigate the taphonomy of fossil feathers preserved in association with the skeleton of the Jurassic theropod Anchiornis huxleyi. Extant feathers were analysed in parallel to test whether the soft tissues morphologically preserved in the fossil also exhibit a high degree of chemical preservation. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) indicate that clays and iron oxide pseudomorphs occur in the surrounding sediment and also reveal the preservation of melanosome-like microbodies in the fossil. Carbon gradient along a depth profile and co-occurrence of carbon and sulphur are shown in the fossil by elastic backscattering (EBS) and particle-induced x-ray emission (PIXE), which are promising techniques for the elemental analysis of fossil soft tissues. The molecular composition of modern and fossil soft tissues was assessed from micro-attenuated total reflectance fourier transform infrared spectroscopy (micro-ATR FTIR), solid-state ¹³C nuclear magnetic resonance (CP-MAS ¹³C NMR) and pyrolysis gas chromatography mass spectrometry in the presence of TMAH (TMAH-Py-GC-MS). Results indicate that the proteinaceous material that comprises the modern feathers is not present in the fossil feathers. The fossil feathers and the embedding sediment exhibit a highly aliphatic character. However, substantial differences exist between these samples, revealing that the organic matter of the fossil feathers is, at least partially, derived from original constituents of the feathers. Our results suggest that, despite the morphological preservation of Anchiornis feathers, original proteins, that is keratin, were probably not preserved in the 160-myr-old feathers.     

Antibacterial activity of sugar maple autumn-shed leaf extract: Identification of the active compound

Ethanolic crude extract prepared from autumn-shed leaves of sugar maple (Acer saccharum Marsh.) was recently shown to have antibacterial activity against Pseudomonas cichorii and Xanthomonas campestris pv. vitians, two bacteria causing diseases in lettuce production. In this study, antibacterial activity of sugar maple autumn-shed leaves (SMASL) extract was further investigated. SMASL ethanolic crude extract was fractionated using HPLC system and geraniin was identified as the antibacterial compound by UPLC/Q-Tof-MS system. Geraniin, an ellagitannin, was then purified from SMASL crude extract using a glass chromatographic C18-reversed phase silica gel column (purification Step 1) and a semi-preparative HPLC system equipped with 5 μm XTerra Prep MS C18 column (purification Step 2). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of purified geraniin (purity of 96%) against P. cichorii and X. campestris pv. vitians were determined. X. campestris pv. vitians (MIC of 0.024 mg ml⁻¹ and MBC of 3.125 mg ml⁻¹) was more sensitive to geraniin than P. cichorii (MIC of 0.781 mg ml⁻¹ and MBC of 6.25 mg ml⁻¹). In the present study, geraniin is reported for the first time as the main antibacterial compound present in SMASL.     

Liana communities exhibit different species composition,diversity and community structure across forest types in the Congo Basin

Lianas are poorly characterized for central African forests. We quantify variation in liana composition, diversity and community structure in different forest types in the Yangambi Man and Biosphere Reserve, Democratic Republic of Congo. These attributes of liana assemblages were examined in 12 1-ha plots, randomly demarcated within regrowth forest, old growth monodominant forest, old growth mixed forest and old growth edge forest. Using a combination of multivariate and univariate community analyses, we visualize the patterns of these liana assemblage attributes and/or test for their significant differences across forest types. The combined 12 1-ha area contains 2,638 lianas (≥2 cm diameter) representing 105 species, 49 genera and 22 families. Liana species composition differed significantly across forest types. Taxonomic diversity was higher in old growth mixed forests compared to old growth monodominant and regrowth forests. Trait diversity was higher than expected in the regrowth forest as opposed to the rest of forest types. Similarly, the regrowth forest differed from the rest of forest types in the pattern of liana species ecological traits and diameter frequency distribution. The regrowth forest was also less densely populated in lianas and had lower liana total basal area than the rest of forest types. We speculate that the mechanism of liana competitive exclusion by dominant tree species is mainly responsible for the lower liana species diversity in monodominant compared to mixed forests. We attribute variation in liana community structure between regrowth and old growth forests mostly to short development time of size hierarchies.     

Amyloid precursor protein is a restriction factor that protects against Zika virus infection in mammalian brains

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer''s diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.