Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG

Ovarian cancer is the fourth most common cancer in women in the Western world. In a pilot scale study, we highlight changes in the total serum glycome of patients with advanced ovarian cancer that might shed insight into disease pathogenesis. These changes include increases in levels of core fucosylated, agalactosyl biantennary glycans (FA2) and sialyl Lewis x (SLe(x)). To investigate further which proteins contribute to these alterations, we developed technology to analyze simultaneously the glycosylation of protein glycoforms contained in single spots excised from a 2D gel (<1 ng protein). The acute-phase proteins, haptoglobin, alpha1-acid glycoprotein, and alpha1-antichymotrypsin from patients contained elevated levels of subsets of glycoforms containing SLe(x). We also established that IgG heavy chains from patients contained twice the level of FA2 compared with healthy controls. Serum CA125 is the only biomarker that is used routinely, and there is a need for complementary markers that will improve both sensitivity and specificity. There was some preliminary indication that combinations of changes in the serum glycome might improve the separation of ovarian cancer and benign tumors; however, a larger study using data receiver operating characteristic curves will be required to draw any firm conclusions.     

Time Space Translation: A Hox Mechanism for Vertebrate A-P Patterning

The vertebrate A-P axis is a time axis. The head is made first and more and more posterior levels are made at later and later stages. This is different to the situation in most other animals, for example, in Drosophila. Central to this timing is Hox temporal collinearity (see below). This occurs rarely in the animal kingdom but is characteristic of vertebrates and is used to generate the primary axial Hox pattern using time space translation and to integrate successive derived patterns (see below). This is thus a different situation than in Drosophila, where the primary pattern guiding Hox spatial collinearity is generated externally, by the gap and segmentation genes.     

NITPICK: peak identification for mass spectrometry data

Background  

The reliable extraction of features from mass spectra is a fundamental step in the automated analysis of proteomic mass spectrometry (MS) experiments.     

PA,a stress-induced short cut to switch-on ethylene signalling by switching-off CTR1?

Constitutive triple response 1 (CTR1) is a protein kinase that represses plant responses to ethylene. Recently, we have shown that CTR1 function is negatively regulated by the lipid second messenger phosphatidic acid (PA) in vitro.¹ PA was shown to inhibit (1) CTR1''s protein kinase activity, (2) the intramolecular interaction between N-terminus and kinase domain, and (3) the interaction of CTR1 with the ethylene receptor ETR1. PA typically accumulates within minutes in response to biotic or abiotic stresses, which are known to induce ethylene formation. Although long-term treatment with ethephon does stimulate PA accumulation, our results show no fast increase in PA in response to ethylene. A speculative model is presented which explains how stress-induced PA formation could switch on downstream ethylene responses via interaction of the lipid with CTR1.Key words: lipid signaling, phosphatidic acid, ethylene, constitutive triple response 1, plant stress signaling, protein kinase, phospholipase D     

Novel function of the endoplasmic reticulum degradation‐enhancing α‐mannosidase‐like proteins in the human hepatitis B virus life cycle,mediated by the middle envelope protein

Cells replicating the human hepatitis B virus (HBV) express high levels of degradation‐enhancing α‐mannosidase‐like proteins (EDEMs), a family of proteins involved in the endoplasmic reticulum associated degradation, one of the pathways activated during the unfolded protein response. Owing to their α‐1,2 mannosidase activity, the EDEM1–3 proteins are able to process the N‐linked glycans of misfolded or incompletely folded proteins, providing the recognition signal for their subsequent degradation. The HBV small (S), medium (M), and large (L) surface proteins bear an N‐linked glycosylation site in the common S domain that is partially occupied in all proteins. The M protein contains an additional site in its preS2 domain, which is always functional. Here, we report that these oligosaccharides are processed by EDEMs, more efficiently by EDEM3, which induces degradation of L and S proteins, accompanied by a reduction of subviral particles production. In striking contrast, M not only is spared from degradation but its trafficking is also accelerated leading to an improved secretion. This unusual behavior of the M protein requires strictly the mannose trimming of the preS2 N‐linked glycan. Furthermore, we show that HBV secretion is significantly inhibited under strong endoplasmic reticulum stress conditions when M expression is prevented by mutagenesis of the viral genome. These observations unfold unique properties of the M protein in the HBV life cycle during unfolded protein response and point to alternative mechanisms employed by EDEMs to alleviate this stress in case of necessity by promoting glycoprotein trafficking rather than degradation.     

The utility of the morphological variation of pollen for resolving the evolutionary history of Billia (subfam. Hippocastanoideae,Sapindaceae)

In this study, we examined the utility of pollen morphology for resolving questions about the evolutionary history of Billia, which is a poorly known genus of Neotropical trees. Billia has been traditionally circumscribed with two species and treated as sister to Aesculus L. However, the number of species in Billia is uncertain, because the genus exhibits abundant morphological diversity but little discontinuous variation. Therefore, Billia may be monotypic and highly polymorphic, or it may have two species with blurred boundaries due to incipient speciation and/or hybridization. Moreover, one recent molecular phylogenetic study shows Billia nested withinAesculus. Our work sought to address the following questions: (i) Are there discontinuities in the pollen of Billia that may suggest species boundaries? (ii) Does the pollen of Billia show evidence for inter-specific hybridization? (iii) Do the exine morphology and size of pollen in Billia differ from those in Aesculus? Our results from scanning electron microscopy showed that pollen exine morphology is not taxonomically informative in Billia but that there are significant differences in pollen size between red- and white-flowered individuals. Thus, our pollen data support the utility of flower color in Billia for species delimitation. Our assessments of pollen viability do not support hybridization in the genus, but cannot be used to rule it out. Finally, pollen exine morphology may lend some support to an evolutionary origin ofBillia within eastern North American Aesculus. In contrast, data on pollen size suggest that Billia may belong in a topological position outside of Aesculus.     

Ferruginous microstromatolites related to Middle Jurassic condensed sequences and hardgrounds (Bucegi Mountains, Southern Carpathians, Romania)

Integrated analyses of ferruginous laminated crusts and macro-oncoids associated with Middle Jurassic (Bathonian-Callovian) hardgrounds and condensed horizons cropping out in the Bucegi Mountains (Southern Carpathians) allowed an assessment of their microbial origin and the paleoenvironmental context of their genesis. The ferruginous microstromatolites reveal different morphological types (or macrofabrics): ferruginous microstromatolites representing the hardgrounds crusts, ferruginous endostromatolites and oncoidal ferruginous microstromatolites. The last are associated with ooidal bioclastic grainstone, ooidal bioclastic grainstone-packstone, bioclastic ooidal packstone-grainstone, oncoidal floatstone and rudstone, stromatolitic bindstone, bioclastic wackestone-packstone and bioclastic wackestone microfacies. The host mineral of the ferruginous microbialites is calcite, but microbially induced iron oxyhydroxides (goethite and magnetite) prevail in the ferruginous laminae. Petrographical and scanning electron microscope (SEM) investigations revealed that these ferruginous microstromatolites were formed by the activity of microbial mats dominated by putative bacterial and fungal filaments. Locations with reduced or no sedimentation, in relatively deep-water, open-marine shelf environments, below fair-weather wave base or near to storm wave base, within the deep euphotic zone, were favorable for the hardening of the seafloor and the development of the microbial mats. The scarcity of an autochthonous benthic fauna and of burrowing, as well as the presence of framboidal pyrite suggest dysaerobic conditions. In such an environment, iron would have been in its soluble state (Fe²⁺) and the activity of micro-aerophylic iron-oxidizing bacteria appears to have been particularly intensive at the dysoxic-anoxic interface, inducing the precipitation of iron oxyhydroxides and the formation of diverse ferruginous microstromatolites.