A fossil stemmiulid millipede (Diplopoda: Stemmiulida) from the Miocene amber of Simojovel,Chiapas, México

A fossil millipede representative of the order Stemmiulida is described on the basis of a well-preserved adult female trapped in amber from the Miocene of Simojovel, Chiapas, south-eastern México. The fossil specimen is named as Parastemmiulus elektron, a new genus and species. As observed in extant stemmiulids, this fossil shows a reduced number of ocelli, the distal larger than the proximal, as well as a total of 46 trunk segments including 2 apodous segments in front of the telson. The head of this ancient stemmiulid has three ocelli and a Tömösváry organ, characteristics not reported before in Stemmiulida, requiring the diagnosis of the order to be emended.http://zoobank.org/urn:lsid:zoobank.org:pub:361400A8-37D4-421F-B4FD-A0AE63BE538C     

Dioxygenase from Aspergillus fumigatus MC8: molecular modelling and in silico studies on enzyme–substrate interactions

Flavoenzymes have been extensively studied for their structural and mechanistic properties because they find potential application as industrial biocatalysts. They are attractive for biocatalysis because of the selectivity, controllability and efficiency of their reactions. Some of these enzymes catalyse the oxidative modification of protein substrates. Among them oxygenases (monoxoygenases and dioxygenases) are of special interest because they are highly entantio as well as regio-selective and can be used for oxyfunctionalisation. Dioxygenase enzymes catalyse oxygenation reactions in which both di-oxygen atoms are incorporated into the product. A dioxygenase enzyme purified from Aspergillus fumigatus MC8 was subjected to protein digestion followed by peptide sequencing. The sequence analysis of the peptide fragments resulted in identifying its match with that of an extracellular dioxygenase sequence from the same species of fungus existing in the protein database. The sequence was submitted to protein homology/analogy recognition engine online server for homology modelling and the 3D structure was predicted. Subsequently, the in silico studies of the enzyme–substrate (protein–ligand) interaction were carried out by using the method of molecular docking simulations wherein the modelled dioxygenase enzyme (protein) was docked with the substrates (ligands), catechin and epicatechin.     

The Golgi Protein ACBD3, an Interactor for Poliovirus Protein 3A,Modulates Poliovirus Replication

We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence.     

Political mobilization of a regional minority: Han Chinese settlers in Xinjiang

The tumultuous events of summer 2009 have brought Uighur protests and minority mobilization in the Xinjiang Uighur Autonomous Region (XUAR) to the forefront. But this focus overlooks similar protests organized by various groups of Han Chinese settlers over the years. This paper contributes to the body of literature on minority mobilization and ethnic relations in Xinjiang by illustrating how the political mobilization of a group that is simultaneously a national majority and a regional minority differs substantially from ‘traditional’ minority mobilization. Reviewing the main instances of Han Chinese political mobilization since the XUAR was created in 1955, I argue that two factors are particularly important in enabling their mobilization: the Han Chinese's subjective perception of discrimination and their close ethnic ties to the state. This paper concludes with a discussion on the presence of a cycle of protests between Han settlers and the Uighurs in Xinjiang.     

Role of Glycoside Phosphorylases in Mannose Foraging by Human Gut Bacteria

To metabolize both dietary fiber constituent carbohydrates and host glycans lining the intestinal epithelium, gut bacteria produce a wide range of carbohydrate-active enzymes, of which glycoside hydrolases are the main components. In this study, we describe the ability of phosphorylases to participate in the breakdown of human N-glycans, from an analysis of the substrate specificity of UhgbMP, a mannoside phosphorylase of the GH130 protein family discovered by functional metagenomics. UhgbMP is found to phosphorolyze β-d-Manp-1,4-β-d-GlcpNAc-1,4-d-GlcpNAc and is also a highly efficient enzyme to catalyze the synthesis of this precious N-glycan core oligosaccharide by reverse phosphorolysis. Analysis of sequence conservation within family GH130, mapped on a three-dimensional model of UhgbMP and supported by site-directed mutagenesis results, revealed two GH130 subfamilies and allowed the identification of key residues responsible for catalysis and substrate specificity. The analysis of the genomic context of 65 known GH130 sequences belonging to human gut bacteria indicates that the enzymes of the GH130_1 subfamily would be involved in mannan catabolism, whereas the enzymes belonging to the GH130_2 subfamily would rather work in synergy with glycoside hydrolases of the GH92 and GH18 families in the breakdown of N-glycans. The use of GH130 inhibitors as therapeutic agents or functional foods could thus be considered as an innovative strategy to inhibit N-glycan degradation, with the ultimate goal of protecting, or restoring, the epithelial barrier.     

Inverted Repeats and Genome Architecture Conversions of Terrestrial Isopods Mitochondrial DNA

Mitochondrial DNA (mtDNA) is usually depicted as a circular molecule, however, there is increasing evidence that linearization of mtDNA evolved independently many times in organisms such as fungi, unicellular eukaryotes, and animals. Recent observations in various models with linear mtDNA revealed the presence of conserved inverted repeats (IR) at both ends that, when they become single-stranded, may be able to fold on themselves to create telomeric-hairpins involved in genome architecture conversions. The atypical mtDNA of terrestrial isopods (Crustacea: Oniscidea) composed of linear monomers and circular dimers is an interesting model to study genome architecture conversions. Here, we present the mtDNA control region sequences of two species of the genus Armadillidium: A. vulgare and A. pelagicum. All features of arthropods mtDNA control regions are present (origin of replication, poly-T stretch, GA and TA-rich blocks and one variable domain), plus a conserved IR. This IR can potentially fold into a hairpin structure and is present in two different orientations among the A. vulgare populations: either in one sense or in its reverse complement. This polymorphism, also observed in a single individual (heteroplasmy), might be a signature of genome architecture conversions from linear to circular monomeric mtDNA via successive opening and closing of the molecules.     

Estimating the age structure of a buried adult population: A new statistical approach applied to archaeological digs in France

Paleodemographers have developed several methods for estimating the age structure of historical populations in absence of civil registration data. Starting from biological indicators alone, they use a reference population of known sex and age to assess the conditional distribution of the biological indicator given age. However, the small amount of data available and the unstable nature of the related statistical problem mean that most methods are disappointing. Using the most reliable reference data possible, we propose a simple statistical method, integrating the maximum amount of information included in the actual data, which quite significantly improves age estimates for a buried population. Here the method is applied to a French cemetery used from Late Antiquity to the end of the Early Middle Ages. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Partitioning of genetic variation across the genome using multimarker methods in a wild bird population

The underlying basis of genetic variation in quantitative traits, in terms of the number of causal variants and the size of their effects, is largely unknown in natural populations. The expectation is that complex quantitative trait variation is attributable to many, possibly interacting, causal variants, whose effects may depend upon the sex, age and the environment in which they are expressed. A recently developed methodology in animal breeding derives a value of relatedness among individuals from high‐density genomic marker data, to estimate additive genetic variance within livestock populations. Here, we adapt and test the effectiveness of these methods to partition genetic variation for complex traits across genomic regions within ecological study populations where individuals have varying degrees of relatedness. We then apply this approach for the first time to a natural population and demonstrate that genetic variation in wing length in the great tit (Parus major) reflects contributions from multiple genomic regions. We show that a polygenic additive mode of gene action best describes the patterns observed, and we find no evidence of dosage compensation for the sex chromosome. Our results suggest that most of the genomic regions that influence wing length have the same effects in both sexes. We found a limited amount of genetic variance in males that is attributed to regions that have no effects in females, which could facilitate the sexual dimorphism observed for this trait. Although this exploratory work focuses on one complex trait, the methodology is generally applicable to any trait for any laboratory or wild population, paving the way for investigating sex‐, age‐ and environment‐specific genetic effects and thus the underlying genetic architecture of phenotype in biological study systems.     

Determination of the binding mode and interacting amino-acids for dibasic H3 receptor antagonists

Due to its involvement in major CNS functions, the histamine H3 receptor (H3R) is the subject of intensive medicinal chemistry investigation, supported by the range of modern drug discovery tools, such as receptor modeling and ligand docking. Although the receptor models described to date share a majority of common traits, they display discrete alternatives in amino-acid conformation, rendering ligand binding modes quite different. Such variations impede structure-based drug design in the H3R field. In the present study, we used a combination of medicinal chemistry, receptor-guided and ligand-based methods to elucidate the binding mode of antagonists. The approaches converged towards a ligand orientation perpendicular to the membrane plane, bridging Glu206 of the transmembrane helix 5 to acidic amino acids of the extracellular loops. This consensus will help future structure-based drug design for H3R ligands.