Integrative modeling of protein-protein interactions with pyDock for the new docking challenges

The seventh CAPRI edition imposed new challenges to the modeling of protein-protein complexes, such as multimeric oligomerization, protein-peptide, and protein-oligosaccharide interactions. Many of the proposed targets needed the efficient integration of rigid-body docking, template-based modeling, flexible optimization, multiparametric scoring, and experimental restraints. This was especially relevant for the multimolecular assemblies proposed in the CASP12-CAPRI37 and CASP13-CAPRI46 joint rounds, which were described and evaluated elsewhere. Focusing on the purely CAPRI targets of this edition (rounds 38-45), we have participated in all 17 assessed targets (considering heteromeric and homomeric interfaces in T125 as two separate targets) both as predictors and as scorers, by using integrative modeling based on our docking and scoring approaches: pyDock, IRaPPA, and LightDock. In the protein-protein and protein-peptide targets, we have also participated with our webserver (pyDockWeb). On these 17 CAPRI targets, we submitted acceptable models (or better) within our top 10 models for 10 targets as predictors, 13 targets as scorers, and 4 targets as servers. In summary, our participation in this CAPRI edition confirmed the capabilities of pyDock for the scoring of docking models, increasingly used within the context of integrative modeling of protein interactions and multimeric assemblies.     

hCOA3 Stabilizes Cytochrome c Oxidase 1 (COX1) and Promotes Cytochrome c Oxidase Assembly in Human Mitochondria

Cytochrome c oxidase (COX) or complex IV of the mitochondrial respiratory chain plays a fundamental role in energy production of aerobic cells. In humans, COX deficiency is the most frequent cause of mitochondrial encephalomyopathies. Human COX is composed of 13 subunits of dual genetic origin, whose assembly requires an increasing number of nuclear-encoded accessory proteins known as assembly factors. Here, we have identified and characterized human CCDC56, an 11.7-kDa mitochondrial transmembrane protein, as a new factor essential for COX biogenesis. CCDC56 shares sequence similarity with the yeast COX assembly factor Coa3 and was termed hCOA3. hCOA3-silenced cells display a severe COX functional alteration owing to a decreased stability of newly synthesized COX1 and an impairment in the holoenzyme assembly process. We show that hCOA3 physically interacts with both the mitochondrial translation machinery and COX structural subunits. We conclude that hCOA3 stabilizes COX1 co-translationally and promotes its assembly with COX partner subunits. Finally, our results identify hCOA3 as a new candidate when screening for genes responsible for mitochondrial diseases associated with COX deficiency.     

Révision du genre Pycnomorphus Thomson, 1864. Systématique et phylogénie (Coleoptera : Lamiinae,Acanthoderini)

Le genre Pycnomorphus Thomson est révisé et quatre espèces nouvelles sont décrites: Pycnomorphus guyanensis n. sp., P. pradosiae n. sp.et P. sarryi n. sp. de Guyane, et P. batesi n. sp. du Nicaragua. Un genre nouveau Pycnomorphidiellus n. gen. est créé pour une nouvelle espèce de Guyane, P. polyphagus n. sp. Une analyse cladistique et une clef d’identification des espèces complètent ce travail.     

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.     

Food security versus biodiversity protection: an example of land-sharing from East Africa

The recent controversial debate on land-sharing versus land-sparing is clearly exemplified in the East African mountains, one of the most diverse biodiversity hotspots on our planet. In these areas, species richness is particularly concentrated in the mountain cloud forests which are surrounded by a sea of dry lowland savannas heavily encroached on by local communities. Sustainable land use practices in the lowlands, however, are necessary to safeguard the natural capital at higher elevations. The interdependence between sustainable land-use and conservation of biodiversity hotspots was underlined during a workshop held in the rural areas of Kenya, East Africa, early spring 2013. It was concluded that close links between livelihoods, natural capital and poverty remains a fundamental challenge in East Africa’s forest conservation efforts.     

Assessment of Overlap of Phylogenetic Transmission Clusters and Communities in Simple Sexual Contact Networks: Applications to HIV-1

Background

Transmission patterns of sexually-transmitted infections (STIs) could relate to the structure of the underlying sexual contact network, whose features are therefore of interest to clinicians. Conventionally, we represent sexual contacts in a population with a graph, that can reveal the existence of communities. Phylogenetic methods help infer the history of an epidemic and incidentally, may help detecting communities. In particular, phylogenetic analyses of HIV-1 epidemics among men who have sex with men (MSM) have revealed the existence of large transmission clusters, possibly resulting from within-community transmissions. Past studies have explored the association between contact networks and phylogenies, including transmission clusters, producing conflicting conclusions about whether network features significantly affect observed transmission history. As far as we know however, none of them thoroughly investigated the role of communities, defined with respect to the network graph, in the observation of clusters.

Methods

The present study investigates, through simulations, community detection from phylogenies. We simulate a large number of epidemics over both unweighted and weighted, undirected random interconnected-islands networks, with islands corresponding to communities. We use weighting to modulate distance between islands. We translate each epidemic into a phylogeny, that lets us partition our samples of infected subjects into transmission clusters, based on several common definitions from the literature. We measure similarity between subjects’ island membership indices and transmission cluster membership indices with the adjusted Rand index.

Results and Conclusion

Analyses reveal modest mean correspondence between communities in graphs and phylogenetic transmission clusters. We conclude that common methods often have limited success in detecting contact network communities from phylogenies. The rarely-fulfilled requirement that network communities correspond to clades in the phylogeny is their main drawback. Understanding the link between transmission clusters and communities in sexual contact networks could help inform policymaking to curb HIV incidence in MSMs.     

Application of high-voltage electrical discharges and high-pressure homogenization for recovery of intracellular compounds from microalgae Parachlorella kessleri

Treatments with high-voltage electrical discharges (HVED) and high-pressure homogenization (HPH) were studied and compared for the release of ionic components, carbohydrates, proteins, and pigments from microalgae Parachlorella kessleri (P. kessleri). Suspensions (1% w/w) of microalgae were treated by HVED (40 kV/cm, 1–8 ms) or by HPH (400–1200 bar, 1–10 passes). Particle-size distribution (PSD) and microscopic analyses were used to detect the disruption and damage of cells. HVED were very effective for the extraction of ionic cell components and carbohydrates (421 mg/L after 8 ms of the treatment). However, HVED were ineffective for pigments and protein extraction. The concentration of proteins extracted by HVED was just 750 mg/L and did not exceed 15% of the total quantity of proteins. HPH permitted an effective release overall of intracellular compounds from P. kessleri microalgae including a large quantity of proteins, whose release (at 1200 bar) was 4.9 times higher than that obtained by HVED. Consequently, HVED can be used at the first step of the overall extraction process for the selective recovery of low-molecular-weight components. HPH can be then used at the second step for the recovery of remaining cell compounds.

     

Emerging techniques for cell disruption and extraction of valuable bio-molecules of microalgae Nannochloropsis sp.

Bioprocess and Biosystems Engineering - Microalgae of Nannochloropsis sp. present valuable source of bio-molecules (pigments, lipids, proteins) that have nutritional potential for the...