T-RMSD: A Fine-grained, Structure-based Classification Method and its Application to the Functional Characterization of TNF Receptors

This study addresses the relation between structural and functional similarity in proteins. We introduce a novel method named tree based on root mean square deviation (T-RMSD), which uses distance RMSD (dRMSD) variations to build fine-grained structure-based classifications of proteins. The main improvement of the T-RMSD over similar methods, such as Dali, is its capacity to produce the equivalent of a bootstrap value for each cluster node. We validated our approach on two domain families studied extensively for their role in many biological and pathological pathways: the small GTPase RAS superfamily and the cysteine-rich domains (CRDs) associated with the tumor necrosis factor receptors (TNFRs) family. Our analysis showed that T-RMSD is able to automatically recover and refine existing classifications. In the case of the small GTPase ARF subfamily, T-RMSD can distinguish GTP- from GDP-bound states, while in the case of CRDs it can identify two new subgroups associated with well defined functional features (ligand binding and formation of ligand pre-assembly complex). We show how hidden Markov models (HMMs) can be built on these new groups and propose a methodology to use these models simultaneously in order to do fine-grained functional genomic annotation without known 3D structures. T-RMSD, an open source freeware incorporated in the T-Coffee package, is available online.     

Myotubes from Severely Obese Type 2 Diabetic Subjects Accumulate Less Lipids and Show Higher Lipolytic Rate than Myotubes from Severely Obese Non-Diabetic Subjects

About 80% of patients with type 2 diabetes are classified as overweight. However, only about 1/3 of severely obese subjects have type 2 diabetes. This indicates that several severely obese individuals may possess certain characteristics that protect them against type 2 diabetes. We therefore hypothesized that this apparent paradox could be related to fundamental differences in skeletal muscle lipid handling. Energy metabolism and metabolic flexibility were examined in human myotubes derived from severely obese subjects without (BMI 44±7 kg/m²) and with type 2 diabetes (BMI 43±6 kg/m²). Lower insulin sensitivity was observed in myotubes from severely obese subjects with type 2 diabetes. Lipolysis rate was higher, and oleic acid accumulation, triacylglycerol content, and fatty acid adaptability were lower in myotubes from severely obese subjects with type 2 diabetes compared to severely obese non-diabetic subjects. There were no differences in lipid distribution and mRNA and protein expression of the lipases HSL and ATGL, the lipase cofactor CGI-58, or the lipid droplet proteins PLIN2 and PLIN3. Glucose and oleic acid oxidation were also similar in cells from the two groups. In conclusion, myotubes established from severely obese donors with established type 2 diabetes had lower ability for lipid accumulation and higher lipolysis rate than myotubes from severely obese donors without diabetes. This indicates that a difference in intramyocellular lipid turnover might be fundamental in evolving type 2 diabetes.     

Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells

Circadian cycles and cell cycles are two fundamental periodic processes with a period in the range of 1 day. Consequently, coupling between such cycles can lead to synchronization. Here, we estimated the mutual interactions between the two oscillators by time‐lapse imaging of single mammalian NIH3T3 fibroblasts during several days. The analysis of thousands of circadian cycles in dividing cells clearly indicated that both oscillators tick in a 1:1 mode‐locked state, with cell divisions occurring tightly 5 h before the peak in circadian Rev‐Erbα‐YFP reporter expression. In principle, such synchrony may be caused by either unidirectional or bidirectional coupling. While gating of cell division by the circadian cycle has been most studied, our data combined with stochastic modeling unambiguously show that the reverse coupling is predominant in NIH3T3 cells. Moreover, temperature, genetic, and pharmacological perturbations showed that the two interacting cellular oscillators adopt a synchronized state that is highly robust over a wide range of parameters. These findings have implications for circadian function in proliferative tissues, including epidermis, immune cells, and cancer.     

Forces,failles et opportunités de la recherche française en écologie trophique

The French National Institute of Ecology and Environment (INEE) aims at fostering pluridisciplinarity in Environmental Science and, for that purpose, funds ex muros research groups (GDR) on thematic topics. Trophic ecology has been identified as a scientific field in ecology that would greatly benefit from such networking activity, as being profoundly scattered. This has motivated the seeding of a GDR, entitled “GRET”. The contours of the GRET's action, and its ability to fill these gaps within trophic ecology at the French national scale, will depend on the causes of this relative scattering. This study relied on a nationally broadcasted poll aiming at characterizing the field of trophic ecology in France. Amongst all the unique individuals that fulfilled the poll, over 300 belonged at least partly to the field of trophic ecology. The sample included all French public research institutes and career stages. Three main disruptions within the community of scientist in trophic ecology were identified. The first highlighted the lack of interfaces between microbial and trophic ecology. The second evidenced that research questions were strongly linked to single study fields or ecosystem type. Last, research activities are still quite restricted to the ecosystem boundaries. All three rupture points limit the conceptual and applied progression in the field of trophic ecology. Here we show that most of the disruptions within French Trophic Ecology are culturally inherited, rather than motivated by scientific reasons or justified by socio-economic stakes. Comparison with the current literature confirms that these disruptions are not necessarily typical of the French research landscape, but instead echo the general weaknesses of the international research in ecology. Thereby, communication and networking actions within and toward the community of trophic ecologists, as planned within the GRET's objectives, should contribute to fill these gaps, by reintegrating microbes within trophic concepts and setting the seeds for trans- and meta-ecosystemic research opportunities. Once the community of trophic ecologists is aware of the scientific benefit in pushing its boundaries forwards, turning words and good intentions into concrete research projects will depend on the opportunities to obtain research funding.     

PtxtPME1 and homogalacturonans influence xylem hydraulic properties in poplar

While the xylem hydraulic properties, such as vulnerability to cavitation (VC), are of paramount importance in drought resistance, their genetic determinants remain unexplored. There is evidence that pectins and their methylation pattern are involved, but the detail of their involvement and the corresponding genes need to be clarified. We analyzed the hydraulic properties of the 35S::PME1 transgenic aspen that ectopically under‐ or over‐express a xylem‐abundant pectin methyl esterase, PtxtPME1. We also produced and analyzed 4CL1::PGII transgenic poplars expressing a fungal polygalacturonase, AnPGII, under the control of the Ptxa4CL1 promoter that is active in the developing xylem after xylem cell expansion. Both the 35S::PME1 under‐ and over‐expressing aspen lines developed xylem with lower‐specific hydraulic conductivity and lower VC, while the 4CL1::PGII plants developed xylem with a higher VC. These xylem hydraulic changes were associated with modifications in xylem structure or in intervessel pit structure that can result in changes in mechanical behavior of the pit membrane. This study shows that homogalacturonans and their methylation pattern influence xylem hydraulic properties, through its effect on xylem cell expansion and on intervessel pit properties and it show a role for PtxtPME1 in the xylem hydraulic properties.     

Cricket calling communities as an indicator of the invasive ant <Emphasis Type="Italic">Wasmannia auropunctata</Emphasis> in an insular biodiversity hotspot

Invasive species are a major concern for the maintenance of ecosystem services and biodiversity but are difficult to mitigate. Upstream solutions to prevent their impact, including their detection, are needed. Wasmannia auropunctata, an invasive ant living in vagile supercolonies, is especially hard to track and is a major threat for tropical ecosystems and local animal communities. As part of such tropical communities, crickets are sensitive to ecological conditions, easy to collect, detectable and identifiable through their species-specific calls. Here, we evaluated the use of an acoustic community of crickets as an indicator of the presence of W. auropunctata in New Caledonia. We evaluated the dominance of the crickets in the soundscape, describe the cricket community structure and diversity along a shrubland to forest gradient, characterize these cricket communities structure and diversity in the light of ongoing invasion by W. auropunctata, and identify cricket species’ indicators of the invasion. Acoustic recordings collected on 24 sites were described using human-listening and spectrographic visualization. The results demonstrated a clear dominance of the cricket group in the New Caledonian nocturnal soundscapes. Each habitat harbored a specific acoustic cricket community related to specific environmental attributes including vegetation height, daily variation of humidity and temperature. The presence of W. auropunctata was significantly associated with a lower cricket acoustic activity and species richness at night. Of the 19 species detected, four nocturnal species were identified as indicator of non-invaded forests and preforests. This work supports the use of acoustic as an alternative method to detect invasion.     

A chemotaxonomic survey of kaurene derivatives in the genus Alepidea (Apiaceae)

Lipophilic extracts from the roots of 16 species of Alepidea were studied by GC-MS for the presence of kaurenoic acids, dehydrokaurenoic acids, kaurenic lactones, hydroxykaurenoic acids and other kaurene derivatives. Various mixtures of these compounds are present in yields of up to 11.8% dry wt. in the rhizomes and roots. Two different isomers of kaurenoic acid occur in Alepidea, the one as a major compound in all the species, the other as a major compound only in some of them. The first isomer is clearly a useful chemical marker for the genus Alepidea, but the apparent chemical dichotomy is not obviously correlated with morphological patterns. Alepidea amatymbica, however, is part of a morphologically isolated group within the genus and also differs from other species in its chemical complexity and in the unique presence of kaurenoic lactones.