Recent HIV-1 infection contributes to the viral diffusion over the French territory with a recent increasing frequency

Objective

To analyse the contribution of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) to the French viral epidemic.

Methods

HIV-1 pol sequences included 987 PHI from the French ANRS PRIMO cohort between 1999 and 2010 and were analysed using a population-based phylogenetic approach. Clinical features, risk factors, sexual behaviour and drug resistance for clustered and nonclustered transmission events were ascertained.

Results

Viruses from 125 (12.7%) of PHI cosegregated into 56 transmission chains, with increasing frequency during the last years (10.2% before 2006 versus 15.2% of clusters in 2006–2010, p = 0.02). The mean number of patients per cluster was 2.44. Compared to unique PHI, clusters involved more often men, infected through homosexual intercourse, of young age, with a high number of casual sexual partnerships and frequent previous HIV serological tests. Resistant strains were found in 16.0% and 11.1% of clusters and unique PHI, respectively (p = 0.11). Overall, 34% (n = 19) clusters included patients followed in French regions far apart, involving 13 clusters with at least one Parisian patient.

Conclusions

PHIs are a significant source of onward transmission, especially in the MSM population. Recently infected people contribute to the spread of the viral epidemic throughout the French territory. Survey of transmitted drug resistance and behavioural characteristics of patients involved into clustered PHI may help to guide prevention and treatment interventions.     

Niche partitioning of the genetic lineages of the oak powdery mildew complex

Recent molecular studies have shown that four genetic lineages, probably cryptic species, cause oak powdery mildew in Europe. We tested the hypothesis of niche differentiation between the two most frequent species (Erysiphe alphitoides and Erysiphe quercicola), by determining their relative prevalences at various times during the growing season. E. quercicola was strictly associated with the flag-shoot symptom in a 2-yr sampling campaign of 35 natural oak seedling populations. Additional sampling during Aug.–Sep. in the same stands showed that E. alphitoides predominated in most (70 %) cases. Time-course monitoring of powdery mildew in two natural regenerating oak populations confirmed the inverse patterns of relative abundance for these two species in early and late season. The coexistence of these two closely related species may be due to the use of different strategies, resulting from a trade-off between overwintering (flag-shoots vs. chasmothecia) and late-season performance.     

Metabolic control analysis is helpful for informed genetic manipulation of oilseed rape (Brassica napus) to increase seed oil content

Top-down control analysis (TDCA) is a useful tool for quantifying constraints on metabolic pathways that might be overcome by biotechnological approaches. Previous studies on lipid accumulation in oilseed rape have suggested that diacylglycerol acyltransferase (DGAT), which catalyses the final step in seed oil biosynthesis, might be an effective target for enhancing seed oil content. Here, increased seed oil content, increased DGAT activity, and reduced substrate:product ratio are demonstrated, as well as reduced flux control by complex lipid assembly, as determined by TDCA in Brassica napus (canola) lines which overexpress the gene encoding type-1 DGAT. Lines overexpressing DGAT1 also exhibited considerably enhanced seed oil content under drought conditions. These results support the use of TDCA in guiding the rational selection of molecular targets for oilseed modification. The most effective lines had a seed oil increase of 14%. Moreover, overexpression of DGAT1 under drought conditions reduced this environmental penalty on seed oil content.     

Efficient purification of small unsaturated oligoglucuronides by reversed-phase chromatography

Ion-exchange chromatography has been applied to purification of unsaturated oligoglucuronans. After an isocratic elution on a strong anion-exchange column, the collected fractions were desalted by low pressure size exclusion chromatography. However, this efficient separation was limited by the time required to desalt. So, we developed a reversed-phase chromatography method using back ionization of oligomers. Two C18 columns were tested with trifluoroacetic acid (TFA 0.7%) as eluent. Different selectivities and column stabilities were observed in this acidic condition. The scale up for semi-preparative applications enabled us to recover pure unsaturated oligoglucuronans without desalting step.     

Muscle dystroglycan organizes the postsynapse and regulates presynaptic neurotransmitter release at the Drosophila neuromuscular junction

Background

The Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila.

Methodology/Principal Findings

We show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site.

Conclusion/Significance

Altogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg.     

Lipid raft localization and palmitoylation: identification of two requirements for cell death induction by the tumor suppressors UNC5H

UNC5H receptors (UNC5H1, UNC5H2, UNC5H3) are putative tumor suppressors whose expression is lost in numerous cancers. These receptors have been shown to belong to the so-called family of dependence receptors. Such receptors induce apoptosis when their ligand netrin-1 is absent, thus conferring a state of cellular dependence towards ligand presence. Along this line, these receptors may limit tumor progression because they induce the death of tumor cells that grow in settings of ligand unavailability. We show here that UNC5H receptors are localized to cholesterol-and sphingolipid-enriched membrane domains called lipid rafts. We then demonstrate that the lipid raft localization of UNC5H2 is required for the pro-apoptotic activity of unbound UNC5H2. We also propose that this lipid raft localization is probably mediated via the recruitment of adaptor protein(s) within the death domain of UNC5H2 but is not dependent on the post-translational modification by palmitoylation of UNC5H2 even though this palmitoylation is required for UNC5H2 pro-apoptotic activity. Moreover we show that the interaction of UNC5H2 with the downstream pro-apoptotic serine threonine kinase DAPk is dependent on both UNC5H2 lipid raft localization and palmitoylation. Thus, we propose that the UNC5H dependence receptors require lipid raft localization and palmitoylation to trigger apoptosis.     

Simulation of potential range expansion of oak disease caused by Phytophthora cinnamomi under climate change

This study examines the effects of climate warming on one of the most widely distributed and destructive forest pathogens, Phytophthora cinnamomi. In Europe, the winter survival of the pathogen is the dominant cue for the development of the disease it causes to oaks, especially Quercus robur and Q. rubra. The potential pathogen and disease geographic ranges were compared in France between two reference periods, 1968–1998 and 2070–2099. Simulations were obtained by combining a physiologically based approach predicting the pathogen winter survival in relation to microhabitat temperature (in the phloem of infected trees) with a regionalized climatic scenario derived from a global circulation model. Positive anomalies in winter temperatures calculated with this scenario were in the range 0.5–5°C between the periods 2070–2099 and the 1968–1998, according to sites and months. As a consequence, higher annual rates of P. cinnamomi survival were predicted, resulting in a potential range expansion of the disease of one to a few hundred kilometers eastward from the Atlantic coast within one century. Based on this example, the study emphasizes the need of a better understanding of the impacts of global change on the biotic constraint constituted by plant pathogens.